A B C

1 Drug Mech of action (& 2nd Messenger) Uses

2
Repro Drug List
Long acting form of GnRH which down
regulates the GnRH receptors on the
gonadotropin cells (anterior pituitary) -
decrease respond to the normal cyclic
3 GnRH surges and LH (and FSH) will not
be produced. Because of lack of LH,
Leydig cells will not produce testicular and prostate cancer, polycystic ovary dz, as well
testosterone. Suppression of the as endometriosis in women (testosterone is a precursor for
Leuprolide HPGonadal axis estrogen); uterine fibroids, precocious puberty; (BPH?)
Treat BPH, Hirsutism and Other Disorders of Androgen
4
Flutamide Androgen receptor antagonist Excess; tx prostatic carcinoma
Potassium sparing diuretic with
5 Androgen receptor blocking function,
Spironolactone see diuretics Hirsutism and Other Disorders of Androgen Excess
Ornithine decarboxylase inhibitor;
6 mechanism of retarding hair growth is not
Eflornithine cream clear FDA approved for treating hirsutism

5-alpha-reductase type II inhibitor,

7 prevents formation of
dihydrotestosterone from testosterone
(DHT synthesis inhibitor) - physically Useful for treating Benign Prostate Hypertrophy (BPH),
Finasteride reduce size of prostate Alopecia

8 5a-reductase type I & II inhibitor, DHT

synthesis inhibitor - physically reduce Useful for treating Benign Prostate Hypertrophy (BPH),
Dutasteride size of prostate Alopecia

Selective 1A blocker - contracts Benign prostatic hypertrophy, prostate has greater number
Tamsulosin prostate smooth muscle of 1A receptors expressed than other tissues.
 A B C

10
Hypertension. See adrengic blockers
Benign prostatic hypertrophy: This use is rapidly being
1-Selective Blockers, see adrenergic supplanted by the 1A selective agents (tamsulosin) which
Terazosin (Hytrin) blockers does not produce orthostatic hypotension

11 Same uses and liabilities as terazosin or prazosin

1-Selective Blockers, see adrenergic Long elimination half-life (24 hr) makes once daily dosing
Doxazosin (Cardura) blockers feasible

12 Estrogen receptor antagonist -

prevents negative feedback to HPO axis,
increases number of follicles to reach
Clomiphene (Clomid) maturity, see extra notes Fertility agent
13 ICI 182,780 (Faslodex): pure anti-estrogen

Parasympathetic (NOT cholinergic!)

stimulation of NO synthetase in the
penis increases NO which increases
14 cGMP which causes vasodialtion of the
corpus cavernosum and spongiosum.
Sildendafil is a phosphodiesterase
inhibitor, which decreases the
Sildenafil (Viagra) breakdown of cGMP Erectile Dysfuntion (4 hr duration)

15
Vardenafil (Levitra) phosphodiesterase inhibitor Erectile Dysfuntion (4 hr duration), faster onset

16

Tadalafil (Cialis) phosphodiesterase inhibitor Erectile Dysfuntion (24-36 hr duration)

Testosterone-enanthate antagonism of prolactin at the mammary suppress lactation before it begins, depot injection given right
17
with estradiol-valerate gland after delivery.

18 Ergot alkaloids: suppresson of lactation

through stimulation of dopamine Treat galactorrhea (by lactation suppression); treat
receptors (D2) and inhibition of prolactin Hypreprolactinemia (especially prolactin secreting
Bromocryptine (Parlodel) secretion adenomas), tx Parkinson's dz
 A B C
Treat galactorrhea (by lactation suppression); treat
19 Ergoline derivative: Longer half life Hypreprolactinemia (especially prolactin secreting
Cabergoline (~65 hr) than Bromocriptine adenomas)

Hormonal agent: a Antiestrogen -

20 Chemopreventive agent in women at
high risk for breast Ca; competitive
partial agonist/antagonist of estrogen
Tamoxifen receptors in estrogen-sensitive tumors. Tx estrogen-receptor-positive breast cancer

SERMS (specific estrogen receptor

modulators): Partial agonist-antagonist
21 at estrogen receptors; Estrogen
derivative having estrogen agonist effects
on the bone and limited effects in breast Tx breast cancer (no increased risk of endometrial
and uterus (no stimulatory effect on cancer); Positive effects on bone and lipids (and brain?) - tx
Raloxifene endometrium or breast) osteoporosis, see endocrine section

22

Replacement of estrogen, see extra Menopause: vasomotor flushes, atrophic vaginitis, osteoporsis
Estrogen (HRT - hormonal notes for physiologic effect and (contoversial, and effectiveness gradually decreases),
replacement therapy) preparations coronary artery disease

23
Ethinyl Estradiol
24 Diethylstilbestrol (DES) Non-steroidal estrogen Post coital contraceptive (eg used after rape)
 A B C

25

High circulating progesterone & estrogen

mimic luteal or pregnancy hormone
concentrations. These steroids by
"The Pile" (Oral negative feedback suppress the
Contraceptive): preovulatory surge of LH and therefore
Progesterone/estrogen ovulation. Birth control - Contraceptive
Does not prevent ovulation or
fertilization but does prevent
26 implantation either by changing the Birth control - Interfere with implantation; for those women
arrival timing of the blastocyst or by who are at risk for certain estrogen-dependent cancers
"The Mini-Pill": Progestin making uterine conditions (motility or Does not decrease milk production and may be an option for
only secretory) unreceptive. lactating women
silastic tubes implanted subcutaneoulsy,
progesterone is slowly released over an
27 extended period and provides a
pharmacologic effect similar to the mini
Norgestrel (Implant) pill

Progestoren Challenge test!! (see extra notes)

28 Contraceptive; used especially for pt with risk of estrogen
dependent neoplasia;
Amenorrhea (especially in <16yo, as E may interfer with
HPOU axis); oral or IM (depot form), long half-life; good for
women needing estrogen free contraception, (breast feeding,
Medroxyprogesterone sickle cell disease, seizure disorders), and women who cannot
acetate (Depo-provera) Progesterone derivative remember to take the pill (teenagers)
Progesterone derivative (19-nor-
29
Norethindrone testosterone derivatives)

30 Progesterone derivative (19-nor- Used in OCs, (not as androgenic as Norethindrone), treat

Desogestrel testosterone derivatives) hirsutism, see extra notes
Progesterone derivative (19-nor- Used in OCs, (not as androgenic as Norethindrone), treat
31
Norgestimate testosterone derivatives) hirsutism, see extra notes
 A B C
Progesterone derivative: (19-nor-
32 testosterone derivatives) 100 times
more potent as a progestin than
Norgestrel norethindrone Used in OCs and implantable contraceptive preparation

Progesterone derivative: very low

33 androgenicity; has even been reported
to have anti-androgenic effects similar in Used in OCs, (not as androgenic as Norethindrone), treat
Drospirenone efficacy to Spironolactone hirsutism, see extra notes; decreased Na and water retention

34
Plan B post coital contraceptive
Levonorgestrel (Plan B) Progesterone derivative Contains high concentration of levonorgestrel (P)

35

Testosterone Androgen
36 Dihydrotestosterone Androgen

37 Androgen; long acting ester of T - Takes

Testosterone Cypionate longer to eliminate
Testosterone androgen: 17-alkyl
38 derivative, this modification increases it
Methyltestosterone elimination time
Androgen; 17-alkyl derivative of Treat anemia caused by deficient RBC (ie Acquired aplastic
39
Oxymetholone testosterone; anabolic; anemia, Myelofibrosis, Hypoplastic anemia)
Progesterone antagonist; also an anti-
40
Mifepristone (or RU486) glucocorticoid t : ~20 hrs Post coital contraceptive
Inhibits the midcycle surge of LH and
41 FSH (feedback regulator, kind of an
estrogen and progesterone
Danazol antagonist) Tx for endometriosis
42 Testolactone aromatase inhibitors
43 Anastrozole aromatase inhibitors
 A B C

44
synthetic Prostaglandin F2alpha lifesaving tx. of postpartum hemorrhage due to uterine atony
Hemabate (PGF2alpha) via myometrial contraction

45 potent ripening of cervix & induction of labor; Notice: keeps

Cervidil Prostaglandin E2 (PGE2) ductus arteriosus open
46 indomethacin see NSAIDs Used to close patent ductus arteriosus (PDA)
Preeclampsia (severe) mandates seizure prophylaxis with
47 magnesium sulfate and control of BP with hydralazine or
Magnesium sulfate Ca channel blocker? labetalol

48
hydralazine or labetalol Control BP in pergnancy
49 Pitocin Synthetic oxytocin

50

Protection against HPV types 6, 11, 16 & 18 (reducing

Gardisil chances of developing cervical cancer (squamous))

51 Treatment for non-acute ectopic pregnancy (pts w/ early,

Methotrexate See cancer chemotherapy unruptured ectopics)
Used to maintain patency of ductus arteriosus (ie
52
Alprostadil PGE1 Transposition of the Great Arteries)
53

54
Renal Drug List
55 Diuretics
 A B C

Extremely efficacious
1. Emergency & Chronic Tx of edematous states (eg M.I.,
CHF; Pulmonary; Ascites secondary to cirrhosis, Renal failure)
- most efficacious under low Creatinine clearance
conditions; Loop diuretics are used for hypertension with
renal insufficiency; used i.v. for hypertensive emergency
2. Hypercalcemia: causes increased Mg++ and Ca++ loss
(Cause of elevated Ca++ is usually hyperparathyroidism or
malignancy, which must be Tx surgically).
56 Loop diuretics can be used as a temporary measure to reduce
hypercalcemia
3. Hypertension: Use for cases that are not responsive to
thiazides (e.g, HTN in the presence of chronic renal failure)
4. Hyperkalemia: Usually occurs secondary to insufficient
renal excretion, causes loss of resting membrane potential
Sulfonamide; loop diuretic: acting in (cardiac problems). Tx is complex. Loop diuretics are useful
loop of Henle because treating chronic renal failure with a diuretic corrects
Inhibit Na+,K+,2Cl- cotransporter the hyperkalemia (see hypokalemia Side-Effects).
(symporter - transports cations and anion 5. Anion poisoning (eg Fluoride, iodide, bromide); symporter
in the same direction with no counter-ion also reabsorbs these anions, give loop agent with NaCl)
Furosemide (lasix, transport) - transporter used by macula 6. Drug of choice for treating HTN in pts with chronic renal
prototype) densa insufficiency or heart failure.

57 Tx similar as Furosemide, for pts with sulfa allergies or

Ethacrynic acid Loop diuretic, non-sulfa prone to gouty attacks (less hyperuricemia than furosemide)

58
Torsemide Loop diuretic Once daily dosing
59 Bumetanide Loop diuretic

60

1. Prophylaxis of renal failure

Osmotic diuretic: inhibit reabsorption of 2. Decrease the pressure and volume of intraocular fluid &
water and (secondarily) Na+ (More water CSF; tx acute angle-closure glaucoma
Mannitol loss than Na loss) 3. hemodialysis
 A B C

1. Seldom used as diuretics (used for metabolic acidosis,

61
Carbonic anhydrase inhibitor: Inhibit
formation of H+ and HCO3- from CO2
and H2O (and vice versa); diminished
Acetazolamide reabsorption of HCO3- and Na+
refractoriness)
2. Glaucoma (not a diuretic effect -- they decrease production
of aqueous humor; given topically, do not gain access to
systemic circulation in high enough dose to effect kidneys).
3. Alkalinization of the urine: Potential use in poisoning with
aspirin, phenobarbital
4. Epilepsy (mechanism??, Specific to CA inhibition, not a
general effect of diuretics. Tolerance develops quickly.)
5. Mountain sickness!!
6. Reduces brain edema!!
7. Pseudotumor cerebri (reduces CSF production)

Purpose: to help eliminate excess volume to treat volume

overload disorders (e.g. edema, CHF)
1. Hypertension (should get a 10-15 mm Hg fall in pressure):
reduce blood volume (volume returns to near normal over 6-
8 weeks, but antihypertensive effect remains); reduce
vascular resistance by relaxation of arterioles (Na+ increases
vessel stiffness, so reducing Na+ relaxes arterioles); reduce
responsiveness of arterioles to NE (also because of lower
62 Na+); DOC isolated systolic HTN
2. Diabetes Insipidus (Vasopressin (ADH) dz): (Generally
controlled with vasopressin replacement), thiazides decrease
urine output by about 50% in these patients, mechanism
unknown
3. Non-emergency edematous states
Thiazide diuretic: Inhibit of Na+,Cl- 4. Hypercalciuria: Volume contraction caused by the thiazide
cotransport (Na/Cl symporter) in distal diuretics stimulates proximal tubule (PT) reabsorption of Ca++
convoluted tubule (DCT); increase urine (?????) So can use to prevent Calcium oxalate stones by
excretion by inhibiting DCT solute and volume contraction (PT will bring more solutes in, including Ca,
Hydrochlorothiazide water reabsorption to decrease Ca in urine, used only profolacticaly until surgery
(HCTZ) corrects)
more potent and has a much longer duraton of action than
63
Chlorothiazide Thiazide diuretic HCTZ
64 Chlorthalidone Thiazide diuretic

65 thiazide-like, indoline derivation

Indapamide

66
Metolazone thiazide-like
 A B C

Not very efficacious diuretics by themselves, by this point in

the transit of Na+ in the kidney, there isnt very much left
1. Used to prevent K+ loss, counteract this side-effect of
67 thiazides and loops
2. Drug of choice for primary aldosteronism syndromes
Potassium-sparing diuretic: (rare occurrence)
aldosterone receptor competitive 3. Approved for Class 4 (& 3?) CHF (prevents tissue
Spironolactone antagonist remodeling)

68 Potassium-sparing diuretic:
aldosterone receptor competitive
Eplerenone antagonist see spironalactone

Potassium-sparing diuretic: inhibit

Na+ transport by the epithelial Na
channels (ENaC) in distal tubules (DT)
69 and cortical collecting ducts; because
less Na is presented to the Na,K-ATPase
on the apical surface of the CD cells, less
Amiloride K is excreted
Not very efficacious diuretics by themselves, by this point in
the transit of Na+ in the kidney, there isnt very much left
1. DOC for treating primary aldosteronism (in men?)
2. DOC for Liddle's syndrome

70 Potassium-sparing diuretic: inhibit

Na+ transport by the ENaC in DT and
Triameterene cortical collecting ducts see amiloride, Liddle's syndrome
71 Other drugs related to HTN

Angiotensin II Receptor (AT1) Blocker

(ARB): This receptor mediates many
angiotensin II effects:
1. Constriction of vascular smooth
72
muscle
2. Release of aldosterone
3. CNS activation of sympathetic
discharge 1. Excellent efficacy as anti-hypertensives
4. Enhanced responsiveness of vascular 2. Blunt the hypokalemia caused by diuretics
Losartan smooth muscle to sympathetic activation 3. uricosuric effect, beneficial for pts with hyperuricemia
(twice daily dosing)
73 1. Excellent efficacy as anti-hypertensives
Angiotensin II Receptor Blockers 2. Blunt the hypokalemia caused by diuretics
Valsartan (ARB) 3. uricosuric effect (for pts with hyperuricemia)
 A B
74
ACE inhibitor: Block conversion of
angiotensin I to angiotensin II by
inhibiting Angiotensin Converting Enzyme
(ACE): decrease angiotensin II-mediated
release of aldosterone; decrease
breakdown of bradykinin; decrease
overly active SNS (little reflex
tachycardia), decreasing preload,
decreasing afterload which then
Captopril [Capoten] decreases BP
ACE inhibitor: pro-drug, converted in
75 liver, no SH groups (less allergy than
Enalapril (Vasotec) captopril?)
76
Lisinopril (Prinivil, Zestril) ACE inhibitor; not a pro-drug
Calcium Channel Blocker (CCB), a
dyhydropyridine: a member of the
77 dihydropyridines class; decrease Ca++
influx, resulting in smooth muscle
relaxation; vascular sm selective;
Nifedipine Block L-type Ca++ Channels
C
(twice per day)
Uses of prils in hypertension:
1. Essential hypertension
2. Efficacious and relatively minimal side-effects
3. High plasma renin
4. Diabetes mellitus (preferred anti-HTN -- dilate efferent
arterioles, reduces proteinuria)
5. Renal insufficiency
6. CHF (preferred anti-HTN decreases mortality)
(1-2 per day), same use as captopril
(once daily dosing)
same use as captopril
1. Hypertension (generally preferred for treating hypertension
over verapamil and diltiazem), efficacious, particularly for
isolated systolic HTN (esp in diabetics)
Because of their higher profile of side-effects related to
therapeutic vasodilation, less preferred than ACE-I or ARBs
 A B C

78
Calcium Channel Blocker, a
nondyhydropyridine: decrease cardiac
contractility and cardiac output, cardiac
myocytes selective (blocks L-type Ca++
Diltiazem Channels)
1. Angina (esp Prinzmetal variant angina)
2. Hypertension (Nifedipine is better; Efficacious, particularly
for isolated systolic hypertension
Because of their higher profile of side-effects related to
therapeutic vasodilation, less preferred than ACE-I or ARBs

1. Angina (esp Prinzmetal variant angina)

Calcium Channel Blocker, a
79 nondyhydropyridine: decrease Ca++
influx; decrease cardiac contractility and
cardiac output, cardiac myocytes
Verapamil selective, Block L-type Ca++ Channels
2. Hypertension (Nifedipine is better; Efficacious, particularly
for isolated systolic hypertension
Because of their higher profile of side-effects related to
therapeutic vasodilation, less preferred than ACE-I or ARBs

80 Used in CHF (produce small increase in myocardial

contracitilty and CO), especially if with concomitant HTN a/o
Amlodipine CCB, dyhydropyridine angina - also no AV block (as with verapimil/ or diltiazem)

81 Used in CHF (produce small increase in myocardial

contracitilty and CO), especially if with concomitant HTN a/o
Felodipine CCB, dyhydropyridine angina - also no AV block (as with verapimil/ or diltiazem)

82 1. (generally replaced by dihydropyridine CCBs)

Arterial Vasodilators: NO formation?
Changes in intracellular Ca++?; open
vascular ATP-sensitive potassium
channels
Hydralazine
Hypertension: reduce BP by decreasing systemic vascular
resistance
Must be combined with a beta blocker and a diuretic
Use only with caution in angina or CHF
2. Acute severe hypertension in pregnancy
(eclampsia/preeclampsia)!!
3. HF: Typically used with isosorbide dinitrate after a failure of
ACEIs (most commonly because ACEIs produced intolerable
cough)
 A B
Arterial Vasodilators: open vascular
ATP-sensitive K channels
(hyperpolarizing): decrease peripheral
83 resistance (PR), causes compensatory
responses (initiated by baroreceptors) of
increased Sympathetic Nervous System
(SNS) and increased Renin/Angiotensin
System (RAS); decreases insulin output
Minoxidil (hyperpolarizes beta cells)
Arterial Vasodilators: decrease PR,
84 causes compensatory responses
(initiated by baroreceptors) of increased
Diazoxide SNS and increased RAS
85 Arteriodilator; D1 agonist (maintains
Fenoldopam renal blood flow)
86
Venoarterial dilator: NO formation by
increasing cGMP which causes
relaxation; dilates arterioles and veins,
Nitroprusside (Sodium) decreasing myocardial oxygen demand
87
Isosorbide dinitrate see nitroprusside
C
Difficult-to-control HTN in chronic renal failure, must be
combined with a beta blocker and a diuretic
Use only with caution in angina or CHF
Used externally for hair growth (alopecia)
Hypertension: reduce BP by decreasing systemic vascular
resistance (Nearly obsolete for hypertensive emergency use)
Must be combined with a beta blocker and a diuretic
Use only with caution in angina or CHF
T1/2 = 10 min; Given by i.v. infusion
Use in HTN emergencies
Uses:
Hypertensive emergencies (see extra note), IV - monitor
pressure
CHF (with hydralazine), Short-term therapy in acute HF
Surgery (controlled hypotension)
CHF (with hydralazine), Short-term therapy in acute HF
 A B C
Nitroglycerin (NTG, see Vasodilator, a nitric oxide (NO) donor,
88
NTG cardio) see cardiac drugs for more detail Angina pectoris (ischaemic heart disease, MI)
89 Labetalol see adrenergics HTN emergencies & drug-induced HTN
90
Na Polystyrene Sulfonate Resin that exchanges Na ions for K in
91
[Kayexalate] large intestine Treat hyperkalemia
92

93 Drugs for UTI

Uncomplicated UTI: Community-acquired, young and females
Complicated UTI: Hospital-acquired infections, older persons, males

94
Structural analogues of p-aminobenzoic
acid (PABA)
Block the incorporation of PABA into folic
acid (dihydrofolic acid) by inhibiting the
Sulfonamide (class) enzyme dihydropteroate synthetase see Co-Trimoxazole
Folate Antagonist - inhibits synthesis of
95 folate; Mechanism of action of
Sulfamethoxazole (SMX) sulfonamide see Co-Trimoxazole

Folate Antagonist - inhibits reduction:

dihydro folate (TH2) to tetrahydro folate
96 (TH4 or FAH4) by blocking dihydrofolate
reductase, FAH4 is a critical precursor of
thymidine, purine, and methionine;
potentiated by Sulfamethoxazole (can
Trimethoprim (TMP) use 1/10 dose) see Co-Trimoxazole
 A B C

97
Uncomplicated UTI: E.coli
Complicated UTI: Klebsilla pneumonia & Staphyloccous
saprophyticus & Enterobacter & Acinetobacter
Prostatitis
Acute pyelonephritis.
Used to treat E. coli acute UTI
Cystitis
Combination of TMP and SMX Chronic suppressive therapy for recurrent urinary tract
Co-Trimoxazole (aka Sulfonamide & trimethoprim act infection
TMP/SMX) synergistically Usually oral

Inhibits bacterial topoisomerase II

(DNA gyrase) Active against a variety of gram (+) and gram (-) bacteria
Prevents relaxation of DNA that is Broadspectrum, primarily gram (-)
98 required for transcription and DNA Complicated UTI: multidrug-resistant bacteria
replication (Pseudomonas)
Synthetic fluorinated analogs of nalidixic To treat STDs caused by Gonococcal & Chlamydial infections
Fluroquinolones (aka acid Diarrhea caused by Shigella, Salmonella, E.coli, H. pylori
quinolones, class) Bactericidal Enterobacter, Gonorrhea, Chlamydia (STDs)

99 Prostatitis
Gonorrhea
Ciprofloxacin Fluroquinolone
100 Norfloxacin Fluroquinolone
101 Ofloxzcin Fluroquinolone

Beta-lactam antibiotics
Inhibits bacterial cell wall
peptidoglycan synthesis (cross-
linking)
102 Inhibits transpeptidase reaction
Activates autolytic enzyme (autolysin)
Bactericidal agent
Highest activity against G (+), some G
Penicillin G (-)
DOC for STD caused by Treponema pallidum (syphilis)
Augmentin = Amoxicillin + clavulanate are given orally to treat
urinary tract infection
Not effective against:
Klebsiella
Pseudomonas
Indole-positive Proteus
 A B C
Uncomplicated UTI by Proteus mirabilis, Enterococcus
103 faecalis
Acute pyelonephritis
Ampicillin a penicillin UTI with pregnancy
104 Amoxicillin a penicillin Greater bioavailability than ampicillin
Ticarcillin, Carbencillin & anit-Pseudomonas penicillins; not Complicated UTI: Pseudomonas (give with penicllin and
105
Azlocillin beta-lactamase resistant clavulanate acid)

Inhibitor of cell wall formaton by inhibiting

106 release of building block carriers
preventing peptoglycan synthesis,
similar to penicillin without beta-lactam Complicated UTI: Enterococcus faecalis (Strep D), S.
Vancomycin (beta-lactamase resistant) aureus (give with aminoglycoside)

Works syndergistically with penicillin/cephalosporin

107 For treatment of UTI caused by gram negative bacteria such
Protein synthesis inhibitor, misreading as Klebsiella, Pseudomonas, Proteus and other gram negative
of mRNA codon message, irreversibly rods
bind 30S, requires O2 dependent Rarely used alone
Aminoglycoside (class) transfer (absent in anaerobes) Used with penicillin or cephalosporin

Used for the treatment of aerobic gram negative bacteria only

Complicated UTI: Enterococcus faecalis & P. aeruginosa
108 (use with ampicillin)
For treatment of UTI caused by gram negative bacteria such
as Klebsiella, Pseudomonas, Proteus and other gram negative
rods
Gentamicin an Aminoglycoside Rarely used alone (Used with penicillin or cephalosporin)

109 For urogenital N. gonorrhea in penicillin allergic patients

Protein synthesis inhibitor - related to to treat gonorrhea caused by beta-lactamase producing
Spectinomycin aminoglycoside, binds 30S ribosome bacteria

110
Beta-lactam antibiotics: Inhibition of
cell wall (peptidoglycan) synthesis (cidal); Complicated UTI: E.coli, Klebsiella pneumoniae (cefazolin),
Cephalosporins (class) does not cross BBB(??) Proteus mirabilis (ceftriaxone)
First line drugs to treat gonorrhea (Neisseria)
111 Complicated UTI: Indole positive Proteus mirabilis,
3rd generation Cephalosporin, good Serratia
Ceftriaxone CNS penetration Acute pyelonephritis; Meningitis; Infectivie Endocarditis
 A B C

112
3rd generation Cephalosporin, good First line drugs to treat gonorrhea
Cefixime oral
Used to treat UTI caused by E. coli and Klebsiella in pregnant
patients because co-trimoxazole cannot be used due to risk of
113 kernicterus to the fetus
pneumoniae, Staphylococcus saprophyticus
Uncomplicated UTI: E.coli, Klebsiella pneumoniae!!,
Cefazolin 1st Generation Cephalosporin Staphylococcus saprophyticus!!

114

Protein synthesis inhibitor - Drug of choice (DOC) to treat UTI by Chlamydia

competition with tRNA for A site on 30 S Acute urethral syndrome from Ureaplasma urealyticum and
Tetracyclines (TC, class) subunit of ribosome; Bacteriostatic Chlamydia trachomatis

115

Doxycycline a tetracycline DOC to treat STD caused by Chlamydia Trachomatis

??Used to treat Huntington's Dz (Caspase inhibitor?? with
116
Minocycline a tetracycline neuroprotective effect)??
Protein synthsis inhibitor of aminoacyl Used for Mycoplasma pneumonia, Bordetella pertussis,
117
Macrolide (class) translocation, 50S Legionella
DOC to treat STD caused by Chlamydia Trachomatis, safe
118
Erythromycin a macrolide with pregnancy
Anti-mycoses: inhibits synthesis of
119 ergosterol (fungal cell wall); Blocks
demethylation of lanosterol; Alters cell
Clotrimazole membrane permeability; Fungistatic OTC, Topical azoles; vulvovaginal candidiasis
Anti-mycoses: inhibits synthesis of
120 ergosterol (fungal cell wall); Blocks
demethylation of lanosterol; Alters cell OTC, Topical azoles; Athlete's foot (Tinea pedis), Vaginal
Miconazole membrane permeability; Fungistatic candidiasis

121
Caspofungin Disrupts fungal cell wall sythesis
 A B C
enters cell and releases nitro moiety
122 which reacts with DNA and inhibits
Metronidazole duplication of bacteria (bacteriacidal) Trichomonas vaginalis (protozoa) Infection
treat Chronic UTI
123 Daily oral dose (100 mg) for adults in UTI
Nitrofurantoin unknown mech Given for months for chronic UTI

Inhibits viral DNA synthesis; Acyclic

guanosine derivative; competitive
inhibition of dGTP for the viral
polymerase with binding to the DNA
template as an irreversible complex chain
124 termination following incorporation into
viral DNA. Requires three
phosphorylation for activation: it is
converted into monophosphate
derivative by virus specified thymidine
kinase, then to the di- and
triphosphate compounds by hosts DOC for genital herpes (STD); Active against herpes simplex
Acyclovir cellular enzyme virus-1 and -2 (HSV-1 & HSV-2)
125

126
Gastrointestinal Drugs

127

PPIs promote healing of ulcers in the stomach, duodenum,

Omeprazole (PRILOSECProton Pump Inhibitors (PPIs):
OTC) Blockade of Gastric Acid Production
Proton Pump Inhibitors (PPIs):
128
Esomeprazole (NEXIUM) Blockade of Gastric Acid Production
and esophagus. They are of particular value in patients who
do not respond to H2 receptor antagonists. Especially useful
for treating Zollinger-Ellison syndrome (gastrin producing
tumors). Used in triple therapy for Helicobacter pylori in
Peptic Ulcer Disease and Chronic Gastritis
see Omeprazole
 A B C
Lansoprazole Proton Pump Inhibitors (PPIs):
129
(PREVACID) Blockade of Gastric Acid Production see Omeprazole
Proton Pump Inhibitors (PPIs):
130
Rabeprazole (ACIPHEX) Blockade of Gastric Acid Production see Omeprazole
Pantoprazole Proton Pump Inhibitors (PPIs):
131
(PROTONIX) Blockade of Gastric Acid Production see Omeprazole

132

H2 antagonists are used for treating duodenal and gastric

ulcers, gastroesophageal reflux disease, stress ulcers,
and hypersecretory states. They also are used as a
H2 Histamine Receptor Antagonists: preanesthetic medication for some surgical procedures to
Cimetidine (TAGAMET) Blockade of Gastric Acid Production reduce the danger of aspiration pneumonitis.
H2 Histamine Receptor Antagonists:
133
Ranitidine (ZANTAC) Blockade of Gastric Acid Production See Cimetidine
H2 Histamine Receptor Antagonists:
134
Famotidine (PEPCID) Blockade of Gastric Acid Production See Cimetidine
H2 Histamine Receptor Antagonists:
135
Nizatidine (AXID) Blockade of Gastric Acid Production See Cimetidine

136

Neutralization of Gastric Acid: use for (1) Simple dyspepsia

Weak bases that react with gastric and (2) as adjuncts to primary therapy with H2 blockers
hydrochloric acid to form a salt and and proton pump inhibitors in duodenal ulcer disease or
water, neutralizing the acid, and raising (3) GERD. Antacid therapy alone (4-8 weeks) is effective for
Antacids the pH of the gastric contents. promoting healing of duodenal ulcers, but not gastric ulcers.
 A B C

Neutralization of Gastric Acid; During anesthesia, coma,

137 cesarean section, or endoscopy, aspiration of gastric contents
can cause aspiration pneumonitis - sodium citrate (Bicitra, a
clear liquid antacid) is used prophylactically to neutralize
Sodium citrate (BICITRA) Antacid gastric contents in these situations.

Mucosal Protective Agent

138
Bismuth subsalicylate
(Pepto-Bismol)
139 Bismuth citrate
(Cytoprotective Agent): Enhances
secretion of mucus and HCO3- and
inhibits pepsin activity. Chelates with
proteins in the base of ulcers and may
form a protective barrier against acid
diffusion and peptic digestion. Bismuth
binds and inactivates enterotoxins.
Mucosal Protective Agents
Effective for treatment and prophylaxis of duodenal and
gastric ulcers, GERD, and diarrhea, especially travelers
diarrhea. May have an antibacterial action against H. pylori.
Bismuth subsalicylate is effective in mild-to-moderate
travelers (infectious) diarrhea. It absorbs bacterial toxins
and has local anti-inflammatory properties.
See Bismuth subsalicylate

Mucosal Protective Agent: a complex of

sucrose octa sulfate and aluminum
hydroxide that at acid pH polymerizes
140 into a sticky, viscous gel that adheres
to gastric epithelial cells and the base
of ulcers. This gel layer protects against
acid, pepsin, and bile acid access to
Sucralfate (CARAFATE) tissue.
Mucosal Protective Agents:
Prostaglandin analog - Prostaglandin
141 E2 and I2, synthesized by the gastric
mucosa, inhibit the secretion of acid and
stimulate the secretion of bicarbonate
Misoprostol (CYTOTEC) and mucus.
142
Muscarinic Antagonists see Anticholinergics
Sucralfate (1 g, one hour before each meal and at bedtime)
promotes healing of duodenal and gastric ulcers. It is
approved for maintenance therapy of duodenal ulcers. It
should not be administered within 30 min of antacids (it
requires an acidic environment for acitivation).
Misoprostol is a slowly metabolized analog of PGE1 approved
as a second-line agent for treating peptic ulcer. Its primary
effect is to inhibit gastric acid production. It is useful for
preventing gastric ulcer disease in patients who require
NSAIDs, e.g., for arthritis.
Antagonists of muscarinic cholinergic receptors can decrease
GI motility and can modestly inhibit gastric acid secretion.
However, large doses of these drugs are required to achieve
these effects leading to significant side effects. H2 blockers
and PPIs are more efficacious acid secretion inhibitors and
have far fewer side effects.
 A B C

Dopamine Antagonists; Prokinetic (Pro-

motility) Agents - a D2 dopamine
receptor antagonist, also 5-HT4
agonist & 5-HT3 antagonist that
143
enhances the motility of the smooth
muscle from the esophagus through the
proximal small bowel and accelerates
gastric emptying and transit in the
Metoclopramide!! duodenum. Also a cholinesterase
(REGLAN) inhibitor
Dopamine Antagonists; Prokinetic (Pro-
144 Trimethobenzamide motility) Agents - D2 dopamine/5-HT3
(TIGAN) antagonist
Used prior to meals and at bedtime to control nausea and
vomiting in diabetic gastroparesis, esophageal reflux, and
pregnancy. Metoclopramide is used during cancer
chemotherapy as an antiemetic in combination with other
drugs. Metaclopramide is the drug of choice for treating
diabetic gastroparesis (peripheral andeopathy). Used for
Migraine HA
modest antiemetic. Less effective than metoclopramide.

145
Dopamine Antagonists; Prokinetic (Pro- Parkinson's dz (counteracting the GI effects of levodopa and
Domperidone motility) Agents - D2 antagonist which bromocriptine); for nausea and vomiting associated with
(MOTILIUM) does not penetrate CNS well gastric stasis

D2 Dopamine Receptor Antagonists -

146 Phenothiazines - block D2-like
Chlorpromazine dopamine receptors in the CTZ and
(Thorazine) solitary tract nucleus, see antipsychotics Antiemetic

147

Prochlorperazine D2 Dopamine Receptor Antagonists -

(Compazine) Phenothiazines, see antipsychotics potent antiemetics
Thiethylperazine D2 Dopamine Receptor Antagonists -
148
(Torecan) Phenothiazines, see antipsychotics potent antiemetics
a dutyrophenone, D2 Dopamine
149
Droperidol Receptor Antagonist
 A B C

150
Macrolide Antibiotics; Prokinetic (Pro-
motility) Agents - macrolide antibiotic
that binds to motilin receptors -
erythromycin increases the frequency
Erythromycin (many and amplitude of antral contractions and Intravenous erythromycin may be useful short-term for an
brands) initiates gastric phase III contractions. acute exacerbation of diabetic gastroparesis.

Opioid agonist act at and receptors

in the GI tract to decrease normal
peristaltic motion, increased renal
151 sphincter tone, reduce secretory activity,
and enhance NaCl and water absorption.
Opioids slow transit time allowing
more time for absorption. The net
effect of increased absorption and
decreased secretion in the small Diarrhea; Opioids are effective against moderate-to-severe
intestine is to decrease the fluid and diarrhea but should not be used for patients with ulcerative
electrolyte load delivered to the colon. colitis, or acute bacillary or amoebic dysentery. Used for
Loperamide (IMODIUM) See opioids symptoms of travelers diarrhea

152
Diphenoxylate (LOMOTIL) Opioid agonist Diarrhea; use for Irritable Bowel Syndrome (IBS)

153
Difenoxin (MOTOFEN) Opioid agonist Diarrhea
Paregoric (generic,
154 camphorated opium Opioid agonist - antidiarrheal,
tincture, morphine) antitussive, and analgesic properties Diarrhea

Diarrhea; peptide must be given parenterally (SQ);

155 symptoms of tumors of the GI tract (carcinoid, VIPoma,
glucagonoma, gastrinoma, insulinoma), AIDS-related diarrhea,
Octreotide acetate and various motility disorders; variceal bleeding! and
(SANDOSTATIN) Somatostatin Analog orthostatic hypotension.
 A B C

Indications for laxative treatment:

156 a) Fecal Impaction - treat immediately.
b) Acute constipation as a result of acute illness, surgery,
perianal disease, severe abdominal or perineal muscle
weakness, drug therapy, irritable bowel syndrome,
uncomplicated diverticular disease, neurological deficits,
severe debilitation, and immobility.
c) Chronic constipation if not relieved after 2-4 weeks of
Dietary fiber bind water and ions, soften nonpharmacological treatment, i.e., dietary fiber.
stools, increase stool bulk, and promote d) Bowel preparation in patients who are to undergo
Bulk-forming Agents colonic bacteria. colonoscopy, barium enema, or colorectal surgery.

Promote accumulation of water and

electrolytes in the colonic lumen and
stimulate motility. Mechanisms include
157 inhibition of Na+, K+-ATPase, increased
permeability of mucosa, increased
leakage at tight junctions, and a possible
increase in synthesis of prostaglandins
Stimulant laxatives and cyclic AMP. increase duky, generally avoided (see bulk-forming agents)

158

Saline laxatives are useful for emptying the bowel prior to

surgical, radiological, and colonoscopic procedures and are a
Act via their osmotic pressure to retain useful adjunct in the elimination of intestinal parasites. May
Saline Laxatives water in the colon also be useful in cathartic doses to treat poisoning.
 A B C

Lactulose - Used to lower blood ammonia levels in patients

159
Osmotic laxatives are not absorbed and
are resistant to digestion, increase
osmotic pressure in lumen and water
Osmotic laxatives content of stools.
with portal hypertension and hepatic encephalopathy.
Glycerin - rectal suppository softens and lubricates the
passage of hard stool.
Polyethylene glycol-electrolyte solutions (Colyte,
GoLYTELY) are the drug of choice for bowel preparation for
colonoscopy, barium enema, or colorectal surgery.

160

Surfactant Laxatives Stool Softeners

161 NK1 antagonist - Neurokinin A and B act

on Nk1 and Nk2 receptors in the CNS,
Aprepitant and are closely related to substance P Chemotherapy-induced n/v

5-HT3 receptor antagonists are

selective serotonin inhibitors,
162 competitively inhibit the binding of
serotonin to 5-HT3 receptors. Their
antiemetic effects are postulated to stem
from blockade of 5-HT3 receptors
located on the nerve terminals of the
vagus in the periphery and centrally in Antiemetic; Used primarily for cancer chemotherapy and
the chemoreceptor trigger zone of the irradiation-induced nausea and vomiting (N&V), but also some
Ondansetron (ZOFRAN) area postrema. post-operative nausea and vomiting (PONV).
163 Granisetron (KYTRIL) 5-HT3 Antagonists See Ondansetron
164 Dolasetron (ANZEMET) 5-HT3 Antagonists See Ondansetron
165 Alostetron 5-HT3 Antagonists for diarrhea-predominant IBS
 A B C

166 use in treating postoperative emesis; prophylactic treatment

Dimenhydrinate Antihistamines - Histamine H1-receptor of motion sickness occurring during mild to moderate travel,
(DRAMAMINE) antagonists , see antihistamines especially if sedation is desired.
Diphenhydramine!! Antihistamines - Histamine H1-receptor
167
(BENADRYL) antagonists motion sickness and vertigo
Antihistamines - Histamine H1-receptor
168
Hydroxyzine (VISTARIL) antagonists motion sickness and vertigo
Antihistamines - Histamine H1-receptor
169
Meclizine (ANTIVERT) antagonists motion sickness and vertigo; given once daily

popular medication for control of inpatient nausea and

170 vomiting; prophylactic treatment of motion sickness occurring
Promethazine! Antihistamines - Histamine H1-receptor during mild to moderate travel, especially if sedation is
(PHENERGAN) antagonists desired.

171 Prototypical muscarinic cholinergic prevention of motion sickness (for rough seas and extended
Scopolamine receptor antagonist, see journeys, transdermal patch is more convenient; less sedation
(TRANSDERM-SCOP) antimuscarinics than dimenhydrinate or promethazine)

172 Cannabinoids - 9- reduce emesis due to moderately emetogenic chemotherapy.

Tetrahydrocannabinol, an active It can also stimulate the appetite and has been used in
Dronabinol (MARINOL) constituent of marijuana, see No, No's patients with AIDS and anorexia.

173 Corticosteroid - suppressing peritumoral

Dexamethasone
174
Methylprednisolone
175
Lorazepam (Ativan)
176 Alprazolam (Xanax)
inflammation and prostaglandin
production, see corticosteroids
Corticosteroid
Benzodiazepine, see anxiolytics
Benzodiazepine, see anxiolytics
Useful adjunct in the treatment of nausea in patients with
widespread cancer/chemotherapy
Useful adjunct in the treatment of nausea in patients with
widespread cancer/chemotherapy
The sedative, anxiolytic, and amnesic properties of these
drugs are useful to reduce the anxiety that may lead to
anticipatory emesis that can accompany chemotherapy.
Used alone these drugs have very weak antiemetic properties.
Also, tx of vertigo
see Lorazepam

Irritable Bowel Syndrome; short-term treatment of

177 constipation-predominant IBS in women; effective in treating
abdominal pain, altered bowel habit (decreased stool
Prokinetic Agent - selective serotonin frequency, hardened stool consistency, straining) and bloating
Tegaserod (ZELNORM) (5HT4) partial agonist associated with constipation-predominant IBS
 A B C

178

Alosetron (LOTRONEX) 5HT3 Antagonist Irritable Bowel Syndrome with diarrhea (second line)

179

TCA antidepressant - slow gut transit

time and also may alter visceral afferent Irritable Bowel Syndrome - slow gut transit time and also
Imipramine neural function, see antidepressants may alter visceral afferent neural function
Irritable Bowel Syndrome - slow gut transit time and also
180
Desipramine Antidepressants may alter visceral afferent neural function
181 SSRIs (e.g., fluoxetine) Antidepressants

182

5-ASA Compound; Anti-inflammatory

Drug - affect multiple sites in the
arachidonic acid pathway critical in the
pathogenesis of inflammation, including
inhibition of the cyclooxygenase
Mesalamine pathway and leukotriene formation. Inflammatory Bowel Disease (UC and CD)

183
5-ASA Compound; Anti-inflammatory Inflammatory Bowel Disease, especially Ulcerative cholitis;
Sulfasalazine (Azulfidine) Drug treatment of Rheumatoid arthritis

184
Olsalazine 5-ASA dimer; Anti-inflammatory Drug Inflammatory Bowel Disease (UC and CD)
 A B C

185

Anti-tumor Necrosis Factor Antibody

(anti-TNF Ab) - a chimeric mouse-human antibody against TNF that is extremely effective in Crohns
Infliximab [Remicade] monoclonal antibody Disease (CD); used especially to treat CD fistula
Anti-TNF- - decreases the
186 immunoreactivity relative to infliximab by
using an) entirely human monoclonal Ab
Adalimumab to TNF- (see) Rheumatoid Arthritis
187 Clindamycin Antibiotic Colitis
188 Amoxicillin-Ampicillin Antibiotic Colitis, Antibiotic Treatment of H. pylori
189 Cephalosporins Antibiotic Colitis
190 Vancomycin Antibiotic Colitis
191 Metronidazole Antibiotic Colitis, Treat C. difficile
192 Bacitracin Antibiotic Colitis
193 Clarithromycin (BIAXIN) Antibiotic Antibiotic Treatment of H. pylori:
Tetracycline
194
(ACHROMYCIN) Antibiotic
Gastrin receptor blocker (on parietal
195
Proglumide cells)
196 Kaolin (OTC) Adsorbent Discourage use in children for diarrhea
197

198
Liver Drugs
 A B C

Potent cytokines that possess antiviral,

immunomodulating, and antiproliferative
actions, activate JAK-STAT tyrosine
199
kinase signal transduction pathway,
leads to the nuclear translocation of a
cellular protein complex that binds to
genes containing an interferon-specific
response element, which synthesis of
over two dozen proteins (causing
inhibition of viral penetration or
uncoating, synthesis of mRNA, Tx Hepatitis (see details below for specific dzs)
translation of viral proteins, and/or viral Tx condyloma acuminatum (papillomavirus)
Interferon- assembly or release)

Synthetic guanosine nucleoside 1. Respiratory syncytial virus (RSV) in infants and young
200 analog children
Active against broad spectrum of RNA & Aerosol, oral, IV
DNA viruses 2. Treat Lassa Fever
Ribavirin Inhibits viral mRNA syntheis 3. Give with INF alpah 2b to treat HCV
201 Interferon -2b See Interferon- Treatment of Hepatitis B

202 Interferon -2a combined

with oral ribavirin See Interferon- Treatment of Hepatitis C

203
Interferon -2b combined
with oral ribavirin See Interferon- Treatment of Hepatitis C
Interferon alfacon-1
204 combined with oral
ribavirin See Interferon- Treatment of Hepatitis C

205 Pegylated interferon -2b

combined with oral
ribavirin See Interferon- Treatment of Hepatitis C (DOC!!)
 A B C

206

inhibits reverse transcriptase activity of Treatment of Hepatitis B (long term therapy relative to
Lamivudine both HIV and HBV interferon alfa)

207
phosphonate nucleoside analog,
Adefovir Dipivoxil administered as the oral prodrug, Treatment of Hepatitis B (including variants resistant to
(Hepsera) inhibits replication of HBV lamivudine)

208

Non-NSAID antipyretic/analgesic, a See NSAIDs; Causes liver toxicity (drug-induced

non-narcotic analgesic; hepatitis): severe centrilobular hepatic necrosis when
Very weak anti-inflammartory activity ingested in large amounts in suicide attempts or accidentally
Acetaminophen (Tylenol) (not used for inflammation) by children.
Ursodiol (ursodexoxycholic acid) -
209 primary bile acid that acts by reducing
Ursodiol cholesterol secretion into bile Dissolve gallstones; tx primary biliary cirrhosis
210

211
Cardio drugs
 A B
212
Cardiac glycoside: Inhibits cell
membrane Na/K-ATPase; Relatively
selective for cardiac enzyme; Binds
preferentially to and stabilizes the
phosphorylated form of the enzyme;
Inhibition of the Na/K-ATPase leads to
enhanced Ca++ inside the cell - leads to BP which in turn tends to lead to a reflex-mediated reduction in
more Ca++ stored in sarcoplasmic
reticulum; Each action potential leads to 7. SVR: If SNA is reduced, SVR will be reduced.
more release of Ca++ from SR, which
Digoxin (Digitalis) leads to enhanced contractility
213
Digitoxin (Digitalis) see digoxin
Increase pump output
1. Vasodilate: Decrease preload
2. Vasodilate: Decrease afterload, but
selectively constrict efferent arterioles
in the glomerulus (filtration pressure is
214 increased)
3. Decrease Na reabsorption in the
kidney (diuretic)
4. Decrease aldosterone
5. Decrease endothelin
6. Decrease NE
Nesiritide (B-Natriuretic Vasodilating without activating either
Peptide) angiotensin or sympathetics
C
1. A positive inotrope increase the contractility without
significant increases in HR such that myocardial energy
demands are not significantly increased;
2. Pulmonary Edema: Reduced, due to enhanced stroke
volume, thereby reducing the volume in the heart and volume
backing up into the pulmonary circuit.
3. Cardiac work: Net is uncertain? Increased contractility
increases work, decreased preload decreases work, and
depending on the HR response there will be an increase or
decrease associated with the HR effect. The reason dig is
given is because of the tendency to decrease or not change
HR. Most inotropic drugs also increase HR.
4. Cardiac dilation: See pulmonary edema above.
5. Cardiac compliance: Since the end-diastolic volume is
reduced, you will typically move to a portion of the compliance
curve for cardiac diastole which increases compliance.this is
GOOD.
6. Sympathetic Activity: Enhanced output tends to improve
SNA.
8. Ejection Fraction: Increased due to augmented
contractility
see digoxin
Treatment strategies for Acute Decompensated HF (see
extra note) - guard against renal insufficiency
Notice: nesiritide is a peptide so cannot be given orally (give
IV)
 A B C

Relax vascular smooth muscle; Mainly

215 relaxation of large veins which decreases Acute angina
venous return which decreases preload Prinzmetals Angina
which decreases O2 demand of the Congestive Heart Failure (increase Cardiac output)
heart (major effect); smaller decrease After MI
afterload; increase in oxygen supply decrease work of heart (reduces preload)
(transient), effective in prevention of decrease platelet aggregation
Nitroglycerin (NTG) coronary vasospasm (Nitric Oxide, NO) Raynauds disease
slower, less potent than NTG, short and
216
Isosorbide dinitrate long-acting preparations Angina prophylaxis
Beta-Blockers (see
217
adrenergic blockers)

Phosphodiesterase inhibitors:
Inhibition of cAMP phosphosdiesterase Inotropic used in CHF
(PDE)- Increases cAMP: In heart Vasodilatory
218 (increase cardiac output) & in vasculature For short-term therapy
(decrease systemic vascular resistance) Parenteral use
& decrease pulmonary capillary wedge Acute heart failure
Imamrinone (aka pressure Available only in IV formulations
amrinone) Net result: improved hemodynamics Requires a large initial dose for positive inotropic effect

219 Short-term therapy - PDE inhibitor of choice for short-term tx

of acute heart failure
Milrinone Phosphodiesterase inhibitors Parenteral administration
220

221
Antiarrhythmics
no longer used for rhythm control, modestly effective, very
toxic
222 Moderate Na channel Blocker which supraventricular and ventricular arrhythmias like atrial
also blocks K channelsprolongs fibrillation & atrial flutter (moderately effective), ventricular
QRS&QTaction potential; reduce extrasystoles and VT(poorly effective)
Quinidine (Antiarrhythmic automaticity and conduction velocity Major clinical use: atrial fibrillation, atrial flutter, &
Class IA) (Phase 0 and phase 3) ventricular tachcycardia
 A B
Na channel blocker; Prolongs APD
and refractoriness (K channel effect);
slows conduction and decreases
automaticity and excitability of the
223 myocardium and Purkinje fibers. N-
acetyl-procainamide (procainamide
metabolite) prolongs APD and
Procainamide refractoriness in atrial and venticular
(Antiarrhythmic mixed myocardium and prolongs the QT
Class IA & III) interval. (Phase 0 and phase 3)
moderate Na channel blocker: Increase
224 venticular refractoriness and prolong the
QT inverval (reduces automaticity and
conduction velocity - phase 0), also
Disopyramide increases AP duration. (Phase 0 and
(Antiarrhythmic Class IA) phase 3)
225 modest Na channel blockers (both
active and inactive Na channels)
Reduce automaticity
Lidocaine (Antiarrhythmic Shorten APD (narrow QRS)
Class IB) Slow conduction velocity
modest Na channel blockers (both
226 active and inactive Na channels)
Reduce automaticity
Mexiletine (Antiarrhythmic Shorten APD (narrow QRS)
Class IB) Slow conduction velocity
modest Na channel blockers (both
active and inactive Na channels)
227 Reduce automaticity
Tocainamide Shorten APD (narrow QRS)
(Antiarrhythmic Class IB) Slow conduction velocity
228 Phenytoin [Dilantin]
(Antiarrhythmic Class IB ) Na channel blocker
C
Used for Supraventricular and ventricular arrhythmias;
acute re-entrant supraventricluar tachycardia and atrial fib and
flutter associated with Wolff-Parkinson-White syndrome
(see extra notes)
Major clinical use: atrial fibrillation, atrial flutter, &
ventricular tachcycardia
Broad range of supraventricular and ventricular
arrhythmias (similar to procainamide and quinidine)
Moderately effective for atrial arrhythmia and poorly effective
for ventricular arrhythmia
Major clinical use: atrial fibrillation, atrial flutter, &
ventricular tachcycardia
acute rapid suppression of V arrhythmias, raises
ventricular fibrillation threshold as well as suppresses
arrhythmias caused by abnormal automaticity (observed pt
continuoulsy for SE), no atria effect; very effective membrane
stabilizer (numbing)
ventricular arrhythmias & refractory arrhythmias; useful in
pts with torsades de pointes (TdP) or long QT syndrome (if
other drugs contra), no effect in atrium; very effective
membrane stabilizer (numbing)
similar to lidocaine
Effective for Atypical Ventricular Tachycardia;
more typically used for seizures (also a membrane stabilizer,
arrthymia in brain)
 A B
highly effective Na channel blocker;
229 Prolongs PR and QRS (prolongs AP),
Flecainide (Antiarrhythmic reduces automaticity and conduction
Class IC) velocity in A and V; negative inotrope
highly effective Na channel blocker;
230 Prolongs PR and QRS (prolongs AP),
Encainide (Antiarrhythmic reduces automaticity and conduction
Class IC) velocity in A and V; negative inotrope
highly effective Na channel blocker;
Prolongs PR and QRS (prolongs action
231 potential), reduces automaticity and
conduction velocity in atria and
Propafenone ventricles; negative inotrope; structurally
(Antiarrhythmic Class IC) similar to propanolol so= blocker
232 Dofetilide (Antiarrhythmic
mixed Class IC & III) similar to Flecainide
See adrenergics; indirect effect via
reduction of sympathetic receptor activity
Blockers and membrane stabilizing activity; mild
233 (Antiarrhythmics class II): effect on automaticity and conduction
Propranolol, Timolol velocity; greatest effect is to slow AV
(nonselective); Metoprolol node conduction, also decrease SA
& Atenolol node automaticity and increase AV node
(cardioselective) refractory period
234 & K & Na & Ca channel blocker;
prolongs QT interval and cardiac
Sotolol (Antiarrhythmic refractoriness;slows sinus rate and
Class III) negative inotrope (slows repolarization)
C
Potent inhibitor of ventricular arrhythmia; effective
stabilization of atrial rhythm; supraventricular arrhythmias in
pt with no structural heart dz
Potent inhibitor of ventricular arrhythmia; effective
stabilization of atrial rhythm;
(similar to Flecainide) many arrhythmias, supraventricular
arrhythmias like atrial fibrillation in pt w/o structural heart dz;
potent inhibitor of ventricular arrhythmia; effective
stabilization of atrial rhythm
similar to Flecainide
ventricular tachycardia, supraventricular arrhythmias, also
AV node re-entry, atrial fibrillation, and atrial flutter; congenital
long QT syndrome; prevents recurrent episodes of
ventricular tachycardia and reduces symptoms of
palpitations and sudden death in pt w/ prior MI
all types of arrhythmias ie supravent and vent arrhythmias,
cannot be used in patients with heart failure
 A B C

235

Amiodarone & K & Na & Ca channel blocker; ONLY used for life-threatening (refractory) Ventricular
(Antiarrhythmic Class III; prolongs PR and QT; slows sinus rate arrhythmias or Atrial fibrillation unresponsive to other
has class I, II, III, and IV (slows repolarization); prolongs AP in antiarrhythmatics (AV nodal re-rentrant tach and Wolff-
activity) fast-response AP Parkinson-White syndrome and sudden death post MI or HF)

236
Ibutilide (Antiarrhythmic K channel blocker; prolongs PR and QT
class III) (slows repolarization) atrial fibrillation or flutter

237
Dofetilide (Antiarrhythmic
class III)
Dihydropyridine group
(nifedipine, amlodipine,
238 nitrendipine, isradipine,
nisoldipine --
Antiarrhythmic class IVs)
239 Diltiazem (non-
dihydropyridine
antiarrhythmic class IV)
atrial flutter and atrial fibrillation; maintenance of sinus
K channel blocker; prolongs QT rhythm after reversion
Ca channel blockers (CCB), SM
selective; see renal CCB; slow
conduction velocity, phase 0 of node small effect on AV conduction and arrhythmia
Ca channel blocker; slows AV node
conduction (moderately), myocardial
selective; slows conduction velocity, slows vent rate with atrial fibrillation or flutter and
phase 0 of node prevents AV nodal re-entrant tach

CCB: Most potent to AV node

conduction (also SA node); negative
240 inotrope; myocardial selective; slows
Verapamil (non- conduction velocity (phase 0) and
dihydropyridine increase refractoriness in tissues with
antiarrhythmic class IV) slow-response AP
Indicated for atrial fibrillatoin and atrial flutter; V response
in SVT and slows V rate w/ A fib or flutter and prevents AV
nodal re-entrant tach; HTN and peripheral vasospasm
disorders

slows AV node conduction (Vagotonic

action), and depress SA node;
241 conduction velocity and slows V
response to SVT; force of heart
contraction via inhibition of the Na+/K+
Digoxin (digitalis) see also ATPase pump less Na to trade for Ca Atrial fibrillation & atrial flutter; and CHF not be controlled
above - cardiac glycosides to exit cell by other med (not antiarrhythmic)
 A B
242
Adenosine (antiarrhythmic Slows AV node conduction - causes
class V) transient heart block in the AV node
Prolongs APD and refractoriness (K
channel effect); slows conduction and
decreasses automaticity and excitability
of atrial and ventricular myocardium and
243 Purkinje fibers. N-acetyl-procainamide
(aka NAPA, procainamide metabolite)
prolongs APD and refractoriness in atrial
and venticular myocardium and polongs
the QT interval (Reduce automaticity
Procainamide and conduction velocity effects phase
(Antiarrhythmic Class III) 4 and 0)
244
245
246
Anticoagulant: Binds with antithrombin
III to inactivates clotting factors IIa, Xa,
IXa, XIa, XIIa, Kallikrein (notice inhibited
(Unfractionated) Heparin active factors)
(UFH) Intrinsic and Common pathways
Anticoagulant: Binds antithrombin III,
247 inhibits Xa (greater ratio of anti-factor Xa
Low molecular weight to antithrombin (IIa) activity and less
Heparins (LMWH) anti-platelet activity)
248 Enoxaparin LMWH
C
DOC for acute Paroxysmal SVT caused by re-entry thru AV
node;
diagnostic tool (see extra notes)
Used for Supraventricular and ventricular arrhythmias
(similar to quinidine, used if quinidine not effective); acute re-
entrant supraventricluar tachycardia and atrial fib and
flutter associated with Wolff-Parkinson-White syndrome
Anticoagulants:
Rapid parenteral anticoagulation (and in vitro
anticoagulation), Heparin is the drug of choice for
parenteral anticoagulant therapy (Usually loading dose
followed by continuous infusion)
1. DVT & PE: treatment and prophylaxis.
2. Extra corporeal circulation (hemodialysis and heart-lung
machine); due to in vitro effects
3. Prophylaxis of postoperative and recumbency thrombosis
4. MI and unstable angina - Lessen incidence of secondary
peripheral venous thrombosis and PE.
5. Disseminated intravascular coagulation (DIC)
6. temporary ischemic attack (TIA) - probably effective, but
very risky - not used if stoke-in-progress
Never given orally or IM
Prophylaxis of DVT and PE; Used (SQ injection) for
prophylaxis of DVT associated with hip, knee, and abdominal
surgery; non ST elevated acute coronary syndrome
See LMWH
 A B C

Slow, sustained, oral anticoagulation (Oral only)

249
Anticoagulant: Inhibits vitamin K
dependent modification of clotting
factors prothrombin II, VII, IX, X, protein
C and S (notice factors inhibited are not
activated); Extrinsic and Common
Warfarin (Coumadin) pathways
Antiplatelet drug: Inhibits platelet
250 formation of Thromboxane A2 (TXA2,
Aspirin platelet aggregation) (see NSAIDs)
1. General: Usually anticoagulant therapy is started with
heparin and followed with warfarin for long term therapy.
2. Deep venous thrombosis and pulmonary embolism
3. Atrial fibrillation (valvular heart disease, CHF, mitral
stenosis, cardiomyopathy)
4. Myocardial infarction (prevent mural thrombosis and
systemic embolism).
5. Rheumatic heart disease (emboli frequently associated with
this disorder).
6. Mechanical prosthetic valves, bioprosthetic mitral
valves.
Prophylaxis and treatment of MI and stroke (see NSAIDs)

Prophylaxis of stroke, MI, PAD, and acute coronary

syndrome;
251 Alternate to, or additive with, aspirin for angina (Reduces
platelet aggregation, NO EFFECT ON PROSTAGLANDINS
Antiplatelet drug: Blocks platelet preferred over aspirin if loop diuretic is being used or if
aggregation by irreversibly blocking kidney disease is present)
Clopidogrel ADP receptors Particularly useful in unstable angina

252 2nd prevention of stroke; pts with prosthetic heart values

and as an alternative to aspirin for secondary prevention of
Antiplatelet drug: Blocks platelet acute myocardial infarction, to prevent stroke in patients with
aggregation, inhibits adenosine uptake transient ischemic attacks, and to maintain potency of
Dipyridamole and cAMP phosphodiesterase inhibitor coronary bypass grafts

253 Prevention of thrombotic stroke in patients who have

Antiplatelet drug: inhibits fibrinogen experienced TIAs
binding to platelets and blocks platelet Prophylaxis of recurrent stroke, prophylaxis of thrombosis
aggregation and clot retraction (blocks during stent placement
Ticlopidine ADP receptor). Adverse side effects limit use!
 A B C

254 Antiplatelet drug: inhibits cyclic AMP

phosphodiesterase III (increasing
cAMP), blocking platelet aggregation,
Cilostazol causes vasodilation Intermittent claudication, peripheral arterial disease

Acute coronary syndromes; percutaneous coronary

255 Antiplatelet drug: Monoclonal
antibody to glycoprotein IIb/IIIa complex,
prevents fibrinogen, thus inhibiting
platelet aggregation (see extra note for
Abciximab Glanzmann thrombasthenia)
angioplasty; Greater antithrombotic activity than aspirin or
heparin
approved for treatment of unstable angina when
angioplasty or atherectomy planned within 24 hrs.

256 Antiplatelet drug: Blocks fibrinogen

binding to IIb/IIIa complex; small peptide Acute coronary syndromes; percutaneous coronary
Eptifibatide analogs of critical domains of fibrinogen angioplasty

257 Antiplatelet drug: Blocks fibrinogen

binding to IIb/IIIa complex; small peptide Acute coronary syndromes; percutaneous coronary
Tirofiban analogs of critical domains of fibrinogen angioplasty

Hemorrheologic Agent = improves

258 blood flow; mechanism is unclear, but
appears to enhance RBC flexibility, intermittent claudication, chronic occlusive arterial disease of
decreases blood viscosity; may decrease the limbs
Pentoxifylline TXA 2 levels and increase PGI2 levels

259 Direct thrombin inhibitor: direct binding

Hirudin to thrombin PE and DVT; alternative to heparin therapy (eg due to HIT)
Direct thrombin inhibitor: direct binding
260
Ximelagatran to thrombin; oral Oral, presently being studied

261
Direct thrombin inhibitor: direct binding Tx of heparin-induced thrombocytopenia (HIT) see extra
Lepirudin to thrombin note
 A B C

262

Direct thrombin inhibitor: Direct Percutaneous coronary angioplasty

binding to thrombin, inhibition of platelet Unstable angina
Bivalirudin activation Pt's with HIT

263 Direct thrombin inhibitor: Direct

binding to thrombin (does not require
antithrombin III for antithrombotic activity
Argatroban and is highly selective for thrombin) Tx of HIT; coronary angioplasty in patients with HIT

264

Thrombolytic: Activator of plasminogen, 1. Acute myocardial infarction

Alteplase (rt-PA) dissolve formed fibrin clots 2. Nonhemorrhagic Stroke (make sure pt is not bleeding!!)

265
Thrombolytic: Activator of plasminogen,
Reteplase (r-PA) dissolve formed fibrin clots Acute myocardial infarction

Thrombolytic: Activator of plasminogen,

dissolve formed fibrin clots; mutated form
266 of t-PA with a prolonged half-life,
increased fibrin specificity, and
increased resistance to inhibition by
Tenecteplase (TNK-tPA) plasminogen activator inhibitors. Acute myocardial infarction
 A B C

267
1. Acute myocardial infarction
Thrombolytic: Nonenzymatic activator 2. Pulmonary embolism
of plasminogen; stimulates dissolution 3. Deep venous thrombosis
Streptokinase of fibrin clots. 4. Arterial thrombosis
1. Acute myocardial infarction
268 2. Pulmonary embolism
3. Deep venous thrombosis
Urokinase Thrombolytic 4. Arterial thrombosis (?)

269

Thrombolytic: Streptokinase
plasminogen complex, dissolve formed
Anistreplase (APSAC) fibrin clots Acute myocardial infarction

270 Competitively blocks plasminogen

Aminocaproic acid activation Tx bleeding induced by fibrinolytic agents

271
Drotrecogin Alfa [Xigris] Activated protein C Tx of sepsis and DIC
272
273 Antihyperlipidemics
 A B C

274

Uses:
1. Elevated cholesterol of all types. Particularly effective at
lowering levels of LDL. If the primary problem is too much
cholesterol, statins are good choices.
HMG-coA Reductase Inhibitor: decrease cholesterol by increasing LDL receptors in the liver
Inhibition of 3-hydroxy-3-methylglutaryl- causing decreased LDL cholesterol (often see a small
coenzyme A (HMG-CoA reductase) from decrease in triglycerides and a small increase in HDL
converting HMG-CoA to Mevalonic acid cholesterol)
-- essential step in cholesterol synthesis. 2. Aggressive therapy in high risk populations: With 2
These drugs are structural analogs of risks, e.g., ischemic disease and diabetes, goal is to reduce
the HMG-CoA intermediate. LDL<70 mg/dL (desirable level without these risk factors is
Leads to increased synthesis of LDL <130); Recent data have shown a 25% reduction in stroke (no
receptors (liver attempts to get more reduction in brain hemorrhage) in at risk populations
Lovastatin (Mevacor) cholesterol from plasma) maintained on statins
275 Atorvastatin

Fibrate Derivatives: increase activity of

lipoprotein lipase (which exist only on
276 endothelial tissue) - cleaves free fatty
acids from triglycerides more readily,
which promotes delivery of triglycerides
to adipose tissue. Decreases VLDL Reduction of triglycerides when VLDL is very high, or when
formation in the liver, leading to IDL is elevated
decrease triglycerides; modest reduction Follow VLDL. If it is elevated, gemfibrozil is a candidate drug.
in LDL (may increase in some patients); If LDL is elevated but VLDL is not elevated, do not use this
Gemfibrozil (Lopid) more impressive rise in HDL drug.
 A B C
Fibrate Derivatives: Same mech as
277
Fenofibrate gemfibrozil
278 Clofibrate

Bile Acid Binder (resin): Enhanced

279 excretion of bile acids, leading to
increased conversion of cholesterol to
bile acids in the liver. Uses:
Loss of cholesterol triggers up Hypercholesterolemia, particularly elevated LDL
Cholestyramine regulation of LDL receptors in the cholesterol
(Questran) liver: therefore, decreasing LDLs Follow LDL. If it is elevated, these drugs are potentially useful
Bile Acid Binder: same as
280
Colestipol (Colestid) Cholestyramine same as Cholestyramine
Bile Acid Binder: same as
281
Colesevelam (Welchol) Cholestyramine same as Cholestyramine

282
Inhibits VLDL secretion (probable main
mechanism not entirely understood),
which leads to decreases VLDL,
decreased LDL and increased HDL
Niacin (Vitamin B3) (catabolism of HDL is decreased)
Used for both hypercholesterolemia and
hypertriglyceridemia - Any lipoprotein disorder, particularly
mixed hyperlipidemia with elevated triglycerides
Have to take gram quantities (NOT acting as a vitamin)
Decreases triglyerides!!

283 Decreases blood glucose, triglycerides,

C-reactive protein levels, and increases
Thiazolidinedion HDLs (and lowers BP in some pts) Metabolic syndrome
 A B C

Inhibitors of Intestinal Sterol

Absorption: Inhibits absorption of
phytosterols and cholesterol; Active
form of drug is glucuronidated!!
284 (Phase II metabolism, see extra note)
Travels through the portal vessels to the
bile, and is then brought back to the
small intestine via enterohepatic
recycling.
recycling. This is an unusual feature
nearly all drugs that are conjugated with
glucuronic acid are inactive. Watch for
this bit of information to be tested on Primarily useful for reducing LDL cholesterol
Boards. Excreted with the bile and Decreases cholesterol absorption approx 50%
acts at the brush boarder of the SI to Does not modify triglyceride absorption
inhibit the uptake of dietary and biliary Often used in combination with a statin
Ezetimibe (Zetia) cholesterol into the enterocytes.

Data support multiple mechanisms for cardio protection

285 Antiatherogenic by reducing triglyceride and VLDL
synthesis in the liver
Requires such large amounts of fish consumption that other
Fish oils Omega-3-Fatty Acids factors come into play (e.g., exposure to methylmercury)
286 Hematopoietic Agents
 A B C

287

Iron is incorporated into the heme

Iron as
Ferrous sulfate, hydrated
Ferrous sulfate, dessicated
Ferrous gluconate
Ferrous fumarate
complex, which is an essential
component of cytochromes, and
component of oxygen carrying proteins
hemoglobin and myoglobin. Many
biological non-heme functions
Treatment of Iron Deficiency Anemia, generally give ferrous
sulfate orally (parenteral for pt who cannot take orally or
severely depleted dialysis pt, then give IV iron dextran)

288
Vitamin B12
Cyanocobalamin (i.m.)
Hydroxocobalamin (i.m.)
Hematopoiesis; production of epithelial
cells; maintenance of myelin. Vitamin
B12 is essential for the synthesis of the
biologically active form of folic acid,
tetrahydrofolate (essential for DNA
synthesis). Thus, in vitamin B12
deficiency, there is an internal folate Megaloblastosis Vitamin B12 deficiency, including
deficiency. pernicious anemia
 A B C

289
Purine and pyrimidine synthesis; amino
acid interconversions. Folate is required
for the synthesis of deoxythymidylate
monophosphate, which in turn is required
Folic Acid (p.o./i.m.) for DNA synthesis. Megaloblastosis due to folate deficiency

290

Erythropoietin and the colony stimulating factors are

Colony Stimulating glycoprotein "growth factors" or hormones that regulate blood
Factors cell proliferation and differentiation. See the following

291

Recombinant EPO is being successfully used to treat patients

Erythropoietin (Epoetin Stimulates the division and differentiation with end stage renal disease (chronic renal failure).
Alpha; Epo; Epogen; of erythroid progenitors in the bone Patients infected with the HIV virus (treated with Zidovudine)
Procrit) marrow and cancer pts treated with marrow suppressant drugs.

G-CSF is a lineage-specific stimulator of Decreases the incidence of infection, as manifested by

292 Filgrastim (Granulocyte the proliferation, differentiation, and end- febrile neutropenia, in pts with non-myeloid malignancies
Stimulating Factor; G-CSF; cell function of the neutrophil line (a receiving myelosuppression anti-cancer drugs (ie neutropenia
Neupogen) granulocyte). due to cancer tx)

1. Acceleration of myeloid recovery in patients with non-

Recombinant human GM-CSF produced
by a yeast expression system. GM-CSF
stimulates partially committed
293 progenitor cells to divide and
Sargramostim differentiate in the granulocyte
(Granulocyte Macrophage macrophage pathways.
pathways. Chemotactic,
Colony Stimulating Factor; antifungal and antiparasitic activities of
GM-CSF; Prokine; granulocytes and monocytes are
Leukine) increased by exposure to sargramostim.
Hodgkins lymphoma, acute lymphocytic leukemia, or
Hodgkins disease undergoing autologous bone marrow
transplantation;
2. Increases WBC counts in patients with myelodysplastic
diseases and in AIDS patients treated with zidovudine;
3. Decrease leukopenia in cancer chemotherapy patients;
4. Corrects neutropenia in aplastic anemia pts
5. Decrease transplantation-associated organ system
damage.
 A B C

294 Treatment of thrombocytopenia. Oprelvekin should be an

Recombinant human interleukin-11;
interleukin-11;
selectively stimulates
megakaryopoiesis (ie production of
Oprelvekin (Neumega) platelets)
invaluable aid in the treatment of severe thrombocytopenia
and help alleviate the requirement for multiple platelet
transfusions, which are currently a principal limitation in many
chemotherapy regimens.

1. Malignant melanoma, chronic myelogenous leukemia,

295 chronic granulocytic leukemia;
2. sickle cell anemia.
3. The principal use of hydroxyurea has been as a
myelosuppressive agent in the myeloproliferative
Inhibits ribonucleotide diphosphate syndromes, especially chronic granulocytic leukemia,
reductase - inhibits formation of polycythemia vera, and essential thrombocytosis. It is also
deoxyribonucleotides from sometimes used to treat some solid tumors, making these
Hydroxyurea ribonucleotieds tumors more sensitive to radiation therapy.
296

Endocrine Drug List

297

298 Diabetes drugs

Treatment of DM type II, rarely used now for favor of second
299
Acetohexamide (Dymelor) First-Generation Sulfonylureas generation sulfonylureas
Chlorpropamide
300
(Diabinese) First-Generation Sulfonylureas see Acetohexamide
301 Tolazamide (Tolinase) First-Generation Sulfonylureas see Acetohexamide
302 Tolbutamide (Orinase) First-Generation Sulfonylureas see Acetohexamide
 A B C

Sulfonylurea (2nd generation, a sulfa

drug); 1) Stimulate Insulin Secretion:
bind to and block an ATP-sensitive K+
303 channel. Blockade of this channel
reduces K+ conductance causing
membrane depolarization and influx of
Ca2+ through voltage-sensitive Ca2+
channels. Ca2+ influx leads to insulin
secretion. 2) prolong binding of insulin to
target tissue receptor 3) reduce serum Oral hypoglycemic agent, Once daily doses with fewer
glucagon levels (indirect inhibition via reported side effects. Can be combined with insulin therapy.
Glimepiride [Amaryl] insulin) Less weight gain than all other sulfonylureas
Oral hypoglycemic agent for T2DM, Potent, intermediate-
304 acting, single dose/day possible; undergoes hepatic clearance
Glipizide [Glucotrol, Sulfonylurea (2nd generation); Stimulate - should be used in pts with mild-to-moderate renal
Glucotrol XL] Insulin Secretion dysfunction
Oral hypoglycemic agent, Potent, intermediate-acting, no
305 Glyburide [DiaBeta, Sulfonylurea (2nd generation); Stimulate longer used (?); Alternative to insulin for Gestational DM
Micronaxe, Glynase] Insulin Secretion (does not cross PBB)

Non-sulfonylurea secretagogues (aka

Meglitinides); Stimulate Insulin
Secretion: binds to the ATP-sensitive
306
potassium channel on pancreatic beta
cells at a different site than
sulfonylureas. The subsequent
depolarization of the beta cell opens the
calcium channel and rapidly increases Oral hypoglycemic agent for T2DM: Short half-life; rapid
Repaglinide [Prandin] insulin secretion. action, taken right before meals
Non-sulfonylurea secretagogues
307 (Meglitinides); Stimulate Insulin Oral hypoglycemic agent for T2DM: Short half-life; rapid
Nateglinide [Starlix] Secretion action, taken right before meals
 A B C

308

a Biguanide; antihyperglycemic agent, Oral hypoglycemic agent; treat Type 2 DM, patients with
decreases hepatic glucose production refractory obesity whose hyperglycemia is due to "insulin
& increases the binding of insulin to resistance", also has significant lipid-lowering effect, does
Metformin [Glucophage] its receptor not increase weight; hirsutism

-Glucosidase inhibitor:
oligosaccharide analogs that bind to the
intestinal brush border enzymes that
309 digest complex sugars (disaccharidases
such as -glucosidase). The competitive
inhibition of sugar digestion by these Oral hypoglycemic agent: The effects of -glucosidase
drugs delays the absorption of inhibitors on HbA1c are modest, so these drugs are most
carbohydrates and limits the postprandial useful for newly diagnosed Type 2 patients with mild
Acarbose [Precose] rise in glucose. hyperglycemia.
310 Miglitol -Glucosidase inhibitor

Thiazolidinediones (TZD); Insulin

Sensitizer, increases glucose disposal:
binds to nuclear transcription factors in
adipose tissues that are involved in the
311
insulin receptor signaling cascade
(PPAR- nuclear receptor). TZDs
resensitize the target tissues to insulin. Oral hypoglycemic agent: TZDs are indicated as an adjunct
(Also decreases FFA) Summary: to diet and exercise or for concomitant use with a sulfonylurea
decreases hepatic glucose output & or insulin to improve glycemic control. Rosiglitazone is used
Rosiglitazone [Avandia] improves peripheral insulin utilization as monotherapy or together with metformin; hirsutism
Thiazolidinediones (TZD); Insulin Oral hypoglycemic agent: Pioglitazone is approved for
312
Pioglitazone [Actos] Sensitizer monotherapy or with insulin, sulfonylureas, or metformin.
Thiazolidinediones (TZD); Insulin
313
Troglitazone Sensitizer
 A B
Amylin analog: Amylin is a naturally
314 occurring peptide that is normally co-
secreted with insulin. (Amylin secretion
is delayed or diminished in both Type 1
Pramlintide acetate and Type 2 diabetics.) See metabolic
[Symlin] effects extra notes
315
Glucagon-like peptide-1 agonist: a
peptide analog of GLP-1 (Incretin) that
Exenatide [Byetta] acts as an agonist at the GLP-1 receptor. satiety).
316 Liraglutide see exenatide
Dipeptidyl Peptidase-4 Inhibitor (DPP-
IV): blocks the Ez that breaks down the 2
incretin hormones glucagon peptide-like
317 peptide-1 (GLP-1) and glucose-
dependent insulinotropic peptide (GIP),
which help regulate glucose metabolism
via increased insulin release, suppressed
Sitagliptin phosphate glucagon release, and delayed gastric
[Januvia] emptying.
318 Vidagliptin see sitagliptin
319
C
Injectable adjunctive treatment: to Type 1 and Type 2
diabetics who are already using insulin as prescribed but need
better control of blood glucose, most useful for pts who
experience wide glycemic swings or those who are
insulin-resistant and require large amounts of insulin.
Pramlintide, added to an existing insulin regimen, has been
shown to decrease HbA1c levels and also results in
significant weight loss.
Injectable adjunctive treatment: approved for use with
metformin alone, a sulfonylurea alone, or in combination with
metformin and a sulfonylurea. When combined with these
more standard treatments, Exenatide is associated with a
significant reduction in HbA1c levels, post prandial
plasma glucose reductions, and weight loss (increase
monotherapy or in combination with metformin or a
thiazolidinedione: intended as a replacement for sulfonylureas
in patients who cannot achieve glucose targets with metformin
or a TZD alone.
Insulin Preperations
 A B C

320
Indications for Insulin Therapy:
SQ (or IV) injections of insulin are the primary therapy for:
1. All Type 1 patients
2. Type 2 patients not controlled by diet and/or oral
hypoglycemic agents
3. Patients following pancreatectomy or with gestational
diabetes.
4. Management of diabetic ketoacidosis.
5. Treatment of hyperglycemic, nonketotic coma.
Lispro [Humalog] Ultra-Short-Acting Insulin (human) 6. Perioperative management of Type 1 and Type 2 patients.

321
Aspart [Novolog] Ultra-Short-Acting Insulin (human) See Lispro

322
Glulisine [Apidra] Ultra-Short-Acting Insulin (human) See Lispro

323
Inhaled insulin [Exubera] Ultra-Short-Acting Insulin (human) See Lispro

324

Regular insulin (R) Short acting insulin (human) See Lispro

325
NPH (neutral protamine
Hagedorn) or Isophane
insulin Intermediate insulin (human) See Lispro
326 Lente Intermediate insulin (human?) See Lispro
 A B C

327

Glargine [Lantus] Long-acting basal insulin (human) See Lispro

328 Detemir [Levemir] Long-acting basal insulin (human) See Lispro
329 Ultralente Long-acting basal insulin See Lispro
330 Thyroid & Antithyroid Drugs

331

Levothyroxine [generic,
Synthroid, Levoxyl, DOC for hypothyroid states (always give solucortef first!! -
Levothroid, Unithroid] Natural isomer of thyroxine (T4) reason? Ask Dr. Tanner)

a Thioamide antithyroid drug: Inhibits

332 the thryoid peroxidase enzyme
(organification) and thus interferes with
the incorporation of iodine into tyrosyl
residues of thyroglobulin and with
coupling of iodotyrosyl residues (MIT,
DIT) to form T3 and T4; PTU also acts by
inhibiting the enzyme 5'-deiodinase,
Propylthiouracil (PTU, which converts T4 to the active form Treat hyperthyroid; Propylthiouracil, but not methimazole,
generic) T3. also inhibits peripheral conversion of T4, to T3.
 A B C
a Thioamide antithyroid drug, only
333 inhibits oxidation of iodine by peroxidase
Methimazole (Tapazole) (no peripheral effect) Tx hyperthyroid; once daily dosing, no peripheral inhibition

334 inhibits the action of the sodium-

dependent iodide transporter located on
Perchlorate follicular cells' basolateral membranes
335 Thiocyanate see perchlorate

Iodides: (1) inhibit thyroid hormone

release; (2) block iodotyrosine and
336 iodothyronine synthesis by blocking
organification; (3) decrease the
vascularity of the thyroid gland. The
Potassium iodide inhibitory effect on hormone synthesis is
solution (SSKI) known as the Wolff Chaikoff effect.
Prevent thyroid storm; pre-surgery preperation of the
thyroid; short-term control of hyperthyroidism. Iodides are
rarely used as sole therapy (PTU or methimazole is used more
typically for pre-surgery thyroid preperation).

1. Hyperthyroidism: relatively safe for treatment of Graves

disease. There is a high incidence of delayed hypothyroidism.
Propranolol and antithyroid drugs can be administered while
337 131I is rapidly taken up by the thyroid, awaiting the effects of the 131I.
incorporated into iodoamino acids and is 2. Hyperthyroidism: with nodular goiter and some
deposited in the colloid of the follicles. metastatic thyroid cancers.
The beta radiation destroys the 3. Diagnostic: for hyper/hypothyroidism and goiter to
Radioactive iodine surrounding parenchymal cells. determine capacity of gland for iodide uptake.

Decrease symptoms of increased adrenergic tone such as

338 heat intolerance, profuse sweating, tremors, and palpitations
Beta Adrenergic Receptor Antagonist: that are associated with hyperthyroid states. MC indications
inhibits thyroxine (T4) conversion to T3 are palpitations and tachycardia. At high doses, beta-
by Ez that catalizes deiodination, see blockers may inhibit conversion of T4 to T3. Use for
Propranolol below for adrenergic antagonistic effects inpatients.
Atenolol (generic,
339
Tenormin) Beta Adrenergic Receptor Antagonist: Outpatient control of symptoms of hyperthyroidism
Metoprolol (generic,
340
Lopressor) Beta Adrenergic Receptor Antagonist: Outpatient control of symptoms of hyperthyroidism
In sufficient quantity, they will
341 Thiocynate, Perchlorate, competitively inhibit the iodine pump
& Pertechnetate (& reducing its ability to concentrate iodine
Llithium) in follicular cell
342 Other endocrine drugs
 A B C
Treat acromegaly, also retard development of IGF-1 mediated
343 Somatostatin analogue (aka insulin-like diabetic retinopathy; Carcinoid syndrome; esophageal
Octreotide growth factor, IGF-1) varice bleeds

344 Blocks GH receptors and results in

Pegvisomant decreased IGF-1 synthesis Blocking Tx of Growth Hormone Adenoma

345 Vasopressin, aka ADH used in pts witout P-Pit function. ADH can be insuffalated
Antidiuretic Hormone V1 (vascular receptor, IP3), V2 (renal as powder, injected i.m. for longer control (2-8 hrs) or injected
(ADH) receptor, cAMP) i.m as a tannate derivative for longest control (1-3 days)

346 Bromocryptine & both are alkaloids, stimulate dopamine Treatment of the prolactinoma depress prolactin secretion (a
Ergonovine receptors. prolactin inhibiting factor or PIF)
347 Cabergaline Treatment of the prolactinoma

Estrogens stimulate a generalized

increase in hepatic globulin synthesis
which includes thyroid binding globulins
(TBG) and corticosteroid binding globulin
(CBG).
348
- Estrogens reduce bone resorption, by
repressing inflammatory cytokine
expression and inhibiting effect of PTH ;
reduce osteoclast differentiation.
Estrogen Rx leads to increased
Estrogen Therapy synthesis of 1,25(OH)D.
SERMS (specific estrogen receptor
modulators): Partial agonist-antagonist
349 at estrogen receptors; Estrogen
derivative having estrogen agonist effects
on the bone and limited effects in breast
Raloxifene (Evista) and uterus.
Treatment of the prolactinoma in females (if pregnancy is
not wanted); Will increase total T4 & T3 (not free T4 & T3);
will increase total cortisol as well as slightly increase free
cortisol.
- Reduce hip fractures by 50%
- Reduce CV risk
- Inc skin thickness
In post -menopausal women produced a 40 % reduction in
risk of vertebral fractures, a 3-4 % increase in bone
density. A significant reduction in new breast cancers was
also observed. Also favorable affect on LDL and cholesterol

Bisphosphonate - Analogues of Reduces hip and spine fractures

350 pyrophosphate (P-C-P); Most effective Tx of postmenopausal and glucocorticoid-induced
inhibitors of osteoclast and bone osteoporosis
resorption by inhibiting farnesyl BPs are the 1st line tx for hypercalcemia of malignancy,
Alendronate diphosphate synthase also used to treat Pagets and tumor bone disease
351 Risedronate Bisphosphonate See Alendronate
352 Editronate Bisphosphonate Older form, no longer used due to mineralization defects
353 Pamidronate Bisphosphonate See Alendronate
354 Androgen Therapy opposite effect to estrogen (above) Will decrease total T4 & T3 (not free T4 & T3)
 A B C

Treat Addison's dz, also Congenital Adrenal Hyperplasia

355 (eg 21-hydroxylase deficiency, 11-Hydroxylase Deficiency, 3-
Dexamethasone & strong glucocorticoids with very little Hydroxysteroid dehydrogenase deficiency, 17-Hydroxylase
prednisolone mineralocorticoid activity deficiency, Cholesterol Desmolase Deficiency)
Treat Congenital Adrenal Hyperplasia (eg 21-hydroxylase
356 mineralocorticoi with little glucocorticoid deficiency, 3-Hydroxysteroid dehydrogenase deficiency,
Fludrocortisone activity Cholesterol Desmolase Deficiency)
Used to confirm secondary (pituitary) adrenal cortical
357 block 11-beta hydroxylase to temporarily insufficiency; to sort between primary (adrenal tumor) vs
Metyrapone prevent cortisol synthesis secondary hyperadenocorticalism (Cushing's S.)

358 opens K+ATP channel in beta cell;

Diazoxide inhibits insulin release. Used to treat hyperinsulinism

359
Calcitonin inhibits bone resorption
while formation continues causing a net
increase in bone Ca deposition. Synthetic salmon calcitonin (more potent than human) used to
Calcitionin also lowers Ca by increasing treat bone disease (eg Pagets disease, hypercalcemia,
Calcimar (fish calcitonin) Ca renal clearance (excretion) osteoporosis)

1,25 (OH)2 D3 (calcitriol) is the most

360 potent in stimulating Ca and PO4
transport in the GI and bone
resorption. T 1/2 is relatively short due
to poor binding affinity with serum Vit D
1,25 (OH)2-D3 (calcitriol) binding protein. Tx hypocalcemia
Effective in increasing Ca and PO4
361 reabsorption from kidney; Weak effects
25 (OH)-D3 (calcifediol) on GI absorption of Ca
24, 25 (OH)2-D3 D3
362
(secalcifediol) May stimulate bone formation
363 Ergocalciferol Vitamin D2 Tx hypocalcemia

364

Isotretinoin Tx severe acne vulgaris

 A B
365
366
367
368
2-selective adrenergic agonists,
Bronchodilator, see adrenergics; 2-
adrenergic agonists stimulate 2-
adrenergic receptor coupled to Gs
protein stimulating adenylyl cyclase and
an increase in intracellular cyclic AMP.
Cyclic AMP stimulates phosphorylation
cascade that leads to decreased
intracellular calcium and smooth
Albuterol (Proventil, muscle relaxation. Also inhibit mediator
Ventolin) release from mast cells.
369
Levalbuterol (Xopenex) new drug, R-isomer of albuterol
370 Pirbuterol (Maxair) see albuterol
371
Terbutaline (Brethaire,
Brethine, Bricanyl) see albuterol
C
Pulmonary Drugs
Bronchiodilators
Asthma (acute, severe asthma), Rapid acting
Therapeutic Use in Asthma and COPD:
Drug of choice for rapid relief of bronchospasm
Highly effective and safe for intermittent, prophylactic
treatment of asthma.
Current Emphasis:
Intermittent use on an as-needed basis for relief of acute,
severe bronchospasm. Not general prophylaxis.
onset<15 min duration: 2-4 (safe during pregnancy (?))
See albuterol, onset<15 min; duration: 2-4; more active isomer
for effect (more expensive)
See albuterol, onset<15 min duration: 2-4
Asthma (acute, severe asthma), Rapid acting; see albuterol,
onset<15 min; duration: 2-4; injectable, inhaled, or tablet;
s.c. for emergency/resistant to nebulizer treatments
Delay pregnancy
see adrenergics
 A B C
Combined treatment with ipratropium and 2-adrenergic
agonists results in a slightly greater and more prolonged
372 bronchodilation than therapy with either agent alone.
Albuterol + Ipratropium Combined therapy can be considered if severe asthma
bromide (Combivent) Combination exacerbations exist.
2-selective adrenergic agonists,
373 Bronchodilator; a prodrug that must be
Bitolterol mesylate converted to colterol, the active Asthma (acute, severe asthma), Rapid acting; longer
(Tornalate) compound, in the lung. period of useful bronchodilation (3-6 hrs)

374 Long-acting (~12 hrs), selective 2- It is not suitable for treatment of acute bronchospasm.
Salmeterol xinafoate adrenergic agonist with slow onset of Salmeterol is useful for prevention of nighttime asthma
(Serevent) action, Bronchodilator attacks and prophylactic brochodilation (BID)
Long-acting, dry powder inhaler for maintenance therapy
375 of asthma or prevention of bronchospasm in COPD &
2-selective adrenergic agonists, exercise-induced asthma. Not for treatment of acute
Formoterol (Foradil) Bronchodilator attacks.

376 Salmeterol + fluticasone Combination - long acting beta2 agonist

(Advair Diskus) + steroid not used for asthma rescue inhalation

Epinephrine can be give s.c. to patients unable to receive

377 aerosolized 2-agonists because of age or asthma severity.
DOC for treatment of (emergent) anaphylactic reactions.
Give SQ (or IM or IV with dextrose)
Nonselective alpha, beta agonist, see Bronchodilation & Vasoconstriction (maintain BP & decrease
Epinephrine adrenergics edema), Inhibition of mediator release
Inhaled Epinephrine Nonselective alpha, beta agonist, see
378
(primatene mist) adrenergics tempory, brief relief of asthma
379 Racemic Epinephrine aerosol used for pediatric patients (nebulizer)
Asthma; somewhat shorter acting and less selective at 2
380 Metaproterenol & receptors than albuterol - these agents are not frequently
isoetharine Nonselective -Adrenergic Agonists used.

381 Nonselective agonist, see Asthma; nonselective and has a still shorter duration of action
Isoproterenol adrenergics (than albuterol), very potent
 A B C

382 Anticholinergic Agents, Bronchodilator,

quaternary amine muscarinic receptor
antagonist (will not cross BBB), block Ipratropium is used exclusively as an inhaled aerosol. The
vagally mediated reflex arcs (blocked principal clinical use of ipratropium is in the treatment of
cGMP) that cause bronchoconstriction, COPD. Also used intranasally to reduce secretion in both the
Ipratropium bromide see anticholinergics; poorly absorbed in upper and lower respiratory tract in allergic rhinitis and
(Atrovent) lungs, GI (less muscarinic SE) chronic postnasal drip syndrome (vasomotor rhinitis).
Anticholinergic Agent, Bronchodilator, Long-acting agent (than ipratropium) used for maintenance
383 quaternary amine muscarinic receptor therapy in chronic bronchitis and emphysema; dry powder
Tiotropium (Spiriva) antagonist inhaler device

Adenosine receptor antagonist (most

likely mech), a Methylxanthine;
Bronchodilator; also inhibit cyclic
nucleotide (cyclic AMP and cyclic GMP)
phosphodiesterases, blocking
384 cAMP/cGMP breakdown (which makes
mast cells less likely to degranulate;
note: at levels observed for this mech,
drug is toxic - the concentrations required
to inhibit these enzymes is not achieved
with therapeutic doses) - relaxes
smooth muscle of the bronchi and
Theophylline (Theo-Dur, pulmonary vessels; also stimulates
Slo-bid) the respiratory center
Aminophylline
385 (theophylline Adenosine receptor antagonist, a
ethylenediamine) Methylxanthine
386 Pulmonary Anti-Inflammatory Agents, Corticosteroids
Formerly a first-line agent for treatment of asthma, now less
used: benefits are modest, narrow therapeutic window,
considerable variation in absorption and elimination between
different patients. Used for both prophylaxis and
symptomatic relief of broncial asthma and COPD
May benefit stable COPD pt in combination with other
bronchodilators
Nocturnal asthma can be improved with slow-release
theophylline, but inhaled corticosteroids and salmeterol are
probably more effective.
Used for status asthmaticus given parenterally (or orally), in
conjunction with beta-blocker and corticosteroid
May improve diaphram contractitlity
used for emergency brochodilation i.v. infusions
 A B C

387 Anti-Inflammatory Agent,

Corticosteroid - bind to intracellular
receptors that translocate to nucleus
and positively or negatively regulate
gene transcription. Inhibit production
and release of cytokines, vasoactive and
chemoattractive factors, lipolytic and
proteolytic enzymes, decrease
mobilization of leukocytes to areas of
Beclomethasone injury, decrease fibrosis. General anti-
diproprionate !! inflammatory effect. Takes time to Asthma (initially given 3 to 4 times daily), inhaled
(Beclovent, Vanceril) effect. See Corticosteroids
Anti-Inflammatory Agent, Asthma, inhaled; (No growth suppression detected in
388
Fluticasone (Flovent) Corticosteroid children)

389
Anti-Inflammatory Agent,
Flunisolide (Aerobid) Corticosteroid Asthma (twice daily), inhaled
Triamcinolone acetonide Anti-Inflammatory Agent,
390
(Azmacort) Corticosteroid Asthma (initially given 3 to 4 times daily), inhaled

391
Budesonide Anti-Inflammatory Agent, Approved for Seasonal & Allergic Rhinitis, inhaled; tx of
diproprionate (Pulmicort) Corticosteroid cough-variant asthma

392 Fluticasone propionate Anti-Inflammatory Agent,

(Fluticasone) Corticosteroid Approved for Seasonal & Allergic Rhinitis only

393 Mometasone furoate Anti-Inflammatory Agent, Approved for Seasonal & Allergic Rhinitis only; (No growth
(Nasonex) Corticosteroid suppression detected in children)
 A B C

Systemic Therapy: Systemic (i.v. or oral) steroid therapy is

used in severe asthmatic attacks requiring
hospitalization/status asthmaticus (refractory to
treatment). For severe asthma, prednisone or
methylprednisolone is given i.v., followed by oral doses and
394 gradual tapering of the dose. For acute, severe
exacerbations, oral prednisone is administered for 1 -2 weeks.

In acute exacerbation of COPD, use steroids routinely to

improve symptoms and lung function (FEV1).
Systemic Corticosteroids, see 20-30% COPD pts improve if adminsistered long-term oral
Prednisone immunosuppressants steroid therapy
395 Methylprednisolone Systemic Corticosteroids IV or oral (ED)
396 Hydrocortisone Systemic Corticosteroids IV or oral
IgE Ab, binds free IgE (blocks from
397 binding to its high affinity Fc receptor on
mast cells and basophils, preventing Asthma (tx moderate persisten asthma in pts >12yo whose
Omalizumab mediator release) symptoms are not controlled with corticosteroids))
398 Other Pulmonary drugs

Anti-Inflammatory Agents - Cromolyn

Compounds; may suppress the
activating effects of chemoattractant
peptides on eosinophils, neutrophils, and
monocytes; does not directly relax
399 smooth muscle but after long-term
therapy bronchial hyperreactivity to 1. Allergic Rhinitis
allergens, histamine, and exercise is 2. Primarily prophylactic to prevent asthmatic attacks
significantly diminished. Indirectly inhibit (used in mild to moderate asthma). Ineffective in treating
antigen-induced bronchospasm and ongoing bronchospasm. When inhaled several times daily,
Cromolyn sodium (Intal & directly inhibit the release of histamine cromolyn will inhibit both the immediate and the late asthmatic
Mast Cell Stabilizer Nasal and other autocoids from sensitized responses to antigenic challenge or exercise. Approved for
Spray - Nasalcrom) mast cells. all ages

Anti-Inflammatory Agents - Cromolyn

400 Compounds; indirectly inhibit antigen-
induced bronchospasm and directly
inhibit the release of histamine and other More potent than cromolyn. Nedocromil is approved for use
Nedocromil (Tilade) autocoids from sensitized mast cells. in asthmatic patients > 12yo
Emphysema resulting from genetic deficiency of the plasma
401 proteinase inhibitor 1-antiproteinase (or 1-antitrypsin).
1-antiproteinase Purified 1-antiproteinase (Prolastin) is available for i.v.
(Prolastin) Purified 1-antiproteinase replacement.
 A B C

402

Pseudoephedrine Sympathomimetic Agents (-agonists,

(Sudafed) see adrenergic) Nasal decongestants (Allergic Rhinitis)
Phenylephrine (Neo- Sympathomimetic Agents (-agonists,
403
Synephrine) see adrenergic) Nasal decongestants (Allergic Rhinitis)
Oxymetazoline (Vicks
404
Sinex, and others) See Sympathetic Agonists Nasal decongestants (Allergic Rhinitis)

405

1. Approved for children 6 to 12yo (2-5yo low dose);

Anti-Leukotriene Drugs: selective
Montelukast (Singulair) reversible LTD4 receptor antagonist
406
Anti-Leukotriene Drugs: selective
Zafirlukast (Accolate) reversible LTD4 receptor antagonist
Blocks production of leukotrienes (from
407 archidonic acid)by inhibiting
Zileuton lipoxygenazse Ez
especially useful for patients who experience aspirin-induced
asthma attacks. Must be taken BID.
2. Allergic Rhinits
Approved for prophylaxis and maintenance therapy of
asthma in adults and children >12yo; especially useful for
patients who experience aspirin-induced asthma attacks
(Aspirin Sensitivity). Must be taken QID
Preventative tx of asthma

408
Guaifenesin (Glyceryl
Guaiacolate) Expectorant - mech unknown Chronic irritating cough
Expectorants: Iodides enhance the
secretion of respiratory fluids, thus
409 decreasing the mucus viscosity. In
addition, iodides may stimulate
Potassium iodide & breakdown of fibrinoid material in
Iodinated glycerol inflammatory exudates. Chronic irritating cough
 A B C
Mucolytic agent - acts by facilitating the
410 depolymerization of Chronic irritating cough (COPD); an effective mucolytic
N-Acetylcysteine mucopolysaccharides in dried airway agent but causes irritation. Use is not currently recommended.
(Mucomyst) secretions. May benefit bronchiectasis when delivered by nebulization

411
Mucolytic agent - acts by facilitating the
depolymerization of
Recombinant DNAase mucopolysaccharides in dried airway
(Dornase alpha) secretions. Cystic fibrosis (Chronic irritating cough)

412
Opioid used as an antitussive (cough
suppressant); believed to act at the CNS
level, by suppression of the cough
reflex. May act at non-opioid receptor Acute control of nonproductive cough; often used for in-
Codeine site. See opioids patient treatment.
Non-opioid used as an antitussive - the
d-stereoisomer of methorphan Acute control of nonproductive cough; has no analgesic
413 structurally related to levorphanol, a or addictive properties and does not act through opioid
narcotic (opioid) analgesic (no opioid receptors. Nearly as potent as codeine and produces fewer
receptor activity); NMDA receptor subjective and GI side effects. Available in many over-the-
Dextromethorphan glutamate receptor? counter preparations.

Non-opioid used as an antitussive; Local

414 anesthetics and demulcents probably act
directly on nerve endings in the
pharynx. Antihistaminics mechanism Acute control of nonproductive cough; Control of minor
Benoxonatate (Tessalon) is unknown. transient cough; local anesthetic

415
Diphenhydramine Non-opioid used as an antitussive; see Acute control of nonproductive cough; Control of minor
(Benyline) Antihistamines transient cough; H1 histamine receptor antagonist

416
Ranitidine H2 antagonist, see antihistamines
 A B C
417 Smoking Cessation pharmacologic intervention
418 Nicotine polacrilex Nicotine replacement chewing gum; to reduce withdrawl symptoms and relapse
Transdermal nicotine
419 patch (Nicoderm, Nicotrol,
Habitrol) Nicotine replacement to reduce withdrawl symptoms and relapse

420 (see) Antidepressant; enhances CNS nonnicotine aid to smoking cessation, aid to pt who have not
Bupropion (Zyban) nonadrenergic function been able to quit smoking with nicotine replacement therapy
Smoking cessation: is the first treatment that specifically
targets the neurobiological mechanism of nicotine
421 dependence - reduces nicotine withdrawal symptoms and
Stimulates dopamine and blocks nicotine cravings, helping to prevent a full relapse; also blocks the
Varenicline (Chantrix) receptors effects of nicotine if patient begins smoking again.

422
Antimycobacterials
DOC, first line for TB disease (According to NEJM)
1. Isonizid alone should be given for 18mo (recommended
given in conjunction with other drugs)
2. Isoniazid + rifampin given for 9mo
3. Isoniazid + rifampin + pyrazinamide for first 2mo,
423 followed by 4mo of continued Isoniazid + rifampin (total of
6mo, ideal treatment)
4. Unless rate of resistance to isoniazid is known to be <4% in
Bacterialcidal; Inhibits mycolic acid community, add ethambutol or streptomycin until susceptbility
formation in outer membrane (mycolic is known
acid is unique to Mycobacteria). Kills both DOC, first line for TB latent infection, treat for 6-9mo
Isoniazid (INH) intra- and extracellular bacteria Safe for latent TB in pregnancy

1. DOC, first line for TB disease; see Isoniazid for

424
Inhibits DNA-dependent, RNA
polymerase; bacterialcidal
Combinations with INH and other drugs
helps prevent emergence of resistant
Rifampin strains
regiment.
Isolated isoniazid-resistant TB should be treated with
rifampin, pyrazinamide, and ethambutol for 6mo
Latent infection: Alternatives to INH therapy for latent TB
daily: rifampin alone for 4mo or rifampin + pyrazinamide for
2mo
2. Leprosy
3. Effective against gram (+) and gram (-) cocci, some
enteric bacteria, mycobacteria, and chlamydia

1. A rifampin substitute, used when drug-drug interactions

425 likely, especially protease inhibitors and nonnucleoside
reverse-transcriptase inhibitors (NNRTI) used to treat HIV.
Rifabutin Sim to Rifampin 2.Treat M. avium complex (MAC)
 A B C
426 Rifapentine Sim to Rifampin a long-acting rifampin-like agent

1. First (Second?) line TB disease; see isoniazid regiments.

427 Resistance emerges rapidly, use only in combinations
Inhibits mycolic acid synthesis and 2. Latent MDRTB treatment
Ethambutol mycobacterial cell wall synthesis 3. M. avium intracellular (MAI)
1. First line TB disease; see isoniazid regiments; Resistance
428
Pyrazinamide mechanism unknown develops rapidly, use in combinations
An aminoglycosis; Parenteral, First (Second?) line therapy for tuberculosis; Employed
bacteriocidal, protein synthesis when an injectable drug required, especially life-threatening
429 inhibitor; penetrates into cells poorly, so illness, e.g., meningitis or disseminated disease or multi-drug
is active mainly against extracellular resistant TB;
Streptomycin tubercle bacilli. kills aerobic gram- enterics (DOC Yersina Pestis)
430 Ethionamide blocks mycolic acid synthesis Second line TB treatment
431 Capreomycin Second line TB treatment; IM drug for MDRTB
432 Cycloserine inhibitor of cell wall synthesis Second line TB treatment

433
Antifungal Agents

434

Polyene macrolide antibiotic; Binds

ergosterol in fungal cells, increase
membrane permeability; cidal, broad DOC for systemic mycoses
Amphotericin B spectrum, extremely poten Slow parenteral administration necessary

435 block the activity of an enzyme Itraconazole has the broader spectrum of activity and is
necessary for ergosterol synthesis available both orally and IV (of azole's)
Itraconazole

436
Flucytosinne Interferes with thymidylate synnthetase Tx cryptococcosis
block the activity of an enzyme
437
Fluconazole necessary for ergosterol synthesis
block the activity of an enzyme
438
Voriconazole necessary for ergosterol synthesis
 A B C
block the activity of an enzyme Tx systemic fungal infections, used to treat Cushings
439
Ketoconazole necessary for ergosterol synthesis disease
Applied topical to skin and mucous membranes
440 complexes with ergosterol (primary Used to treat local candidiasis (thrush, vaginal, etc)
membrane sterol of fungi) and causes Polyene macrolide like Amphotericin B but too toxic for
Nystatin the membrane to become leaky parenteral administration
441 Clotrimazole, Miconazole Topical Azoles
Used for systemic treatment of dermatophytosis (griseofulivin
442
Griseofulvin Interfers with mitotic spindle funtion concentrates inn the stratum corneum)
Used for systemic treatment of dermatophytosis (especially
443
Terbinafine blocks ergosterol synthesis tinea unguium/neil infection)
444

445
Antiviral Agents
446 Prophylaxis of type A influenza; Treatment initiated within 48
Inhibit uncoating of RNA viral nucleic hours after initial appearance of symptoms is effective; Tx
Amantadine acids, Inhibit viral replication Parkinson's dz

447 Inhibit uncoating of RNA viral nucleic Prophylaxis of type A influenza; Treatment initiated within 48
Rimantadine acids, Inhibit viral replication hours after initial appearance of symptoms is effective
inhibits neuraminidase (Ez necessary
448 for viral replication and for release of
Zanamirvir infected cell) Tx and prophylaxis of both influenza A and B
449 Oseltamivir inhibits neuraminidase Tx and prophylaxis of both influenza A and B
1. Respiratory syncytial virus (RSV) in infants and young
Synthetic guanosine analog children
450 Active against broad spectrum of RNA & Aerosol, oral, IV
DNA viruses 2. Treat Lassa Fever
Ribavirin Inhibits viral mRNA syntheis 3. Give with INF alpah 2b to treat HCV

Inhibits viral DNA synthesis; Acyclic

guanosine derivative; competitive
inhibition of dGTP for the viral
polymerase with binding to the DNA
template as an irreversible complex chain
451 termination following incorporation into
viral DNA. Requires three
phosphorylation for activation: it is
converted into monophosphate
derivative by virus specified thymidine
kinase, then to the di- and
triphosphate compounds by hosts DOC for genital herpes (STD); Active against herpes simplex
Acyclovir cellular enzyme virus-1 and -2 (HSV-1 & HSV-2)
 A B C
452 Ganciclovir DOC for CMV (eg cytomegalovirus retinitis with HIV pt)
453 Foscarnet
Prevents viral attachment: 3-methyl
isoxazole group binds the floor of the
454 canyon structure at the vertices of the
virion, which normally attach to cell
Pleconaril receptors If administered early, inhibits poliomyelitis infection (polio)
Produces proinflammatory cytokines,
stimulates release of TH1 cytokines,
455 binds to Toll-like receptor of dendritic
cells and M0 and enhances cell-
Imiquimod mediated IR Tx HPV
456

457
Antihistamines

Clinical indications of antihistamines

1. Allergic conditions - DOC for allergic rhinitis and
458
urticaria; vasomotor rhinitis, allergic conjunctivitis, mild,
uncomplicated urticaria and angioedema; ineffective in
bronchial asthma; adjunctive (to epinephrine) therapy in
anaphylactic reactions (parental)
2. Motion sickness/nausea - esp. diphenhydramine,
dimenhydrinate, zines
3. insomnia
Diphenhydramine H1 receptor antagonists: prevents Comments specific for diphenhydramine: Marked
(Benadryl, first generation, phosphoinositol hydrolysis, preventing sedation; anti-motion sickness activity; high
Ethanolamine class) increased intracellular Ca++ antimuscarinic activity

459 Dimenhydrinate (first

generation, Ethanolamine) H1 receptor antagonists Motion sickness/nause; see diphenhydramine

460 Cyclizine (first generation,

Piperazine derivatives) H1 receptor antagonists Motion sickness/nause; see diphenhydramine
Hydroxyzine (first
461
generation) H1 receptor antagonists Motion sickness/nause; see diphenhydramine
 A B C

462 Meclizine (first generation,

Piperazine derivatives) H1 receptor antagonists Motion sickness/nause; see diphenhydramine

463
Topical Nasal Spray Antihistamine: given intranasally, with
the advantage of rapid onset of action and the disadvantages
of twice-daily dosing; may be useful in pts with mucosal
Azelastine (Astelin) H1 receptor antagonists irritation and/or epistaxis from nasal corticosteroids.

464 Chlorpheniramine (Chlor-

Trimeton, first generation, See diphenhydramine; common component of OTC cold
Alkylamines class) H1 receptor antagonists medication.

Promethazine
465 (Phenergan, first
generation, Phenothiazine
derivatives) H1 receptor antagonists See diphenhydramine
Ophthamlmic H1 receptor
466 noncompetitive antagonists and
stabilizes mast cells, long duration of
Ketotifen action, little systemic absorption Allergic conjunctivitis

467

Fexofenadine (Allegra,
2nd generation,
Piperidines class) H1 receptor antagonists See diphenhydramine; Newer agent; Allergic Conjunctivitis

468
Desloratidine (2nd Gen) H1 receptor antagonists See diphenhydramine; Newer agent; Allergic Conjunctivitis
Loratadine (Claritin, 2nd See diphenhydramine; Newer agent; longer action; Allergic
469
Gen) H1 receptor antagonists Conjunctivitis

470 Cetirizine (Zyrtec, 2nd

Gen) H1 receptor antagonists Long-acting (24 hr): Allergic Conjunctivitis
 A B C

H2 receptor antagonists: selective,

471
reversible competitive blockers of H2
receptors, decreases secretion of Indications
gastric acid; also block the acid 1. Peptic Ulcer
secretion stimulated by gastrin, 2. Gastric ulcer
cholinergic agonists, vagal stimulation 3. Zollinger Ellison Syndrome (see extra notes)
cimetidine (Tagamet) food, insulin, caffeine, etc. 4. Reflux disorder

472
ranitidine (Zantac) H2 receptor antagonists, see cimetidine see cimetidine

473
famotidine (Pepcid) H2 receptor antagonists, see cimetidine see cimetidine

474
nizatidine (Axid) H2 receptor antagonists, see cimetidine see cimetidine
475

476 Sympathetic Agonists (Sympathomimetics):

Drugs that mimic the actions of sympathetic stimulation. Frequently referred to as adrenergic agents. (Catecholamine vs. non-Catecholamine, Direct vs. indi

477
Induces vasoconstriction
Increases BP (arterioles) & Increases cardiac return (veins)
Expect reflex bradycardia. Also
1. Nasal decongestant
2. Infiltration with local anesthetics.
Phenylephrine - Non 3. Pressor agent (drug that increases bp) to maintain bp
Catecholamine Agonist 4. Ocular examination. Mydriasis without affecting
(selective) selective 1 agonist accommodation.
 A B C

Agonist at all adrenergic receptors (1,

2, 1, 2, 3).
1. Heart: (beta-1 mediated) Positive
inotropic effect, Positive chronotropic
effect, Increased automaticity (latent
pacemakers become active = increased
ectopic beats. Note: arrhythmias also
may occur because refractory period
following an action potential is reduced);
Increased conduction rate in the AV
node. Epinephrine (E) widens the pulse
pressure because it stimulates 2
receptor on arterioles, causing
vasodilation
478 2. Blood Vessels: Skeletal muscle
arterioles: both 1 and 2 receptors are
present (at physiological quantities see
vasodilatation (2), with pharmacological
doses typically see vasoconstriction
(1)).
Veins: 1 (pure constriction).
Coronaries: vasodilate (2)
Kidney, skin, mucosa: vasoconstriction
(1). 1. Bronchial asthma. Administered by inhalation.
Cerebral: unchanged Bronchodilation (2) and inhibition of antigen-induced
3. Metabolic Effects: Calorigenic effect histamine release.
and tremors in skeletal muscle (2). 2. Anaphylactic shock (give IV or SC) Improves breathing by
Mechanisms related to increased same mechanisms as in 1 above, plus increases blood
glycogenolysis (2) and lipolysis (3) at pressure and reverses edema (a1).
Epinephrine - various organ sites (liver, skeletal muscle 3. Infiltration with local anesthetics.
Catecholamine (Prototype and adipocytes.) 4. Topical for hemostasis.
sympathomimetic) 4. Lungs: Bronchodilation 2
Receptor selectivity. 1, 2 and 1
1. Heart: 1 direct effects (increases
479 Norepinephrine inotropic/chronotropic).
(Levophed)- 2. Vasculature: 1 vasoconstriction, Clinical use: manage hypotension by iv infusion.
Catecholamine (activates baroreceptors) (& treatment of shock)
 A B C

1 and 2 stimulant. (no alpha effects).

480 1. Heart: Positive inotropic and
chronotropic effect.
2. Vasculature: Vasodilatation of skeletal
Isoproterenol (Isuprel)- muscle arterioles (2 receptors on
Catecholamine arterioles).
Relatively limited because of intense cardiac effects.
1. Bronchial asthma (Aerosol) Relatively limited because of
intense cardiac effects. (see Pulmonary drugs)
2. Heart block (give by IV. catheter.)

481
Albuterol - Direct Acting
2 Agents (Selective 2
adrenergic agonist) see
extra notes for additional Direct Acting 2 Agents (Selective 2 Used in bronchial asthma. Aerosol for acute effects and p.o.
beta 2 agonists adrenergic agonist) (post op) for chronic treatment. (see Pulmonary drugs)

482

Ritodrine (Yutopar): Beta-2 Adrenergic Agonist used to delay labor

De-carboxylated tyrosine
No direct effect on receptors
Enters nerve terminal via the re-uptake
483 pump. Massive NE releases
Does not cross BBB to any significant
extent (no CNS effects, contrast this to
amphetamine derivatives, which do cross
Tyramine - Indirect Acting BBB and do cause profound CNS
Sympathomimetic effects)

Blocks re-uptake of dopamine (abuse

mechanism), serotonin, and
485 norepinephrine (effects on heart and
BP)
Cocaine - Reuptake Prolongs and intensifies the actions of
inhibitors NE and E
 A B
Agonist at D1 (& D2) receptors
D1 (& D2) receptors in kidney; leads to
vasodilation in the kidney
486 Agonist at 1, leads to increased cardiac
output
Agonist at 1 (less potent than for D1
and 1), which can lead to
Dopamine (Intropin) vasoconstriction
487 catecholamine - Increase in cardiac
output; decrease in ventricular filling
pressure(??)
1(predominant) and 2 agonist effects
Dobutamine (Dobutrex)
Large group of drugs with high abuse
potential (Schedule II). All are indirect
acting non-catecholamines. Release
488 NE from adrenergic nerves. Also release
dopamine in CNS. These agents are
taken up into nerve terminals via the
uptake one mechanism. They also
compete with and reduce NE and
Amphetamines dopamine reuptake.
489 Ephedrine (eF-a-drine) - indirect (releases NE) but also a direct
naturally from genus beta-adrenergic receptor agonist (and
Ephedra alpha agonist, so similar effect to E)
490
psuedoephedrine - OTC
C
Shock, particularly Hypovolemic shock (and cardiogenic in
the early stages)
1 effects benefit cardiac output
1 effects increase blood pressure
(D1 vasodilation prevents renal failure)
Short-term therapy only
Especially useful to increase splanchnic and renal blood
flow
Often switch patients in cardiogenic shock from dopamine (or
occasionally norepinephrine) to dobutamine once blood
pressure is stable. (According to Dr. Olgasby dobutamine is
used more for cardiogenic shock because of beta1 agony
without the alpha1 vessel increased resistance and bp??)
Short-term support of cardiac output in advanced HF
Tolerance prohibits long-term use. The inotropic effect
occurs with little change in heart rate (HR).
Clinical Uses:
1. Narcolepsy
2. Attention Deficit Hyperactivity Disorder children (ADHD).
3. Obesity; anorexiant effect. No longer FDA approved. Abuse
potential is far too great. Derivatives of amphetamine that
have less abuse potential are still used as anorexiants.
Pharmacological Actions. Like a longer acting but less
efficacious epinephrine. Ephedrine penetrates the CNS.
Cardiovascular: mild positive inotropic effect (may cause
palpitations and arrhythmias), vasoconstriction
CNS: stimulation
Nasal decongestant
 A B C

OTC Agents for Topical Decongestion: Used for local

vasoconstriction (e.g., nasal decongestants);
Tetrahydrozoline (as Tyzine), Xylometazoline (Otrivin), &
Oxymetazoline (Afrin):
491 Nasal passages have a dense supply of 1 receptors
Tetrahydrozoline (Tyzine, vasculature
Visine), Xylometazoline Edematous fluid can be prevented by squeezing the arterioles
(Otrivin), & and veins of this vascular bed
Oxymetazoline (Afrin) - Tetrahydrozoline (as Visine):
Common OTCs Alpha 1 Effects (direct) shrink injected conjunctiva (soothes red eyes)
492

493 Sympatholytics chemicals

tending to oppose the physiological results of sympathetic nervous activity or of sympathomimetic drugs

Alpha2 agonist
Periphery: 2 receptor is an
autoreceptor on norepinephrine nerve
terminals. When stimulated it decreases
release of norepinephrine.
CNS: stimulation of 2 receptors and
494 imidazolin receptors lowers CNS
sympathetic outflow. Consider the
action as turning down the gain on the
control mechanism regulating HTN emergencies, used for drug-induced HTN (for limited
sympathetic nerve activity. The brainstem duration only), such as cocaine/amphetamine overdose;
is the main site of action as anti- Withdrawal symptom treatment for opiates and sedatives
hypertensive. Part of effect may be via (noradrenergic neurons in the locus ceruleus), see opioids;
Clonidine imidazoline receptors in brainstem May be helpful in reducing craving for cigarettes.
Extremely well studied in pregnancy. If a woman is
495 Methyldopa (aka alpha- Alpha2 agonists (central acting); Pro- hypertensive prior to the start of pregnancy, this is the drug
methyl-DOPA) drug of choice during the pregnancy.
496 Guanfacine Centrally acting alpha-2 agonist Tx of mild to moderate HTN

497 Adrenergic neuronal depleting agent:

blocks vesicular uptake and storage of
NE (and others monoamines). Result is
depletion of monoamines throughout the
Reserpine body, including the CNS Outmoded
 A B C
Adrenergic neuronal depleting agent:
Inhibits release of NE from sympathetic
498 nerves and depletes NE from storage
granules. Must be taken up via NE
reuptake pump. Does NOT get into CNS
Guanethidine (highly polar) Outmoded
drug of choice for noemergent HTN in pregnancy (though
499 Olgasby says use methyldopa??????????? (same thing, diff
Aldomet name??)
500

501 Adrenergic Blocking Agents

sin = blocker
lol = blocker

502
Non-Selective, Block 1 & 2
Affinity is 1 = 2 (non-selective)
Also is an agonist at muscarinic and
histamine receptors
Phentolamine is a competitive blocker of
alpha receptors. It shifts the NE dose-
Phentolamine - non- effect curve to the right. Note that the full
selective alpha blocker effect of NE can be re-obtained with
(competitively binds) higher NE dose
Pheochromocytoma (see extra notes)-- control acute
hypertensive crisis
Treat necrosis due to vasoconstrictors such as NE and
phenylephrine (should be rare)
Note: non-selective alpha blockers have essentially no use in
essential hypertension (see extra note).
 A B C

1. Vascular. Blocks the effects of

endogenous NE -- reduces blood
pressure.
2. Cardiac. Reflex tachycardia.
Reducing BP causes sympathetic
activation. Because 2 receptors on
adrenergic nerves are blocked, this
further increases NE release at the heart,
503 where NE can act on beta-1 receptors.
3. CNS. Lipophilic agent that crosses
blood brain barrier. 1. Pheochromocytoma: Pre-operative management to treat
Nausea, vomiting and weakness may be vascular effects of high circulating catecholamines.
signs of non-specific CNS effects. Tumor tends to dump NE when physically disturbed (i.e.,
4. Others: miosis, inhibition of surgery).
ejaculation, stuffy nose (related alpha Given in combination with a beta blocker, phenoxybenzamine
Phenoxybenzamine blockade et cetera) protects vasculature; beta blocker protects the heart.
(Dibenzyline) - non- (Notice - Onset is slow (several minutes 2. Peripheral Vascular Disease, e.g. Raynauds syndrome (see
selective alpha blocker for formation of covalent linkages), extra notes)
(covalently binds), aka Offset is very slow, elimination t1/2 of 24 sympathetic tone to peripheral vasculature is high
non-competitive blocker hours. New receptors must be Vascular. Blocks the effects of endogenous NE -- reduces
synthesized.) blood pressure.
 A B C

Non-selective competitive antagonist at

1 and 2 receptors (also 3). High
therapeutic doses may also have a non-
receptor-related membrane-stabilizing
effect (?)
1. Heart (decreases CO): Decreases HR
(negative chronotrope); Decreases
contractility (negative inotrope);
Decreases spontaneous pacemaker
504 activity (depresses ectopic foci more than
SA node); Decrease caridac work
(decrease O2 consumption, no effect on
O2 supply); decrease PVR (decreasing 1. Angina pectoris: Reduces cardiac work and O2
O2 demand) consumption.
2. Blood vessels: Reduction in renin 2. Hypertension: blocks renin release (slow working);
release (renin release is controlled by 1 Decrease in cardiac output and decrease in peripheral
receptors in the kidney), leading to resistance (decreased CO allows peripheral vasculature to
decreased angiotensin and decreased relax over time).
aldosterone. Results in a slow developing 3. Migraine headache (Prophylactic treatment)
decrease in peripheral resistance 4. Arrhythmias (see antiarhythmic drugs)
3. Bronchial Smooth Muscle: Blocks 5. Pheochromocytoma
relaxation. Watch out for bronchospasm 6. Thyrotoxicosis
Propranolol (Inderal) - in conditions where sympathetic tone 7. Adjunctive treatment of anxiety (particularly performance
Non-selective competitive maintains the airway (e.g., asthma) anxiety related to fine motor skills)
antagonist at 1 and 2 4. Metabolic: Blocks lipolysis (3) and 8. Reduce mortality post MI
receptors (also 3) glycogenolysis (2). 9. Management of heart failure (non-acute)

505 Non-Selective Beta Blockers (similar to Actions and uses are much like propranolol
Nadolol (Corgard) propranolol); long 14-24hr half-life Very long duration of action (once daily dosing)
Much like other beta blockers for systemic uses (eg HTN,
angina)
506 Treats glaucoma by decreasing synthesis of aqueous humor.
Timolol (Blocarden; Non-Selective Beta Blockers (similar to Administered topically as Timoptic or in various combinations
Timoptic) propranolol) with other drugs.
 A B C

507
hypertension, angina & CHF
Slightly preferred (compared to propranolol) in individuals
who also have: asthma, diabetes, peripheral vascular disease
1 (Cardioselective) Blocker; Short (Usual recommendation is to avoid beta blockers in these
Metoprolol half-life limits utility patients if possible)

508 hypertension, stable angina

1 (Cardioselective) Blocker, Metoprolol As compared to metoprolol, only requires once daily dosing
Atenolol (Tenormin) is prototype (advantage over an agent that must be taken 2-3 times daily)

509 Betaxolol (Kerlone; 1 (Cardioselective) Blocker, Metoprolol

Betoptic) is prototype hypertension, glaucoma

510

1 (Cardioselective) Blocker, Metoprolol

Bisoprolol (Zebeta) is prototype hypertension, CHF

Ultra short acting (t1/2 of 10 min)

Structure has ester linkage that is easily hydrolyzed
When infused i.v., steady state is reached very rapidly without
511 the danger of a loading dose
Offset is very rapid when terminated; Onset/Offset
characteristics make this an excellent agent for emergency
use in severely ill patients (e.g. intraoperative and
ultra-short-acting 1-selective postoperative hypertension, and sometimes for
Esmolol (Brevibloc) adrenoreceptor antagonist hypertensive emergencies assoicated with tachycardia))

hypertension, dysrhythmias. Has slight vasodilation

512 Beta1-Selective Partial Agonists (Beta1 (because of slight activation of beta2). Lowers BP by
Blockers with ISA - intrinsic decreasing vascular resistance and appear to supress CO or
Acebutolol (Sectral) sympathomimetic activity) HR less than other beta-blockers
 A B C

513

Non-selective partial beta agonists

(Intrinsic Sympathomimetic Activity, see Systemic uses and liabilities of these agents are no different
Pindolol (Visken) Extra Note) than propranolol

514 Systemic uses and liabilities of these agents are no different

Carteolol (Cartrol; than propranolol. Ocupress is an ophthalmic preparation as
Ocupress) Non-selective partial beta agonists 1% drops

515

Benign prostatic hypertrophy (see extra notes)

1-Selective Blockers (block 1 but not
Prazosin 2 adrenergic receptors).
b.i.d. dosing and orthostatic hypotension limit use of this agent
compared to newer drugs
Hypertension
Orthostatic hypotension limits usefulness
Reflex tachycardia is minimal if at all

Hypertension. Selective 1 blockers can be used, but

because of side-effects, particularly orthostatic hypotension,
which is severe with initial doses, they are used infrequently
516 for that indication.
Benign prostatic hypertrophy: This use is rapidly being
supplanted by the 1A selective agents (tamsulosin) which
Terazosin (Hytrin) 1-Selective Blockers does not produce orthostatic hypotension
 A B C

517 Tamsulosin (selective 1A Benign prostatic hypertrophy, prostate has greater number
blocker) Selective 1A blocker of 1A receptors expressed than other tissues.
Same uses and liabilities as terazosin or prazosin
518 Long elimination half-life (24 hr) makes once daily dosing
Doxazosin (Cardura) 1-Selective Blockers feasible

Hypertension: Dilates both resistance and capacitance

vessels; Antihypertensive at doses that do not alter cardiac
520 output; appropriate first-line drug for HTN in pregnancy
Combined Alpha/Beta Blockers: Hypertensive Emergencies (including drug-induced, eg
b1 antagonist coke/amphetamine)
Labetalol (Normodyne, b2 partial agonist Slow onset. Used in combination with shorter acting drugs
Trandate) a1 antagonist Pheochromocytoma

Management of chronic CHF - Critical point is that once

521 patients are stable, therapy with beta blockers extends life
Combined Alpha/Beta Blockers: expectancy. Carvedilol was one of the first drugs used in
Non-selective b1/b2 antagonist clinical trials to document this effect.
Carvedilol (Coreg) a1 antagonist Hypertension
522

523
Cholinergic agonist (Muscarinic Receptor Agonis
Drugs which produce effects similar to those observed during the stimulation of postganglionic parasympathetic fibers i.e., drugs which exert their effec
muscarinic receptors. (Typically) Parasympathetic postganglionic innervation to a muscarinic receptor on cardiac & smooth muscle, gland cells and nerve
have sympathetic muscarinic receptors).

Muscarinic receptors are all G protein

coupled metabotropic receptors (all
524 blocked by atropine):
M1 (nerves) (IP3; DAG)
M2 (cardiovascular) (K+; decrease
cAMP)
M3 (glandular) (IP3; DAG)
M4 & M5 CNS functions unclear
devoid of nicotinic effects (historic basis
Muscarine (naturally for classification of muscarinic receptors), No therapeutic use; of interest only because it is the toxin
occurring alkaloids) resistant to cholinesterases; responsible for mushroom poisoning
 A B C
Glaucoma (lowers IOP - intraocular pressure)
525 Dry mouth (xerostomia) (e.g., cancer therapy)
Pilocarpine (naturally Dominant muscarinic actions in periphery and CNS; clinical
occurring alkaloids) Tertiary amine use only as topical

With certain exceptions, muscarinic

effects of acetylcholine are similar to
parasympathetic nerve stimulation (see
Chol Agonist Martin.doc for more detail):
1. Cardiovascular
526
2. Extravascular smooth muscle
3. GlandsIncreased refractory period
Nicotinic effect (see extra note): *
sympathetic and parasympathetic
Acetylcholine - Prototype ganglia, * the adrenal medulla, * skeletal
and choline ester muscle Ophthalmic surgery to produce rapid miosis
Postoperative or neurogenic urinary retention
Bethanechol (increase smooth muscle Postoperative atonic bowel without obstruction
527 tone) has only muscarinic effect, no Lazy bladder syndrome
nicotinic, and is not susceptible to Will not activate nicotinic receptors (so chemical is much
Bethanechol (Choline cholinesterase (not broken down as different than ACh which activates both muscarinic and
esters) quickly as acetycholine) nicotinic receptors)

528 Carbachol (Choline Both muscarinic & nicotinic activity,

esters) but is not susceptible to cholinesterase Glaucoma (lowers intraocular pressure); miosis during surgery
Not a muscarinic drug, but a Tx glaucoma (lowers intraocular pressure by increasing
529
Latanoprost prostaglandin analog aqueous outflow)
(oral medication) for treatment of dry mouth in Sjgren's
syndrome (also dry mouth of cancer pt - xerostomia)
530 Devoid of nicotinic effects; resistant to cholinesterases;
Synthetic muscarinic agonist; M3 Little or no CNS actions
Cevimeline selective Also used for dry eye

531
Methacholine (Choline stimulates sm contractions in the Diagnostic applications: Provocholine (methacholine) for
esters) bronchioles diagnosis of subclinical asthma
532

533 Anticholinergics (Cholinergic receptor antagonis

Drugs that occupy muscarinic receptors and prevent the muscarinic actions of endogenous acetylcholine or other muscarinic agonists. Antimuscarinics
antagonism of acetylcholine binding to muscarinic receptors.
 A B
Non-quaternary compound; Tertiary
amine (enter CNS); 1. Heart: high dose
tachycardia; low dose - bradycardia
(Due to presynaptic inhibition and CNS
effects)
2. Vascular - no (direct) effect (CBP113);
except at toxic doses (some normal
doses), dilate cutaneous vessels (red as
a beet) mechanism unknown
(sympathetic, cholinergic); block
hypotensive effect of muscarinic agonists
3. Eye: mydriasis (dilation of iris
sphincter) & cycloplegia (relaxation of
534 ciliary muscle) 4. Bronchial: dilation,
decrease bronchial secretions 5. GI
Tract: decreased tone, motility
(antispasmodic effect) 6. Urinary:
relaxation of detrusor, ureter; constriction
of sphincter 7. Glands decrease in all
secretions 8. Action at respiratory center
therapeutic dose: faster deeper
breathing
larger doses: depression of respiration
9. Cerebral centers:
low doses: sedation
high doses: restlessness, amnesia,
delirium
higher doses: stupor; coma
Note: with therapeutic doses, atropine
Atropine - alkaloid & generally has less CNS sedative effects
tertiary amine than scopolamine
Non-quaternary compound
535 Tertiary amines (enter CNS); in
Scopolamine - alkaloid & prophylactic treatment via CNS action in
tertiary amine vestibular nuclei and reticular formation
536 Quaternary amine compounds:
Ipratropium (Atrovent) - Due to quaternary structure these do
Quaternary amine not enter CNS to an appreciable extent
compounds See pulmonary drugs
C
Anesthesiology
Prevention of bronchial and salivary secretions
Prevent bronchospasm
Reversal of reflex bradycardia or hypotension during surgery
Ophthalmology
production of mydriasis and cycloplegia of long or short
duration
choice of agent depends upon requirements.
routine examination: short duration; minimal cycloplegia.
many appear in combinations with alpha adrenergic drugs
Gastroenterology:
Inhibit gastrointestinal motility - antispasmotic
Peptic ulcer treatment.
Can reduce basal and nocturnal acid secretion
(other drugs are better, e.g., H2 antagonists)
Reduce pain and prolong actions of antacids
Reduce motility for reduction of pain, constipation, or diarrhea
Irritable bowel syndrome
Urologic disorders
Detrusor hyperreflexia, enuresis
Increase bladder capacity
Decrease bladder pressure
Muscarine poisoning: muscarinic mushrooms (Inocybe) or
cholinesterase inhibitors
Motion sickness
Scopolamine is useful in prophylactic treatment via CNS action
in vestibular nuclei and reticular formation
Muscarine poisoning
Inhalational drug to reverse bronchial constriction and
secretion
Emphysema, chronic bronchitis (COPD).
Sometimes asthma
COMBIVENT = albuterol + Ipratropium bromide
 A B C

537 Quaternary amine compounds:

Due to quaternary structure these do inhibit secretions (and inhibit bronchiole constriction???).
Tiotropium (Spiriva) - not enter CNS to an appreciable extent (emphysema, chronic bronchitis; asthma); long acting (24 hr)
quaternary amine See pulmonary drugs QD dosing

Gastroenterology (atropine & dicyclomine have similar

results): Inhibit gastrointestinal motility - antispasmotic
Peptic ulcer treatment - Can reduce basal and nocturnal acid
538 secretion (other drugs are better, e.g., H2 antagonists);
Reduce pain and prolong actions of antacids
Quaternary amine compounds: Irritable bowel syndrome - Reduce motility for reduction of
Propantheline (Pro- Due to quaternary structure these do pain, constipation, or diarrhea; Muscarine poisoning:
Banthine)- quaternary not enter CNS to an appreciable extent poisoning with muscarinic mushrooms (Inocybe) or
amine cholinesterase inhibitors

Quaternary amine compounds:

539 Due to quaternary structure these do
glycopyrrolate - not enter CNS to an appreciable extent
quaternary amine

Peptic ulcer treatment - rarely used now;

Irritable bowel syndrome (reduce motility for reduction of
540 pain, constipation, diarrhea);
Urologic disorders: detrusor hyperreflexia (unihibited
neurologic bladder?, denervated bladder?); enuresis:
Non-quaternary compounds (Tertiary increases bladder capacity, decreases pressure. (enuresis: an
dicyclomine Amines) involuntary discharge of urine : incontinence of urine)
Non-quaternary compound
541 Anticholinergic (Tertiary Amine) with
Oxybutynin antispasmotic properties incontinence, Urologic disorders
Non-quaternary compounds (Tertiary
542
oxyphencyclimine Amines) Peptic ulcer treatment, rritable bowel syndrome
Non-quaternary compounds (Tertiary
543
tolterodine Amines) incontinence, Urologic disorders

544 Ocular: For routine examination, shorter-acting which produce

Non-quaternary compounds (Tertiary little cycloplegia are preferred. Duration of Action 12-48 hr
homatropine - ocular Amines) (least cycloplegia of the three ocular cholinergic blockers)

545 Non-quaternary compounds (Tertiary Ocular: For routine examination, shorter-acting which produce
cyclopentolate - ocular Amines) little cycloplegia are preferred. Duration of Action 12-24 hr
 A B C

546 Non-quaternary compounds (Tertiary Ocular: For routine examination, shorter-acting which produce
tropicamide - ocular Amines) little cycloplegia are preferred. Duration of Action 1-2 hr
547

548
Anticholinesterase (Cholinemimetics):
DEFINITION: Drugs that inhibit cholinesterase enzymes and allow acetylcholine released from cholinergic nerves to accumulate, bind to and stimulate posts
are indirectly acting.

549 A non-quaternary compound,

irreversible.
Pharmacological Effects: result from the
increase in concentration of acetylcholine
at muscarinic and nicotinic sites which
occurs following carbamylation
inhibition of cholinesterases
(irreversible). Note: these effects occur
Physostigmine (tertiary only where innervation is present.
amine) - Carbamate See extra notes for ACh organ effect
Reserved for reversal of serious atropine or scopolamine
type poisoning where the CNS is involved. Used cautiously
because of its own side-effects. Not routinely used for
overdose of drugs with secondary anticholinergic effects. May
exacerbate bradyarrhythmias and AV conduction blocks in
tricyclic antidepressant overdose. Readily distributes to all
tissues. Well absorbed orally, binds irreversibly.

i) to improve muscle strength in myasthenia gravis (MG)

(Note that MG therapy often involves other measures,
including thymectomy, corticosteroids, or other
550 Variable absorption, p.o. This quaternary immunosuppressive agents) (see Neurology below)
ammonium compound has actions ii) reversal neuromuscular blockade caused by non-
mainly on the peripheral nervous system, depolarizing agents such as pancuronium, vecuronium, etc.
Neostigmine - quaternary binds covalently (carbamylation/ iii) gastric atony (rarely)
amine & a carbamate irreversible). (see Neurology below) iv) urinary retention (rarely)
 A B C

i) Diagnostic aid for myasthenia gravis (see extra note) (not

551
Edrophonium (Tensilon,
Reversol) - alcohol
Pyridostigmine -
552 quaternary amine & a
carbamate
Brief duration of action, rapid onset
(essentially, a short-acting neostigmine.)
Only one truly reversible anticholinergic
agent, edrophonium, is an alcohol, half
life is 2-10 minutes. (see Neurology
below)
same as neostigmine (see Neurology
below)
primary diagnostic, but can be used to distinguish MG from
other neuromuscular disorders); also to determine
over/under medication for myasthenia gravis (improves -
under medicated, exacerbates - over medicated)
ii) Differentiation of myasthenia crisis from cholinergic crisis
during therapy for myasthenia gravis (infrequently used, not
considered reliable) (see Neurology below)
iii) Reversal of non-depolarizing neuromuscular blockers (e.g.
tubocurarine)
iv) Treatment of paroxysmal atrial tachycardia (PAT) (historical)
Uses and mechanisms are identical to neostigmine but longer
duration of action and less toxicity

highly lipid soluble group (except a) Treatment of open angle glaucoma.

echothiopate - quaternary) of
organophosphate agents which bind
covalently to and inhibit
cholinesterases. Half life in 100s of
553 hours
a) The pharmacological actions of these
compounds are due to irreversible
inhibition of cholinesterases.
Organophosphates b) Muscarinic and nicotinic actions.
(Isoflurophate (DFP), c) Lipid soluble get into CNS.
echothiophate, parathion, d) Absorbed by all routes.
malathion, soman, tabun, e) Hydrolyzed slowly in the body by
sarin, VX) phosphorylphosphatases.
Echothiopate and isoflurophate (DFP) are used but not
preferred because of potential for development of cataracts
and other side-effects. Echothiopate is quaternary
ammonium which limits its systemic absorption.
b) Insecticides: In insects parathion is preferentially
converted to the more toxic compound, paraoxon. (similarly,
malathion is converted to malaoxon)
Mammals can preferentially oxidize these chemicals to a less
toxic compounds. Parathion and malathion are only
preferentially toxic to insects. In high doses they are extremely
toxic in man.
c) Nerve gas: (soman, tabin, sarin). Developed for volatility,
rapid absorption and rapid aging

Cholinesterase reactivation (not an

anticholesterase!!!)
a) Pralidoxime possesses a cationic site
(quaternary ammonium) which attracts it
554 to the anionic site on cholinesterase.
b) The oxime moiety reacts with the
organophosphate bound to the enzyme
forming an unstable complex.
c) The oxime-organophosphate complex
splits off the enzyme and the enzyme is
reactivated.
Pralidoxime (2-PAM) - d) Administration: Slow i.v. infusion. Tx Organophosphate poisoning
 A B C
555 Electron Transport Chain Inhibitors

Organic pesticide that inhibitor of

556 complex I (aka NADH dehydrogenase)
of the electron transport chain (binds to
Rotenone the ubiquinone binding site, aka CoQ) Organic pesticide
Barbituate - site of action same as
557
Amytal rotenone
An antibiotic that blocks electron flow
558 from cytochrome b to c1 (blocks
Antimycin A complex III)
Binds to cytochrome c oxidase
559 (complex IV) and prevents electron
Cyanide transfer to oxygen
Inhibit several Ez processes (lipoic acid-
560 containing Ez, such as alpha
ketoglutarate dehydrogenase), also Ez
Arsenic involved in oxidative phosphorylation
Inhibits electron transport chain at
561
Carbon monoxide complex IV (mech??)
Inhibits F0 "stalk" of ATP synthase
562
Oligomycin (F1F0 ATPase) complex V

Uncoupling agent - increases

563 permeability of mitochondrial innner
membrane, causing a decrease of H+
gradient and increased O2 consumption -
2,4-Dinitrophenol no ATP (e- chain continues)
564 Other Poisions
565 Iron Forms reactive oxygen species

566 Interferes with heme synthesis (d-

aminolevulinic acid and ferrochelatase),
Lead alters cell membrane structure
567 Copper Accumulation in Wilson's dz
568

569 Neuromuscular-blocking drugs:

Drugs that interact with nicotinic type cholinoceptors at the motor end plate (NM) to block cholinergic neurotransmission and produce
 A B C

Non-depolarizing blockers ; Direct-

acting nicotinic receptor antagonist
1. Occupy NM sites on depolarizing Na+
and K+ channels of skeletal muscle end
plate
2. Prevent channel opening in response
570
to ACh, thereby preventing
depolarization.
3. Muscle becomes weak and
subsequently flaccid and unresponsive to
stimulation
4. Blockade is surmountable so that
tubocurarine (prototype of anticholinesterases (e.g. neostigmine)
a non-depolarizing can reverse the neuromuscular
blockers) blockade and paralysis.
Surgery setting
1. Facilitate laryngoscopy and endotracheal intubation by
paralyzing muscles of jaw, throat and larynx.
2. Overcome laryngospasm
3. Facilitate surgical exposure
4. Facilitate mechanical ventilation.
Non-surgical
1. Terminate convulsions in status epilepticus
2. Terminate convulsions in local anesthetic toxicity

571
mivacurium (non- Non-depolarizing blockers, see
depolarizing blockers) tubocurarine see tubocurarine
Non-depolarizing blockers, see
572
Vecuronium tubocurarine
Non-depolarizing blockers, see
573
Atracurium tubocurarine

574 pancuronium (non-

depolarizing blockers) see tubocurarine see tubocurarine
 A B C

Direct-acting nicotinic receptor

agonist
1. Neuromuscular effects are the same
as acetylcholine except they are more
persistent because the drug is
ineffectively metabolized at the synapse.
2. Reacts with NM receptor to open the
channel and cause depolarization of
the end plate. Also enters channel to
575 inhibit ion conductance.
3. Membranes remain depolarized
(repolarization is prevented) and are
unresponsive to additional impulses.
(Phase I block). A phase II (desensitizing)
block may occur subsequently, but is
unlikely to occur under conditions of Surgery setting (intubation, electro-compulsive shock
clinical use. therapy)
4. Effect on muscle is fasciculation 1. Facilitate laryngoscopy and endotracheal intubation by
followed by paralysis paralyzing muscles of jaw, throat and larynx.
5. In contrast to non-depolarizing 2. Overcome laryngospasm
blockers, the neuromuscular blockade 3. Facilitate surgical exposure
produced by succinylcholine is 4. Facilitate mechanical ventilation.
facilitated by anticholinesterase. The Non-surgical
Succinylcholine neuromuscular blockade CANNOT be 1. Terminate convulsions in status epilepticus
(depolarizing blocker) reversed pharmacologically. 2. Terminate convulsions in local anesthetic toxicity
blocks effector cells of skeletal muscle
576 innervated by somatic nerves (NM)
Curare

577
Local anesthetic, Amide class; blocks
Lidocaine (class IB) voltage-dependent Na+ channels Local anesthetics, see antiarrhythmics
578 Bupivacaine Amide class Local anesthetic
579 Etidocaine Amide class Local anesthetic
580 Prilocaine Amide class Local anesthetic
581 Ropivacaine Amide class Local anesthetic
582 Mepivacaine Amide class

583
Procaine Ester class Local anesthetic
584 Benzocaine Ester class Local anesthetic
 A B C
585 Chloroprocaine Ester class Local anesthetic
586 Cocaine Ester class Local anesthetic
587 Tetracaine Ester class Local anesthetic

588
Tetrodotoxin (puffer fish) Block voltage-dependent Na+ channels

589 Batrachotoxin (SA

poisonous frog) Open voltage-dependent Na+ channels
590 Hemicholinium Inhibit uptake of choline
591 Vesamicol Block transport of ACh into vesicle
Blocks inhibitory neuronal input by
592
Strychnine binding glycine receptors

593 Inhibits Renshaw cell release of glycine

Tetanus toxin (inhibitor) through presynaptic binding
Botulinum toxin Block vesicle docking and ACh release at
594
(Botox) neuromuscular junction
Black widow spider (Presynaptic binding) causes explosive
595
venom release of Ach
Snake venoms (-
596
bungarotoxin) Block nicotinic receptors (irreversible)

Autonomic ganglion cells of

sympathetic and parasympathetic nerves
597 (NN) blocked by hexamethonium
Adrenal medullary cells and some
adrenergic nerve terminals (NN)
Hexamethonium blocked by hexamethonium
598
599 Anesthetics

600

Halothane depolarizing agent (?) general anesthesia

601

602
Opioid Analgesics and Antagonists
 A B C

603

Endogenous Compound - Mu receptor

activation ususally (Opioid receptors are
Beta Endorphin of the Mu, Kappa, and Delta variety) No clinical use found
Endogenous Compound - Delta/mu
604 receptor activation (methionine
Met-enkephalin containing penta peptides) No clinical use found
Endogenous Compound - Delta/mu
605 receptor activation (leucine containing
Leu-enkephalin pentapeptide) No clinical use found

606 Endogenous Compound - Kappa

Dynorphin A receptor activation No clinical use found

607
Endogenous Compound - Kappa
Dynorphin B receptor activation No clinical use found
 A B C

High efficacy mu opioid - Prototypic

Opioid Analgesic; binds to all opioid
receptor subtypes; highest affinity is for
mu receptors.
608
low oral:parenteral potency ratio
(Morphine is highly polar; hence, it is
both slowly and incompletely absorbed
after oral administration, both factors are
Morphine (High efficacy important in its lower potency by the oral Useful in pulmonary edema (with SOB, see notes),
opiod (HEO)) route). High efficacy for analgesia analgesia (high efficacy)

609
Meperidine (Demerol) Analgesia; given less due to:
HEO High efficacy mu opioid Shorter elimination half-life

610
High efficacy mu opioid, synthetic, also
blocks NMDA receptors and
Methadone (Dolophine) monoamine reuptake pumps
HEO (antidepressant mechanism)
More efficacious than morphine in difficult to treat pain -
enhanced by antidepressant effects. Opioid abuse treatment
programs

611 High efficacy mu opioid; most lipid Surgery analgesia (particularly cardiovascular) with minimal
soluble, highest potency agents (~100 cardiodepressant effects (due to low dose requirement);
Fentanyl (Sublimaze) HEO x more potent than morphine) transdermal patch for vomiting pts
High efficacy mu opioid; Diacetyl
612 morphine - gets to brain quickly, and is
Heroin (Schedule 1) HEO deacetylated to morphine No clinical use; see No No's

613 High efficacy kappa opioids (& partial Post surgery pain with less potential for respiratory
Butorphanol (Stadol) HEO agonists at mu receptors) depression

614
Post surgery, when patients have respiratory depression,
High efficacy kappa opioids & mu often used to remove the respiratory depressant effects of mu
Nalbuphine (Nubain) HEO antagonist agonists given prior to surgery (still provides analgesia)
 A B C

615
Hydrocodone Analgesia: Efficacy is enhanced by adding aspirin or
(Intermediate efficacy acetaminophen. (Numerous formulations exist, including
opioid (IEO)) Partial -opiate agonist Vicodin; Lortab).

616

Oxycodone (Percocet)
IEO See Hydrocodone

617 Moderate kappa agonist with either

partial agonist or pure antagonist at mu
Pentazocine (Talwin) IEO receptors Oral analgesic with limited abuse potential

Propoxyphene Napsylate/
618 Acetaminophen Tablets
[Darvocet] Low efficacy Primarily affects -opioid receptors, Not recommended for use, low analgesic acitivity, unsuitable
Opioid (LEO) partial agonist for severe pain

619 Partial agonists at mu receptors

(kappa antagonist); long duration of
action and high affinity for mu receptor;
Buprenorphine considered an agonist-antagonists; see
(Buprenex) LEO extra notes Narcotic treatment programs
Central-acting analgesic predominantly
by enhancing seroteonergic
620 neurotransmission; also weak mu
partial agonist and inhibits NE transporter
Tramadol [Ultram] funtion Chronic neuropathic pain; used to tx some fibromyalgia
 A B C

621 High doses is an agonist at non-mu

receptors (sigma?); slow conversion of
codeine to morphine by
Codeine (High efficacy demethylation, occurs by a cytochrome Opioid of choice for cough, ceiling on analgesia in not limited
see notes) (CYP2D6) by efficacy per se

Opioid agonist act at and receptors

in the GI tract to decrease normal
peristaltic motion, increased renal
sphincter tone, reduce secretory activity,
622 and enhance NaCl and water absorption.
Opioids slow transit time allowing
more time for absorption. The net
effect of increased absorption and Diarrhea; Opioids are effective against moderate-to-severe
decreased secretion in the small diarrhea but should not be used for patients with ulcerative
intestine is to decrease the fluid and colitis, or acute bacillary or amoebic dysentery. Used for
Loperamide electrolyte load delivered to the colon. symptoms of travelers diarrhea

623 Diphenoxylate + atropine

(Lomotril) see loperamide Diarrhea; use for Irritable Bowel Syndrome (IBS)
Difenoxin + atropine
624
(Motofen) see loperamide Diarrhea
Paregoric (generic,
625 camphorated opium Opioid agonist - antidiarrheal,
tincture, morphine) antitussive, and analgesic properties Diarrhea

626
Opioid Antagonist; Prototype, blocks DOC opioid overdose (or even slight possiblitiy, ie coma)
effects of full agonists, blocks mu useful in treating some drug-free addicts
Naloxone (Narcan) receptors Short acting, injected/parentral only (inactive oral)

627
Naltrexone (Revia, Opioid Antagonist; blocks effects of full
Trexan) agonists, block mu receptors Long acting, oral route only
628 Nalmefene (Revex) Opioid Antagonist
 A B C

Alpha2 agonist
Periphery: 2 receptor is an
autoreceptor on norepinephrine nerve
terminals. When stimulated it decreases
release of norepinephrine.
CNS: stimulation of 2 receptors and
629 imidazolin receptors lowers CNS
sympathetic outflow. Consider the
action as turning down the gain on the HTN emergencies, used for drug-induced HTN (for limited
control mechanism regulating duration only), such as cocaine/amphetamine overdose;
sympathetic nerve activity. The brainstem Withdrawal symptom treatment for opiates and sedatives
is the main site of action as anti- (clonidine compensates for lack of inhibition in the locus
hypertensive. Part of effect may be via ceruleus (noradrenergic outflow));
Clonidine imidazoline receptors in brainstem. May be helpful in reducing craving for cigarettes.

630 L-alpha-acetylmethadol
acetate (LAMM) Synthetic opioid Prevent heroin relapse (substitution)

631 Non-opioid available OTC; binds NMDA Cough, and when used with opioids increases the cough
Dextromethorphan receptors suppressant activity of the opioid
632

633
Rheumatic Disease & Gout
634 Rheumatic Disease Drugs

635
Hydrochloroquine Malaria tx; mild to moderate (early) rheumatoid arthritis
(Plaquenil) Mechanism of action unknown (rapidly absorbed), safe and convenient
 A B
636
inhibitor of dihydrofolate reductase
(an antifolate); it blocks synthesis of
Methotrexate!! purines needed for DNA and RNA
(Rheumatrex) DMARD synthesis during the S phase
Mechanism in RA is not entirely clear
637 (may be related to its ability to inhibit
Leflunomide (Arava) tyrosine kinase activity and inhibit de
DMARD novo pyrimidine biosynthesis)
5-ASA Compounds (derivative of
salicylic acid): Mechanism of action is
638 unknown, most likely inhibit
prostaglandin formation in the
intestinal mucosa. A member of the
Sulfasalazine (Azulfidine) sulfa drug class (other sulfonamides do
DMARD not share its anti-rheumatic actions).
Inactivates T cells by interfering with
the activation process. T cells are
activated by first binding an antigen-
presenting cell (APC), and then by
639 releasing CD28 that interacts with CD80
or CD86 on the APC, leading to
activation. Abatacept binds to CD80
and CD86, blocking activation and
Abatacept (Orencia) thus it reduces the T-cell-induced
DMARD inflammation/joint damage of RA
C
potent immunosuppressive activity that makes it useful in
cancer chemotherapy and in the treatment of various immune
diseases. It is used at low doses to treat rheumatoid
arthritis (RA)
Alternative to methotrexate and can be given with it to treat
RA
Tx inflammatory bowel dzs - ulcerative colitis and Crohns
dz!!
Sulfasalazine and a newer related drug, olsalazine, are used
as second-line drugs for the treatment of other autoimmune
dzs including rheumatoid arthritis, ankylosing spondylitis,
and seronegative spondyloarthropathy
Pts with moderate to severe rheumatoid arthritis who
haven't adequately benefited from methotrexate or TNF-
inhibitors, are candidates for abatacept. Relieves RA and
reverse some signs of joint damage disease modification.
 A B C

640
RA (usually given with methotrexate) and used for active
Rituximab (Rituxan) Reduces B lympocytes (targets CD20- moderater to severe RA that does not respond to TNF alpha
DMARD containing B lymphocytes) drugs

641

Infliximab (Remicade) Monoclonal antibody which binds TNF- RA Tx - given as an IV infusion every several weeks with
Anti-TNF- (chimeric mouse/human) methotrexate usually
Recombinant protein (genetically
engineered) consisting of the two soluble
642 portions of the TNF- receptor molecule
Etanercept (Enbrel) Anti- and the Fc portion of human IgG. It
TNF- binds two molecules of TNF- RA Tx - injected sub Q twice a week

643 (Decreases the immunoreactivity relative

Adalimumab (Humira) to infliximab by using an) entirely human
Anti-TNF- monoclonal Ab to TNF- RA Tx

644
Recombinant form of human interleukin-1
Anakinra (Kineret) Anti-IL1 receptor antagonist (IL-1ra) Efficacy as good as DMARD for RA Tx
Cyclosporine inhibits T lymphocytes, see Organ transplants & for RA when it fails to respond to
645
(Sandimmune) Immunosuppressants other therapies
Purine antimetabolite that interferes
with purine synthesis and also causes
646 DNA damage through formation of false
nucleotide substrates for DNA synthesis, Cancer, transplant rejection, SLE, and severe refractory
Azathioprine (Imuran) see Immunosuppressants RA
 A B
Analog of the amino acid cysteine that
can slow bone destruction in
rheumatoid arthritis by unknown
647 mechanisms;It works by reducing
numbers of T-lymphocytes, inhibiting
macrophage function, decreasing IL-1,
D-Penicillamine decreasing rheumatoid factor, and
(Cuprimine) preventing collagen from cross-linking.
nitrogen mustard alkylating agent,
648 alkylates DNA interfering with synthesis
and function causing T and B cell
Cyclophosphamide suppression (and all rapidly proliferating
(Cytoxan) tissues), see Immunosuppressants
649 Ifosfamide nitrogen mustard alkylating agent
650 Initially releases substance P, local
Capsaicin (Zostrix) depletion of substance P (long-lasting) Cream applied for relief of pain associated with OA and RA
651 Gold salts probably inhibit the
maturation and function of
mononuclear phagocytes and of T
Aurothioglucose cells, thereby suppressing immune
(Solganal) Gold Salt responsiveness
Gold salts probably inhibit the
maturation and function of
652 mononuclear phagocytes and of T
Gold sodium thiomalate cells, thereby suppressing immune
(Myochysine) Gold Salt responsiveness
Gold salts probably inhibit the
maturation and function of
653 mononuclear phagocytes and of T
Auranofin (Ridaura) Gold cells, thereby suppressing immune
Salt responsiveness
654
Meloxicam [Mobic]
655
C
Immunosuppression: tx rheumatoid arthritis (if other tx have
failed); also tx Scleroderma
It is used as a chelating agent:
Wilson's dz (binding to accumulated copper and elimination
through urine)
Cystinuria (binds with the cystine to make it more soluble)
Tx mercury poisoning.
primarily as an anticancer agent; severe autoimmune
disease especially when systemic complications like
vasculitis are present
Suppress but do not cure RA. Early active arthritis
especially for diseases which progress despiite NSAID use.
Water soluble used in intramuscular injections given weekly
until 1 gram has been achieved leading to accumulation of
gold in the tissue
Suppress but do not cure RA. Early active arthritis
especially for diseases which progress despiite NSAID use.
Water soluble used in intramuscular injections given weekly
until 1 gram has been achieved leading to accumulation of
gold in the tissue
Suppress but do not cure RA. Early active arthritis
especially for diseases which progress despiite NSAID use.
Hydrophobic administerd as oral dose for about 6-9 months
better tolerated than injectable but less efficacious
treat tenderness, swelling and pain caused by the
inflammation of osteoarthritis and rheumatoid arthritis
Gout Drugs
 A B C

656 Xanthine oxidase inhibitor (purine DOC for chronic gout (intercritical or tophacious) and
analog competetively inhibits), reduces treats hyperuricemia primary to gout or from malignancy or
Allopurinol (Zyloprim) uric acid production renal failure. Once daily oral dose

657
Uricosuric - block proximal tubular
secretion (low dose) and resorption (both
Probenecid (Benemid) occur at high dose) of uric acid Gout; delayed excretion (secretion) of penicillin

Uricosuric - block proximal tubular

658 secretion (low dose) and resorption (both
occur at high dose) of uric acid; sulfa
Sulfinpyrazone (Anurane) derivative Gout

Binds to tubulin in mitotic spindles

and other microtubular structures causing
659 arrest of cell division, cell mobility, and Use to be the DOC, provides symptomatic relief if
release of granules. This mechanism is administered early, and provides diagnostic confirmation
believed to prevent migration of given it relieves symptoms of gout only; slow onset; commonly
Colchicine granulocytes into the inflamed area used with allopurinol
NSAID: inhibiting prostaglandin synthesis
(analgesic); also, NSAIDs inhibit
660 phagocytosis (M0) of urate crystals (anti-
inflammatory - Note that other NSAIDs
with lower SE can be used, see NSAIDs
Indomethacin (Indocin) below). Initial DOC for acute gout attacks
661

662
Non-Steroidal Anti-Inflammatory Drugs
 A B C

Patent Ductus Arteriosus - closure

Low dose aspirin together with diet and exercise is useful for
the prophylaxis of:
coronary artery disease
deep vein thrombosis
unstable angina
prophylaxis and treatment of MI and stroke
Colorectal cancer
Therapeutic Uses: Analgesic/Antipyretics - symptomatic
relief for pain of low-to-moderate intensity:
Headache
Dysmenorrhea (see extra note)
663 Analgesic, Antipyretic, Anti- Arthralgia
inflammatory Myalgia
All NSAIDS inhibit the enzyme Neuralgia
cyclooxygenase (COX), which is a key Arthritis
enzyme responsible for the synthesis of Therapeutic Use as Anti-Inflammatory Agents
prostaglandins. Prostaglandins contribute Rheumatoid Arthritis
to a number of inflammatory processes. Osteoarthritis
Common mechanism of action leads to Gout and Crystal Arthritis
common side effects. Systemic Lupus Erythrematosus
Aspirin covalently (irreversibe and Seronegative Spondyloarthropathy
noncompetitive antagonism) inhibits Arthralgia
COX 1&2, recovery of COX in most Myalgia
tissues is by synthesis of new enzyme, Bursitis, Tendonitis
Platelets cannot synthesize new COX, so External application: salicylic acid is used topically to burn
inhibition is irreversible. (Note, aspirin is off warts, calluses, and corns, i.e., keratolytic. Methyl
Aspirin [generic], OTC - the only NSAID that covalently bind, all salicylate (oil of wintergreen) is found in some liniments as
Osalicylate & prototype others are competitive inhibitors) an external irritant

Used for chronic treatment; commonly used for relief of pain

and fever as over the counter medications. Significant
advantages over aspirin - better tolerated (have all of the
664 detrimental features of NSAIDs). Uses: Rheumatoid Arthritis,
Osteoarthritis (not an inflamatory dz, but does involve pain),
Gout and Crystal Arthritis (acute gouty arthritis), SLE,
Ibuprofen [Advil, Motorin, Seronegative Spondyloarthropathy, Arthralgia, Myalgia,
Nuprin], OTC - Propionic analgesic, antipyretic, anti-inflammatory; Bursitis, Tendonitis, Ankylosing spondylitis, Arthralgia, Myalgia,
Acids COX 1&2 competitive inhibitors Acute Bursitis, Tendonitis, primary dysmenorrhea
 A B C

used for chronic treatment; commonly used for relief of pain

and fever as over the counter medications. Significant
advantages over aspirin - better tolerated (have all of the
665 detrimental features of NSAIDs).
Uses: same as ibuprofen
Naproxen [Aleve, analgesic, antipyretic, anti-inflammatory. Used instead of Aspirin during childhood infection with
Naprosyn], OTC - COX 1&2 competitive inhibitor, longer varicella and other viruses, especially the influenza virus
Propionic Acids half-life (14hr) (chose ibuprofen or naproxen)

Used for chronic treatment; commonly used for relief of pain

and fever as over the counter medications. Significant
advantages over aspirin - better tolerated (have all of the
666 detrimental features of NSAIDs).
Uses: analgesia of acute tendinitis, bursitis, and primary
analgesic, antipyretic, anti-inflammatory; dysmenorrhea, rheumatoid arthritis, osteoarthritis, ankylosing
Ketoprofen [Orudis] COX 1&2 competitive inhibitors spondylitis, and acute gouty arthritis.
Never used for routine analgesia
Can be used in resistant rheumatoid disease,
667 osteoarthritis, ankylosing spondylitis, and acute gout.
Indomethacin [Indocin] - more potent than aspirin; COX 1&2 Suppression of uterine contraction in preterm labor and
Indoleacetic Acids competitive inhibitors closure of patent ductus arteriosus
Etodolac [Lodine] - Postoperative analgesia (single dose lasts for 6-8 hours).
668
Indoleacetic Acids relatively COX-2 selective Treatment of osteoarthritis and rheumatoid arthritis.

Can be used orally, IM, or IV; used for 5 days or less

One of only a few NSAIDs that can be given parenterally!!!
669 Used for post-operative pain, as an alternative to opioids
(not obstetrics)
Ketorolac [Toradol] - Potent analgesic, weak antiinflammatory Unlike opioids, it is not associated with tolerance, withdrawal
Heteroaryl Acetic Acids effect; COX 1&2 competitive inhibitors effects, or respiratory depression.

Originally approved for dysmenorrhea, osteoarthritis, and

rheumatoid arthritis (RA), acute post-operative pain
COX-2 specific NSAIDs were preferred for chronic treatment,
670
Selective COX-2 Inhibitors; contains but there use now (Celebrex only) is very controversial.
sulfur Studies show reduction in number of polyps with COX-2
Significantly less GI ulcers (by inhibitors (COX-2 is overexpressed in several human
endoscopy, decreased GI bleeding still cancers). Increasing evidence suggest that COX-2 inhibitors
unproven). may be effective for prevention or treatment, especially for
Celecoxib [Celebrex] Do not effect platelets and bleeding time. colorectal cancer
 A B C

671

Valdecoxib [Bextra] Selective COX-2 Inhibitors, Withdrawn

672
Refocoxib [Vioxx] Selective COX-2 Inhibitors, Withdrawn

673 1. Commonly used for relief of pain and fever as over the
counter medications; useful analgesic/antipyretic for
children and those with contraindications to aspirin.
Non-NSAID antipyretic/analgesic, a 2. Initial DOC for treatment of pain in osteoarthritis (which
non-narcotic analgesic; is a non-inflammatory condition)
Very weak anti-inflammartory activity 3. Combined with opioid agonists for additive postoperative
Acetaminophen [Tylenol] - (unknown mech; not used for pain relief [Percocet, Lortab, Vicodin, Darvocet, Tylenol with
non-narcotic, non-NSAID inflammation) Codeine]
Zafirlukast [ACCOLATE] & prophylactic treatment of chronic asthma in patients >
674 Montelukast Anti-leukotriene Drugs - LTD4- 12 years old. As yet, these agents are not approved for
[SINGULAIR] leukotriene receptor antagonists treatment of other inflammatory conditions
675 Sulindac
treat tenderness, swelling and pain caused by the
676
Meloxicam [Mobic] inflammation of osteoarthritis and rheumatoid arthritis
677

678
Corticosteroid Drugs
Glucocorticoids (metabolic) inhibit the production and release of many different cytokines that normally would stimulate the proliferation and function of B and T lym
phospholipase A2 from forming arachidonic acid from phosphoipids.
O=oral; I=injectable; T=topical; Inh=inhaler; E= eye drops
 A B C

Rheumatic and autoimmune disorders - Rheumatoid

arthritis, systemic lupus erythematosus, etc.
Chronic inflammatory diseases - ulcerative colitis, Crohns
disease
Organ transplant rejection
679 Asthma: Inhalation localizes drug to the lung and minimizes
systemic absorption; Prophylaxis only - acute attacks treated
with beta2-adrenergic agonists; Emergency treatment of status
asthmaticus
Treatment of Allergic Reactions: Anaphylactic reactions -Epi
first, steroids for delayed reactions
Potent, efficacious anti-inflammatory Important drug for treatment of dermatologic inflammatory
and immunosuppressive agent. reactions and diseases (many different topical glucocorticoids
Glucocorticoids inhibit the production and available, absorption after topical application is enhanced if
release of many different cytokines that covered with an occlusive dressing)
normally would stimulate the proliferation Cancer chemotherapy: Anti-leukemia/lymphoma properties,
and function of B and T lymphocytes. enhancement of antiemetic drug effects
Cortisol: short acting (8-12 hrs) (T, I, O) Cerebral edema and trauma
Lipocortin-mediated inhibition (protein Edematous, Gastrointestinal, Ophthalmic, Sarcoidosis (by
which inhibits) of PLA2 (phospolipase A2) no means an exhaustive list of uses)
Cortisol (aka Suppression/redistribution of leukocytes A single dose, even a large one, is virtually without
Hydrocortisone) Immune/CNS feedback harmful effects

680
Prednisolone Intermediate acting (12-36 hrs) (O, I, E)
Intermediate acting (12-36 hrs) (O); 4
681 times more potent than cortisol, about a
Prednisone third of the mineralcorticoid effect see Immunosuppressant drugs bellow
682 Methylprednisolone Intermediate acting (12-36 hrs) (T, I) Used for spinal injuries, slows progression of degeration
Intermediate acting (12-36 hrs) (O, T, I,
683
Triamcinolone Inh)
684 Beclomethasone Long acting (36-54 hrs) (Inh) See pulmonary drugs
 A B C

potent, long-acting; Dexamethasone is also effective in

preventing acute mountain sickness (dexamethasone, 4 mg
685 4 times per day, if the condition is severe). The recommended
Long acting (36-54 hrs) (T, I, O); 30 times prophylactic dosage for adults is 2 mg every 6 to 8 hours. In
more potent than cortisol with no addition, Gingko biloba has been suggested as a useful
Dexamethasone mineralcorticoid effect prophylactic agent but has not been sufficiently studied
Mineralocorticoid (O) (super active, 125
686 or 250 (depending on source) salt-
retaining activity relative to cortisol which
Fludrocortisone is 1) aldosterone replacement (addison's d.)
687 Corticosterone Mineralocorticoid
similar to the insecticides DDT and DDD
688 and has relatively selective toxicity for the
Mitotane adrenal cortex used to treat inoperable adrenal tumors.
Aminoglutethimide inhibitor of the initial and rate-limiting used to decrease hypersecretion of cortisol in patients with
689
[Cytadren] step of steroid biosynthesis Cushings syndrome.
an antifungal agent that at high doses
690 inhibits adrenal and gonadal Tx systemic fungal infections, used to treat Cushings
Ketoconazole [Nizral] steroidogenesis disease
691 Mifepristone [RU-486] progesterone receptor antagonist use (in Europe) to terminate early pregnancy

Potassium-Sparing Diuretic that

competes for the mineralocorticoid
receptor (ie an aldosterone antagonist)
692 and thus inhibits Na reabsorption in the
kidney. It can also antagonize effective for treating hyperaldosteronism. The drug is also
aldosterone and testosterone synthesis. useful for the treatment of hirsutism in women, probably due to
Spironolactone See diuretics competition at the androgen receptor of the hair follicle.
second-line drugs for Rheumatoid Arthritis (along with glod
693
Methotrexate See cancer chemotherapy below salts)
694

695
Immunosuppressant Drugs
 A B C

Calcineurin inhibitor: Cyclosporine

binds directly to calcineurin
(cylophilin?); Calcineurin is a cellular
protein that assists enzyme functions and
the complex processes of IL-2 in
signaling between immune cells;
reduction in IL-2 production leads to:
696 1. decreased clonal proliferation of T
cells; 2. decreased IL-2 receptor
expression. 2. reduced activation and
clonal expansion of cytotoxic T cells from
CD8+ precursor cells; 3. reduced
functional activity of effector T-cells that Although it is a potent immunosuppressive agent, it has no
are involved in cell-mediated responses, effect on acute inflammation reactions; Cyclosporin is used
such as delayed type hypersensitivity; 4. alone or incombination with other immunosuppresive agents.
some reduction of T cell mediated B cell It is primarily used for organ transplantation. It has also
Cyclosporine responses. been used to treat psoriasis and asthma.

Calcineurin inhibitor: interfers with the

ability of IL-2 to communicate with the T-
cell receptors, suppressing the activation
and replication of the T-cells. Tacrolimus
697
a) is not structurally related to cylosporin Immunosuppression for organ transplantation. It is effective
and b) binds to an immunophilin for preventing rejection of solid organ transplantation,
binding protein called FK-binding even after failure of standard rejection therapy. On a
protein (FK-BP). The FK-506/FK-BP weight basis tacrolimus is 10- to 100-fold more potent than
complex inhibits calcineurin, inhibiting cyclosporin (and so requires lower dose of steroids in
Tacrolimus (Prograf) IL-2 production. combination therapy).
inhibits signaling from the IL-2
698 receptor - suppress activation and
differentiation of nave T cells (and thus
Rapamycin all IR required of T cells)
Dimeric fusion protein that binds to CD2
on memory-effector T cells, resulting in
699 the inhibition of T cell activation and a
reduced number of memory-effector T
lymphocytes; causes apoptosis of T
Alefacept cells Tx of Psoriasis
 A B C

Cytotoxic Agents: kill rapidly

proliferating cells, suppression of WBC
700 proliferation; interfers with purine
metabolism during lymphoid cell
proliferation that follows antigen
stimulation. Effect nucleic acid
synthesis that is required for cell
proliferation. Cellular immunity (T cell
mediated) and both primary and
Azathioprine (aka 6- secondary antibody responses are
mercaptopurine, Imuran). blocked by these agents
a. to inhibit the immune response that causes rejection of
kidney transplants.
b. for the treatment of severe, active rheumatoid arthritis. It
is considered a "second-line," or "slow- acting" drug and is
usually reserved for rheumatoid arthritis patients who do not
respond to other first-line or second-line medications.
c. to treat Crohn's Disease (inflammatory bowel disease) and
multiple sclerosis.

Immunosuppressive Abs: engineered

monoclonal antibody that targets and
blocks the function T3 or CD3 antigen
expressed on T cells a) associated with OKT3 prevents or reverses graft rejection by blocking the
701 the antigen recognition structure b) is cytotoxic activity of T cells. Reversal of rejection occurs in
essential for signal transduction. Binding about 95 percent of patients given the drug. The major
of OKT3 to T cells results in early problem with this drug has been with side effects. Used to
activation, which leads to cytokine treat patients in the first few weeks after transplant. After
OKT3 (muromonab-CD3 release, followed by blocking T cell termination of OKT3 therapy, T cell function usually returns to
(Orthoclone OKT3)) functions. normal within one week.
Converted to the active metabolite
mycophenolic acid, which inhibits de
702 novo synthesis of the guanine
nucleotid (lymphocyte proliferation
Mycophenolate mofetil dependent upon this purine synthesis) Immunosuppresive therapy
Ab with high-affinity for IL-2 receptor
703
Daclizumab on activated T-cells Immunosuppresive therapy

704 Ab with high-affinity for IL-2 receptor

Basiliximab on activated T-cells Immunosuppresive therapy

705 inhibits T-cell proliferation by binding the

serine-threonine kinase, mTOR, which
Sirolimus is necessary for cell cycle progression Immunosuppresive therapy (minimal renal toxicity)
 A B
Nitrogen Mustard alklayting agent:
prodrug which must be activated by the
liver P-450 mixed enzymes to 4-hydroxy-
cyclclophosphamide; a bivalent
alkylating agent; the effect on
706 lymphocytes appears to be primarily due
to cross-linking of DNA strands. This
decreases the antigen-dependent
proliferative response in lymphocytes;
destroys proliferating lymphoid cells.
Although similar damage occurs in both T
and B cells, the slower recovery of the B
cells leads to a pronounced effect on
Cyclophosphamide humoral immunity.
707 Ifosfamide Nitrogen Mustard alklayting agent
Glucocorticosteroid:
1. can reduce the size and number of
cells in the lymph nodes and spleen,
with little effect on erythoid stem cells in
the bone marrow.
2. are cytotoxic to subsets of T cells.
However, immunosuppressive effects are
predominantly due to the modification of
function rather than cytotoxicity.
708
4. inhibit the production of
inflammatory mediators, such as
leukotrienes, prostaglandins, histamine
and bradykinnin.
5. attenuate chemotaxis and impair
bactericidal and fungicidal activity of
monocytes and neurtrophils, without
altering phagocytic activity.
6. can alter leukocyte and neurtorphil
distribution causing cells to sequester
in lymphoid tissue.
7. inhibit IL-1 production, leading to
reduced IL-2 & IFN- production.
8. attenuate both cellular and humoral
Prednisone mediated immune responses.
C
a. Tx of autoimmune disorders such as systemic lupus
erythematosus and multiple sclerosis or Wegener's
granulomattosis (an autoimmune hemolytic anemia).
b. Tx of cancers including lymphoma, leukemias, multiple
myeloma, mycosis fungoides, neuroblastoma, retinoblastoma,
and cancers of the breast and ovary.
c. Immunosuppressive for organ transplantation.
1. suppress organ rejection
a. allergic reactions bee stings, contact dermatitis, allergic
drug reactions, allergic rhinitis
b. collagen-vascular disorders lupus erythematosus
rheumatoid arthritis
c. eye disorders allergic conjunctivitis, optic neuritis
d. GI disorders inflammatory bowel disease
e. hematologic disorders and malignancies leukemia,
autoimmune hemolytic anemia, multiple myeloma
f. Systemic inflammation acute respiratory distress syndrome,
gram (-) septicemia to suppress excessive inflammation
h. joint inflammatory disorders arthritis, bursitits
i. neurlogical disorders cerebral edema (to minimize
postoperative cerebral edema), multiple sclerosis
j. pulmonary disorders bronchial astma, infant respiratory
distress syndrome
k. skin disorders dermatitis xerosis
 A B C

Prompt suppression of inflammatory conditions, including

rheumatoid arthritis, systemic lupus erythematosus, acute
gouty arthritis, psoriatic arthritis, ulcerative colitis, and Crohn's
disease. Severe allergic conditions that fail to respond to
709 conventional treatment may respond to
methylprednisolone include; bronchial asthma, allergic
rhinitis, drug-induced dermatitis, and contact and atopic
dermatitis. Chronic skin conditions treated with
methylprednisolone include dermatitis herpetiformis,
pemphigus, severe psoriasis and severe seborrheic dermatitis.
Glucocorticoid: Methylprednisolone is Chronic allergic and inflammatory conditions of the uvea, iris,
a synthetic corticosteroid. Its meachnism conjunctiva and optic nerves of the eyes also are treated with
Methylprednisolone of action is similar to prednisone. methylprednisolone

710
1. control a wide number of disease states which are
characterized by excessive inflammation, including, a) severe
allergic reactions, b) inflammation of the lungs in asthma and
c) inflammation of the joints in arthritis.
2. decrease the numbers of white blood cells and is used
to prevent the rejection of organ transplants
3. treat cancers, including acute lymphatic leukaemia and
myelomas
Glucocorticoids: meachnism of action 4. treat some autoimmune diseases, including systemic lupus
Deflazacort is similar to prednisone erythematosus and rheumatoid arthritis.
711

712 Cancer Chemotherapy

 A B C

713

Hodgkins Disease & testicular tumors: used to treat germ

Antitumor antibiotic - Single & double
strand DNA breaks from free radical
formation; cell cycle specific, G2
Bleomycin phase specific.
714
Mechlorethamine Nitrogen Mustard, Alkylating Agent
cell tumors of the testis & ovary, squamous carcinomas of
the head and neck, esophagus, and genitourinary tract. It is
often used as a component of combination therapy of
Hodgkins and Non-Hodgkins lymphomas. (Does not cause
BM suppression!)
activity historically against Hodgkins Disease. Not used
commonly anymore due to toxicities associated with it

715
most commonly in the treatment of multiple myeloma or non-
Melphalan Alkylating Agent resectable epithelial carcinoma of the ovary
Alkylating Agent: a Platinum
716
Carboplatin compounds

primary use is in GI malignancy, most commonly as adjuvant

717 therapy or use in metastatic colon cancer, but is also used in
Alkylating Agent: a Platinum other GI malignancies, and is being investigate for use in lung
Oxaliplatin compounds cancers, as well as other malignancies
 A B C

718 Alkylating Agent: a Platinum

compounds - Kills cells in all stages of
cell cycle, inhibits DNA synthesis, &
cross-links DNA!! Cell-cycle-active
but non-phase-specific (CCNS, also Bladder Ca, esophageal Ca, head/neck Ca, lung Ca,
Cisplatin known as cycle-independent) osteogenic sarcoma, ovarian Ca, testicular Ca

Oxazaphosphorine, Classic Alkylating

Agent - Highly reactive; spontaneously
transfer their alkyl groups to DNA,
719 protein, or other cell constituents
producing cytotoxic effects. Cross-link
DNA & strand breakage. Non cell cycle-
specific (CCNS) but cells most
susceptible during late G1 and S phases. Bladder Ca, breast Ca, chronic lymphocytic leukemia, lung Ca,
Cyclophosphamide see immunosuppresants above non-Hodgkin's lymphoma, ovarian Ca, soft tissue sarcoma
720 Ifosfamide See cyclophosphamide See cyclophosphamide
Mixture of a mAb directed to CD33 Ag
on hematopoietic cells and the cytotoxic
721 antibiotic, calicheamicin - enters the
lysosomes of CD33+ cells and releases
calicheamicini, which induces DNA
Gemtuzumab ozogamicin strand breaks AML
Tx Chronic lymphocytic leukemia (CLL) annd ovarian cancer;
722
Chlorambucil Nitrogen mustard alkylating agent other lymphomas

723 Atypical Alkylators: old alkylator, used in breast cancer or ovarian cancer and can be given
Thiotepa CCNS intravesically for bladder cancer. It can be given intrathecally.

palliative treatment of CML. In high doses, it has activity in

724 acute leukemia and lymphoma. It is most commonly used
today in high doses as part of a bone marrow transplant
Busulfan Atypical Alkylators, CCNS regimen
 A B C

They are the most lipid soluble and also are among the most
carcinogenic.
725 They are used for brain tumors and BCNU has activity
against lymphomas, Hodgkins Disease and melanoma.
They arent used very frequently, except BCNU comes in a
Nitrosureas - alkylating agent; cross wafer form placed in the brain after resection of brain
Carmustine the BBB, CCNS tumors.
726 Lomustine Nitrosureas, see carmustine see carmustine
used in metastatic islet cell tumors of the pancreas
727 Nitrosurea antibiotic: Potent inhibitor (insulinomas!). It also has some activity in lymphomas and
of alkyltransferase, the DNA repair carcinoid tumors.
Streptozotocin enzyme, CCNS Poorly tolerated

An anthracycline - planar multi-ring

structures that are active by 1) insertion
of the planar ring between base pairs
(G-C sequence) of DNA; 2)
728 Topoisomerase II inhibitor & also 3)
generates intracellular free radicals
which are highly cytotoxic 4) disrupts fluid
and ion transport across cellular
membranes. These drugs are Cell Bladder Ca, breast Ca, gastric Ca, hepatocellular Ca,
Cycle Nonspecific (CCNS). Hodgkin's disease, lung Ca, non-Hodgkin's lymphoma,
Doxorubicin Resistance occurs through P osteogenic sarcoma, soft tissue sarcoma. Doxorubicin is
(Adriamycin) glycoprotein mechanism one of the most useful anticancer drugs (Broad spectrum)
See doxorubicin; an antitumor
729 antibody - inserts between DNA bases
Daunorubicin and induces DNA strand breaks
730 Idarubicin See doxorubicin

Derived from Streptomyces sp.; most

active in G1 phase, but is considered cell
731 cycle independent; It intercalates itself
particularly at guanine bases. It
interferes with DNA-dependent RNA
synthesis, which leads to protein Most commonly used in Wilms Tumors (nephroblastomas),
Dactinomycin synthesis inhibition. rhabdomyosarcoma, testicular and uterine cancers.
 A B C

Antitumor Enzymes: cleaves

asparagine into aspartic acid and
ammonia. This takes place
extracellularly. Most cells have high
732
levels of asparagine synthetase, so are
not affected, but T cells and many
malignant lymphocytes have low levels
and are therefore reliant on extracellular
pools of asparagine. This leads to protein
L-asparaginase synthesis inhibition and cell death used in ALL and some T cell Lymphomas.

Immunotherapy: creates an
733 inflammatory cascade, attracting
chemokines, cytokines which attract
BCG (Bacillus Calmette- macrophages and T cells which kill tumor originally developed as TB vaccine. Its use is in the bladder
Guerin) cells and provides immunologic memory against superficial bladder cancers.

734 Used in melanoma and renal cell c. (both usually resistant to

Directly modulates the immune chemo), chronic hepatitis B and C; Tx multiple sclerosis
Recombinant Interferon response and directly affects (reduce exacerbations)
alpha-2a proliferation of tumor cells.

Normally secreted by TH1 cells to

735 increases TH1 proliferation (autocrine),
activate CTL, and activate M0 (cell-
Interleukin-2 mediated IR)
Must first be converted to thio-IMP by
HGPRT Ez (purine salvage pathway);
736 thio-IMP acts as purine analog, which
inhibits PRPP Amidotransferase which
inhibits purine synthesis. S Phase indicated for the induction and maintenance of remission of
6-Mercaptopurine specific, Self-limiting ALL
Antimetabolite: derivative of the antiviral used in B lymphocyte malignancies
737
Fludarabine agent, vidarabine Very effective Low grade malignancies

738 Cladribine (2-

chlorodeoxyadenosine, Antimetabolite: analog of
2CDA) deoxyadenosine used in hairy cell leukemia (a B lymphocyte malignancy)
Adenosine analog, that bind and inhibit
739
Pentostatin adenosine deaminase targets lymphoid malignancies; hairy cell leukemia
 A B
Antimetabolite: a nucleoside composed
740 of cytosine and a sugar link (araCTP). It
is analog to naturally occuring
Cytarabine (cytosine deoxycytosin; competitively inhibit DNA ALL, AML, non-Hodgkins lymphoma
arabinoside) polymerase; Inhibits replication
Antimetabolite: a pyrimidine analogs -
Inhibitor of thymidylate synthase;
Inhibits DNA synthesis; strand breakage;
741 Inhibits RNA processing and function -
induce cytotoxicity by serving as false
substrates in biochemical pathways; cell-
cycle-active and are specific mainly for
Fluorouracil (5FU) the S phase.
742 It is an oral agent, converted into 5-
Capecitabine fluorouracil
743
Levamisole enhances cell-mediated immunity
744 Antimetabolite: a Folic Acid
Antagonists - inhibits dihydrofolate
reductase and the conversion of folic
acid to tetrahydrofolic acid (DHF to THF); GVHD and as an immunosuppressive agent in BM and organ
thus, inhibits synthesis of thymidine,
purines and DNA. S phase specific,
self-limiting (?); It crosses the BBB and treatment for non-acute ectopic pregnancy.
Methotrexate can be given intrathecally
Antimetabolite: inhibits the enzyme
ribonucleotide diphosphate reductase,
which converts ribonucleotides to
745
deoxyribonucleotides (XDP to dXDP).
This is a critical and rate-limiting step in
de novo DNA synthesis. Kills cells that
are rapidly dividing during the S phase
(those with short G0 phase and cycling
Hydroxyurea times); crosses the BBB.
C
It can also be given intrathecally and crosses the BBB readily.
Virtually all adenocarcinomas and some squamous
malignancies; Breast Ca, colorectal Ca, esophageal Ca,
gastric Ca ; Direct hepatic artery infusions for the treatment of
hepatic metastases
Indicated in colorectal adenocarcinoma, as well as other GI
malignancies, especially when fluoropyrimidine therapy is
preferred. Other indications: breast cancer
Used in combination with 5FU to tx certain colon cancers
1. Cancer Tx: (higher doses) Acute lymphoblastic leukemia
(ALL), systemic and CNS lymphomas (NHLs), leukemias;
choriocarcinoma (gestational trophoblastic Ca) and
carcinomas of the breast, head and neck, ovary, bladder, and
osteogenic sarcoma.
2. Transplant & autoimmune immunosuppressant: (lower
doses) severe psoriasis (treats both skin and arthritis), IR in
transplant procedures; dermatomyositis, rheumatoid arthritis,
Wegeners granulomatosis, and Crohns disease; also
(High dose therapy with Leucovorin rescue)
Chronic myelogenous leukemia (CML), essential
thrombocytosis; the principle use of hydroxyurea has been
as a myelosuppressive agent!! in the myeloproliferative
syndromes, particularly chronic granulocytic leukemia,
polycythemia vera, and essential thrombocytosis; some solid
tumors; sickle cell disease (reduces the number of painful
crises, the frequency of acute chest syndrome and
hospitalization, and the need for blood transfusions);
HIV/AIDS.
 A B C

Hormone agent: a Gondotropin-

Releasing Hormone Analog - Indirect
746 antiandrogen; function as LHRH agonists
cause transient release of FSH & LH
followed by inhibition of release of FSH &
LH, decreasing testosterone levels. Prostate cancer, used with flutamide, bicalutamide, or
Leuprolide Functional castration after 2-4 wks. nilutamide

747 Hormone agent: antiandrogen;

Flutamide androgen receptor antagonist Prostate cancer, used with leuprolide
Hormone agent: antiandrogen;
748
Bicalutamide androgen receptor antagonist Prostate cancer, used with leuprolide

Hormone agent: pure, nonsteroidal

antiandrogen with affinity for androgen
749 receptors (but not for progestogen,
estrogen, or glucocorticoid receptors).
Blocks actions of androgens of adrenal
and testiuclar origin that stimulate growth Tx adenocarcinoma of the prostate. Usually given with
Nilutamide of normal nad malignant prostatic tissue. injections of leuprolide

Hormonal agent: an
adrenocorticosteroids - Lympholytic
750 effects and suppress mitosis in ALL; CLL; Non-Hodgkins lymphoma - very useful in Tx of
lymphocytes; CCNS. See acute leukemia & malignant lymphoma in children and adults.
immunosuppressants or corticosteroids Also useful to reduce edema related to tumors in critical areas,
Prednisone above i.e., mediastinum, brain, spinal cord.
751 Dexamethasone see prednisone see prednisone

752 Hormonal agent: a Antiestrogen -

Chemopreventive agent in women at
high risk for breast Ca; competitive
partial agonist/antagonist of estrogen
Tamoxifen receptors in estrogen-sensitive tumors. Tx estrogen-receptor-positive breast cancer
Plant alkaloid: a Taxane - act by
753 stabilizing microtubules (MT) and
preventing their disassembly, M phase
Paclitaxel (Taxol) specific. Ovarian and breast CA
 A B C
Plant alkaloid: a Taxane - act by
754 stabilizing microtubules (MT) and
preventing their disassembly, M phase
Docetaxel specific.

Plant alkaloid: a Vinca alkaloid - bind to

tubulin and cause depolymerization of
MT in the cytoskeleton and mitotic
755 spindle. They block chromosome
segregation during mitosis and thus are
cytotoxic predominately during the M Bladder Ca, breast Ca, Hodgkin's disease, lung Ca, non-
phase of the cell cycle. Resistance Hodgkin's lymphoma, metastatic testicular tumors;
develops due to amplification of P lymphomas, Kaposis sarcoma, neuroblastoma, and
Vinblastine glycoprotein pump. carcinoma of the breast and choriocarcinoma

756

Plant alkaloid: a Vinca alkaloid, see Acute lymphoblastic leukemia, Hodgkin's disease, non-
Vincristine vinblastine Hodgkin's lymphoma, metastatic testicular tumors

Camptothecins: function as
topoisomerase I inhibitors. Topo I
induces single strand breaks in
757 supercoiled DNA. Topoisomerase I (II??)
reseals the break when unwound; block
the dissociation of TOPOI from the DNA
and a double strand break occurs,
Topotecan, irinotecan leading to cell death.

(epi)Podophyllotoxin: a Topoisomerase
II inhibitor. TOPOII is a repair enzyme
that binds, DNA, cleaves the double
strands, causes one strand to pass
758 through the break, and then reseals the
cut. Etoposide inhibits the resealing of
cleaved DNA, leading to irreparable DNA
damage and cell death. S-G2 phase
Etoposide specific Testicular and small cell carcinoma
A monoclonal mouse antibody directed at Diffuse Large B Cell Lymphoma when given with CHOP
759 CD20-positive lymphocytic disease (B (Cyclophosphamide, adriamycin, vincristine and Prednisone),
Rituximab cell) ITP
 A B C

760

Monoclonal antibody that binds to

Trastuzumab (Herceptin) Her2/neu, a growth factor receptor Breast Ca

761
Tretinoin or ATRA (all- combination with idarubicin for treatment of promyelocytic
trans retinoic acid) leukemia

762

Imatinib mesylate Interfere with the action of the CML; Gleevec treatment has led to hematologic remission
(Gleevac) abnormal Bcr-Abl tyrosine kinase (control of WBC levels) in almost all patients.
treatment for malignant hypercalcemia from bone mets or from
763 Alendronate, clodrinate, Bisphosphonates - turn off paraneoplastic syndromes such as increased PTH-like
etidronate and osteoclasts; leading increased bone peptide production from squamous cell lung cancer;
pamidronate strength and stabilization Osteoporosis, Paget's dz of the bone
Aromatase Inhibitors: 2nd gen; Either
steroidal or non-steroidal, they work by
764 blocking the conversion of adrenal
androgens into estrogens (non-
Anastrozole steroidal drug???) Breast CA; recurrent and metastatic breast CA
Aromatase Inhibitors: 2nd gen; Either
steroidal or non-steroidal, they work by
765 blocking the conversion of adrenal
androgens into estrogens (non-
Letrozole steroidal drug???) Breast CA; recurrent and metastatic breast CA
Prostate Hormonal Agents: LH/RH
analogs that inhibit gonadotropin
766 secretion, preventing production of
testosterone, which is the source of
Goserelin, leuprolide growth for majority of prostate cancers.
Vascular Endothelial Growth Factor
767
Bevacizumab Receptor Inhibitors
 A B C
Epithelial Growth Factor Receptor
768
cetuximab or erlotinib Inhibitors
769 sorafenib or sunitinib Multikinase inhibitors renal cell cancer and melanoma

770 recombinant IL-2, immunostimulant -

enhance circulating numbers of cytotoxic
Aldesleukin T-cells (destroy or remove tumros cells) melanoma

771
Antibiotics
772 Beta Lactams
Competetive inhibitor of the
773 transpeptidase enzyme; inhibits bacterial
Penicillin G cell wall synthesis Strep pneumonia
774 Penicillin V Same
775 Aminopenicillins
776 Amoxicillin Same
777 Ampicillin Same
778 Penicillinase resistant
779 Methicillin Same

780
Nafcillin Same
781 Oxacillin Same
782 Cloxacillin Same
783 Dicloxacillin Same
784 Antipseudomonal
785 Carbenicillin Same
786 Ticarcillin Same
787 Pipercillin Same
788 Mezlocillin Same

789

Cephalosporons
Cephalosporin 1st
790
generation Gram +

791
Cephalothin-1st generation Same

792
Cephalexin-1st generation Same
793 Cefazolin-1st generation Same
794 Cefadroxil-1st generation Same
 A B C
Cephalosporin-2nd
795
generation Klebsilla, H. influenzae, and anaerobes
796 Cefamandole Same
797 Ceflacor Same
798 Cefuroxime Same
799 Cefoxitin Same
800 Cefotetan Same
801 Cefmetazole Same
802 Cefonicid Same
803 Loracarbef
Cephalosporin 3rd
804
generation Gram -
805 cefixime Same
806 cefotaxime Same Severely ill ICU patients with pneumonia
807 ceftazidime Same
808 ceftizoxime Same

809 Severely ill ICU patients with pneumonia (especially H.

influenzae, M. catarrhalis, and most strains of S. pneumoniae
ceftriaxone Same and K. pneumoniae); treatment of HACEK (eg endocarditis)
Cephalosporin4th
810
generation Gram + & -
811 Cefepime
812 Carbapenems
Inhibits the bacterial wall synthesis (block
813 peptidoglycan cross-linking) - resistant Broad spectrum, especially enterobacter, anaerobes (and
Imipenem/Cilistatin to beta-lactamases!! most Gram + and -)
814 Meropenem See imipenem See imipenem
815 Monobactams
Tx of gram-negative UTIs, lower respiratory tract, and skin,
816
Aztreonam beta-lactam antibiotic and for intra-abdominal infections
817 Other

818
Bacitracin

819
AntiRibosomal
820 50S-CLEAN
 A B C

821 Inhibits prokaryotic

peptidyltransferase (high levels may
also inhibit mitochondrial protein 2nd line antibiotic - tx of serious infections when less toxic
Chloramphenicol synthesis) alternatives are inappropriate

822 Lincosamide; Bind irreversibly to a site Excellent anaerobic coverage, most useful "aboe the
on the 50S subunit of the bacterial diaphragm" anaerobic infections (in part becasuse of the
Clindamycin ribosome, thus inhibiting translocation polymicrobial nature of lung absceseses)

823 Macrolide - Bind reversibly to a site on

the 50S subunit of the bacterial
Erythromycin ribosome, thus inhibiting translocation Ambulatory pneumonia
Pneumonia: Effective coverage to atypical pathogens (eg
824 Legionella and Moraxella (mycoplasm?)), some gram
Azithromycin Macrolide - See erythromycin negative pathogens, and most strains of S. pneumoniae
825 Clarithromycin Macrolide - See erythromycin

826
Linezolid Blocks initiation complex formation, 50S Used for vancomycin-resistant infectons
827 30S-TAG

828

Tetracyclines
Ambulatory pneumonia; Used for renal insufficienct pts,
829 excreted in feces; used prophylactically for chloroquine-
Doxycycline see tetracycline resistant strains of plasmodia/Malaria
Used for renal insufficienct pts, excreted in feces; tx acne
830
Minocycline see tetracycline vulgaris
831 Methacycline see tetracycline
832 Oxytetracycline see tetracycline
833 Demeclocycline see tetracycline
834
 A B C

Protein synnthesis inhibitor

(irreversibly bind 30S bacterial ribosomal
subunit, and actis to inhibit the
835 formation of the initiaiton complex,
causes mRNA misreading leading to
non-functional proteins; also induces the Severe infection with gram-negative rods (eg sepsis,
dissolution of polyribosomes during chronic UTI, endocarditis (especially with vancomycin),
Aminoglycosides protein synthesis pneumonia, Pseudomonas infections
836 Gentamicin see aminoglycoside see aminoglycoside
see aminoglycoside, used for preparation for bowel surgery
837
Neomycin see aminoglycoside (kiills bowel flora)
838 Tobramycin see aminoglycoside see aminoglycoside
839 Amikacin see aminoglycoside see aminoglycoside
protein synnthesis inhibitor (binds the
30S bacterial ribosomal subunit, and
840 actis to inhibit the formation of the
initiaiton complex) essentially an
Streptomycin aminoglycoside

841
DNA Gyrase
MC used agent for traveler's diarrhea, UTI, URT, gonococcal
infections, atypical pneumonia; gram negatives
842 (Pseudomonas, Neisseria, Haemophilus, Enterobacter,
Fluoroquinolones Inhibit bacterial DNA gyrase thus causing Legionella, Mycoplasma)
(quinolone) breaks in the DNA DOC for complicated UTI

843
(quinolone) Inhibit bacterial DNA gyrase
Ciprofloxacin thus causing breaks in the DNA Anthrax
Newer quinolone - additional gram-positive
844 coverage/increased activity, especially to S. pneumonia!
Levofloxacin quinolone (some Staph), also covers P. aerguinosa
Newer quinolone - additional gram-positive coverage (S.
845
Gatifloxacin quinolone pneumonia, some Staph
Newer quinolone - additional gram-positive coverage (S.
846
Moxifloxacin quinolone pneumonia, some Staph; Anaerobe coverage
Gets gram + and - including pseudomonas only for severe
847
Trovafloxacin quinolone pnumonia due to LIVER TOXICITY

848
Sparfloxacin quinolone CAP - increased activity, especially to S. pneumonia!
849 Nalidixic acid quinolone Excreted rapidly, rarely used
 A B C
metabolized to a compound that
850
Nitrofurantoin damages bacterial DNA Used for recurrent UTI

851
Vaccinations
852

Pneumococcal vaccine Pneumococcal pneumonia

853 Influenza vaccine Influenza

854

Polio vaccine Poliomyelitis

Japanese encephalitis
855
vaccine Japanese encephalitis mosquito-borne dz

856
Yellow-fever vaccine Yellow fever
857 Tyhoid vaccine Thyroid fever

858
Pertussis vaccine

859
Tetanus vaccine Tetanus
860 Varicella vaccine Chickenpox
861

862
Neurologic Drugs
863 Headaches

864
Tension Headaches (Combination: NSAIDS + Butalbital +
NSAIDs (non-steroidal see NSAIDs above; inhibit prostaglandin Caffeine); Tx of Migraine (must be taken very early in the
anti-inflammatories) synthesis attack to be effective!)
 A B C

Barbiturate (member of the sedative-

865 hypnotic family); Mechanism is
facilitation of GABA
neurotransmission; Predominant effect Tension Headaches (Combination: NSAIDS + Butalbital +
Butalbital is sedation/anxiolytic Caffeine)

Competitive antagonist at adenosine

receptors! (which are presynaptic on
sympathetic terminals, where the
866 receptor decreases amount of NE, thus
blocking receptor increases NE and
causes vasoconstriction) & at higher
dose they are phosphodiesterase Tension Headaches (Combination: NSAIDS + Butalbital +
Caffeine inhibitors (potentiate beta1 or beta2) Caffeine)

867

Prophylactic Tx of Tension HA; also prophylaxis of

Migrane (give at night due to drowsy SE); useful tx for
Amitryptiline TCA, see antidepressants fibromyalgia
868 Doxepin Older antidepressants (not SSRIs) Prophylactic Tx of Tension HA

869
Imipramine TCA, see antidepressants Prophylactic Tx of Tension HA

870
Sumatriptan (prototype,
Imitrex) (Sumatriptan is prototype) 5HT1 Agent, Tx of Migrane (acute tx, take during prodromal phase);
Rizatriptan (Maxalt) Agonists at 5-HT1b & 5-HT1d sites (Gi Sumatriptan has ~2hr effect (so usually taken several times
Zolmitriptan (Zomig) coupled receptor) - inhibits vasodilation per episode), given both orally and parenterally, not used
Naratriptan (Amerge) (Sub P & CGRP, see extra notes) (5- prophylactically for migrane
Frovatriptan (Frova) Hydroxytryptamine (aka serotonin)) Tx for acute Cluster HA
 A B C

871

Ergot Alkaloids; 5-HT1b/1d stimulation

(also dopaminergic, and alpha- Tx of Migranes ONLY (not general analgesic, and efficacious
Ergotamine (Ergomar) adrenergic receptor activity) only if used early in attack)
Tx of Migrane:
Ergot Alkaloids; 5-HT1b/1d stimulation Moderate migraine - Used orally if the migraine is
872 (actually binds all types of 5HT receptors) accompanied by significant nausea
Dihydroergotamine Minimal to no effect on peripheral arterial Severe migraine - If significant functional impairment, used
(Migranal) construction; Potent venoconstrictor i.m. or i.v. in ED (can be given well into attack)

873

Acute Treatment of Migraine, also anti-emetic (See

Metoclopramide (Reglan). Antagonists at D2 receptors gastrointestinal drugs above)
Acute Treatment of Migraine (especially non-responsive pts
874 Chlorpromazine Antagonists at D2 receptors or who have contraindications to vasoactive abortive agents),
(Thorazine) (neuroleptic) also anti-emetic
Acute Treatment of Migraine (especially non-responsive pts
875 Prochlorperazine Antagonists at D2 receptors or who have contraindications to vasoactive abortive agents),
(Compazine) (neuroleptic) also anti-emetic
Prophylaxis of cluster!
876
Verapamil CCB Prophylaxis of Migraine
Non-selective beta-blockers, see
877
Propranolol & Timolol adrenergic blockers above Prophylaxis of Migraine

878
Valproate see Seizure Medication Prophylaxis of Migraine; Prophylaxis of Cluster
 A B C

879
Prophylaxis of Migraine:
Ergot derivative; blockade of 5-HT2a and Without benefit when given during an attack
5-HT2c receptors (blocks serotonin Protective effect develops over 1-2 days.
Methysergide receptors) Prophylaxis of Cluster HA

880

Treatment of Cluster Headaches (DOC) - acts in ~5min

Oxygen (issue is it is a pain to carry around)

881

1) Chronic Cluster HA (Narrow theraputic range before

toxicity, monitor closely)
Lithium See Mood Stabilizers 2) Tx Carbon monoxide poisioning!! (100% O2 antidote)
Prophylaxis of cluster HA; treatment of Giant Cell Arteritis (aka
882
Steroids temporal arteritis)
883 Motor Disease and Muscle Spasticity Drugs

884

Antimuscarinic (Anticholinergic):
Centrally-acting competitive inhibitors of
Biperiden muscarinic cholinergic receptors.
Antimuscarinic (Anticholinergic):
885 Centrally-acting competitive inhibitors of
Trihexyphenidyl muscarinic cholinergic receptors.
Antimuscarinic (Anticholinergic):
886 Centrally-acting competitive inhibitors of
Benztropine muscarinic cholinergic receptors.
Early stage treatment of Parkinson's Dz (if under 65yo) -
Improve tremor and rigidity, but not bradykinesia.
Early stage treatment of Parkinson's Dz (if under 65yo) -
Improve tremor and rigidity, but not bradykinesia
Early stage treatment of Parkinson's Dz (if under 65yo) -
Improve tremor and rigidity, but not bradykinesia
 A B C

887 Selective inhibitor of MAO-B at

relatively low doses. MAO-B is the
Selegiline (Deprenyl; isozyme responsible for the degradation
Eldepryl) of DA (dopamine) in the striatum Early stage treatment of Parkinson's Dz (neuroprotective)

888
Rasagiline (Azilect) Selective inhibitor of MAO-B Early stage treatment of Parkinson's Dz (neuroprotective?)

889 May influence synthesis, release, or

reuptake of DA. Has anticholinergic and Early stage treatment of Parkinson's Dz (benefits short
Amantadine antiglutamatergic! effects as well lived)

890 Dopamine replacement: Historic

treatment for disabling-PD involves the
DA precursor levodopa, which can be
converted to dopamine in
catecholamine neurons via the enzyme
dopa decarboxylase. Therapy with the
precursor levodopa is necessary
Levodopa (l-dopa; L- because DA itself does not penetrate the
DOPA) CNS.
Treatments for Disabling-Parkinsonism (especially
akinesia/bradykinesia) - Currently less popular as initial
treatment in disabling-Parkinsonism because of perceived
advantages of DA agonists (see below). Do not give L-DOPA
without carbidopa!

891 Dopamine replacement. Carbidopa Treatments for Disabling-Parkinsonism (Carbidopa reduces

Levodopa/Carbidopa prevents peripheral DA conversion the on-off phenomenon, and the smooths out end-of-dose-
[Sinemet] (Carbidopa does not cross BBB) faliure phenomenon)

892
Dopamine replacement (D2); ergot
Bromocriptine alkaloid (Old) Treatments for Disabling-Parkinsonism

893
Dopamine replacement (D1/D2); ergot
Pergolide alkaloid (Old) Treatments for Disabling-Parkinsonism
 A B C

894
New Treatments for Disabling-Parkinsonism (especially
akinesia/bradykinesia); Possibly a neuroprotective agent.
Dopamine replacement (D3, part of the Effective in both early and advanced PD as monotherapy or in
D2 family); Non-ergot dopamine combination with levadopa. Neuroprotective as it is an
Pramipexole agonists; (antioxidant) antioxidant. Midigates on-off phenomenon
Dopamine replacement (Relatively Effective in early or advanced PD alone or in combination;
895
Ropinrole selective D2 agonist) Midigates on-off phenomenon

Catechol-O-Methyltransferase
inhibitors (COMT inhibitor): Inhibition of
dopa decarboxylase causes activation of
COMT pathway, increasing 3-O-
896 methyldopa (3OMD); 3OMD is
associated with poor therapeutic
response to levodopa (competes for the capones may smooth response to levodopa and may
absorption into brain); only active in the permit lowering of levodopa dose for PD (only used with L-
Entacapone periphery DOPA); typically started with L-DOPA/carbidopa therapy

Spasmolytics of the CNS; GABA

897 analogue; GABA-B receptor agonist,
causes hyperpolarization by increased
K+ conductance. Inhibits release of
excitatory amino acids and substance P
(may reduce pain). Target is intrafusal Tx spasm: less effective in cerebral accident; more effective in
Baclofen (Lioresal) afferent (Ia) of muscle spindle spinal injury and MS. effective in ALS.
Antiseizure drug (see seizure medication below); has been
898 studied in patients with MS with positive results
Gabapentin (Neurontin) Spasmolytics of the CNS Neuropathic pain, Trigeminal Neuralgia

899 Centrally acting skeletal muscle relaxant

that is structurally related to tricyclic muscle spasm or a strianed muscle (skeletal muscle
Cyclobenzaprine antidepressants relaxant)
CNS depression (no direct action on the Muscle relaxation - adjunct to rest, physical therapy, and
900 contractile mechanism of striated muscle other measures for relief of discomfort in various
Methocarbamol or nerve fiber) musculoskeletal conditions)
 A B C
Spasmolytics of the CNS; Mechanism
901 not clear: spasmolytic effect likely due to For treatment of ALS, spasmolytic effects reported. Extends
Riluzole (Rilutek) inhibition of glutamate release survival and time to tracheostomy

Spasmolytics of the CNS; Analogue of

902 clonidine; CNS mechanism not
understood; Reinforces inhibitory effects Spasm associated with cerebral palsy, multiple sclerosis, and
Tizanidine (Zanaflex) in spinal cord, reduces pain conduction stroke

Spasmolytics of the CNS; Acts by

increasing GABA-Aergic
903 neurotransmission, leading to
enhanced presynaptic inhibition
(internuncial neurons); Target is
intrannuncial (inhibitory interneuron).
Diazepam (Valium) See Seizure Medication
Most effective for MS, spinal lesions. Less effective for
cerebral lesions. Not effective in ALS
May be used in combination with baclofen to control night-time
spasms (MS) See Seizure Medication

Spasmolytics of the PNS; skeletal

904 muscle relaxant; interferes with release 1) Cerebral spasticity; not used for ALS
of Ca ions from sarcoplasmic 2) i.v. for malignant hyperthermia (eg D2 blocker induced
reticulum; can reduce contractions by such as antipsychotics)
Dantrolene (Dantrium) only 75% 3) external sphincter hypertonicity
Other nervous system
905
drugs

906
Mineralocorticoid, see corticosteroids;
resorbing Na at kidney (K and H lost) Treat orthostatic hypotension due to autonomic
Fludrocortisone causing retension of water dysfunticon

907
Midodrine Alpha agonist (see adrenergics) Treat orthostatic hypotension due to autonomic dysfunticon
908 Benzodiazepines Dystonias
909 Botox Dystonias
910 Anticholinergic drugs Dystonias
911 Alprazolam Essential Tremor
912 Propranolol Essential Tremor
913 Primidone Essential Tremor (usually given with propranolol)
914 Seizure Medication
 A B
915
Voltage gated Na+ Channel Blocker
(Antagonist) - limits the capability of
neurons to fire at high-frequency rates
Phenytoin!! (Dilatin) (increases refractory period)
Voltage gated Na+ Channel Blocker;
916 same as phenytoin but has phosphate
group attached so that it doesnt sting (?) Prodrug for parenteral use, see dilatin (doesn't sting when
Fosphenytoin (Cerebyx) Thus can give faster IV
917
Voltage gated Na+ Channel Blocker
Carbamazepine!! (Antagonist) - limits the capability of
(Tegretol) neurons to fire at high-frequency rates
918 Topiramate inhibits neural cell Na channels
919
Oxcarbazepine Voltage gated Na+ Channel Blocker
920
Inhibits T-type Ca++ current,
decreasing glutamate release in
Ethosuximide (Zarontin) thalamus. No effect on seizure spread
C
Generalized tonic-clonic seizure (grand mal, GTCS)
Partial seizures (simple and complex)
(Makes absence (petit mal) worse)
Non-sedative
Note cardiac uses: digitalis-induced ventricular arrhythmia
given IV)
Partial seizures (Jacksonian);
Generalized tonic-clonic
Makes absence (petit mal) worse
Note use for obsessive compulsive disorder, trigeminal
neuralgia, bipolar affective disorder
Epilepsy
less potent, fewer adverse effects, fewer drug interactions than
Carbamazepine; 3/d dosing - compliance issue
Prevents and reverses absence seizures (petit mal)!! without
GTCS;
Never used to treat GTCS of any origin
Not sedative
 A B C

Effective against partial & generalized tonic-clonic &

absence seizures!!
Increased use as monotherapy for generalized tonic-clonic;
921 Treat Juvenile Myoclonic Epilepsy
Valproic Acid aka Block BOTH Na+ & Ca++ channels; Possibly prophylactic following head injury
Valproate (Depakene, Also increases brain levels of GABA Note: use for migraine and bipolar affective disorder
Depakote) (indirect, mech unknown) Epigastric distress reduced by Depakote

Adjunct for Partial seizures & Generalized tonic-clonic

Labeled for adjunctive use or monotherapy when withdrawn
from phenytoin or carbamazepine; increasing use as first-line
922 agent
Well-tolerated in the elderly
Effective against absence seizurescalcium channel
mechanism
Lamotrigine Block BOTH Na+ and Ca++ channels Also used in bipolar disorder
923 zonisamide Adjunct use for partial seizures

Barbiturate - direct GABA(A);

924 ( duration Cl- channel opening) long
acting
Glutamate receptor (AMPA receptor) less
important
Barbiturates stimulate chloride flux Generalized tonic-clonic seizures
(chloride ionophore), thereby facilitating Alternative for febrile convulsions in children <5 years
Phenobarbital GABA-induced inhibition Simple partial seizuresrelatively larger doses

Benzodiazepines - direct GABA(A); (

frequency Cl channel opening) short
acting (addiction); benzodiazepine
925 allosteric site - GABA-mediated
inhibition via Cl- ionophore; elevates
seizure threshold and limits spread.
Suppresses spread from epileptogenic
foci; does not abolish the abnormal focal
Diazepam (Valium) discharge Status epilepticus

926
Benzodiazepines - direct GABA(A), see
Lorazepam!! (Ativan) Diazepam Status epilepticus
 A B C
absence; myoclonic, akinetic, atonic seizures
927
Clonazepam (Klonopin) Benzodiazepines - direct GABA(A) Infantile Spasms (Wests Syndrome)
Benzodiazepine - indirect GABA(A);
928
tiagabine Uptake inhibition

929 Benzodiazepine - indirect GABA(A);

Inhibit degradation; Irreversible inhibitor Wests Syndrome
Vigabatrin of GABA-transaminase. adjunctive therapy of partial seizures

930
Enhances GABA activity; Blocks
glutamate activity; but many other
mechanisms, including other ion
Alcohol channels Good Anticonvulsant?
Antiseizure drug; has been studied in patients with MS with
931 Benzodiazepine - indirect GABA(A); positive results
Gabapentin (Neurontin) unknown mech; Spasmolytics of the CNS Neuropathic pain, Trigeminal Neuralgia

932
Corticosteroids (eg
corticotropin, prednisone,
dexamethasone) (Mechanism unknown) Infantile Spasms (Wests Syndrome)
933 Multiple Sclerosis Drugs & Myasthenia Gravis

Inhibits IFN-gamma (TH1 cytokine

which activates M0); (Slows freqency and
934 accummulation of physical
disability/clinical exacerbations)
modulating conversion of TH1 to TH2. Treatment of Multiple Sclerosis
Interferon-1a (Avonex; May form Ab (NAb) (The rate of NAb Reduce attack rate of MS
Rebif) & Interferon-1b production is probably less with IFN-1a Relapsing/remitting MS
(Betaseron) treatment than with IFN-1b treatment) Secondarily progressing MS
 A B C

935 (Mechanism in MS is not established) -

Mimics myelin basic protein (?IS
attacks the glatiramer instead of self
myelin?) May affect bodys IR by
converting the TH1 type to a TH2 type
IR. Neutralizing antibodies do not Treatment of Multiple Sclerosis (Approved for Relapsing
Glatiramer (Copaxone) arise Remitting MS)

Suppresses cell-mediated immunity,

936 which may reduce immune cell attack of
Mitoxantrone the myelin sheath Tx for secondary progression (?) MS

Monoclonal antibody directed to specific

937 adhesion molecules, reduces leukocyte
Natalizumab entery into the CNS Tx MS

Used for Myasthenia Gravis;

938 Indicated for acute and/or chronic use in a number of immune-
mediated disorders
Relapsing Remitting MS acute exacerbation (only during
Corticosteroids See immunsuppresants above exacerbations).

Decreased lymphoid cell production;

Azathioprine converted to
mercaptopurine; interferes with purine
939 nucleic acid metabolism, dramatically
interferes with the wave of lymphoid-cell
proliferation that normally follows
antigenic stimulation Used for Myasthenia Gravis
Azathioprine See Immunosuppresants above Often used in MS, but evidence-based medicine is lacking

Inhibits the production of helper T-

940 cells; works more quickly than
azathioprine, usually within one or two
months.
Cyclosporine See Immunosuppresants above Used for Myasthenia Gravis
 A B
941 I.V. Ig: Gamma globulin, immune
globulin, intravenous immunoglobulin
(slows down membrane attack
IVIG [Gammagard] complex???)
A procedure that filters the blood's
plasma component (blood is
centrifuged, plasma portion is removed.
942 Cells are returned to the pt, diluted with
fresh plasma or a substitute (to reduce
allergic rx, usually a substitute)).
Plasmapheresis Used to remove abnormal antibodies in
(Treatment modality) specific cases (as in lupus or MG).
943
see Anticholinesterases above;
Quaternary drugs do not penetrate
Pyridostigmine CNS, so no intoxication/seizure problem
944 see Anticholinesterases above;
Quaternary drugs do not penetrate
Neostigmine CNS, so no intoxication/seizure problem
945
Alcohol; see Anticholinesterases
above; brief duration of action, rapid
Edrophonium (Tensilon) onset
946
947
Tacrine Acetylcholinesterase
C
Long Hx of use for treating various conditions where
concentration of gamma globulin is low
Also effective in autoimmune disorders (such as MG;
mechanism in these conditions is unknown)
Used for immediate improvement in MG pts (much faster
than azathioprine or cyclosporine)
Main uses:
relieve a myasthenic crisis
patients scheduled for a thymectomy and post-operatively
covering the increased weakness that may occur when
corticosteroid treatment is begun
DOC for Myasthenia Gravis (long acting); Use in conjunction
with an antimuscarinic to block excess ACh in the
parasympathetic nervous system
Used for Myasthenia Gravis; Use in conjunction with an
antimuscarinic to block excess ACh in the parasympathetic
nervous system
Uses
Diagnostic aid for myasthenia gravis (not primary
diagnostic, but useful for distinguishing MG from other
neurological disorders)
Differentiation of myasthenic crisis from cholinergic crisis
(iatragenic). see Tensilon test extra notes
Alzhemier Drugs
Symptomatic Tx of Alzhemier dz
 A B C
948 Donepezil Delays progression of Alzheimer dementia
949

950
Antidepressant Drugs

951

Selective Serotonin Reuptake

Fluoxetine (generic, Inhibitors (SSRIs) - selective inhibition
Prozac) of 5HT (serotonin) reuptake Treat depression

952

Sertraline (Zoloft) SSRI Treat depression

953

Paroxetine (generic, Paxil) SSRI Treat depression

954

Citalopram (generic,
Celexa) SSRI Treat depression

955
Escitalopram (Lexapro) SSRI Treat depression
 A B C

956 Fluvoxamine (generic,

Luvox) SSRI only labeled for obsessive-compulsive disorder (OCD)

2nd & Subsequent Generation

Antidepressants; Negligible actions on
NE & 5-HT reuptake; at therapeutic
957 concentrations occupies about 25% of
DA uptake sites; Inhibitor of neuronal
nicotinic receptors. (inhibitor of both DA
Bupropion (generic, uptake and neuronal nicotinic Treat depression; Also used in smoking cessation (helps with
Wellbutrin) cholinergic receptors) cravings???)
Bupropion with altered
958
dosage [Zyban] See bupropion Smoking cessation (nicotinic receptor inhibition)

Heterocyclic anti-depressant;
959 Marketed as an SSNRI (selective
serotonin and norephinephrine
reuptake inhibitor - inhibits 5-HT and
NE reuptake); more potent at 5-HT site;
Venlafaxine (Effexor) hence, at low doses acts like an SSRI Treat depression
inhibits neuronal uptake of serotonin
and NE; acts as an antagonist of
960 postsynaptic 5-HTA receptors and of
alpha1-adrenergic receptors. Not
chemically related to SSRI, tricyclic,
Nefazodone tetracyclic, or MAOI Tx depression and anxiety; no sexual SE or weight gain

961 2nd & Subsequent Generation

Antidepressants; a 5-HT2 antagonist
Trazodone (generic, and a weak, selective 5-HT reuptake
Desyrel) inhibitor Treat depression

962 Treat depression; particularly useful in the treatment of

2nd & Subsequent Generation painful physical symptoms of depression. It has received
Duloxetine (Cymbalta) Antidepressants; SSNRI FDA approval for treating diabetic neuropathic pain.
 A B C

Heterocyclic anti-depressant;
marketed as an NaSSA (Noradrenergic
and Specific Serotonergic
Antidepressant),
963 Blocks 2-adrenergic autoreceptors
which increases NE release; & increase
in 5-HT cell firing due to increase NE
release and block of 2-adrenergic
heteroreceptors on 5-HT nerve terminals
Selective stimulation of 5-HT1
Mirtazapine (generic, receptors due to blockade of 5-HT2 & Treat depression (refractory major depression who need to
Remeron) 5-HT3 receptors. gain weight)

Treat depression!
964 Other Clinical Uses:
Tricyclic Antidepressant (TCA): block chronic pain!
monoamine reuptake (NE, 5-HT, DA), Enuresis
Amitriptyline (generic, down-regulate NE and/or 5-HT Panic disorder
Elavil) receptors Attention deficit hyperkinetic disorder
Nortriptyline (generic,
965
Aventyl, Pamelor) TCA see amitriptyline
966 Imipramine TCA see amitriptyline
967 Clomipramine TCA Tx obsessive-compulsive disorder

968

Monoamine Oxidase Inhibitors

Phenelzine (Nardil) (MAOIs): irreversible inhibitor Treat atypical depression (not used commonly)
Tranylcypromine
969
(Parnate) MAOIs: reversible inhibitor Treat atypical depression (not used commonly)
970 Iproniazid MAOI Treat atypical depression (not used commonly)
971 Isocarboxzid MAOI Treat atypical depression (not used commonly)

972
Selective norepinephrine uptake
Atomoxetine (Strattera) inhibitor Treatment of attention deficit hyperactivity disorder (ADHD)
 A B C

973
Mood Stabilizers

974 Mood Stabilizing Drug: Substitutes for

Na in generating action potentials,
substitutes for Na in Na/NA exchange
across membrance, variable effects on
neurotransmitters (DA, 5HT, ACh), many
of these seen acutely though it must be
taken for 2-3 weeks before clinical effect
is seen; depletion of PIP2; other May be used prophylactically. Main use is for bipolar
Lithium mechanisms, see extra notes disorder (though 20-40% do not respond)

975 Valproic Acid + Sodium Mood Stabilizing Drug: May act through Anticonvulsant mood stabilizer and the combo of these two
Valproate = Divalproex increasing GABA, see Seizure causes less GI distress. Both for acute and maintenance
Sodium Medication above therapy (see notes about therapy approaches)

976 Partial, secondarily generalized seizures. Labeled for

Mood Stabilizing Drug: Sodium channel adjunctive use or monotherapy when withdrawn from
blocker (and/or Ca) voltage dependent phenytoin or carbamazepine.
inactivation of channels; anticonvulsant, Bipolar disoder; not effective in acute mania.
Lamotrigine see neuro drugs Can be used as a potentiating agent for antidepressants

977 Partial, general tonic clonic seizures

Obsessive compulsive disorder
Mood Stabilizing Drug: Sodium channel Trigeminal neuralgia
Carbamazepine (Tegretol) blocker Bipolar affective disorder
 A B C

978 Olanzapine, Haloperidol,

Risperidone, Quetiapine, With bipolar dz, primarily for acute mania.
Ziprasidone, and MC used for Tx of Psychosis and Schizophrenia, see
Aripiprazole Antipsychotics antipsychotics below

979 Given to control acute mania (biploar dz, often as an adjunct

Benzodiazepine, see neuro drugs and to treatment with an antipsychotic drug or other mood
Clonazepam (Klonopin) anxiolytics stabilizing drug) - typically given with a mood stabalizer
980 Lorazepam (Ativan) Benzodiazepine, see clonazepam see clonazepam

981
Antipsychotics

982

Original Atypical Antipsychotic - block

DA receptors (esp D2) receptors as
well as higher affinity as antagonists
for 5-HT2 receptors (both actions
appear important to their efficacy in
schizophrenia. Efficacious for positive Tx of Psychosis and Schizophrenia; Most efficacious
and negative symptoms!! See extra antipsychotic, particularly against negative symptoms
Clozapine!! (Clozaril) notes
Tx of Psychosis and Schizophrenia; Frequently prescribed
983 atypical has replaced olanzapine as most prescribed of this
class
Quetiapine (Seroquel) Atypical Antipsychotic Being promoted for use in bipolar disorder
 A B C

984
Atypical Antipsychotic: blocking D2
receptors & block 5-HT2 receptors;
Olanzapine is rapidly becoming the
standard against which both typical and Tx of Psychosis and Schizophrenia
Olanzapine (Zyprexa) atypical antipsychotics are judged Bipolar dz - primarily for acute mania

985 Atypical Antipsychotic - in addition to

high affinity to antagonize 5-HT2
receptors, also has high affinity to
antagonize D2 receptors with little Tx of Psychosis and Schizophrenia
Risperidone (Risperdal) affinity for muscarinic receptors Bipolar dz - primarily for acute mania

Atypical Antipsychotic - partial

dopamine agonist; efficacy against both
schizophrenia (as a weak partial-agonist
it blocks the full agonist, dopamine) and
986
depression (efficacy as a partial agonist
is enough to provide therapeutic efficacy
think of the mechanism of bupropion). Efficacious against positive & negative symptoms of
1) D2 partial agonist schizophrenia as well as depression. This drug is becoming
2) 5-HT2 antagnoist a tremendously popular choice when prescribing an
Aripiprazole (Abilify) 3) 5-HT1a partial agonist antipsychotic.

987
Ziprasidone Atypical Antipsyychotic - IM formula Rapid relief of agitation and distress; weight neutral
 A B C

988

Typical Antipsychotic - Butyrophenone;

Relatively clean D2 antagonist
Some anti-serotonergic and alpha- Tx of Psychosis and Schizophrenia; Highly effective against
adrenergic effects, but relatively minor; positive symptoms; some effect against negative symptoms
Haloperidol!! (Haldol) high potency ED use for aggressive pts (calms everybody!)
Injectable depot preparation form - used for tx of noncompliant
989
Haloperidol Decanoate Haloperidol ester, long-acting pts

Typical Antipsychotic - Phenothiazine;

prototype - block DA receptors,
990
particularly the D2 receptor. Their
clinical efficacy against positive
symptoms is relatively well correlated
with this action. Not particularly Because of SE profile and other reasons chlorpromazine is
Chlorpromazine efficacious against negative symptoms; generally of historic interest for Tx of Psychosis and
(Thorazine) low potency Schizophrenia;
Typical Antipsychotic - Phenothiazine;
991
Fluphenazine (Prolixin) high potency Tx of Psychosis and Schizophrenia

992
Thioridazine Typical Antipsychotic - Phenothiazine Tx of Psychosis and Schizophrenia

993 Promethazine (Phenergan Typical Antipsychotic - Phenothiazine;

special use) first-generation H1 receptor antagonist Anti-nausea use; Tx of Psychosis and Schizophrenia

994 Prochlorperazine
(Compazine special use) Typical Antipsychotic - Phenothiazine Anti-nausea use; Tx of Psychosis and Schizophrenia

995 Typical Antipsychotic? - Thioxanthene;

Thioxanthixene S2 antagonist (also alpha1 and H1) Tx of Psychosis and Schizophrenia

996
Anxiolytics & Hypnotics
997 Anxiolytics
 A B C

998

BZD are generally used for situational care (and not long term
care)
Anxiolytic, hypnotic
Muscle relaxant
Pre-anesthetic (anesthetic + above)
Blocks convulsions in ethanol or BZD withdrawal
Benzodiaezepin (BZD) - prototype: 2nd line status epilepticus (given i.v.; Second behind
Increases Cl- conductance on GABA lorazepam - see extra notes)
Diazepam (Valium) channels; long half-life (approx 50+ hrs) - Alcohol withdrawal
Prazepam, quazepam,
999
and flurazepam See diazepam See diazepam
Used for anxiolytic and hypnotic effect
some potential for early morning awakening
1000 said to be less sedative than other BZDs (use as hypnotic
Benzodiaezepin - Increases Cl- may be based on anxiolytic effect)
conductance on GABA channels; Often a BZD of choice for pts PRN (eg fear of flying)
Alprazolam (Xanax) Intermediate acting Panic disorder; generalized anxiety

Benzodiaezepin - Increases Cl-

1001 conductance on GABA channels; much DOC for status epilipticus
more water soluble (than diazepam) - so Used for anxiolytic and hypnotic effects
Lorazepam (Ativan) rapid acting; intermediate acting Alcohol withdrawal (with liver dz)

1002
Benzodiaezepin - Increases Cl-
conductance on GABA channels;
reliable pharmokinetics, especially for Anxiolytic and for sleep induction
Oxazepam (serax) the elderly; intermediate acting Alcohol withdrawal (with liver dz)
 A B C
Temazepam and
1003
chlordiazepoxide Benzodiaezepines

1004 Benzodiaezepin - Increases Cl-

conductance on GABA channels; short
Triazolam (Halcion) acting See Hypnotics below

Used i.v. as anesthetic pre-op; significant amnesia

1005
Benzodiaezepin - Increases Cl-
conductance on GABA channels; Water
Midazolam (Versed) soluble - very short acting
1006
Benzodiaezepin antagonist - non-
Flumazenil (Romazicon) competitive antagonist
(anterograde)
Anxiolytic, plus patients are sleepy but can be aroused
(useful feature for moving patients to O.R. table)
Muscle relaxant
Post anesthesia (quicker recovery if midazolam is still on
board)
**BZD overdose (only for acute use of BZD, not if BZD
dependence, see SE)
**mixed poisoning (no longer approved)

Tx Anxiety (If SSRIs are ineffective in controlling anxiety,

recommendation is often buspirone either tried alone or added
1007 to the SSRI);
5HT1a partial agonist - increase K No efficacy in sleep disorders
conductance via same channels as (No sedation; no motor impairment)
Buspirone (Buspar) GABAb receptors Better effects for OCD if given with SSRI than SSRI alone
Prevents jitters associated with excess stimulation of b2
receptors
1008 Used for tx of performance anxiety - use where
Beta blocker, see adrenergic blockers sympathetic outflow is high and serves no purpose (e.g., stage
Propranolol (inderal) above fright)
1009 Hypnotics

1010

Benzodiezapam - Increases Cl-

Triazolam (Halcion) conductance on GABA channels Sleep
 A B C

1011 BZD alpha 1 subunit Selective Binder

(bind selectively to GABA receptors alpha
Zolpidem (Ambien) 1 subunit); Not a BZD, see extra notes Sleep

1012 Sleep (shorter half life though than zolpidem) Pushed as PRN
before bedtime or upon awakening in the middle of the
Zaleplon (Sonata) Same as zolpidem; very short half life night (if more than 4 hours remain in sleep cycle)

1013
Pineal hormone that regulates useful for sleep problems related to jet-lag or changing
Melatonin sleep/wake cycle (peaks at 2 am) day/night working hours

1014
Binds melatonin receptors (MT1 and
Ramelteon (Rozerem) MT2) and not GABA Sleep

Barbituates - indirectly potentiate

GABAa receptor activity in the brain,
thereby increasing the flow of Cl- to
1015 hyperpolarize cell membrane, Sedative (tx anxiety and insomnia)
Pentobarbital, decreaseing acitivty of the neurons of Phenobarbital for seizure control
Secobarbital, the CNS; high does may cause direct SUPERVISED use of other agents for sleep i.e., they should
Phenobarbital activity, see extra notes only be used in medical facilities, not on out-patient basis
1016 Theopental Barbituate induction of anesthesia
1017 antihistamines (e.g. hydroxyzine)??????????
1018 chloral hydrate

1019
Additional Psych Drugs
1020 ADHD Drugs

CNS stimulant, enhances dopamine

(DA) in the synapse; enhanced
norepinephrine (NE) neurotransmission
1021 in the CNS is probably involved as well
(facilitation of release of central DA and
NE). Mech in ADHD is unknown (as an
amphetamine-type drug, presumably is
Methylphenidate (Ritalin) dopamine) ADHD
 A B C
Methylphenidate ADHD - extended release version Concerta effects last 12-14
1022
(Concerta) SAA hours so no administration needed during school

Indirect acting non-catecholamines;

release NE from adrenergic nerves,
also release DA in CNS; these agents
are taken up into nerve terminals via the
1023 uptake one mechanism and thus interfer
with active uptake (at presynaptic neuron
membrane as well as at the transporter
into the vessicle) amphetamine
interfers with both processes some
Amphetamines (Adderall claim it actually reverses these
is a combination product) transporters ADHD (immediate affect)

1024
Structurally similar to methylphenidate;
Pemoline (Cylert) relatively long duration of action (7-h) ADHD; essentailly no abuse potential

Treatment of attention deficit hyperactivity disorder in

1025 children & adults (ADHD). Non-stimulant, low abuse
Selective norepinephrine uptake potential, long acting (once a day) equal to methylphenidate in
Atomoxetine (Strattera) inhibitor effectiveness
1026 Narcolepsy
1027
d-Amphetamine See above ADHD drugs Narcolpesy, used at low dose typically

1028
Methylphenidate (Ritalin) See above ADHD drugs Narcolpesy

1029
Amphetamine related by structure, DEA DOC for narcolpesy and sleep disturbances associated with
Modafinil (Provigil) Schedule IV drug jobs that involve shift changes (day shift to night shift)
1030 Appetite Control
 A B C

1031

Amphetamine-related anorexiant:
Modification of NE and dopamine; work Weight loss, decreased appetite, loss of interest in food, less
in appetite control centers of the pleasure from eating, increased satiety with eating, decrease
Benzphetamine (Didrex) hypothalamus (likely a NE mechanism) in total energy intake

1032
Diethylproprion (Tenuate) See Benzphetamine Extended release available, See Benzphetamine
Previosly used with fenfluramine (Fen-Phen) popularity
1033 See Benzphetamine; Long acting increased once fenfluramine removed from market; See
Phentermine (Fastin) sympathomimetic Benzphetamine
1034 Fenfluramine (Not avail) See Benzphetamine No longer available

1035 Fluoxetine (generic, Non-sympathomimetic anorexiant -

Prozac) SSRI, see antidepressants Produces satiety ("fullness") rather than anorexia.

Non-sympathomimetic anorexiant:
1036 Inhibits reuptake of 5HT and NE (SNRI
reuptake inhibitor), as well as being an
Sibutramine (Meridia) MAOI Weight loss; take without regards to meals

Non-anorexiant derivative of lipstatin -

covalently binds and inhibits gastric
1037 and pancreatic lipases preventing
hydrolysis of triglycerides to absorbable
FFA and monglycerols; not absorbed
Orlistat (Xenical) systemically Weight loss

1038
Herbals See extra notes Weight loss
 A B C

1039 Progesterone derivative - increases

Megestrol appetitie Weight gain (associated with antineoplastic therapy)

1040
Drugs of Abuse & Treatment
1041 Alcohol

1042

GABA gated Cl- channel is facilitated;

Glutamate gated Ca++ channel is
inhibited; EtOH used because it has a
higher affinity (lower km) for alcohol
Alcohol (Ethanol or Ethyl dehydrogenase -- inhibit formation of
Alcohol) toxic aldehydes
1) Pleasure (recreation) to abuse to dependence
2) Cardiovascular benefit (~1 drink/d)
3) Methanol (MeOH) & Ethylene Glycol (antifreeze)
Poisoning (used in conjunction with hemodialysis, emesis,
gastric lavage, correction of acidosis and supportive care)

1043 Reduces cravings in alcoholics; (also opioid OD, see

Naltrexone Mu selective opioid antagonist opioids)
Treating abstinent alcoholics (meaning alcoholic with a
1044 problem getting a drink), reduces cravings in alcoholics (Not
Blocks NMDA (glutamate) receptors metabolized, not contraindicated if there is hepatic
Acamprosate and activates GABA(A) receptors impairment)
 A B C

1045

Alcohol consumption treatment: with ethanol consumption,

produces acetaldehyde syndrome - used for court ordered
Disulfiram (Antabuse) Blocks aldehyde dehydrogenase aversive therapy
aka 4-methylpyrazole; inhibit the action
1046 of alcohol dehydrogenase thereby
reducing the synthesis and accumulation
Fomepizole (Antizol) of toxic aldehydes. Methanol (MeOH) & Ethylene Glycol (antifreeze) Poisoning
1047 Other Terribly Delicious No, No's

1048

Psychostimulants; blocks DA
transporter (also binds NE and 5-HT
transporters); (benzoylecgonine
Cocaine metabolie in plasma 1-3 days) Local anesthetic effect
 A B C

1049

Psychostimulants; presynaptic release

of DA (amphetamine runs the re-uptake
transporter in reverse); in plasma for 1-2
Amphetamines days; see ADHD drugs ADHD & Narcolepsy
1050 Ammonium chloride Acidify urine Hasten amphetamine excression

1051

Psychostimulants; agonist at CNS &

peripheral nicotinic sites; (Cotinine
metabolite in plasma 1-2 days);
Stimulates the release of dopamine and
Nicotine glutamate.

1052

LSD; LSD-like drugs (eg

mescaline and
psilocybin) Hallucinogens
 A B C

1053

Hallucinogen; non-competitive blocker

Phencyclidine (PCP) of NMDA receptors

1054

Hallucinogen; non-competitive blocker

Ketamine of NMDA receptors

1055
Methylenedioxy-
methamphetamine
(MDMA) Hallucinogen

Dronabinol (Marinol): L-delta-9-transtetrahydrocannabinol

1056
Marijuana (Pill form:
Dronabinol (Marinol))
1057 Fentanyl analogs
1058 Heroine
(delta-9-THC)
Glaucoma - advantage not established
Nausea/vomiting (cancer chemotherapy; advent of 5-HT3
agents has minimized this use; FDA has disapproved
marijuana for this. Dronabinol, a synthetic delta-9-THC analog
is approved for antiemetic effects)
Hallucinogen; binds to cannabinoid Anorexia - for weight loss in AIDS
receptors Non-medical
Opioid effects
See opioids above

1059
Related to GABA, but mechanism not
Gamma-hydroxybutyric known; detectable in plasma only for
acid (GHB) hours
 A B C

1060
BZD; detectable in plasma less than 7
Flunitrazepam days

1061
Inhalants: Organic
solvents

1062 Inhalants: Used medically to relieve pain in people with heart disease,
Nitrates/Nitrites (amyl amyl is a vasodilator -- it causes blood vessels to open wider,
nitrite, butyl nitrite and easing the heart's labors, allowing blood to flow more freely,
isobutyl nitrite) Amyl is a vasodilator and temporarily increasing the pulse rate.
 D E F
1 Side Effects & Toxicies Contraindications Memory Technique

st 2

Pt with severe vertebral dz or

3 bladder obstruction as
temporary surge of T (before
functional castration) may
worsen symptoms by feeding
prostate cancer
Rem: Lou lied (Leuprolide) about taking his
hormones (sGnRH) for his prostate cancer so
he wouldn't be castrated and get boobies. He
wants to still be able to play his skin flute (flut-
amide used together)

7 5% ejaculation problems Rem: that's a fine ass 2 ride (Fin-as-te-ride, 2 =

10% erection problems type II), but oops, no erection. The man has a
5% libido problems (all from androgen tupe to cover his balding head, but notices hair
blockade) growth
5% ejaculation problems
8 10% erection problems
5% libido problems (all from androgen Rem: Do taste the BPH, see if its ripe (large)
blockade) (Du-taste-ride)

Retrograde ejaculation (more than

Terazosin), incidence increases over time
 D E F

10
Retrograde ejaculation, orthostatic HTN
(light headed, syncope with first dose);
Asthenia ("feel" weak, will not show
objective evidence); Stuffy nose
Retrograde ejaculation, orthostatic HTN
(light headed, syncope with first dose)
11 though this is minimal with time; Asthenia
("feel" weak, will not show objective
evidence); Stuffy nose

12
Rem: "clone me friend, many times." (Clo - mi
Multiple births - phene)
13

14 Blindness is rare (unique to Sildenafil),
some pt complain of a "blue aura" in visual Warning: ED drugs of sildenafil-
field and decreased visual accuity;
Headache (15%), Flushing, G.I. upset,
Nasal congestion (4%), priapism
Headache (15%), Flushing, G.I. upset,
15
Nasal congestion (4%), priapism
Tx with nitrites/nitrates,
Patients with angina are at
risk; BP < 90/55
type should not be used within 4
hrs of alpha blockers (does not Put your penis on the (window) sill, then the fill
apply to tamsulosin) (of the vagina with semen)Sill-den -da -fill
see sildenafil

16
Headache (15%), Flushing, G.I. upset,
Nasal congestion (4%), priapism see sildenafil

17

18
plagued by high incidence of nausea and
vomiting
 D E F

19

20 Hot flashes; thrombo-embolism; vaginal

bleeding & discharge (vaginitis);
thrombocytopenia peripheral edema,
increased risk of endometrial cancer

21

Rem: relax, I'm fine, I'm on a partial agonist, I

might even give a SERMon

22 Rem: Sertoli, the gay Italian, converts

testosterone to estradiol with his aromatics
(aromatize)
Rem: estriol I o Little baby (placenta), E3 =
history of venous thrombosis; es-tri-ol
Cancer of the breast (past, Rem: Estrone I own you says the big mean
present or family history); old lady (rone~own), E1 = Estr1
Cancer of the endometrium (Eone=estrone)

23
24
 D E F

DVT is absolute
25 contraindiction; Pregnancy;
Women with Hx of E-dependent
Thromboembolism, Cardiovascular risk, neoplasms or breast cancer; Hx
Hypertension. Because high doses of thromboembolic disorder or liver
steroids, side effects range from minor disease; Heavy smokers
discomfort (water retention, nausea) to (cardiovascular risk is higher if
cosmetic (chloasma) to dangerous >35yrs of age) (big
(hypertension, embolic disorders) contraindication); Migrane HA

26
Some women may hoave moral or ethical
objections to the mini pill but not the standar pill

27

N/V!
Weight gain, 5lbs at 1 year, lbs by the
2nd, 12lbs by the 5th.
Massive weight gain in 1-2 % of patients.
Bone loss!
28 Should use for no longer than 2 years
without a break
Slow return to fertility
average 10 months, can be as long as 2
years
Some metabolise quickly, some very slow
Pt keeps eatting heavily too

29
Androgenic effects such as hirsutism

30
higher risk of thromboembolism

31
 D E F

32
very high androgenicity

33

Rem: Dro-spirenone similar to spirono-lactone

34

35

36

37

38

39

40
Rem: Are you for 86ing this pregnancy (RU486)

41
Rem: Dan - you have endometriosis??; Dan-an
tagonist (Danazol)
42
43
 D E F
Rem: abate/stop the hemorrhage (Hemabate);
44 Rem: PGF2 For Fucks sake, save that
woman; or Fuck that baby (2nd trimester
pregnancy termination)

45
Rem: PGE2 E-gads, get that baby out
46

47

48
49

50

Rem: Guard dis li vagina (gar-dis-il)

Perform a laparoscopy for acute ectopic
51 Stomatitis, neutorpenia (usually pregnancy (hemodynamically stable pt), or
moderate), rarely alopecia laparotomy (hemodynamically unstable pt)

52
53

st 54

55
 D E F

Should be used under careful medical

supervision
56 Excessive fluid and electrolyte loss:
1. hypokalemia (watch out for CHF
patients on digoxin), K+ is lost in the CD,
not the loop or the DT 2. hypokalemic
metabolic alkalosis: Metabolic alkalosis is
secondary to hypokalemia (Excess Na+ at
CD drives K+ and H+ into lumen) 3.
hyperuricemia (hypovolemia enhances
reabsorption of urate at proximal tubule) 4. Remember: a ferocious (Furosemide) lion
hypomagnesemia 5. ototoxicity (usually jumping through a firey loop and pissing
reversible -- watch for patients also taking (diuretic) out fire; notice the SE - bunch of
aminoglycosides) 6. hypovolemia 7. hypo's and 2 hypers (glycemia and uricemia)
interstital nephritis (furosemide) and an oto

57

58
59

CHF - Transient expansion of

60
Headaches, nausea, vomiting
Long-term: hypernatremia, dehydration
extracellular fluid volume,
hyponatremia (mannitol is
distributed in the extracellular
compartment and draws water
from the intracellular
compartment, can result in
cardiac failure and/or pulmonary
edema. Do not use these agents
in patients with diminished
cardiac capacity)
Non-electrolytes, but highly polar; Confined to
ECF (doesn't enter cells); Freely filterable at
glomerulus; Not reabsorbed; Provide a higher
solute load in the nephron osmotic pressure
prohibits normal water reabsorption; More
water loss than Na loss; Poorly absorbed, given
parenterally
 D E F

61

1. Hyperchloremic metabolic acidosis, K+

depletion
2. Renal stones!! Remember: throw an ace ta soul of mine (Ace-
3. Hypersensitivity reactions (rare): rash, ta-zol-a-mide), splitting my carbon (carbonic)
fever, bone marrow suppression body, breaking it

1. Hypokalemia (watch digoxin)

2. Hypokalemic (hypochloremic)
metabolic alkalosis
3. Hyperuricemia
(These 3 above are same toxicities and
same mechanisms as for Loops)
62 4. Hyponatremia with hypovolemia
5. Hyperglycemia: decrease insulin
secretion -- may unmask latent diabetes
mellitus, usually clinically important only at
high dose Usually reversible with correction
of hypokalemia
5. Increase serum cholesterol usually
clinically important only at high dose
6. Allergic reactions
7. Erectile dysfunction: Frequency is
even greater than with beta-blockers
8. hypercalcemia

63
64 a sulfa based drug
thiazide-like; have key portion of Remember: India (indapamide) produces
65 sulfonamide structure hypersensitivity cheap thiazide knockoffs (thiazide-like), many
cross-reactions people allergic (HS)
Remember: thiazide ring made from metal
66 thiazide-like; have key portion of (Metolazone), many people have allergy (HS);
sulfonamide structure hypersensitivity or me to lazy to get up and go to bathroom so
cross-reactions I'll pee right here
 D E F

1. Hyperkalemia (esp. with ACE inhibitors,

NSAIDs, b-blockers); Most common when
67 co-administered with K+ supplement, which Remember: tell potassium to take a SEAT
is not rational 2. Anti-androgen effect (Spironolactone, Eplerenone, Amiloride,
(steroid structure leads to competitive Triameterene), all of the K spareing diuretics;
inhibition of androgen receptors): Rem: spiro no!! (no spiral shaped erection), but
gynecomastia; impotence Renal failure man with gynecomastia
Intended in development to be an
aldosterone antagonist with no
68 antiandrogen effects; Side-effect profile
shows gynecomastia, consequently, little
different from spironolactone Renal failure

69 1. G.I. (nausea, vomiting)

2. Dizziness Remember: Amelia (Amiloride) riding a shinny
3. Leg cramps K horse, but the horse refuses to lick Liddle's
Renal failure Fiddle of salt lick
1. G.I. (nausea, vomiting) Remember: try a meteor (triameterene) for
70 2. Dizziness breakfast made from K, the meteor splashes
3. Leg cramps into the milk (Ca) which splashes onto your
4. Nephrolithiasis Renal failure kidneys (nephrolithiasis)
TN 71

Side-effect profile approaches placebo

72
(Dr. Dubin scoffs at this statement)
Avoid during pregnancy (2nd & 3rd
trimester), teratogenic: If pregnancy occurs
while on these drugs, no adverse effects Remember: lo sartan means the frying pan or
occur if the drugs are discontinued early taint of him, so Angi was tense because
on. Toxic to the developing kidneys someone blocked her boyfriend's taint receptor

73
see losartan
 D E
Predictable, typically mild, dose-related
side-effects: 1. Cough!! 2. Initial dose
hypotension, esp. if hypovolemic; also
initial dose rise in creatinine and K
(transient, also find with ACEI use) 3. Skin
rashes/neutropenia (is captopril worse than
others?) 4. Acute renal failure in renal
74 artery stenosis!! (bilateral stenosis or
single kidney stenosis) 5. Angioedema!!
(d/t bradykinin - swollen tongue, etc, can be
life threatening) 6. African-Americans and
elderly may not respond well 7.
Contraindicated in 2nd & 3rd trimester
pregnancy, teratogenic (fetal
malformations (thin facial bones),
hypoplasia of lungs, hypotension and renal
failure(anuria)), probably not good in first
trimester either 8. Hyperkalemia possible
(esp. if combined with other drugs that
increase K)
75
76
Side Effects associated with excessive
77 vascular dialtion: HA, postural
dizziness, flushing, peripheral edema
especially ankle edema, parethesia,
gingival problems.
F
Rem: Cap full of Ace's that were stolen from
men's hypertension club poker game
Rem: ACEI - think CAPTOPRIL:
Cough (dry)
Angioedema/ Agranulocystosis
Proteinuria/ Potassium excess
Taste changes
Contraindicated in 2nd & 3rd Orthostatic hypotension
trimester pregnancy, Pregnancy contraindication/ Pancreatitis/
teratogenic (fetal malformations Pressure drop (first dose hypertension)
(thin facial bones), hypoplasia of Renal failure (and renal artery stenosis
lungs, hypotension and renal contraindication)/ Rash
failure(anuria)), probably not Indomethacin inhibition
good in first trimester either Leukopenia/ Liver toxicity
Pt with CAD, do not use Rem: knee fed a pen (ni-fed-i-pine) blocking
dihydroopyridine CCBs and knocking his Ca teeth into his dilated
without a beta blocker vessels
 D E F

78

1. headache; flushing; orthostatic problems

2. potential problem of heart block if
verapamil and diltiazem are used with Remember: tilling an angina heart with a dill
beta-blockers pickle (dil-tia-zam), Ca flying everywhere

1. Constipation!!
2. headache; flushing; orthostatic
problems
79 3. potential problem of heart block if
verapamil and diltiazem are used with Remember: a bear (ver) rapping (rap), falls with
beta-blockers pain of angia, chocking on Ca so bad that he
4. CHF can't poop

80

81

1. Hypotension (orthostatic) is a
significant side-effect for most patients.
Profound reflex SNS activation and
tachycardia as well as peripehal edema.
Consequences of increased myocardial O2
consumption - angina; increased
myocardial work - induction of CHF is more
82 likely; hypotension side-effects such as
palpitation, pounding headache,
flushing; edema secondary to Na+ and
H20 retention; GI
2. tachyphylaxis
3. Drug induced systemic lupus (hapten
mech - high doses, slow acetylators,
reversible)
4. Coronary Steal syndrome in pts with remember: pregnant hydra with using visin for
ischemic dz the butterfly rash around face
 D E F

83

see hydralazine
Adverse effects: SNS activation, angina,
edema, hirsutism

84
see hydralazine Remember: an ox in the day opening all of the
window (arteries)
Remember: "Fen? old o pam, she's D one
85 Typical arteriodilator toxicities who's got the HTN problem, but great kidneys",
says her old friend

86

excessive hypotension
cyanide/thiocyanate toxicity with
prolonged use
Tolerance!!

87

Tolerance, give at night (see extra notes)

 D E F
88
89
90
91
Hypokalemia
92

I 93
ng and females
er persons, males

94
Act synergistically with sulfonylurea
hypoglycemia by increasing the release of
insulin
reduce blood glucose level
Drug interactions of
sulfonamides - Displace
bilirubin from plasma albumin -
bilirubin is then free to pass into
central nervous system, cause
kernicterus (neural symptoms
associated with high levels of Rem: Sulfonamides (eg Sulfamethoxazole)
bilirubin) - contraindicated block dihydropteroate Synthase, TRimethoprim
during pregnancy blocks dihydrofolate Reductase

95

96
 D E F

97
Toxicity:
Crystalluria
Hemolytic anemia in G6PD deficient
patients (Afro Americans)
Stevens-Johnson syndrome: severe and
usually fatal conditions involving blistering
of the skin, mouth, eyes and genitalia, often
accompanied by fever, polyarthritis, and
kidney failure
Hyperkalemia
Drug interactions of
sulfonamides - Displace
bilirubin from plasma albumin -
bilirubin is then free to pass into
central nervous system, cause
kernicterus (neural symptoms
associated with high levels of
bilirubin) - contraindicated
during pregnancy
Remember: TMX/SMX: T = tree or respiration
(S. pneumonia and H. inflenazae); Mouth = GI,
diarrhea (Shigella, Salmonella, E.coli); Pee =
UTI, urethritis, prostatitis (enterics such as E.
coli); SMX = Syndrome or AIDS (profolactive to
prevent P. Carinii when T count below 200, also
T gondii)

Toxicity: n, v, d
98 Achilles tendonitis, tendon rupture
CNS such as HA, insominai, restlessness Contraindicated with patients
Epigastric distress under 18 years of age;
Damage cartilage do not give to children as
Suprainfection with streptococci, Candida causes cartilage damage

Contraindicated with patients

99 under 18 years of age;
do not give to children as
causes cartilage damage
100
101

102

Safe drugs to use

Only side effect is allergy & hypersensitivity
 D E F

103
Allergy and hypersensitivity
104
105

106 Remember: the people in the AV club don't go

out much, stay entero (inside) (A
-aminoglycoside, V-vacomycin), entero-
enterococci

Very toxic agent:

Auditory (ototoxicity)
Contraindicated during pregnancy.
107 Causes hearing loss in the fetus or
newborn Rem: A stripper (Streptomycin), a G'
Vestibular dysfunction (loss of) (gentamicin), Mr. T (Tobramycin), and Neo
Nephrotoxicity Contraindicated during (Neomycin) are all hangin out with a mean guy
Neurotoxicity pregnancy (aminoglycoside)

108

see aminoglycoside, causes polyuria

109
Remember: You 'spectin to get gonorrhea

110

MRSA and enterococci are

Allergy & hypersensitivity resistant to cephalosporins

111 Remember: all 3rd gens have t in them

(except cefotetan, a 2nd gen), and apparently
Cefixime
 D E F

112 Remember: cefixime, easy way to get your oral

fix, and need to fix cefixime by putting a t in the
word to make it fit with the other 3rds

Remember: 1st generation have ph in them, to

113 know 1st gen must have a PhD, however
cefazolin doesn't have a pph, don't let that faze
you (and don't let the red current jelly faze you
(Klebsiella)

114
Teeth discoloration, bone deformity in
children, Fanconi's syndrome
(aminoaciduria, phosphaturia, acidosis, and nails of the fetus
glycosuria), photosensitityity
115
Relatively toxic
Contraindicated during
pregnancy
cross the placenta to reach the
fetus and cause deformity and
growth inhibition
damage to teeth, bones, and Remember: VACUUM your Bed Room Tonight:
Vibro cholera, Acne, Chlamidia, Ureaplasma
Renal toxicity Urealyticum, Mycoplasma pneumonia, Borrelia,
Suprainfection Rickettsia, Tularemia,
Do not give during pregnancy:
Congenital limb abnormalities,
tooth discoloration, inhibition of remember: a daschund (dog, doxicycline) on
bone growth in fetus, bicycle coming out of your ass (excreted in
suprainfection. feces)

116

117

118

119
Oral therapy causes GI disturbances. Remember: clostridium for clottage cheeze

120
Remember: Miconazole for fungus of the toe;
severe GI disterubances also Azoles hate ergosteroles
Rem: Casper the ghost messin with the fungus
121 wall synthesis (moving around all the pieces
needed), the fungus just doesn't get why it can't
complete its wall
 D E F

122 Remember: GET out of its way, Giardia,

Entamoeba, Trichomonas

123

124

Nausea, diarrhea, headache, renal

insufficiency, neurologic toxicity
125

Drugs
126

127
Generally well tolerated; occasional
nausea, diarrhea, abdominal colic,
headache, dizziness, skin rash. PPIs are
metabolized and can inhibit cytochrome
P450 (CYP2C19 & CYP3A4, especially
omeprazole) and therefore decrease the Prazole = PPI; Rem: pray so (pra-zole) the
clearance of other drugs such as pumps stop pumping acid onto our heads;
benzodiazepines, warfarin, phenytoin, and Rem: put your H. pylori CAP on (tx with
others. clarithromycin, amoxicillin, and PPI)

128
see Omeprazole
 D E F
129
see Omeprazole

130
see Omeprazole

131
see Omeprazole

Cimetidine (but not other H2 blockers)

inhibits the activity of cytochrome P450,
132 thereby slowing the metabolism of many
drugs (phenytoin, theophylline,
phenobarbital, cyclosporine, some
benzodiazepines, carbamazepine,
propranolol, Ca2+ channel blockers,
quinidine, sulfonylureas, warfarin, and
tricyclic antidepressants). If drug
interactions must be avoided, use an H2
blocker other than cimetidine.
tidine = H2 blocker; Rem: tied up in (tid-ine) an
H2 hummer; Rem: see me (Ci-me-tidine) tied
up with all sorts of drugs In the H2 (inhibits
P450); Rem: Major Cytochrome P-450
inhibitors: FREaCKI Grapefruit gets stuck in
Ez - Ketoconazole, Isoniazid, Cimetidine,
Fluoxetine, Ritonavir, Erthyromycin, Grapefruit

133
Very little SE

134
Very little SE

135
Very little SE

Change in bowel habits, systemic cation

absorption and alkalosis (usually only if
renal impairment present). Low sodium
content is recommended, especially for
hypertensive and CHF patients. Drug
interactions result mainly from changes
in GI motility or pH. Alumina and
136 magnesium change mobility and can
change absorption of other drugs. Al3+
can cause precipitation of some drugs in GI
tract, reducing their absorption. Changes
in luminal, serum, or urinary pH can change
absorption or elimination rates of many
drugs. Advice: Do not take antacids
within 1-2 hours of administration of
other drugs.
 D E F

137

138

Causes black stools and sometimes Rem: bi - bicarb increased, mu - mucus

black tongue. increase (Bi-s-mu-th), and bismuth besmirches
Extremely safe at recommended doses. your tongue black
139

140
Rem: Ralph was sucking (Suc-ral-fate) on a
sticky viscous sucrose and aluminum sucker
that coated his stomach and relieved him of the
Constipatoin fate of his ulcer just to give him constipation

141
potential abortifacient, Rem: Miso-prostol is Prosta-glandin soup, but
therefore it is contraindicated in causes Japanese baby abortions; miso is good
Causes diarrhea in 30% of patients pregnancy. for the belly; prost = prostaglandin

142
 D E F

143
Side effects are significant, especially
with chronic treatment, and include:
hyperprolactinemia, galactorrhea, breast
tenderness, menstrual irregularities,
extrapyramidal symptoms, anxiety, and
depression.
144
Rem: Me is such a dope (anti-D2) that me toe I
cloped (Me-to-clop-ramide), screaming like a
girl (giving me girly stuff (SE)) while my GI
functions better with the diabetes. Rem: Me to
D 2 (D2 and DM2)
Rem: try meth Ben (Trimethobenzamide), its a
dope (dopamine) used to prevent vomiting and
nausea "2 dope" he exclaims

145
Rem: the PD pt cracked open a bottle of
central side effects less than (Domperidone) now that his gastric stasis is
metoclopramide solved

146

SLE SE

147

148

149
 D E F

The major side effects of erythromycin and

other macrolide antibiotics relate to
150
abdominal pain and cramping (51%);
nausea (up to 37%); diarrhea (24%); and
vomiting (7%). These side effects are
especially troublesome in patients with
gastroparesis who may already suffer from
similar symptoms. Rem: Macrolide bind Motilin receptors

151

Prolongs fever in pts with shigellosis, toxic Rem: the pt took Loperamide and is now
megacolon in pts with C. difficile; and HUS lopping around from the opioid (opioids work at
in children infected with Shiga toxin- Ulcerative colitis, or acute the MD receptos, mu and delta); or Rem: (the)
producing E. coli. Should be avoided in pts bacillary or amoebic dysentery; l'opera makes you slow, opiods make on lop;
with bloody diarrhea bloody diarrhea lopping amide the diarrhea in the streets

152 Rem: Dip the ox and hen in a vat of opium so

they stop with their diarrhea (Dip-hen-ox-ylate)

153 Rem: dive in (Dif-en-oxin) the opioid haze; or

Rem: dip ox (dif-en-ox-in) in opium vate

154
Schedule II

155 Rem: an octopus tree (Octreotide) stand in the

sand (somatostatin) with tumor diarrhea,
orthostatic HTN, and esophageal varices on
the branches
 D E F

156

Phenolphthalein causes pink to red

colored urine and feces, gastric irritation,
electrolyte imbalance, and allergic
157 reactions are possible.
Anthraquinone derivatives: may produce
an excessive laxative effect and abdominal
pain and yellowish brown to red urine. May
cause nephritis

158

Adverse effects such as dehydration and

electrolyte imbalances can be caused by
injudicious use of these agents.
 D E F

159

Rem: like to loose (Lac-tu-lose) your ammonia

and portal HTN and hepatic encep

160

161
Rem: a prep for chemo puking - Aprepitant, "No
Kidding" as he pokes you (NK1 antagonist)

162
setron = antiemetic; Rem: seeing Tron won't
make you puke, in fact, it will make you feel
pretty good (seritonin receptor); Rem: Tron
throwing his frisbee at the seritonin receptor
inhibiting it; or Rem: O' dan is so strong
(Ondansetron), you can give him 5 hits in 3
rounds (5HT3)
163
164
165
 D E F

166
Rem: Men die from saying hi to nate, (Di-men-
hy-dri-nate, Hi is H1 antagonist)

167

168

169
Rem: zine = H1 blocker

Rem: a pro method magazine that has photos

170 of skaters pulling methods with snot pooring
Dizziness, dry mouth, nausea and vomiting, out (rhinitis), splattering on the camera (camera
rash man vomits up mushrooms - muscarinic SE)
Very high incidence of anticholinergic
171 side effects when given orally or
parenterally. It is better tolerated as a
transdermal patch.
Hallucinations, disorientation, vertigo, and
172 other adverse effects limit the use of these
drugs to patients refractory to other Rem: the stoner was a drone (Dronabinol) from
therapy. all the Cannabinoids

173

174

175 Rem: Lora is scared of ze Pam, so takes

Benzodiazepines to relax; Lora's ass is so nice,
it will hypnotize you
176

177 Rem: (Tegaserod) touch the gas with the rod

and it expodes, punching a hole through the
Removed from market due to CV SE (ie MI, IBS; or to gas and shit right when your IBS is
unstable angina, strokes) treating you wrong, tegaserod
 D E F

178
This drug was previously withdrawn due to
very serious adverse effects, including
ischemic colitis and serious
complications of constipation.
setron = antiemetic; Rem: seeing Tron won't
make you puke, in fact, it will make you feel
pretty good (seritonin receptor);

179

Rem: tricyclic antidepressants prey on the mind

(pra-mine)

180
181

182

183 Rem: Sal farting sulfer cause relief to his UC

(sulf-a-sal-azine); 5-ASA compound -
BM suppression, n/v, HA, malaise sulfASAlazine

184
 D E F

185
Must check for latent TB and other
infections before administration. One side
effect is a lupus-like syndrome, which is
rare and reversible after stopping the drug.
Anti-double-stranded DNA antibodies occur Rem: to fix CD, inflict a flick to their bowel
in 9% but are not associated with clinical (Infliximab), don't flick too hard or will give them
lupus. TB SLE or knock free the TB

186

187
188
189
190
191
192
193
194

195
196
197

198
 D E F

systemic "flu-like" symptoms, marrow

199
suppression, emotional lability,
autoimmune reactions (especially
autoimmune thyroiditis), and
miscellaneous side effects such as
alopecia, rashes, diarrhea, and numbness
and tingling of the extremities. With the Rem: Jak, stop interferoning with me stat! or I
possible exception of autoimmune am gonna synthesize over 2 dozen proteins on
thyroiditis, all these side effects are your ass
reversible upon dose lowering or cessation (interferon turns on jak stats and they make a
of therapy. bunch o crap)

Rem: Lassa is so skinny, her Rib's avirin from

200 her side, covered with guano, and she is
having a hard time breathing, has turned yellow
for all to C (Guanosine analog, breathing is
anemia teratogenic RSV, and yellow plus C = Hep C)
201 See Interferon-

202
See Interferon-
See INF-alpha; Very rarely, interferon alfa-
203 2b, recombinant used alone or in
combination with ribavirin capsules may be
associated with aplastic anemia.

204
See Interferon-
See INF-alpha; Very rarely, interferon alfa-
205 2b, recombinant used alone or in
combination with ribavirin capsules may be
associated with aplastic anemia.
 D E F

206

Negligible

Usually well tolerated; asthenia, headache,

207 diarrhea and abdominal pain High dose
are risk factors for azotemia and renal
tubular dysfunction. Hepatitis flares may Rem: What B AILing you (Adefovir, interferon
occur after adefovir is stopped. alpha 2b, and lamivudine for treating B)

208

alcoholic liver disease

209

210

s 211
 D E F

212

GI most predominate, see extra notes for

all side effects. Loop diuretics may
exacerbate digitalis associated
hypokalemia (and hypomagnesemia); do
not give with quinidine (displaces digoxin
from binding sites on albumin)

213
see digoxin

214

B for brain; Rem: "Neh, sir, the tide is changing

(Ne-sir-i-tide), where gonna bring this pt back
hypotension from certain death (acute decomp)"
 D E F

Headaches, dizziness (Monday disease

people who work (factory) with nitrates
often experience worse HA/dizziness
immediately after the weekend because
215 tolerance is lost over about 24 hr)
Orthostatic hypotension & reflex
tachycardia. Drugs for erectile dysfunction --
Tolerance - Dose/frequency dependent afils are contraindicated with
(Try to maintain patients nitrate free for at nitrates: sildenafil, tadalafil &
least 8-hr /day; mechanism?; Drug holidays vardenafil (the afil class), Rem: put your dick on a sill and it will fill (afil,
can alleviate) including severe hypotension. sildenafil)

216
See NTG

217

218 GI (nausea, vomiting)

Thrombocytopenia
Abnormal liver function
If used long term, increased mortality

Short Term - Fewer than amrinone, so

219 preferred
Long Term - Increased Mortality, Half-life = 30-60 minutes
Arrhythmias
220

cs 221

Increased TdP = hypotension syncope

and sudden death within the 1st few
222 days; Nausea, diarrhea, abdominal
cramping; Cinchonism = vertigo, HA,
tinnitus, psychosis, blurred vision; rash, Do not use in pt with long QT
thrombocytopenia, hemolytic anemia;lupoid syndrom, TdP history, or
hepatitis and 2X to 3X increase in mortality hypokalemia (increases TdP) Put Na in your tonic and call it quinidine
 D E F

223
Salty (Na) old man weiding his cain in NAPA
valley, whacking hot Lupus chick, giving her
lupus-like syndrome!! arrhythmia may be Do not use in pt with long QT butterfly rash; Rem: its not HIPP to get drug
aggravated, development of TdP; syndrom, TdP history, or induced-LE - (Hydralizine, INH, Phenytoin,
agranulocytosis, BM depression hypokalemia Procainamide)

224

Remember: dis o' pyramid sitting in sand of Na,

anticholinergic SE - stops peeing, can't piss or poop (anticholinergic), just wants 1
pooping, salivating impaired ventricular function Ass (1A) movement

CNS symptoms: seizures!! (mental

225 status changes), drowsiness, dyarthria,
dysesthesi, and coma; can depress cardiac Remember: class I be (B) ventin (works only on
function leading to decreased clearance, ventricle) with the short fuse temper (shortens
and produce greater SE; sinus node AP)
dysfunction
CNS symptoms: seizures!! (mental
status changes); dose related tremor, Remember: the Mexican (Mexiletine) injected
226 visual blurring, dizziness, dysphoria, and his toe (tocainamide) with lidocaine to numb
nausea; thrombocytopenia and postivie the 1 Bee sting (class IB), but goes into a
ANA; worsen heart block with high seizure and wishes he'd injected dilantin
concentration instead

227

228
Remember: die laughing so had a seizure
 D E F

proarrhythmia!!; CHF; CNS=blurred drug interactions: cimetidine

229 vision, headache, ataxia;decreases LV its clearance its half-life;
function and depresses the SA node in pt digoxin, propranolol, & Remember: flick a cain in someones one eye
with SA node dysfunction amiodarone its levels and they can't see (1C)

230

proarrhythmia!!

drug interactions: increases

digoxin, theophylline,
231 cyclosporine levels and warafin
effects;cimetidine increases its
proarrhythmia!! nausea, vomiting, metallic levels;phenobarbital, phenytoin, Prop a phone against Kofi in one sea (1C), the
taste to food rifampin decreases its levels sea is rough (proarrhythmia)

232
similar to Flecainide

Severe systolic heart failure

233 (from massive myocardial
damage, RV infarction, or acute
high doses=fatigue and depression; valvular regurgitation) and
bronchospasm, bradycardia and AV block, active wheezing from reactive
myocardial contractility, impotence, CHF airway dz

proarrhythmia, bronchospasm, worsens

heart failure;instability in pt w vent
234 arrhythmias post MI;TdP in those w
bradycardia, prolonged QT intervals, and
hypokalemia;normal side effects of
blockers
Remember: Jaba the Hut saying Sotolol
(meaning solo) for Han Solo, who is a master
bounty hunter and will pull in any criminal,
including & K & Na & Ca channel blocker
criminals
 D E F

irreversible pulm fibrosis!!

hepatotoxicity (jaundice and cirrhosis);
235
hyper- & hypothyroidism, corneal
deposits; agranulocytosis, bluish
discoloration of skin & photodermatitis,
nausea, constipation, bradycardia,
hypotension with IV due to contractility
and peripheral vascular resistance
236 TdP (esp in women w vent function or
electrolyte disoders--all TdP), heart
block, hypotension, nausea
TdP; drug interactions which increase
237 levels: erythromycin, diltiazem, cimetidine,
or ketoconazole; causes massive
diarrhea!
Remember: Amy and Yoda sitting together
eatting bananas (K), yoda got corneal deposits
in eyes and is bitch'n because he has
drug interactions: digoxin and pulmonary fibrosis and toxic liver, but stoked
cyclosporine levels and cause he can have a prolonged orgasm (half
wafarin effects life)
dont give to those w
hypokalemia,
hypomagnesemia or a QTc
>440msec
Rem: Do fret, I lied (Do-fet-i-lide)
- though your heart can be fixed
by bananas (K), it causes
massive diarrhea

238
reflex tach due to vasodilation; edema
and orthostatic hypotension

239
moderate in LV contractility,
bradycardia and hypotension

240 peripheral edema, moderate in LV

contractility (V. Fib.) and hypotension
(peripheral vasodilation); constipation; CHF (because of decreased
hemodynamic collapse inotropic effect)

promotes atrial and vent irritability;

hypokalemia, loss of appetite, nausea,
vomiting, diarrhea, blurred vision & yellow-
241 green halos (xanthopsia), confusion,
drowsiness, dizziness, nightmares, Wolff-Parkinson-White
agitation,depression; do not give with syndrome (direct
quinidine (displaces digoxin from binding connection/reentry tachy - dig
sites on albumin) would exacerbate)
 D E
facial flushing, dyspnea, or chest pressure
242 lasts <60 sec; sometimes nausea,
lightheadedness, headache, sweating,
palpitation, hypotension and blurred vision
243
Arrhythmia may be aggravated,
development of TdP; lupus-like
syndrome; agranulocytosis
244
245
1. Hemorrhage from inadvertent overdose,
bleeding from undiagnosed disease site
(ulcer, carcinoma).
2. Hematoma formation at surgical site or
from SC or IM injection
3. Heparin-induced thrombocytopenia
246 (HIT). Heparin induces transient
thrombocytopenia in as many as 25% of
patients but his usually resolves
spontaneously. However, in approximately
5% of patients a severe thrombocytopenia
can evolve days after the initiation of
therapy (Ab formation, see extra note).
4. Less common side effects include acute
hypersensitivity, alopecia, platelet
aggregation, osteoporosis (1 year therapy),
and priapism.
247
Bleeding
248 Bleeding
F
dont use for AFib, sick sinus
syndrome, or 2 and 3 heart
block unless they have a
pacemaker
Do not use in pt with long QT
syndrome, TdP history, or
hypokalemia
Active bleeding!!
Also: severe HTN, aneurysm,
hemophilia, thrombocytopenia,
intracranial hemorrhage, active
tuberculosis, ulcerative lesions
of the GI tract, threatened
abortion, or visceral carcinoma;
withhold during/after surgery of
the brain, eye, or spinal cord;
lumbar puncture or regional
anesthetic block; visceral Remember: hepar-in-trinsic Remember: PiTT -
carcinoma The drug should be intrinsic, Brad Pitt is a hep dude (heparin) and
used only where clearly gets a suck on Angalena Jolee's TT's (thrombin
indicated in pregnant women, time); Remember: The hemaphiliac (A) ate
despite its apparent lack of (eight) nine Christmas Bees (B), see (C) at
transfer across the placenta. eleven (11) on the news
Rem: Enoxaparin = LMWHeparin
 D E F

1. Hemorrhage (bleeding): incidence 2

4%, serious bleeding approximately 1%
249 2. Anorexia nausea, vomiting, diarrhea
3. Cutaneous lesions: skin necrosis
(usually associated with protein C or S
deficiency causing hypercoagulation and Remember: PeT - extrinsic, walk your PeT
thrombus), begins as bulla that may be down on the Warf (warfarin); Remember: slow
purpuric or show dermatitis, urticaria, prolonged bloody war, as told by the oral
alopecia - followed by necrosis Contraindications are similar to tradition, don't let the pregnant woman listen
4. Drug-Drug Interactions!!! heparin, but include pregnancy (teratogen), it's too horrible for their fragile state

250

251 Clopidogrel increases the risk of

bleeding during coronary bypass surgery, Remember: clop/slap the ADP receptors face
so this drug usually is not started if the to piss them off so they will stop aggregating,
patient is considered to be a surgical so we can drill (clopidrogel) prophalactically
candidate. open the a. of brain and heart

252
Rem: Love cAMPing outside a pyramide,
planned go into the pyramide but passout from
vasodilation and die from eatting spicy mole
(though drug prevents stroke)

Life-threatening hematological adverse

reactions, including
neutropenia/agranulocytosis, thrombotic
253 thrombocytopenic purpura (TTP) and Remember: tickling opie (Ticlopidine) while he
aplastic anemia; severe diarrhea. Use dines spagetti (fibirin) and meatballs (platelets),
should be reserved for pts who are but the spagetti and meatballs will not mix, and
intolerant or allergic to aspirin therapy or worse, he spills his blood wine
who have failed aspirin therapy. (neutropenia/anemia)
 D E F

254 Rem: she'll stall all (cilostazol) the platelets

(blocking them) and vasodilates open their
faces so she won't be lame for the cAMPing
CHF trip at CHF park

255

Remember: ET learning his ABCs in jail

(Eptifibatide, Tirofiban, ABCiximab, jail =
IIb/IIIa)

Remember: ET learning his ABCs in jail

256 (Eptifibatide, Tirofiban, ABCiximab, jail =
IIb/IIIa); Remember: go up to the fibrinogen tide
(Ep-ti-fiba-tide) and stop it by mimicing it

257 Remember: the tyranny (tiro-fiban) of fibrinogen

will end by replacing it during heart surgery
(PTCA) with a analog

258
Remember: a pent up ox in a RBC that that is
doing yoga to become more flexible

259 Bleeding; Disadvantage of the direct

thrombin inhibitors is lack of revesibility
Bleeding; Disadvantage of the direct
260
thrombin inhibitors is lack of revesibility

261 lepard attacks heparin and rudely (lepirudin)

Bleeding; Disadvantage of the direct latches on with its claws, so heparin HIT the
thrombin inhibitors is lack of revesibility lepard
 D E F

262

In the bivouac (bivalirudin) the solider was rude

Bleeding; Disadvantage of the direct
thrombin inhibitors is lack of revesibility
263
Bleeding; Disadvantage of the direct
thrombin inhibitors is lack of revesibility
to the thrombin and platelet commanders,
jutting his fingers into their hearts (PCA)
Remember: needed a direct thrombin binding
drug, so went into the LAB to create it
(Lepirudin, Argatroban, Bivalirudin);
Remember: Argatroban, an aligator bites and
sticks (binds) to thrombin, and so is banded
from the HIT club on Miami beach

264

Remember: alteplase alters the plasminogen to

active plasmin, also alto (stops) at the boarder
hemorrhage of the thrombus, also stops the MI

265 Remember: rent a place (Reteplase) to

"activate" plasminogen - a seedy hotel room
deep in the getto (clot), its so good you don't
hemorrhage have a MI

266

hemorrhage
 D E F

267

Active or recent internal Remember: SARA T. is thrombolytic (heart

bleeding; intracranial surgery or throb) - Streptokinase, Alteplase, Reteplase,
hemorrhage pathology Antistreplase (APSAC), tenecteplase

268 Active or recent internal

bleeding; intracranial surgery or
hemorrhage pathology

269

Remember: a nap sack (APSAC) filled with

inactive steptokinase and plamin complexes,
but seeps through the sack, becoming active
hemorrhage and bloody-fibrin lysed blood dripping
Rem: the amgios (aminos) gonna cap the
270 rollers, killing them before they can kill (Amino-
Thrombosis cap-ro-ic)

271
272
273
 D E F

Numerous, but incidence is low and

severity is relatively lesser than with other
lipid lowering drugs. Most frequent is
hepatic damage (1-2%). Elevated serum
hepatic enzymes occur, and they can
cause hepatitis. Monitor liver enzymes after
1-2 months and then every year.
Increasing number of reports of peripheral
neuropathies. Appear reversible on
discontinuation of the drugs.
Watch for myalgia (1-5%), myopathy
274 (<1%) and rhabdomyolysis (rare).
Monitor for myopathy more carefully when
combining with niacin (2%) or fibrate drugs
(5%), which can cause the same toxicity).
These toxicities occur more frequently.
Monitor creatine phosphokinase (CPK; CK)
Avoid combining with erythromycin (dec.
metabolism of statins, with inc. myopathy);
also verapamil, diltiazem & grapefruit juice
(increases statin levels).
Test on Board examinations: Lovastatin
and simvastatin cross BBB and may cause Contraindicated in hepatic
sleep disturbances disease
Frequency of toxicities is generally low, Contraindicated in pregnancy
most are reversible on discontinuation of (fetus needs cholesterol for
drug formation of cell walls)
275

(relatively long list, but low incidence):

Blood cell deficiencies, skin rash and other
hypersensitive rx
G.I. problems
liver enzyme abnormalities (usually
276 transient)
myositis -- myopathy and
rhabdomyolysis are reported when
combined with HMG-CoA reductase
inhibitors Remember: the gem (gemfibrozil) VLDL (very
lithiasis (increase biliary cholesterol luminuous during lumination) is found in Brazil;
excretion). Do NOT use in pts with gall Also notice Fibrate Derivatives have fibr inside
bladder problems. pts with gall bladder problems. their name (gemifibrozil and fenofibrate)
 D E F
Remember: the fen fenofibrate fell over and
277
vibrated, breaking the gems (VLDL)
278

GI distress: Constipation and a feeling

of bloating, also causes steatorrhea
279 Text says this is easily controlled with a
high fiber diet. However, patient compliance
is not good because of these side effects.
Unpalatable
Increase Triglycerides!! (associated with
atherosclerotic plaques that rupture)
Do not use in pts with multiple
other medications as bile acid
sequestrants are notorious for
binding other medications,
particularly beta-blockers,
thiazides, digoxin, and warfarin

280
same as Cholestyramine same as Cholestyramine

281
same as Cholestyramine same as Cholestyramine

Itching, flushing and unpleasant

sensation of being warm.
Prostaglandin mediated - give aspirin
(blunts, but does not remove, this effect).
G.I. distress (may activate ulcers)
282
Elevates transaminase levels and may
(rarely) cause hepatitis
Glucose intolerance aggravates
diabetes
Inhibits urate secretion. Hyperuricemia in
20% of pts.

283 Rem: I am Thiazolidinedione, I can decreases

blood glucose, triglycerides, C-reactive protein
levels, and increases HDLs, what can you do?
 D E F

Relatively benign side-effects, particularly

compared to the g.i. effects of the bile-acid
binding resins. Angioneurotic edema.
Reversible change in liver function.
Like statins, if pushed to aggressively with
dose, may see myalgia/rhabdomyolysis
phenomena. The literature is somewhat
284 unclear on this point, but my reading is that
the incidence is less than with statins.
When combined with a statin, the
probability may be higher. Note, however,
that the most popular form of this drug
(Vytorin) is in a fixed dose combination with
simvastatin. On balance this is not like
combining a statin with a fibric acid drug,
which clearly has greatly enhanced Remember: Tim is all pissed at you because
prospects of rhabdomyolysis. your eating to much plantsterols (seeds) and
(Very low systemic toxicities because choleterol, so you say "Easy, Tim, I be donnin
majority of drug isolated to intestine) much betta" in a Jamacin accent

285

286
 D E F

287

GI distress is the most prominent adverse

effect of oral iron therapy (15 to 20% of
patients). Abd pain, n/v, or constipation
often lead to noncompliance. Although
small doses of iron or iron preparations with
delayed release may help somewhat, GI
SE are a major impediment to the effective Rem: (Deferoxamine) talk to da farrow cat to
treatment. save your kid from the iron overdose

288

Rem: the co-balla (Cyanocobalamin) flying a

B12 bomber (plane been around for a while =
long storage in body), but co-balla probably
shouldn't be flying it because of his neuro
damage
 D E F

289

290

291

292 Rem: Fill gas (Fil-gras-tim) in BEN's car so we

can go pick up some granulocytes (BEN -
basophil, eosinophil, neutrophil)

293

Rem: Sargent Slaughter (Sar-gramo-stim) will

stimulate BEN and macrophages to get back to
work
 D E F

294 Rem: Oprea thought that by being vegan

Fluid retention and must be used (Opre-l-vekin) she could get ride of her
cautiously in patients with CHF or cardiac thrombocytopenia, but instead she had fluid
arrythmias. This drug may harm the retension by eating those 3 carrots (3 carrots =
fetus and pregnant women. I-ll)

MC SE include myelosuppression
(leukopenia, thrombocytopenia, anemia),
GI symptoms (eg n/v, stomatitis, anorexia,
appetite disturbances), and dermatologic
toxicity (eg rashes, skin ulcerations, facial
erythema). Rarely (at high doses)
295 neurologic disturbances (eg drowsiness,
dizziness, HA, and convulsions, altered
renal function, alopecia). Mutagenic
potential is unknown, avoid when possible
in pregnant women. Causes
macrocytosis, may mask the incidental Rem: hydrated urine (hyrdoxy-urea), when
development of folic acid deficiency, give pissed on R to D 2 (ribonucleotide to
prophylactic folic acid deoxyribonucleotide) shuts him down
296

List
297

298
Rem: first generation sulfonylureas have
299
-amide

300
alcohol-induced flush!!
301
302
 D E F

303

Rem: use a cell phone (sul fon) to call

Hypoglycemic reactions, including coma
- caution in elderly patients with renal
failure and others predisposed to
hypoglycemia; HS rxn - many pts are
allergic to sulfa's
potassium to throw a insulin releasing party -
Pts with Type 1 DM, sulfa Sulfonylurea. Rem: 'ide' drugs are commonly
allergies, pregnant or nursing hypoglycemic agents Rem: (Glimepiride)
mothers, and significant Glee, my pride for doing so well with my new
hepatic or renal insufficiency. DM drug. Let's throw the insulin party

304
Hepatic insufficiency, sulfa
See Glimepiride allergies, pregnancy Rem: Glee (Glipizide) and ide

305
See Glimepiride See Glimepiride Rem: Glee (Glyburide) and ide

306

Adverse effects are comparable to

sulfonylureas but these drugs should be Rem: 'gli' and 'ide' drugs are commonly
used cautiously in the elderly and those hypoglycemic agents - but 'glinide' are Non-
with liver dysfunction. sulfonylurea secretagogues
Rem: 'gli' and 'ide' drugs are commonly
307 hypoglycemic agents - but 'glinide' are Non-
sulfonylurea secretagogues
 D E
308
Lactic acidosis!!; abdominal discomfort,
anorexia, nausea, metallic taste, and
diarrhea
309
flatulence, diarrhea and GI upset due to
undigested carbohydrate
310
311
moderate weight gain, edema and mild
anemia, all due at least partly to fluid
retention; can precipitate frank anemia.
Potential liver damage
312
See rosiglitazone
313
Hepatotoxic (monitor LFTs)
F
Metformin should not be
administered to patients with
renal impairment (CI if
>1.5mg/dL), hepatic disease, a
history of lactic acidosis,
cardiac failure, or chronic
hypoxic lung disease because
of the concern for the
development of lactic acidosis.
Rem: a car and bus (Acarbose) filled with
diabetic ketoacidosis, cirrhosis, people with explosive diarrhea, their splatter
inflammatory bowel disease, splattering their sugar lolly pops such that they
colonic ulcers, or partial don't want to eat them (inhibits glucose
intestinal obstruction. digestion)
Rem: the glitter zone (glitazone), everyone is
here in the nuclear gliter zone, sensitized to
insulin's hypnotic music - P-party!! (PPAR-) -
Heart dz and liver dz! the heart and liver weren't invited
Heart dz and liver dz!
Heart dz and liver dz!
 D E F

314
Risk of hypoglycemia and nausea. Other
side effects include decreased appetite,
vomiting, stomach pain, tiredness,
dizziness, or indigestion.
Rem: the new baby Amylin in the pram
(flatbottom boat or baby carrige, Pram-lintide)
is so fat it already has DM

315
Nausea, vomiting, diarrhea and upper
respiratory symptoms are the most Rem: I threw my ex in the tide (Ex-en-a-tide) to
common adverse effects. Incidents of drowned because of her glib tongue (GLP), that
hypoglycemia are relatively low. fat diabetic bitch
316

317

Rem: Sit the Ez that breaks down GLP by

punching, smashing it in the face (Sit-a-GLP,
SitaGLiPtin);
318
319
 D E F

320

Rem: Lis is a pro (Lis-pro) at having her ass

Lispro is associated with a lower risk of
hypoglycemia (than Regular insulin).
pulled apart for quick insulin insertion
Rem: use GLUT to (GLUT2) activate insulin
production at islets of Langerhans
Rem: use GLUT for (GLUT4) glucose (and aa)
transportation to muscle (and adipose)

321 Rem: pull her ass apart (as-part) and quickly

insert insulin (ultra-short-acting) - no do it faster
Rem: Lis got sick of her ass being rapidly
322 pulled apart so she glued it closed, now it
glissens (Glulisine)

323

324

325

326
 D E F

327

Rem: the diabetic glared at you for a very long

time (Glargine), he was very determined
(Detemir)
328
329
gs 330

331

332
Toxicity to thioamide drugs occur in 3-12%
of treated patients. The most common
adverse effect is a maculopapular pruritic
rash (super itchy!!). The most dangerous Rem: they are for (pro) piling (pyl) up the iodine
(potentially fatal) complication occurring in because drug blocks Ez that forms MIT, DIT,
0.3 0.6% of patients is agranulocytosis and thyronines. Rem: Theo Huxtable amist
(BM failure) heralded by a sore throat (thio-amide) all the trendies with ther peroxide
and fever. Goiterogen bleached hair (peroxidase)
 D E F

333 congenital scalp defects (aplasia cutis),

see propylthiouracil Pregnancy, see PTU extra note

334

335

336

337

338

339

340

341
Remember: Perchlorate prefers it makes active
Goitrogen receptors to chocolate than iodine
342
 D E F
Remember:: the orc tree had acromegaly so
343 was chopped down to prevent it from growing
(GH inhibiter) taller - Octreotide
Rem: a ginormous Peg (Pegvisomant) standing
344 on Camp bowie blocking traffic (blocks GH
receptors)

345

Remember: His/'Er breasts are gone, a vine

346 plugged up the leaky milk and took the breasts
away - Ergonovine
347

Bloating, Breast tenderness and uterine

bleeding.
348
Women who have an intact uterus must
take a progestin to avoid risk of
endometrial carcinoma.
Long term use increases risk of
thromboembolism and might increase risk
of breast cancer

349
Adverse effects. Hot flashes and leg
cramps. Also increase risk of
thromboembolic disorders.

Heartburn, esophageal irritation and reflux,

abdominal pain and diarrhea; To avoid GI
350 discomfort take orally after an overnight
fast with 8 oz of plain water; Calcium
supplements taken at the same time may Rem: drowned nate (Alen-dro-nate) in milk
interfere with the absorption of BPs. (Ca) because he is pro-osteoclast
351
352 mineralization defects
353
354
 D E F

355

356
Remember: flood (flud) the mineral mine

357 Remember: cortisol met Tyra and fell inhibited

-metyrapone

358 Remember: insulin dies so (dia zo) K channels

can live, K channels are open - Diazoxide

359

Vit D3 is converted to metabolites in the liver

360
T1/2 is relatively short due to poor binding
affinity with serum Vit D binding protein
(25 hydroxy-D3) and kidney (1,25 and 24, 25
dihydroxy D3) Rem: 1 liver and one number
one type (25 hydroxy-D3), 2 kidneys and 2
numbers and 2 types (1,25 and 24, 25
dihydroxy D3)

361

362
363
Dry skin and chelitis!! Pseudotumor
cerebri, vision impairment, HA, myalgias,
364 arthralgias; also BM suppresion, Teratogen - must confirm pt is
hepatotoxicity, hypertriglyceridemia and not pregnant with two negative
pancreatitis; depression and suicide pregnancy tests
 D E F
365

gs
366

367

368 Exceeding the recommended

dosage will intensify side effects,
SE more apparent by the oral route: but a greater danger is the
hypotension, muscle tremors, (relflex) tendency of patients to continue HS type I (Allergic Asthma): Early phase:
tachycardia, hypokalemia (low [K+] in self-medication during periods Allergen-IgE mediated release of preformed
blood), see extra notes. Effects on blood when their symptoms are mediators causes bronchospasm and
glucose are variable. escalating. To avoid a medical infiltration of more mast cells.
Caution in hyperthyroidism, DM, emergency, patients should Late phase: hours later, eosinophils,
cardiovascular disorders be encouraged to seek neutrophils, and other inflammatory cells can
Skeletal Muscle Tremors (2 receptors on medical attention as soon as cause reactive hyperemia, edema, cellular
skeletal muscles mediate increased energy possible after they detect a inflammation, bronchospasm.
production, excess high energy compounds marked decline in the efficacy Repeated exposure: heightened bronchial
are reduced by muscle contraction - of their usual therapeutic reactivity to specific and nonspecific stimuli.
tremors)
see albuterol, fewer effects on the heart regimen.
rhythm (ie tachyarrhythmia) and fewer
369
occurrences of tremors
370 see albuterol

371
see albuterol, use with caution in pts with Remember: Terbutaline - tear a butt to help
CHF or history of arrhythmias person breath and delay pregnancy
 D E F

372

see albuterol, ipratropium

373 Rem: Bite old turd role (Bit-ol-ter-ol), bad taste,

but opens your lungs for longer than albuterol;
Bitolterol has a disagreeable taste. best to eat turd when riding a colt (colterol)

374 Salmeterol - a salmon swimming slowing in

lungs, it is wearing a night cap (used for
nighttime asthma)

375 Rem: for motor roles (Formoterol), put COPD

and exersize-induced asthma pt in charge of
vehicle maitenance, will role the car fo-sho

376

377 Typically, epinephrine is administered by s.c.

injection. It causes vasoconstriction that limits
edema and swelling of the upper airways,
produces bronchodilation, and inhibits mediator
release from mast cells.

378
379

380

IV not recommended for

381 treatment of asthma because of
risk of MI
 D E F

382
Quaternary compounds can block nicotinic
receptors and may have ganglion or
neuromuscular blocking action
Overdose with quaternary more likely to be
fatal because of neuromuscular
blockade.
383
see ipratropium
a rat from Ip was rowing his boat with four
paddles (quaternary) because he thought the
sea air would open his lungs (reverse bronchial
constriction), his boat was overflowing with
sizziling mushrooms
Tio is spanish for uncle, the uncle of
ipratropium who tries to spit, but sizzling
mushrooms in his mouth wont let him

Theophylline should only be used where

384 methods to periodically measure blood
levels are available (hepatic metabolism
varies amongst pts). Normal plasma
concentrations are 5-20 mg/L. Anorexia,
nausea, vomiting, abdominal
discomfort, headache, and anxiety often
occur if blood levels reach 15 mg/L.
Higher drug levels may cause seizures or
arrhythmias.

385

Corticosteroids
386
 D E F

Potential Adverse Effects Associated with

Inhaled Glucocorticoids, see
corticosteroids for more complete list
a. Hypothalamic-pituitary-adrenal axis
suppression - low risks until high dosages
are used.
b. Bone resorption/ osteoporosis/
asseptic necrosis of femoral head
387 c. Effects on carbohydrate and lipid
metabolism - minor risks
d. Cataracts and skin thinning - dose-
related
e. Purpura - dose-related
f. Dysphonia - usually resolves with no
consequences
g. Candidiasis - incidence reduced with
use of a spacer device and rinsing mouth Be close to the "method zone"
after dosing. (Beclomethasone) for greatest asthma relief,
h. Growth retardation - of concern when that what all the roid bodybuilders do; no not
high doses used in children. blow (beclo), inhale

388
See corticosteroid SE

389
See corticosteroid SE

390
See corticosteroid SE

391
Budda is so nice (Budesonide) to alleve pt of
See corticosteroid SE allergic/sesonal rhinitis
flew to kazakhstan (Flu-ti-casone propionate) to
392 apropriate drugs for my rhino (seasonal/allergic
See corticosteroid SE rhinitis)
mo' meat is on (Mometasone) this rhino
393 (allergic/seasonal rhinitis), let your kid ride on
See corticosteroid SE his back (no growth retardation)
 D E F

394

See corticosteroid SE
395 See corticosteroid SE
396 See corticosteroid SE

397

398

399

Conan saying "Crom" (his god) while bear

hugging a mast cell, preventing release of
Essentially no local or systemic toxicity. histamine

400 Need a crow mill (Ned-o-cro-mil) to make a

potent (than cromlyn) asthmatic liquor, aged at
Adverse effects are infrequent and least 12yrs, out of ground up crows - the drink
generally mild. of Conan - the Mead of Crom

401
 D E F

Rebound congestion is a problem with

these agents; insomnia, excitability,
402 headache, nervousness, palpitations,
tachycardia, arrhythmia, hypertension,
nausea, vomiting, and urinary retention;
Used topically they are likely to cause
systemic effects; Rhinitis medicamentosa
Rebound congestion is a problem with
403
these agents.

404

405
Dyspepsia (indigestion) is the most
common side effect. Liver toxicity has
been noted in some patients and the drugs
are contraindicated in patients with
abnormal liver function.
lukast - inhibits leukotriens. Monte is a young
boy (6-12yo) with asprin triggered asthma, so
he takes lukast but gets a stomach ache
instead.

406
see Montelukast

407

408
Rem: fence in the throat guana (sputum),
delivered from throat (Gua-i-fenesin)

409
Because of the potential for adverse effects
(?), other agents are usually preferred.
 D E F

410
causes irritation

411

Rem: re-combine mucous with a cystic fibrosis

pt and get a depolymerized pt - they are broken
up into tinny bits sugar (polysaccharide)

Adverse effects (Most common with

codeine)
1. CNS: euphoria, depression of respiratory
and vasomotor centers
412
2. GI: constipation, nausea, vomiting 3.
GU: urinary hesitancy or retention 4. Drug
Interactions: additive CNS depression with
sedative hypnotics, phenothiazines, and
tricyclic antidepressants. 5. Opioid
dependence supported by codeine

413 Rem: give the damn dextrose (sugar) to the

damn meth orphan (Dextro-meth-orphan) so
he'll stop his damn non-productive coughing, so
Less constipation than codeine what if its actually opium

Rem: Ben knocks on Nate's taint

(Benoxonatate) which happens to be in the
414 back of his mouth at the pharynx, numbing it
with locally so he doesn't cough (antihistamine
effects), Nates pissed, cause its not opium, its
non-opium

The General made non-history (antihistamine),

415 when he drove his army green hummer H1 and
died into a fire-hydrant (Di-phen-hydramine)
but he wasn't coughing
The rich bastard ranted to Dean (ranitidine),
416 because some ran into his H2 hummer (H2
histamine)
 D E F
intervention
417
418

419
local skin irritation

420

421
nausea, vomiting, gas, headache and Rem: I am very inclined to stop smoking (Var-
insomnia. enicline)

ials
422

423 Rem: I saw Red Pyre (Isoniazid, rifampin,

Elevated liver enzymes and hepatitis (risk
increases with age); peripheral neuritis
(treat with pyridoxine HCL (vit B6)); drug
interactions
Fatal OD
pyrazinamid) buring a liver (hepatitis); "I son, I
am a TB lung zit, pop me" (I son I a zid); Major
Cytochrome P-450 inhibitors: FREaCKI
Grapefruit gets stuck in Ez- Ketoconazole,
Isoniazid, Cimetidine, Fluoxetine, Ritonavir,
Erthyromycin, Grapefruit

Can cause body secretions to turn orange

(harmless); rifampin strongly induces
cytochrome P450 enzymes which
424 increases the elimination rates of
numerous other drugs (warfarin,
glucocorticoids, narcotics, oral
antideabetics, estrogen, decrease effect of
contraceptives); hepatitis, fever,
thrombocytopenia
Rem: Rifampin - think Red (Red body fluids,
also inhibits DNA dependent-RNA polyermase);
Rem: orange flavored TB rye (ri) toast; Rem:
RC PP induces P450 (rifampin,
carbamazepine, phenobarbital, phenytoin)

425 Rem: rif with a button, an AIDS pt jammin on

the guitar, playing a happy song cause his TB
is undercontrol
 D E F
426

SPIRE TB (streptomycin (2nd), pyrazinamide

427 Can cause optic neuritis (may present as (1st), isonazid (1st), rifampin (1st), ethambutol
painful loss of vision), red-green color (2nd); Rem: AM (etham) radio or TB on the
blindness radio, TV shows only red and green colors
GI intolerance; hyperuricemia; hepatic
428
effects

429 Auditory, vestibular, and renal effects,

eosinophilia; hypokalemia;
hypomagnesemia
430
431
432

nts
433

Severe side effects

Delayed nephrotoxicity major dose-
limiting toxicity, Renal hypokalemia
(increased CRT, BUN)
Acute reaction to IV - fever, chills,
434 headache, nausea, vomiting, hypotension,
tachypnea
Weight loss, malaise, anemia,
thrombocytopenia and mild leukopenia can
occur
Usu given with steroid, heparin, and
antihistamine to reduce SE; usu give KCl
supplement
potent inhibitors of cytochrome P450
(CYP3A4) and can lead to unacceptably
435 high levels of co-administered drugs that
are normally metabolized by CYP3A4
(especially some HIV drugs)
HIV pts (may cause BM
436
suppression)

437

438
 D E F
439

440

441
442
Pregnancy

443
444

ts 445

Lady has a man to dine (amantidine) with who

446 keeps trying to undress but she keeps stopping
him (prevents uncoating) so she dont get
CNS SE in elderly pregnant (teratogenic)

447
CNS SE in elderly

448

449

450

anemia teratogenic

451

Nausea, diarrhea, headache, renal

insufficiency, neurologic toxicity!
 D E F
452
453

454

455 Rem: She had to quit the mods cause their

leader gave her HPV (Imi-qui-mod), she's got
to pay the toll when she rides her scooter
456

es 457

Side Effects: Sedation most common

(less prominent with newer drugs); Other
CNS effects: dizziness, tinnitus,
nervousness, insomnia, fatigue, blurred
vision; GI: nausea, vomiting, loss of
appetite; Antimuscarinic; dryness of
458
mouth, nasal passages; urinary retention,
frequency; Hypersensitivity reactions
Poisoning:
1. Central effects: child excitation;
hallucinations, ataxia, incoordination and
convulsions
2. Fixed dilated pupils with flushed face Rem: The General made non-history
and fever are common (antihistamine), when he drove his army green
3. Terminally there is deepening coma with hummer H1 and died into a fire-hydrant (Di-
cardiorespiratory collapse and death phen-hydramine)but he wasn't coughing
Rem: men die from saying hi to nate (Di-men-
459 see diphenhydramine; Marked sedation; hydri-nate) because they have runny noses by
high antimuscarinic activity choking on mushrooms
Rem: 'zines' are H1 antagonists with slight
460 sedation; anti-motion sickness activity; and no
see diphenhydramine; Slight sedation antimuscarinic activity

461
see diphenhydramine
 D E F

462
see diphenhydramine

463
sometimes leaving a bitter taste, and
sometimes causing sedation.
Rem: has a lasting (az-e-lastine) effect when
At very high doses (280x), is squirt this up the rhino's nose (allergic rhinits),
teratogenic in mice; dont use but he gets pissed cause the bitter taste in his
during pregnancy. mouth

464 Rem: stick the chloride (Chlor-phen-ir-amine)

down the histamines ear to burn it so bad its
Slight sedation nose stops running

Rem: a pro method magazine that has photos

465 of skaters pulling methods with snot pooring
Marked sedation; antiemetic and out (rhinitis), splattering on the camera (camera
antimuscarinic activity. man vomits up mushrooms - muscarinic SE)

466

467

free of sedative effects; decreased risk of

arrhythmia (e.g., Terfenadine (Seldane) and
Astemizole (Hismanal)).

468
Rem: Lo-ratidine is lo-nger actingin 2nd gen H1
469
little sedation. antagonist

470
 D E F

Adverse Effects - low incidence

Antiandrogenic effects (cimetidine)
gynecomastia, galactorrhea
471
GI - constipation, nausea/vomiting,
diarrhea (cimetidine)
CNS - headache, dizziness, hallucinations
Hematologic - agranulocytosis,
thrombocytopenia, etc.
liver toxicity Rem: all of the H2 antagonist have 'tidine'
The rich bastard ranted to dean (ranitidine),
472 because some ran into his H2 hummer (H2
see cimetidine histamine)

473
see cimetidine

474
see cimetidine
475

pathomimetics):
476
amine vs. non-Catecholamine, Direct vs. indirect acting, Re-uptake inhibitors)

477

Increases BP (arterioles)
Expect reflex bradycardia. Remember: phenylephrine is a picky hot bitch
Increases cardiac return (veins) who feels (phenyl) out ephrine (who is similar
to epinephrine) and only takes his 1 qualities.
 D E F

478

Contraindications
1. Hypertension
2. Shock (non-anaphylactic??)
3. Hyperthyroidism - E may have
enhanced cardivascular actions
in pt with hyperthyroidism. If E
1. Arrhythmias - particularly in conjunction is required in such an indivildual,
with the gaseous anesthetic halothane; E the dose must be reduced. The
increases the frequency of ectopic beats in mechanism appears to involve
Purkinje fibers by accelerating spontaneous increased production of
depolarization. adrenergic receptors on the
2. Cerebral hemorrhage vasculature of the hyperthyroid
3. Necrosis distal to site of injection individual leading to a Rem: I had a cat named NED
(potential problem with infiltration) hypersensitive response. (Catecholamines; NE, E, Dopamine) - all
4. CNS effects: anxiety, headache 4. Angina pectoris derived from tyrosine (which is derived from
phenylalanine)

479
slow, forceful (pounding) heart beat,
elevated BP, anxiety, headache.
 D E F

480

Common: tachycardia, flushing, headache,

rapid pounding heart.
Serious: arrhythmias, angina

Usual side effects more apparent by the

oral route: hypotension, muscle tremors,
tachycardia, hypokalemia (low [K+] in
blood). Effects on blood glucose are
481
variable.
Skeletal Muscle Tremors (2 receptors on
skeletal muscles mediate increased energy Remember: Terbutaline - tearing a butt to help
production, excess high energy compounds person breath and delay pregnancy; Salmeterol
are reduced by muscle contraction - - a salmon swimming slowing in someones
tremors) lungs
Skeletal Muscle Tremors (2 receptors on
skeletal muscles mediate increased energy
482 production, excess high energy compounds
are reduced by muscle contraction - Give mother ritodrine to prevent early arrival of
tremors) ritoline (sp?) kid

Potential for hypertensive crisis in patients

on MAO inhibitors.
Tyramine is found in many foods (red wine,
aged cheeses, peanuts, etc)
483 It normally is subjected to such a large first-
pass effect by MAO in the gut and liver that
it never enters the circulation
Watch out in pts taking MAO inhibitors.
A classic drug interaction. Disastrous
hypertension.

485
 D E F

Tachycardia (worse than dobutamine)

486 At higher doses, increase in systemic
vasuclar resistance; mechanism is alpha
agonist
Dobutamine is generally a better choice

487
Atrial fibrillation; Tachycardia with possible
increase in myocardial oxygen
consumption (angina)

Side effects:
488 insomnia, anxiety, arrhythmias, nausea,
vomiting
Toxicity:
Acute: convulsions, coma, death
Chronic: abnormal mental state (paranoia),
weight loss, psychotic reactions.

489 Like amphetamine (dopamine mechanism),

ephedrine has abuse potential; now
banned in the U.S.

Oral decongestants have a preolonged

490 duraton of action but may cause more
systemic effects, including nervousness,
excitability, restlessness, and insomnia
 D E F

491 Side-Effects: Rebound edema (typically

happens with prolonged or excessive-dose
use). Clears in 24-48 hrs.
Toxicities: Necrosis of the nasal tissue.
(This occurs only with gross overuse,
usually in combination with cocaine abuse)
492

emicals
493
tivity or of sympathomimetic drugs

CNS: drowsiness/sedation, dry mouth,

494 depression
Rebound hypertension (from abrupt
discontinued oral administration, can elicit
hypertensive crisis, common board Remember: the clone goes into the bank to
question) make a withdrawl so he can by cigarettes,
Do not give with beta blocker because cocaine, heroine, (used to treat drug withdrawl)
excessive bradycardia and he is agonizing over his need (alpha 2
Inhibits insulin secretion agonist)

495 May cause autoimmune hemolytic Remember: give meth and dopa to pregnant
anemia and SLE woman with high bp
496

Unacceptable side effects:

CNS -- depression!!, nightmares (dont
use if history of depression)
497 nasal stuffiness
unopposed parasympathetic activity: Remember: red (re) serpent/snake (serpine)
miosis, bradycardia, aggravation of ulcers, Do not give with beta blocker, crawls into your brain and drains the body of
diarrhea may cause excessive monoamine causing depression and
fluid retention bradycardia nightmares
 D E F

498 Remember: Adrenergic guana/poop

(guanethidine) got everywhere, except your
Na+ and water retention are marked (given head (CNS) - sucks the happiness from
with diuretic) NEbody (NE depletion, depression)

499

500

g Agents
501

502

Orthostatic hypotension
Tachycardia
Combined alpha blocking and
muscarinic/histamine agonist actions Remember: the phens are hens that are bitchy
Diarrhea and charge a tole to all the alpha males that is
Nausea too steep for them to pay, so they keep them
out/block them.
 D E F

503
1. Cardiac. Reflex tachycardia.
Reducing BP causes sympathetic
activation. Because 2 receptors on
adrenergic nerves are blocked, this further
increases NE release at the heart, where Remember: Phen is Hen and
NE can act on beta-1 receptors. they're bitchy birds that block all
2. CNS. Lipophilic agent that crosses blood alpha's, and the word is
brain barrier. impressive -
Nausea, vomiting and weakness may be PhenoxyBENZAMINE -
signs of non-specific CNS effects. showing its strength to
3. Others: miosis, inhibition of ejaculation, irreversibly bind to the alpha
stuffy nose. receptors covalently
 D E
1. AV block!!
2. Severe Bradycardia
3. Bronchospasm and respiratory
distress in asthma, COPD!!!
4. Exacerbation of acute CHF and
pulmonary edema!!
504 5. CNS effects: dizziness, tiredness,
nausea, depression, vivid dreams (&
nightmares)
6. Impotence
7. Constipation, diarrhea
8. Severe reactions: rash, purpura, fever. Cardiogenic shock
9. Hypokalemia
Chronic use: Hypertriglyceridemia,
increased VLDL and decreased HDL
cholesterol; 28% increased risk of
developing NIDDM!!; rebound angina
Propranolol Drug Interactions: Additive degree heart block.
with hypotensive agents; Prolongs
hypoglycemia in patients taking
hypoglycemic agents. Mask signs of
hypoglycemia & mask symptoms of
hyperthyroidism
505
506
F
"KISS and KICK till you're SICK of SEX"
(QISSS and QIQ till you're SIQ of SQS) = Gq,
Gi, or Gs. Receptors are in alphabetical order,
starting twice:
alpha1=Q
alpha2=I
beta1=S
beta2=S
beta3=S
M1=Q
M2=I
M3=Q
Contraindications: D1=S
Asthma D2=I
Obstructive pulmonary dz H1=Q
H2=S
Acute treatment of heart V1=Q
failure (contrast this to use of V2=S
beta blockers in management of Rem: A cutesie (A-q-C; alpha1 is a Gq protein
stable heart failure) causing phospholipase C to make PIP2 which
3rd degree heart block, 2nd forms IP3 (which increases Ca from ER) and
DAG (which activates Protein Kinase C)
Contraindications with Rem: drugs that are inotropic: GAP (gycosides
unstable angina are reactive (cardiac), adreneroreceptor antagonists,
airway disease, sinus node phosphodiesterase inhibitors) - slave drivers at
dysfunction or AV block, and the GAP whipping their employees to work hard
severe heart failure. (increasing force of contraction)
Remember: propranolol says to nadolol that it
has to keep working, and nadolol says na-doie
Timmy from south park uses for his glacoma
 D E F

Dyslipidemia
AV block!!
All 1-selective drugs lose selectivity at
high doses.
507
Use very cautiously if at all in patients with
reactive (asthma) airways.
Symptomatic hypotension common initially
Fluid retention: may have to increase
diuretics remember: lol blocks beta, me too (meto)
Heart failure may worsen initially selective for beta 1
Rem: Aten, very selective for who he is a god
of (beta 1), he is a (long lasting) god; Rem:
508 beta1 blockers is "A BEAM" straight to the
heart (cardioselective; acebutolol, betaxolol,
esmolol, atenolol, metoprolol)

509 They must be used very cautiously if at all

in patients with reactive (asthma) airways.

All 1-selective drugs lose selectivity at

high doses.
Use very cautiously if at all in patients with
510 reactive (asthma) airways.
Symptomatic hypotension common initially
Fluid retention: may have to increase
diuretics Remember: biso-prolol is busy taking care of
Heart failure may worsen initially CHF

511

eskomos are short, especially metoprolol

eskomos

512

May exacerbate angina ace but means 1 but = 1 beta

 D E F

513

pin doll (pindolol) of propranol, not as effective

May exacerbate angina as the full blow thing

514

shopping cart partially full of propranolol

Generally reflex tachycardia and orthostatic

hypotension are less prevalent than with
non-selective alpha blockers.
Syncope is noted when first administered
515 in a large group of patients, first-dose
hypotension (can be severe), caution
patients to avoid sudden postural
changes.
Increased risk for aggravating or causing
CHF
Nasal congestion
Salt and water retention (must use diuretic)
Orthostatic hypotension, including chronic sin is alpha blocker, prazosin is short word so
fatigue and light headedness only blocks the 1

516
Note: non-selective alpha blockers have
essentially no use in essential hypertension
(see extra note at phentolamine).
 D E F

517

518

520
Orthostatic hypotension - alpha blocking
effects make this more likely than with pure
beta blockers contraindication similar to
Others side effects are like propranolol. propranolol

Orthostatic hypotension (and see

propranolol side effects)
Use very cautiously if at all in patients with
521 reactive (asthma) airways.
Fluid retention: may have to increase
diuretics contraindication similar to Rem: Carving with a dildo, which cut the alpha
Heart failure may worsen initially propranolol and beta receptors off
522

Receptor Agonists):
523 i.e., drugs which exert their effects largely via activation of peripheral
tic fibers
c & smooth muscle, gland cells and nerve terminals. (Notice eccrine sweat gland
ors).

Contraindications for
cholinoceptor agonist drugs
Potential Side Effects of Muscarinic Bronchial asthma (constricts
Agonists bronchiols)
Bradycardia Urinary obstruction (force urine
524 Syncope (caused by asystole) against ob)
Orthostatic hypotension Peptic ulcer (already too much
Cardiac dysrhythmias acid secr.)
Gut or urinary urgency Gastrointestinal lesion or
Diaphoretic effects (sweating) obstruction
Sialogogic effects (salivation) Hyperthyroidism (precipitates
Abdominal cramping arhythmia)
Coronary insufficiency (would
slow heart further)
 D E F

525 a pine tree pealing a car open to release its

see muscarine aqueous fluid (mushrooms flooding in aqueous
See Muscarin side effects contraindications fluid)-pilocarpine to treat glacoma.

526

see muscarine
See Muscarin side effects contraindications

527
See Muscarin side effects, also no nicotinic see muscarine Beth-ann was agonizing over lossing her
effect contraindications boyfriend, who started dating a mushroom

528 see muscarine

See Muscarin side effects contraindications

529

530
see muscarine s'have (cev) you eat a melon (meline) for you
See Muscarin side effects contraindications dry mouth.

531
see muscarine Remember: the method (Metha) to diagnose
See Muscarin side effects contraindications asthama.
532

ceptor antagonist):
533
er muscarinic agonists. Antimuscarinics exert their effects through competitive
inic receptors.
 D E
534
Toxicity of Atropine-like drugs :
Xerostomia, constipation, Urinary
retention, hyperthermia, Mydriasis,
headache, Blurred vision, Dizziness
Flushing, dry skin, Excitement Heart
palpitation, Mental confusion, memory loss,
hallucinations
Contraindications for Antimuscarinics:
535 Glaucoma
Prostatic hypertrophy
Toxicity more severe in children
Quaternary compounds can block nicotinic
receptors and may have ganglion or
536 neuromuscular blocking action
Overdose with quaternary more likely to
be fatal because of neuromuscular
blockade.
F
Contraindications for
Antimuscarinics: Glaucoma
Prostatic hypertrophy
Toxicity more severe in children
Contraindications for
Antimuscarinics: Glaucoma
Prostatic hypertrophy A skull (sco) spining on a pole (pol), to signify
Toxicity more severe in children motion sickness
a rat from Ip was rowing his boat with four
Contraindications for paddles (quaternary) because he thought the
Antimuscarinics: Glaucoma, sea air would open his lungs (reverse bronchial
Prostatic hypertrophy, Toxicity constriction), his boat was overflowing with
more severe in children sizziling mushrooms
 D E F

Quaternary compounds can block nicotinic

receptors and may have ganglion or
537 neuromuscular blocking action
Overdose with quaternary more likely to
be fatal because of neuromuscular
blockade.
Contraindications for
Antimuscarinics: Glaucoma, Tio is spanish for uncle, the uncle of
Prostatic hypertrophy, Toxicity ipratropium who tries to spit, but sizzling
more severe in children mushrooms in his mouth wont let him

538
Contraindications for
Antimuscarinics: Glaucoma
Prostatic hypertrophy
Toxicity more severe in children
bunch of ladies standing in line picketing (pro)
for pans and have 4 (quaternary) pans each
that are frying mushrooms (muscarinic
antagonist)

Contraindications for
539 Antimuscarinics: Glaucoma
Prostatic hypertrophy
Toxicity more severe in children

540

541

542

543

544
remember: can drive home (hom) after
contraindicated in pt with BPH ophthamologist treats eye with hom-atropine

545 A pen got caught in the cycle spoke and fell

because at eye doc and now too late
 D E F

546
Got eyes checked to see well in the tropics
547

nemimetics):
548
o accumulate, bind to and stimulate postsynaptic cholinergic receptors. Thus, they

549

predictable (parasympathetic overactivity)

plus CNS stimulation followed by coma.

550

Toxicities are readily predictable from

knowing distribution of AChE. Note that
drug does not cross into the CNS.
 D E F

551

Rem: Ed's on the phone to give you the

Toxicities are limited because of brief diagnosis (MG) and he was a little tense
duration of action and poor penetration to (tensilon test) so he had a couple of drinks
CNS (alchohol)
Remember: a pirate-door (Pyridostigmine)
552 stuck open for a long time (long lasting) on my
thenia's ass (myasthenia gravis)

In overdose, initial signs usually relate to

parasympathetic overactivity. If the dose
is high enough, death occurs via
553 asphyxiation due to muscle paralysis. If the
victim survives these initial insults, a variety
of CNS and ANS signs may occur until
recovery or death.
Treatment (for organophosphate
posioning): Support respiration; Atropine
"heroic doses" (muscarinic receptor
antagonist); Cholinesterase reactivator
pralidoxime (2-PAM)

554

Side effects: weakness, dizziness,

headache, diplopia, nausea, tachycardia.
 D E F
bitors
555

556

557

558

559

Rem: the city of LA is poison (lead, arsenic),

560 would die there, murder capitol (di-mercaprol
tx) of the West if without dimercaprol (and
penicillamine)

561

562
Rem: 0ligomycin inhibits the F0

563 Rem: the nitro speed the e- chain train so fast,

it popped off its track and slammed through the
wall (Di-nitro-phenol; punches holes in the
membrane)
564
565 Rem: tx with De-fer-oxamne (ferrous = iron)

566
Rem: LEAD - EDTA
567
568

ng drugs:
569
olinergic neurotransmission and produce muscle paralysis.
 D E F

1. Blockade of ganglionic nicotinic

receptors (NN) contributing to hypotension
(Tubocurarine)
570
2. Release of histamine (also resulting in
hypotension) (tubocurarine, mivacurium)
Tubocurarine: Toxicologic effects
Apnea
bronchial constriction
cardiovascular collapse
Treatment
neostigmine, edrophonium Notice 'cur' in middle of all non-depolarizing
artificial respiration neuromuscular blocking drugs names

571
Release of histamine (also resulting in
hypotension) (tubocurarine, mivacurium)

572

573

574 Block of cardiac muscarinic receptors

(tachycardia)(pancuronium)
 D E F

575
Depolarizing blocker (succinylcholine)
(effects predictable based on similarity to
acetylcholine)
1. Stimulates SA node muscarinic
receptors and ganglionic nicotinic receptors
and may produce various cardiac
arrhythmias.
2. Low doses produce negative
chronotropic effect (blocked by atropine)
whereas higher doses may produce
positive inotropic and chronotropic effects Psuedocholinesterase
via activation of ganglia. deficiency - idosyncratic apnea
Malignant hyperthermia, see extra notes (monogenetic response) (this is
Hyperkalemia (succinylcholine promote K not predictable); Malignant
efflux from muscle cells) hyperthermia

576
Amazonian Indian arrow poisons

577
puffer fish has needles filled with lidocaine
578
579
580
581
582

583 Rem: Ester took cocaine with Ben, who says

he's gonna Professionally inject Tetrado-fish
with Cloro (Spanish for Chlorine)
584
 D E F
585
586
587
588
Puffer fish gets caught in the Na channel

589 Frog sends his bat which rakes your back,

opening your Na+ channels and parylising you
590
591 Vesam blocks transports to vesicle

592

593

594
Remember: an blackwidow storm
595
(acetylcholine storm)
Beavis saying "bungaro" with a smoke (nicotine
596
receptor) as he is bitten by a snake

597

598
599

600 cardiac arrythmias, or in

situations related to high Rem: drugs that cause hepatic necrosis: "Very
Malignant hyperthermia; lethal hepatitis catecholamine levels such as Angry Hepatocytes" - Valproic acid,
(hapten mech) pheochromocytoma Acetaminophen, Halothane
601

Antagonists
602
 D E F

603

Most opioids have an abuse potential.

General rule the greater the efficacy
against pain, the higher potential for abuse

604

605

606

607
 D E F

Rem: FM (MM) radio HErOine plays musak

(Fentanyl, Morphine, Meperidine, Methadone,
Heroine - all High Efficacy Opiods - mu
608
receptors)
Rem: for tx of acute MI - MONA B (Morphine,
O2, Nitrates, Aspirin, and Beta Blockers); when
MI pt discharged - ABC2 (Aspirin, Beta-blocker,
Captopril (ACEI) and Cholesterol-lowering
See extra notes!! drugs

609 Rem: "Me pear I dine on (prickly pear, Me-per-

Metabolites can cause seizures!! See e-dine) caused me to go into seizures, and me
extra notes lips to go numb (analgesia)," says the pirate

610

See extra notes

Rem: Fentanyl - Fat (lipid soluble), Rem: a fat
611 tan man with a big punch (the blow causes the
If given IV can quickly cause truncal receiver to go stiff (truncal rigidity) like a
rigidity; see extra notes cartoon)

612
Schedule 1
Rem: Bo tore his flannel (Bu-tor-phanol) in his
613 state of dysphoria after Luke was capped
Dysphoria (kappa agonists) Schedule 4 (kappa), trying to be a HErO

Rem: Bufred (Nal-buph-ine) kapped the surgen

because he kept changing the musak channel
614 (antagonist of mu receptor). Rem: if you
kap(pa) someone, they aren't going to have
respiratory distress (cause their dead - ghost -
Dysphoria (kappa agonists) Schedule 4 dysphoria/disassociation)
 D E F

615

Nausea and vomiting

616

Rem: drugie Limbaugh

Rem: the drug dealer was pent up in jail from
617 the sin of kapping his girlfriend, but only
partially blowing her mutha f&#ckin face off
(Pent-azo-cine; mu partial agonist)

618
Abuse potential is higher than analgesia Rem: a pox on any physician who recommends
potential propoxyphene

619
Not readily reversed by an opioid
antagonist (e.g., naloxone); difficult to
reverse respiratory depression
Rem: give Buprenorphine to the orphine to
treat his drug habit, but only give him a partial
dose (partial mu agonist) cause he's weak
(LEO)

620

Seizures epilepsy
 D E F

621
Non mu receptor action may cause
unpleasant side effects and limit abuse
potential (ceiling of efficacy due to sigma?
mediated SE)

622

Prolongs fever in pts with shigellosis, toxic
megacolon in pts with C. difficile; and HUS
in children infected with Shiga toxin-
producing E. coli. Should be avoided in pts
with bloody diarrhea
Rem: the pt took Loperamide and is now
lopping around from the opioid (opioids work at
the M/D receptors, mu and delta); or Rem: (the)
l'opera makes you slow, opiods make one lop;
lopping amide the diarrhea in the streets

623 Rem: Dip the ox and hen in a vat of opium so

they stop with their diarrhea (Dip-hen-ox-ylate)
Rem: dive in (Dif-en-oxin) the opioid haze; or
624
Rem: dip ox (dif-en-ox-in) in opium vate

625
Schedule II

626
Precipitate withdrawal symptoms on
individuals dependent on mu agonists
(chronic users of opioids)

627

628
 D E F

629
CNS: drowsiness, dry mouth, depression
Rebound hypertension (from abrupt
discontinued oral administration, can elicit
hypertensive crisis, common board Rem: the clone goes into the bank to make a
question) withdrawal so he can buy cigarettes, cocaine,
Do not give with beta blocker because heroine, (used to treat drug withdrawl) and he
excessive bradycardia is agonizing over his need (alpha 2 agonist)

630

631
Less constipation than codeine
632

& Gout
633

s 634

Well tolerated but toxicities are numerous

and include ocular (most dangerous)
635 inclusing corneal deposits, extraocular
muscular weakness, loss of accomodation,
and retinopathy with may lead to Rem: got hydrochloride in your eye and now
irreversible vision loss you're blind (Hydrochloroquine, SE)
 D E F

Nausea & mucosal (oral & GI, aka

stomatitis) ulcers are the MC SE
observed at the doses used for treating RA;
At higher doses or with longer-term therapy,
severe depression of white blood cell
count (bone marrow depression), liver
636 cirrhosis, pneumonia-like syndrome
(pneumonitis!!) renal toxicity,
osteoporosis, & alopecia can develop.
Most of these SE are reversible upon
termination of the drug; however, the
pneumonitis does not necessarily improve
when methotrexate is stopped. Milder than Rem: Me so tricky/tricksie (Methotrexate), I
at chemo therapy range doses and convinced cancer to die by giving it a
compliance is higher as compared to water/folate reduction sauce (dihydrofolate
other medications, so has the highest reductase) over its fibrotic lung dinner, but
possibility of still being used after 5 years Leucovorin came to its recue
Elevated liver enzymes (monitor liver Ez); Rem: "Le flu no mide" is translated the flying of
637 other toxicities are related to suppression no mind, meaning the RA pt figuratively flew
of fast-turnover cells (GI problems, when leflunomide stopped their arthritis, and as
alopecia) he flew, so to did his liver Ez elevate

Rem: Sal farting sulfer cause relief to his UC

(sulf-a-sal-azine); 5-ASA compound -
638 sulfASAlazine; Rem: Put the RA pt in a relaxing
sulfur bath, with a inflammatory bowel
magazine to read, easing their joint pain (Sulfa-
Hypersensitivity reaction to sulfa drugs sal-azine); hope that it is not so relaxing that
and mild gi problems they shit the hot tube (IBD)

639
Rem: take a bat and beat the T cells 80 to 86
times, to stop them (A-baT-acept blocks
CD80/86) from harming the RA pt; but a COPD
pt jumps you first smashing the back of your
COPD as it can make it worse head with his O2 tank (COPD contraindicated)
 D E
640 Flu like symptoms, and occasional
profound reactions: breathing problems,
cardiac rhythm disturbances, cardiogenic
shock most of which occur after first dose
641
URI, and since it is chimeric mouse/human
antibody immunological reaction may
occur; drug induced-lupus
642
long term safety concerns still an issue
643
644 Generally well tolerated; Injection site
reactions, pneumonia at a higer rate, when
combined with TNF alpha inhibitor, high
incidence of severe infection seen
645
Expensive and renal toxicity
646 Bone marrow suppresion (pancytopenia)
and heaptotoxicity; allopurinol increases
levels
F
Rem: wear your tux (Rituximab) when you
diffuse the B-bomb (Diffuse Large B Cell
Lymphoma); with it diffused you can then get
back to the party with your hot 20yo RA date
(who has a flu, lots of snot and breaths loud
through her nose) (CD20, flu SE, breathing
problems)
Rem: to fix Chrons's Dz inflict a flick to their
bowel (Infliximab) and their joints (RA), don't
flick too hard or will give them SLE or knock
free the TB; also notice that infliximAb = Ab to
TNFalpha
Rem: Dr. Tanner grabing two TNF-alpha
cytokines and tying them into pretzils (E-taner-
cept)
Rem: add the whole Ab for less IR (Ad-alimum-
Ab)
Rem: (Anakin-ra) Anakin Skywalker is the ill
one (IL-1), meaning both bad-ass and sick with
infection
 D E F

647 Rem: Da penicillin (D-Penicillamine) that

wanted to be an amino acid (cysteine), got no
Prolonged treatment leads to bones about dressing up like an amino acid
dermatological problems, nephritis, and (analog, slows bone destruction, bone also for
aplastic anemia!! B6 deficiency aplastic anemia)

648

hemorrhagic cystitis
649 hemorrhagic cystitis

650

MC SE associated with the use of gold

compounds involve lesions of the skin
651 and mucous membranes, usually of the
mouth. Skin reactions vary from simple
erythema to severe exfoliative dermatitis.
Other less frequent SE include kidney
damage and severe blood dyscrasias

652

See Aurothioglucose

653

See Aurothioglucose

654
NSAID gastropathy
655
 D E F
MC hypersensitivity reactions (rashes),
656 precipitate an acute attack of gout (low Acute attack (increases pain
dose to minimize this). Hepatotoxicity even though decreasing uric
(rare, lethal) acid)

657
Low incidence of GI irritation, used with
caution in pts with history of ulcers. Impaired renal function or
Hypersensitivity, sulfa allergies patients prone to urate stones
May induce hypoglycemia by inhibiting
metabolism of oral hypoglycemics.
658 Hepatic metabolism of warfarin
impaired. GI irritation in 10-15%; sulfa
allergies

Diarrhea, nausea, vomitting, and

659 abdominal pain (wickly toxic in GI track).
Long term use may lead to myopathy,
agranulocytosis, aplastic anemia, and
alopecia

660
GI toxicities; BM suppression and renal do not give with renal
damage insufficiency
661

matory Drugs
662
 D E
Gastrointestinal Side Effects:
Epigastric distress
Nausea
Vomiting
Microhemorrhage
Ulceration
Anemia
Prolonged bleeding time (anti-platelet
effect)
Patients scheduled for surgery taken off of
663 aspirin for one week prior
Hypersensitivity
asthma, nasal polyps, chronic urticaria
predisposed
progresses from hives, nasal secretion and
edema to acute asthma attack, severe
dyspnea, hypotension, and shock
Drug-drug interactions (This high
degree of protein binding is a potential
source of drug-drug interactions, 50-
99%):
antacids
protein displacement; phenytoin, thyroxine,
thiopental
risk of bleeding for patients on
anticoagulants
uricosuric effect in gout patients
664
F
Use of aspirin and salicylates
are associated with the
development of Reyes
syndrome (severe hepatic
injury and encephalopathy).
The use of salicylates in children
or adolescents with varicella
(chicken pox) or influenza is
contraindicated.
Salicylism - see extra note
Overdose = acute medical
emergency; fever, dehydration,
delirium, hallucination,
convulsions, coma, respiratory
and metabolic acidosis, death;
children especially vulnerable
Avoid use during third
trimester unless absolutely
necessary
Hypersensitivity to aspirin.
Patients intolerant of aspirin also
may suffer a severe reaction
from ibuprofen-like drugs. Alter
platelet function and prolong
bleeding time. These
compounds can cause GI side
effects, but these effects are
usually less severe than with
aspirin
 D E
665
666
Toxicity (worse than aspirin) limits its
usefulness. GI bleeding, severe frontal
667 headache, associated with long-term
administration, not commonly used for
therapy as an analgesic or antipyretic
668
669
Hematologic toxicity
670
HS reaction to sulfa
No effect on platelets and bleeding time.
But caution with patients on warfarin.
F
Hypersensitivity to aspirin. alter
platelet function and prolong
bleeding time. These
compounds can cause GI side
effects, but these effects are
usually less severe than with
aspirin
Hypersensitivity to aspirin. alter
platelet function and prolong
bleeding time. These
compounds can cause GI side
effects, but these effects are
usually less severe than with
aspirin
Hypersensitivity to aspirin; do
not give with renal
insufficiency
Hypersensitivity to aspirin
Rem: key-toe roll ack (Ketorolac) is an attack
that is so effect that it actually eliminates pain,
minor or chronic pain but its so strong it cause blood toxicities
Contraindicated in aspirin
allergy, 3rd trimester pregnancy,
and pts with a family Hx of
CAD!
 D E F
Valdecoxib is associated with an increased
rate of serious and potentially life-
671 threatening skin reactions (e.g., toxic Lesser incidence and less serious GI side
epidermal necrolysis, Stevens-Johnson effects (than aspirin and other non-COX2
syndrome, erythema multiforme) Hypersensitivity to aspirin inhibitor NSAIDs)

672
Hypersensitivity to aspirin

673
Well tolerated, lacks many of the side
effects of aspirin (especially GI, platelet
(bleeding), uric acid excretion)
Acute Overdose: can be fatal due to
delayed liver damage (fatal hepatic
damage, self-poisonings and suicides
has grown), see Liver drugs

674

675
676
677

rugs 678
e the proliferation and function of B and T lymphocytes. Also Corticosteroids inhibit
m phosphoipids.
= eye drops
 D E F

HPA axis suppression and withdrawal

Most frequent problem - flare-up of the
underlying disease.
Most severe complication - acute adrenal
insufficiency
Less severe withdrawal - fever, myalgias,
arthralgias, and malaise.
Toxicity Due to Continued Use of
Supraphysiological Corticosteroid
Doses (Consequences of
679 Immunosuppression):
Poor wound healing
Opportunistic infections (& reactivation of
latent tuberculosis)
Cushings Habitus
Toxicity:
Hyperglycemia
Hypertension
Peptic ulcers
Myopathy (proximal)
Behavioral changes
Cataracts
Osteoporosis
Growth retardation
Suppression of HPA axis and life-
threatening susceptibility to stress upon
withdrawal.

680

681

682
683
684
 D E F

685
Rem: I'll bet-a deck-a cards that I can piss
further (Betamethasone and Dexamethasone;
longest half-life)

686

687

688

689

690
gynecomastia
691

692

693
694

t Drugs
695
 D E F

696
Toxicites are numerous and frequent. They
include a) nephrotoxicity, b) HTN c)
hyperglycemia, d) liver dysfunction, e)
hirsutism and f) hyperkalemia
Increased risk of lymphoma, karposi's
sarcoma and skin cancer have also been
documented.
also toxic to nerves, kidneys, and can
cause diabetes; metabolized by P450

697
also toxic to nerves, kidneys, and can
cause diabetes and hyperkalemia; HTN;
risk of developing post transplant Remember: an organ rolling in tacks, creating a
lymphoproliferative disorders & tack shield that prevent IL-2 from reaching T
lymphomas & de novo nonlymphoma cells inside, steps on some kidneys while he
solid tumors; neutropenia is a rare does it

698

699

Lymphopenia
 D E
700
leukopenia, anemia and/or
thrombocytopenia, resulting in an
increased risk of infections; nausea,
vomiting, and loss of appetite; liver
toxicity; bacterial infection, cancer
(these last two pretty common for most
immunosuppressants); allopurinol
increases levels Pregnancy/nursing
When side effects occur, they typically are
701 seen within a few hours after the first dose.
With the first or second doses, flu-like
symptoms, headaches, chills and fever,
and nausea, diarrhea, and breathing
problems have been reported.
702
703
704
minimal renal toxicity, though synergistic
705 renal toxicity if mixed with cyclosporine;
hyperlipidemia, thrombocytopenia, and
lekopenia
F
Remember: Use as a thigh opener
(Azathioprine), to reach in that thigh and tear
out WBC by the puny purines. But as you tore
in, blood poured out causing leukopenia,
anemia and/or thrombocytopenia; and a
pregnant woman carring a child in arms and
womb began lapping up the blood but you told
her to stop because it will get to the baby she is
nursing and the baby she is carrying. She
looks at you, mad from her gout pain, and
begins to scream but only cancer comes out
her mouth
Remember: "OK, call in the T3 (terminator3)"
as he can fight the steroid resistant acute graft
rejection. He doen't need no stinking steroids,
as he is an ANTI-BODY (an etherial being who
doesn't require a corporal form). He aint cute
Rem: Dac-LI2-zu-mab Daclizumab
Rem: fresh basil growning on a T cell IL-2
receptor, and Basiliximab comes along and just
puts his mouth right on it and sits there
 D E F

(Sim to Mustard gas) Immediate

toxicities include a) nausea and vomiting,
b) cardia toxicity (vascular insult leading to
myocardial hemorrhage) and c)
electrolyte imbalance; BM suppression, Remember: a cyclops who weilds a
706 hepatotoxicity. phosphamide sword to slay WBC, at the cross
Delayed toxicities include a) alopecia and roads of DNA (by cross-linking) but accidentally
hemorhagic cystitis, b) increased risk of catches his own bladder with the hilt, which
non-Hodgkin lymphoma, bladder cancer, starts to bleed profusely and then becomes
acute non-lymphoblastic leukemia and skin bladder cancer. The WBCs then see this and
cancers. rebel, cursing him with the nons: non-Hodgkins
Bladder cancer occurs in about 10% of lymphoma and non-lymphoblastic leukemia.
patients treated cronically with He then lays down from burden and finally gets
cyclophosphamide. skin cancer
707 hemorhagic cystitis

Metabolic side effects include the following:

1. Iatrogenic Cushing's syndrome
(rounding and puffiness of the face (moon
faces)). 2. redistribution of fat to the trunk
708
and neck 3. increased growth of fine hair
on face thichs and trunk 4. acne 5.
insomnia 6. increased appetite 7.
increased need for insulin with weight gain
8. development of insulin resistant
diabetes. Other side effects include 1.
peptic ulcers 2. masking the effects of
bacterial and mycotic infections 3.
nausea, dizziness and weight loss 4.
hypomania or acute psychosis (large Glucocorticoids must be used
doses) 5. increased intraocular with caution in patients with
pressure, posterior subcapsular peptic ulcer, heart disease of
cataracts and glaucoma 6. impaired HTN psychosis, tuberculosis After excluding common causes, one should
wound healing 7. hypocalcemia and diabetes osteoporosis of also consider prednisone-induced neutropenia,
osteoporosis glaucoma although this aetiology is rare.
 D E F

Side effects include fluid retention, weight

gain, high blood pressure, potassium loss,
headache, muscle weakness, puffiness of
709 the face, hair growth on the face, thinning
and easy bruising of the skin, glaucoma,
cataracts, peptic ulceration, worsening of
diabetes, irregular menses, growth
retardation in children, convulsions, and
psychic disturbances. Psychic disturbances
may include depression, euphoria,
insomnia, mood swings, personality
changes, and even psychotic behavior.

a) insomnia, b) depression, c) glaucoma, d)

weight gain, e) irregular menstrual cycle, f)
secreased functioning of the adrenal gland
710
(adrenal suppression), g) thinning of the
bones (osteoporosis), h) ulceration of the
stomach or intestine, i) increased
susceptibility to infections, j) acne, k)
increased risk of fractures of the bones, l)
increased hair growth (hirsutism), m)
vaginal yeast infection (candidiasis), n)
suppression of growth in children and
adolescents and o) muscle wasting and
weakness
711

erapy
712
 D E F

713

Rem: mycin sounds like an antibiotic, which

Nausea & vomiting; fever pneumonitis;
pulmonary infiltrates & fibrosis; little
myelosuppression; fever with
administration. This can develop rapidly
with hyperpyrexia, hypotension and shock.
Bleomycin ~is but for cancer, but pt will not be
able to blow (bleo) with pulmonary fibrosis.
Also, Bleo wanted to be a G too (G2 cell cycle)
so he joined a radical group (forms free
radicals) and is initiated by fire (fever) and balls
stomping (tx testicular cancer)

714
BM suppression and GI upset

bone marrow toxicity leading to

715 pancytopenia, which is sometimes delayed
It is considered the most leukemogenic of
the classic alkylators

716
BM toxicity!! Rem: -plantin = Platinum Alkylating Agent

717 short-term neurotoxicity that is related to

cold:a sensation of burning associated
with cold objects or foods (~72hrs) Rem: -plantin = Platinum Alkylating Agent
 D E F

Renal tubular damage, ototoxicity Rem: Plantin' (Cis-platin) a platinum tree with
718 Extremely toxic CH3s hanging off branches (alkylating agent),
Nausea & vomiting!! and its roots form an X (cross-links). The tree
Bone marrow suppression! is so beautiful it causes you to vomit up your
GI irritation kidney (renal failure), which causes you to
Gonadal suppression sceam, however it only falls on deaf ears
Secondary leukemias (ototoxicity)

Hemorrhagic cystitis!!
719 Extremely toxic
Nausea & vomiting
Bone marrow suppression
GI irritation
Gonadal suppression
Secondary leukemias see immunosuppresant
720 See cyclophosphamide

721

myelosuppression and hypersensitivity

722
Rem: tx ChLorambuciL

723

most feared complication is pulmonary

fibrosis.
724 It can cause hepatic veno-occlusive
disease and the oral form is preferred to Rem: MC BB pulm toxicity (rhyme it) -
help prevent HVOD. methotrexate, carmustine, bleomycin, busulfan
 D E F

725 Rem: MC BB pulm toxicity (rhyme it) -

Carmustine associated with pulmonary
toxicity (fibrosis?), BM suppression; N/V!
726
methotrexate, carmustine, bleomycin, busulfan;
Put some super charged nitro urine (urea) in
your brain, that will cure the brain cancer;
mustine must enter your brain
Rem: mustine must enter your brain

727
N/V!

728
Nausea & vomiting, Bone marrow
depression; cardiotoxicity (especially
dysrhythmias); alopecia; stomatitis;
hyperuricemia,; leukemia
Rem: the bison (ru-bicin) rode his bike (anthra-
cycline) over topo (Topoisomerase inhibitor)
because it was infected with anthrax (anthra-
cycline) which caused his giant heart to
explode from his little body (cardiotoxicity) thus
freeing the radicals from his tyranny

729

730

731

Rem: Tackin' (Dactin-) between the guanine on

BM suppression the giant tumor on the kids kidney
 D E F

732

733

flu-like syndromes; *Depression is a major

side effect that needs to be recognized
734 early and treated and if depression is not
controlled, the drug needs to be stopped.
Suicide is common in those depressed on
IFN.

flu-like symptoms, but a deadly side effect

735 of Capillary Leak Syndrome; delirium,
due to CLS and brain edema.

736

737
Inhibits T cells (sim to AiDS pt) Rem: ribine/rabine are antimetabolites
Rem: clay dripping from your hair; ribine/rabine
738 are antimetabolites; give the man 2CD-A
Very toxic in large dose, give in short doses (canadian saying it) for catching the hairy
over several days monster

739
 D E
740
Profound myelosuppression
GI toxicity, oral mucositis
741
Nausea & vomiting, bone marrow
depression, palmar-plantar
erythrodysesthesia!!
742
743
744
Nausea & vomiting, oral and GI
ulceration, bone marrow depression
(anemia and thrombocytopenia),
pulmonary infiltrates & fibrosis, liver
cirrhosis, renal toxicity, osteoporosis,
alopecia, others
Nausea & vomiting, bone marrow
depression; produces a predictable
745
leukopenia that is usually reversible within
days of discontinuing therapy.
Gastrointestinal toxicity is usually mild.
Patients receiving long-term hydroxyurea
therapy may develop mild dermatologic
changes.
F
Rem: ribine/rabine are antimetabolites
Rem: Flew over a carousel (Flu-or-ouracil), but
a woman's thigh made me late (thy-midy-late
synthase) cause I "thought" about it too long,
and had to run to the plane which prohibited
me from metabolizing my dinner
(antimetabolite), and on the way I tripped and
fell, spilling of my BM out like a snake (S
phase), and the snake bit my palm and foot
causing erythrodysesthesia
Rem: ribine/rabine are antimetabolites
Rem: Levi missles (Leva-misole) will make your
immune system bad ass
Rem: Me so tricky/tricksie (Methotrexate), I
convinced cancer to die by giving it a
water/folate reduction sauce (dihydrofolate
reductase) over its fibrotic lung dinner, but
Leucovorin came to its recue
Rem: CML (country music lover) going to show
this weekend for some R&R (ribonucleotide
diphosphate reductase), but pissed cause
gotta bring the sickle cell kid, that kids in a
Sucky phase of his life (S phase)
 D E F

746 Rem: Lou lied (Leuprolide) about taking his

hormones (sGnRH) for his prostate cancer so
he wouldn't be castrated and get boobies. He
wants to still be able to play his skin flute (flut-
Hot flushes, impotence, gynecomastia amide used together)

747

748

749

Rem: need a night light (Ni-lut-amide, slow dark

Delayed adaption to the dark (from the adaption) to see your massive metastatic
light; sec to min) prostate

750
Fluid retention (?used to reduce edema??),
hypertension, diabetes, increased
susceptibility to infection, moon facies.
751 see prednisone

752
Hot flashes; thrombo-embolism; vaginal
bleeding & discharge (vaginitis);
thrombocytopenia peripheral edema, Rem: Tammy on an ox with big ol lumpy
increased risk of endometrial cancer breasts covered with estrogen receptors

753 Rem: 'taxel' are Taxanes which tack MT

Hypersensitivity reaction, Bone marrow together, preventing their release; and anytime
depression, peripheral neuropathy your talking MT your talking M phase
 D E F

754 Rem: 'taxel' are Taxanes which tack MT

together, preventing their release; and anytime
your talking MT your talking M phase

755

Tissue damage with extravasation, Bone

marrow depression, Peripheral Rem: Vin blasted christine and depolarized her
neuropathy; Also alopecia, paralytic ileus MT and M phase; vin-blastin your bones (BM
(Neurotoxicity?) suppresion)

see vinblastine; Neurotoxicity!! is dose-

limiting with vincristine and is manifested as
756 peripheral sensory neuropathy and/or
an autonomic neuropathy. With
continued use of the agent, a motor Rem: Christine is very neurotic (neurotoxicity),
neuropathy may develop. she'll drive you crazy

757

Rem: Topo inhibitor - Topotecan,

758

Rem: Topo inhibitor - Etoposide; Pasidin

(Greek God = II = roman arches) sows his oats
BM suppression (sow = testicles, oast = small cell)
Rem: wear your tux (Rituximab) when you
759 diffuse the B-bomb (Diffuse Large B Cell
Lymphoma); -mab = monoclonal Ab
 D E F

760

Rem: it tries to zoom (Trastuzumab) in her two

new (Her2/neu) breasts; Rem: -mab =
cardiotoxic monoclonal Ab

761

762

Rem: Country music lover's (CML) stop at the

road side vendor and by some local Imatinib

763
Rem: -dronate ~ bisphosphonate

Rem: Anastrozole steals the soul (zole) from

764 aromatase, the man cannot become the
May have increased risk for osteoporosis woman (inhibits androgens conversion to
compared to Tamoxifen estrogen)

Rem: Let-ro-zole steals the soul (zole) from

765 aromatase, the man cannot become the
May have increased risk for osteoporosis woman (inhibits androgens conversion to
compared to Tamoxifen estrogen)

766

767
 D E F
768
769

770 Rem: I'll just dust some IL-2 on your back and
then whipe the melanoma right off. (al-des-
leukin)

771

772

773
Allergic reaction; rare hemolytic anemia
774
775
776
777
778
779 Interstitial nephritis!! I met a nasty ox

780
Interstitial nephritis!! Also neutropenia I met a nasty ox
781 I met a nasty ox
782
783
784
785
786
787
788

789

790

791

792
793
794
 D E F
Rem: I met man tanned the foxes fur; all have
795
f's - all 2nd generations
796
797
798
799
800
801
802
803
804
805
806
807
808

809
Eosinophilia, thrombocytosis, and
leukopenia

810
811
812
Seizures (especially renal insufficency pts
813 or previous CNS pathology), allergic
reaction Rem: see, it stays in (C-il-istat-in)
814 See imipenem
815
816
817

818

l 819

820
 D E F

821

Gray baby syndrome

822

Major Cytochrome P-450 inhibitors: FREaCKI

823 Grapefruit gets stuck in Ez- Ketoconazole,
Erythromycin mimics motilin so it causes Isoniazid, Cimetidine, Fluoxetine, Ritonavir,
increased GI motility; inhibit p450 Erthyromycin, Grapefruit

824
inhibit p450
825 inhibit p450
826
HA Rem: the Godzilla Lizard (linezolid)
827

Teeth discoloration, bone deformity in

children, Fanconi's syndrome (diminished
828 absorption in the proximal tubules -
aminoaciduria, phosphaturia, acidosis, and
glycosuria), photosensitityity, pseudotumor
cerebri

829

830
831
832
833
834
 D E F

Nephrotoxicity (acute tubular necrosis,

especially cephalosporin); otoxicity
(especially loop diuretic use); teratogen;
835 neuromuscular blockade (especially
when administered with neuromuscular
blocking agents or pts with impairment of
neuromuscular transmission such as Rem: amiNOgycoside - Nephrotoxicity,
myasthenia gravis) Ototoxicity (Rem: two o's in oto, two o' in loop)
836
837
838
839

840

841

842 Arthropathy, myalgias, and leg cramps in

children <18yo (tendonitis and tendon
rupture)
GI irritability like erythomycin and
doxycycline, damages cartilage (avoid in
843 children), achilles tendonitis, rare CNS
effects like headache, restlessness, and
insomnia

844 Drink this moxi take my gat and lev this

pneumonia dead
Drink this moxi take my gat and lev this
845
pneumonia dead
Drink this moxi take my gat and lev this
846
pneumonia dead

847
PHOTOSENSITIVITY and prolongs the QT Sun burned boxer gyrating and sparring for a
848
interval QT
849
 D E F
GI upset, neuropathy, hemolytic anemia in
850
G6DP

s 851

852

853

854

855

856
857

858

859

860
861

gs 862

863

864

see NSAIDs above

 D E F

865
Rebound HA (with overuse); abuse Do not take with alcohol Rem: (But-al-bital) , Barbiturate - relaxes
potential (schedule 3 with tylenol) (additive effects) muscles

Excess dose:caffeine causes palpitations

866 and anxiety
Termination of taking caffeine in patients
who are dependent on caffeine provokes
headaches. Rem: Caffeine Aids in antagonizing you (Aden
antagonist)

More anticholinergic than other

antidepressants. Side-effects are typical of
atropine (in the low dose range = dry
mouth & urinary retention; as the dose Rem: Amy tripped (Ami-trip-tyline) so much she
867 increases = tachycardia and CNS got horrible migranes and depression (anti-
intoxication - lethal arrhythmias!); Deadly in overdose. Alters depressive), so she pulled a very tight condom
selected for evening administration cardiac electrical properties; over her head (prophylaxis for tension and
because they cause sedation and difficult to dialyze due to large migranes), the condom was dry (no urine or
drowsiness at the start of each dose. volume of distribution. spit - anticholinergic)
868 See Amitriptyline
Less toxic and less anticholinergic than
869
amitriptyline

870 Most frequently encountered are mild in

severity: Altered sensation (tingling,
warmth, dizziness, muscle weakness), pain
at site of injection.
Rarer (1-5% in various studies), but more
important, is chest discomfort!! (occurs
because of vasoconstriction!); can cause
HTN crisis!!
Contraindications:
Coronary artery disease
Prinzmetal angina (triptans can
cause coronary vasospasm)
Uncontrolled hypertension
Rem: Triptans are BD (B and D receptors)
this is Never gonna work (naratriptan is the
slowest onset)
 D E F

As opposed to triptans, significant SE,

including nausea. At higher doses,
including those that can be reached with
871
repeated use for long-lasting migraine, they
are dangerous because of alpha agonist
effects (peripheral vasoconstriction);
hallucinations & bizarre behavior,
gangrene and abortion (with eating moldy
rye-bread)
Rem: I got a HA, ergo I took an ergot alkaloid
ergo I got nausea, ergo I hallucinated; Rem:
Just remember that ergot mold is where LSD
came from and then picture yourself tripping
and all of a sudden you have an abortion, your
Do not use with Triptans fingers fall off (gangrene)

872
see Ergotamine, less nausea than
ergotamine, but still requires anti-emetic Rem: Dihydroergotamine is an ergot alkaloid

Side effects are significant, especially

with chronic treatment, and include:
hyperprolactinemia, galactorrhea, breast
873 tenderness, menstrual irregularities,
extrapyramidal symptoms, anxiety, and
depression.
Rapidly Occurring Neurologic SE (rare; due
to Extra-pyramidal effects), three main
types: Parkinsonism!! Dystonias!! (seen
most frequently when treating migraine),
Neuroleptic Malignant Syndrome

874
See Metoclopramide, drug induced SLE

875
See Metoclopramide

876
see CCB above

877
asthmatics, COPD
hepatotoxicity & thrombocytopeina, weight
878
gain
 D E F

Do not give in combination

Usually mild and transient - GI (burning,
diarrhea, nausea & vomiting) Potentially
879 serious: inflammatory fibrosis, including
retroperitoneal fibrosis,
pleuropulmonary fibrosis and coronary
fibrosis. Usually reversible on
discontinuation
with a triptan
hypertension/vasospasm risk;
Note: if methysergide is being
used prophylactically and a Meth is your guide to turn on the AC cuz it is so
migraine headache occurs, damn hot and you have been up for 2 days
treatment options are decreased (protects you after 2 days) with your
dramatically inflammatory fibrosis

880

Polydipsia & Polyuria (common, even at

therapeutic levels)
Tremor (clear sign of excessive dose)
Gastric distress (common)
881 Edema
Weight gain Picture a bunch of bipolar people clustering
Hypothyroidism together (lithium used for bipolar disorder)
Cardiac conduction problems peeing all over themselve, shaking, and all fat
Mild cognitive impairment and shit

882

city 883
Drugs

884
Classic side effects of antimuscarinics (dry
mouth, urinary retention, constipation etc). Prostatic hyperplasia,
Will make dementia worse (especially obstructive GI disease,
Alzehimers, antimuscarin exacerbates). glaucoma

885
See Biperiden See Biperiden

886
See Biperiden See Biperiden
 D E F

Metabolites include amphetamine,

methamphetamine, and
887 desmethylselegiline, the last of which may Interactions:meperedine, Rem: sell the gel (selegiline) that, when you
be anti-apoptotic. Amphetamine & trcicyclics, SSRI's. Nonselective pour it over the MAOist (MAOI), they stop their
Methamphetamine appear responsible MAOI's should not b eused destruction of the dope (dopamine) cultures.
for insomnia, and eventually psychosis (HTN crisis) Rem: MAOist never sleep (insomnia)
Does not have metabolites of Selegiline,
888
therefore decreased SE profile
Many SE: insomnia, restlessness,
889 depression, GI disturbances. Toxic
psychosis in overdose but normally well-
tolerated. Seizure disorders, CHF

Nausea and vomiting with tolerance after

4-6 weeks. Cannot use phenothiazine
(H1 receptor antagonists) antiemetics to
relieve this side effect. Cardio arryhtmia
due to increased catecholamines. Rem: an Athen/Greek slithering around on the
890 Dyskinesia - 80% of patients: chorea, ground (athetosis); remember: you call that (ca
ballismus, athetosis, tics, tremor; occur in dat) a striped tiger? (caudate nuclei) plus bitch
face trunk or limbs. Cant treat with man who is always in both, hes the bitch of the
haloperidol or other dopamine-receptor ganglia (putamen) = striatum.
blocking drugs. See extra notes. Also, Rem: So putamen, ganglias bitch, and the
dose-related fluctuations in motor globe (globus pallidus) celebrating lent world
function that tend to worsen in late PD wide = lenticular nucleus.
under levodopa therapy. Postural
hypotension!! Arrhythmias

Rem: curb (carbi) the L-DOPA from forming

891 dopamin in periphery (and 5-hydroxytryptophan
from forming serotonin (?)), makes them both
bit the curb.

erythromelalgia, vasospasm;
892 Psychotomimetic and dyskinetic effects
typical of dopaminergic treatment of PD;
Postural hypotension nausea, somnolence,
mental disturbances, hallucinations
See bromocriptine; also cardiac Rem: (Pergolide) Pergo lied about her age, she
valvulopathy involving one or more valves said she was 21 (D1/D2) but she was really old
893 - consistent with the valvulopathy (old treatment of PD), you could tell by the
associated with carcinoid syndrome and horrendous sound of her cardic valve
with the use of other ergot alkaloids. flapping/snapping
 D E F

894
No ergot associated side effects; postural
hypotension (D2 agonists are hypotensive
via peripheral DA receptors in vasculature), Rem: the Parkinson's pt felt so good after
dyskinesi, nausea, somnolence, Mental taking his Pramipexole he primed his pecks
disturbances, hallucinations, etc. (Pra-mi-pex-ole) for his new date tonight.

895
See Pramipexole

Rem: the Capones make an offer that meth

896
Adverse effects related to increased
levodopa exposure (lower dose by 30% in
first 48 h to avoid complications)
trafficers (Catechol-O-Methyltransferase) can't
refuse, and so they lower the cost (amount) of
dopa (in the system). The Capones listen to
OMD on the way in the car (poor theraputic
response)

897

drowsiness, fatigue and hypotension Rem: Baclofen has an l and an a (la)

898

Anticholinergic SE: somnolence,

899 xerostomia, mydriasis, and tachycardia;
also blurred vision, urinary retention and
constipation

900
 D E F

901 Many adverse reactions: GI hemorrhage,

sepsis, convulsions, neoplasm Contraindications: Lactation Rem: Riluzole treats Lou Gehrig's dz (ALS)

Rem: the doc exclaims "Ti-zan (a-dine)" as he

902 Adverse effects - result from alpha-2 sprinkles Tizanidine over the spasming pt, and
agonist adrenergic effects (hypotension, they stop but begin grotesquely dividing into
drowsiness) clones (clonidine)

903

Rem: Dan was able to get back to working at

the Whataburger cause he's taking his
Dantrolene for his cerebral spasticity, dan-tro-
904 lean, if you got time to lean you got time to
clean. (notice, you need peripheral limbs to
muscle weakness (avoid use in ambulatory lean and clean well, and enjoy a milk shake
patients); dose-related hepatocellular injury (Ca inhibitor) (PNS))

905

906
(if give at night, it will cause really high bp,
so only give in morning and at noon)

907
908
909
910
911
912
913
914
 D E F

Antiepileptic drug idiosyncratic rxns (see

extra note)
Cerebellar and vestibular systems (ataxia,
nystagmus, vertigo, diplopia), pt looks
915
drunk;
gingival hyperplasia (20% of patients on
chronic medication), pt has bad breath;
hypertrichosis, hirsutism, osteomalacia,
megaloblastic (RBC) anemia
hypersensitivity, hyperexcitability in children Designated FDA category D
Induce P450 (increases metab of (benefits outweigh risks) based
contraceptives); also increase steroid H on considerably greater
binding prt pregnancy risk associated with Rem: RC PP induces P450 (rifampin,
Teratogen: Cardiac damage, cleft palate uncontrolled seizures carbamazepine, phenobarbital, phenytoin)

916

Antiepileptic drug idiosyncratic rxns (see
extra note) Toxicity: ataxia, rash, blood
917 dyscrasias (leukopenia or aplastic
anemia!!), diplopia, teratogen
Induce P450 (increases metab of
contraceptives); also increase steroid H
binding protein. Hyponatremia
918 Sedation, weight loss, nephrolithiasis
919
Serious: Hyponatremia (more common in
elderly), rash
FDA pregnancy category D
Rem: zepine and zepam seems to be generic
for seizure; Rem: A car exploded (Car-bam-a-
zepine), set by a group of salt mine workers
(Na) who are angery and protesting because
they got seizures from their working conditions;
Rem: RC PP induces P450 (rifampin,
carbamazepine, phenobarbital, phenytoin)
Rem: the ox driving the car (Ox-car-bazepine)
eating fries, heavily salted (Na channel blocker)
- the ox keeps dumping more Na on to fix his
hyponatremia

Blood dyscrasias; Skin reactions; GI

(diarrhea, nausea, vomiting, anorexia) and
920 CNS (headache, dizziness, etc.) effects.
Tolerance develops to GI effects; Rem: Ethel sucks a mean one (Ethosuximide),
Behavioral effects (restlessness, anxiety that's why she's absent today (petit mal, Ca T
and aggressiveness) Tubule), swallow the milk
 D E F

Rem: Val is such a pro (Valproic) she can

921 reduce both Na and Ca will increasing GABA,
Possibility of hepatotoxicity (do not give too bad she's a drunk (hepatotoxicity); she is
to Hep B/C pt); Thrombocytopeina; FDA pregnancy category D also such a bad ass that she can treat GTCS,
Idiosyncratic rxns (see extra note) partials (simple or complex), and absence

Nonserious: Tics and insomnia

Serious: Rash, including Stevens
Johnson and toxic epidermal necrolysis
(increased risk for children, also more
922 common with concomitant valproate use
and reduced with slow titration); Rem: the lamo trying again to stop the seizures
hypersensitivity reactions, including risk of (Lamo-tri-gine) to block both Na and Ca
hepatic and renal failure, and arthritis. channels, then you can hang out with the old
Idiosyncratic rxn people and Steve Johnson
923 Weight loss

Induces P450; Idiosyncratic rxn; sedation

(but tolerance may develop); subtle
cognitive impairment
Respiratory depression!!
osteomalacia (interferes with vitamin D
924 metabolism and Ca2+ absorption)
rash (1-2%)
paradoxical hyperactivity in children
megaloblastic anemia
sudden reduction or elimination of dosage Pregnancy, pts with liver dz, Rem: Phenobarbital is a Barbiturates; Rem: RC
may cause status epilepticus pts with porphyria; pts taking PP induces P450 (rifampin, carbamazepine,
Teratogen? Recent studies show low risk alcohol or BZD phenobarbital, phenytoin)

Idiosyncratic rxn; Benzodiazepines:

Toxicity
IV: cardiovascular and respiratory
925 depression (high dose)
chronic oral: sedation and ataxia (some
tolerance to sedation and ataxia, but not as
much as with barbiturates)
seizures are sometimes exacerbated
behavioral disturbances

926 Rem: Lora's ass is so nice (Lorazepam), it

would put anyone into status epilepticus -
Idiosyncratic rxn (see diazepam) ZEPAM! (or take them out)
 D E F
927
Idiosyncratic rxn Rem: Clonazepam treats myoclonin
Nonserious: weakness; Serious: Stupor or
928
spike wave stupor; Idiosyncratic rxn
Rem: the vegan (viga-batrin) battered her infant
indirectly (indirect GABA) by throwing (GABA-
929 transaminase) the baby from a moving car to
another moving car while on a road trip West
Idiosyncratic rxn (West syndrome)

Lowers seizure thresholds; Binge

drinking triggers microseizures - spiral
930 effect (makes further seizures more likely);
Cessation of drinking (withdrawal)
increases seizure risk due to upregulation
of glutamate and downregulation of GABA;
Idiosyncratic rxn

931 Weight gain, peripheral edema, behavioral

changes; Idiosyncratic rxn

932

Idiosyncratic rxn
enia933
Gravis

Injection site inflammation

Depression
Flu syndrome: fever, myalgias. Note that
934 much of the unpleasant muscle symptoms
of the flu result from the bodys production
of interferon.
Liver function monitoring is recommended. Rem: Interferon-1a (Avonex; Rebif) &
These side-effects abate to level of placebo Interferon-1b (Betaseron) & Glatiramer
at 1-year (Copaxone) the ABC drugs for MS
 D E F

935 Generally well tolerated; Injection site

irritation (itching and inflammation), Rotate
site of injection to minimize;
Transient reactions (~15 minutes in
duration, flushing, chest pain, dyspnea, Rem: the glatiator (Glatiramer) had MS, so
urticaria, these occur after several months instead of fighting he playing shell game,
of treatment) switching TH1 to TH2

936

Rem: Natalie has MS, but it makes her

937 stripping that much more exciting (Natali-
zumab)

938

See immunsuppresants above See immunsuppresants above

939
Bone marrow suppression (leukopenia), GI
signs (diarrhea, vomiting typical of high
dose); Allopurinol increases 6-
mercaptopurine levels
Toxicities are numerous and frequent;
nephrotoxicity and hypertension are
940 notable -- limits use in patients with pre- Toxicities are numerous and frequent;
existing renal disease or uncontrolled nephrotoxicity and hypertension are notable --
hypertension. See Immunosuppresants limits use in patients with pre-existing renal
above disease or uncontrolled hypertension.
 D E F

During the infusion: headache, muscle

aches, chills
Post-Infusion:
941 MC are fatigue, fever and nausea (lasts
approximately 1 day); rarer but more
problematic are migraines and allergic
reactions

Pt may experience dizziness, nausea,

numbness, tingling, or lightheadedness
942 during or after the procedure. These effects
usually pass quickly, allowing the patient to
return to normal activities the same day.
Also - infection, particularly when a central
line is used.

943

see Anticholinesterases above

944
see Anticholinesterases above

945

see Anticholinesterases above

946

947
 D E F
948
949

rugs
950

951 sexual dysfunction - decreased libido /

decreased arousal / anorgasmia (all three
can be seen with SSRIs, but anorgasmia
most prevalent); initial agitation & initial
insomnia (very common with fluoxetine);
initial nausea, weight loss (??), Potential
for many drug interactions due to potent
inhibition of 2D6 and long half life. MAOI
sexual dysfunction - decreased libido /
decreased arousal / anorgasmia;
952 sedation; most likely of the SSRIs to
produce GI disturbances (diarrhea); Low
potential for drug interactions due to P450 Rem: Ser-traline = ser-otonin; Serah had
interactions. MAOI diarrhea; ine can mean SSRI

sexual dysfunction - decreased libido /

decreased arousal / anorgasmia;
953 Discontinuation Syndrome; more weight
gain, sexual dysfunction and
discontinuation symptoms than other
SSRIs; Potential for many drug interactions
due to potent inhibition of 2D6. MAOI

954

sexual dysfunction (especially

anorgasmia), Low potential for drug
interactions due to P450 interactions.
sexual dysfunction (especially
955 anorgasmia), Low potential for drug
interactions due to P450 interactions.
Rem: Sital will keep the jizz inside (Cital-
MAOI opram), but you won't be depressed
Rem: a skittle will not help you have an orgasm
MAOI (E-scital-opram)
 D E F

956 Rem: the voice (vox) said Fluvoxamine, said

MAOI Fluvoxamine, said Fluvoxamine..

957

Stimulating effects and little or no sexual

dysfunction. contraindicated in those with a
Potential for seizures at high doses seizure disorder (epilepsy Hx).

958

Low sedative and antimuscarinic effects.

959 Dose-related hypertension &
tachycardia (NE effects)!!
More intense withdrawal than SSRIs
Greater toxicity in overdose than SSRIs
acts more like a TCA

960

Strong inhibitor of cytochrom P450 IIIA4

First antidepressant developed that was not

lethal in overdose
few antimuscarinic effects Rem: Travis dawned a swollen, purple boner
961 highly sedating (individual differences) that almost killed him (Traz-o-done) and he fell
sometimes used in combination with asleep in the ED with everyone stairing
MAOIs which disturb sleep (serotonin sedation); the cock almost killed him,
Can cause life-threatening priapism not the OD

962 Rem: this drug is deluxe (duloxe-tine) cause

not only does it treat pain, but also treats DM
pain
 D E F

963

very significant sedation!! (due to potent

antihistaminergic effects)
increased appetite / weight gain

964 Multiple side effects including

antimuscarinic & antihistaminergic
effects (see extra notes) such as Rem: Anti-HAM effects: histaminic, adrenergic
precipitating acute narrow glaucoma. and muscarinic
High toxicity in overdose!!
see amitriptyline; can affect sexual
965
performance by lowering blood pressure
966 see amitriptyline
967

MAOIs are rarely used because of the risk

of interactions with many foods (those
968 high in tyramine) & drugs
(sympathomimetic agents: ephedrine,
methylphenidate, phenylephrine and
pseudoephedrine)
Serotonin syndrome if used with SSRIs SSRI

969
See Phenelzine SSRI
970 See Phenelzine SSRI
971 See Phenelzine SSRI

Rem: Adam was an atom bomb of activity in

972 dry mouth, then urinary retention (ContraI the class till they gave him an atom of
in males with BPH, glaucoma); also Atomoxetine - will inhibit NE-body (NE reuptake
idiosyncratic liver damage inhibitor, effects both child and adult)
 D E F

rs
973

Narrow therapeutic window!! (acute 1-

1.5 meq/L, maintenance ~0.6-1.2 meq/L,
toxic at 2.0 meq/L) so monitor plasma
levels. Worsens extrapyramidal syndromes
produced by older antipsychotic drugs.
Tremor!! (MC effect, treated with
974 propranolol or atenolol), decreased
thyroid function! (usually
nonsymptomatic, monitor serum TSH every
6-12 months), mild cognitive impairment,
transient acne eruptions, leukocytosis,
renal dysfunction (polydipsia and (thiazides, NSAIDs, see extra
polyuria) see extra notes. Gastric distress notes) Brady/tachycardia
(use divided dose), edema, weight gain (SICK SINUS) as it depresses
(30% pts and not from edema) the sinus node.
GI distress (n/v), idiosyncratic
hepatotoxicity (can be lethal), congenital
975 neural tube defects, thrombocytopenia,
alopecia, and increased appetite and
weight gain Pregnancy

Rash (including Steven Johnsons and toxic

epidermal necrolysis increased for kids,
976 and more common with concommitant Rem: the lamo is super excited to try again
valproate use and reduced with slow (bipolar) to stop the seizures (Lamo-tri-gine) by
titration), hypersensitivity reactions (hepatic pouring salt and milk on the twitcher (Na and
or renal failure, arthritis), blurred or double Ca channels blocker), Steve Johnson just
vision, loss of coordination, dizziness watches

Blood dyscrasias (aplastic anemia),

ataxia, rash, pharmacokinetic tolerance
977 through autoinduction of metabolism,
hyponetremia (~3%), diplopia, ataxia, GI Car exploded from the p450 time bomb set by
upset, sedation, wt gain, teratogen may salt mine workers who were upset about their
worsen other seizure types (petit mal) anemias and flipper babies
 D E F

978

979

980

cs 981

982

Essentially devoid of extrapyramidal motor

side-effects
Blood dyscrasias (agranulocytosis)!! in
2% of pts - monitor blood, particularly
between 6th and 18th week, can only be
prescribed under a blood-monitoring
program
Other SE are strong sedation,
anticholinergic effects (urinary retention),
seizures, and hypotensive effects
Rem: claw the crazy out of their head, lots of
bleeding (Cloz-apine, blood dyscrasias);
Rem: atypical antipsychotic drugs work Due 2
5-HiTs 2 the CROw, "AQ it squacks",
antagonizing it (Clozapine, Risperidone,
Olanzapine, Aripiprazole, Quetiapine)

983
Somewhat more sedative (give at night); Rem: Quetiapine quites the voices in the
Implicated in type 2 diabetes incidence schizo's head
 D E F

With the exception of weight gain and

somnolence, the SE profile is much more
acceptable with this drug. Recent
controversy concerning this drug (and most
atypical antipsychotics) causing type 2
984
diabetes. Perhaps because of this, and
perhaps because of remarkable efficacy
against both schizophrenia and depression, Rem: "O' land ho" screams the voice in the
aripiprazole (see below) is sweeping the schizo's head, (O-lanzapine); "land ho? Looks
market since its introduction in autumn, more like Land O'lakes" butter with that weight
2002. gained - fattie gonna get DM2

Because of higher affinity for D2 sites (this

drug most like old typicals), it has a higher
potential than other atypical
985 antipsychotics for extrapyramidal SE,
including a small propensity for tardive
dyskinesia; SE include: Anxiety,
Somnolence, Extrapyramidal symptoms,
Dizziness, Type-2 diabetes, weight gain

986

Remarkably low incidence of SE, including Rem: Ari only gave the schizo a partial slice of
no tardive, and less weight gain than pie (Ari-pi-prazole; partial D2 agonist), even
olanzapine; No incidence of Type 2 though he wasn't gonna get the diabetes or get
diabetes; akathisia very common fat
Potential for polongation of QTc intervals
987 (caution pts with hx of AV block and
arrhythmia)
 D E F

Greater potential for neurologic

(extrapyramidal) motor SE than many
typical (and all atypical) antipsychotics
Extrapyradmidal effects include:
Dystonias
988 Parkinsonism
Neuroleptic Malignant Syndrome
Also dyphoria, and tartive dyskinesia with
long term use (especially haloperidol);
transient leukopenia or leukocytosis, many
other SE, see extra notes
Galctorrhea and ammenorrhea (females),
gynecomastia (males)

989

Orthostatic hypotension because of

alpha-receptor blockade
Dry mouth and urinary retention because of
anti-muscarinic effect
Extrapyradmidal effects, dyphoria, tartive
990
dyskinesia, and many more - see extra
notes
Galctorrhea and ammenorrhea (females),
gynecomastia (males)
Drug Induced Liver Dz - idiosyncratic Rem: all of the typicals are azine (except
(slow metabolizers) hadoperidol)

991
See Chlorpromazine

992
See Chlorpromazine

993 See Chlorpromazine; dizziness, dry mouth,

nausea and vomiting, rash

994
See Chlorpromazine

995 Little significant SE???, anticholinergic

effects

notics
996

997
 D E F

998

Benzodiezapam SE: Sedation, altered

mental status, ataxia; Tolerance; Physical Rem: your GABAa ABCs (a and alcohol) B
Dependence (Abstinence (barbiturates and benzodiazepines) and C
Syndrome/Withdrawal) (Cl-)

999
See diazepam

1000
Potential for early morning awakening,
tolerance/dependence if over used Rem: -am = BZD

1001
Leukopenia; mild elevation of lactate
dehydrogenase

1002
 D E F
1003

1004 Rebound insomnia and other withdrawal

signs particularly with conitnued use. Rem: of the zolam's, Triazolam and Midazolam
Amnesia, tolerance with continued use both work for a short TM (= short TiMe)

1005

Watch out for precipitated withdrawal;

1006 Seizures!! (potentially lethal gran mal and
cardiac collapse ) the big issue in BZD
dependence/withdrawal BZD dependent pt

1007 10% can't tolerate because it increasses Rem: can drive the bus (no motor impairment,
anxiety; High dose can cause anxiety. Bus-pirone), to the zoo to see the Piranhas (no
Poor patient acceptance, dizziness, anxiety to see them) and throw 5 partial
nausea, vomiting. MAOI will increase BP bananas (K+) to the monkeys

1008

1009

Rebound insomnia!! and other withdrawal

1010 signs, particularly with continued use.
(some individuals show mild aspects of this
phenomenon with a single dose);
antegrade amnesia; Tolerance with Rem: Triazolam, z for zzz's (sleep) and am for
continued use BZD
 D E F

1011 Just as likely to potentiate the

lethal effects of alcohol as a
Slight grogginess next day BZD Rem: Zolpidem gets your zzz's

1012 Just as likely to potentiate the

lethal effects of alcohol as a Rem: Zaleplon gets your zzz's; also shorter
Less grogginess due to short half life BZD word for short half life, and PRN (zaleplon)

1013
Depression or hx of depression
is contraindicated

Do not use with fluvoxamine

1014 (inhibits ramelteon metabolism)
and careful in folks with history Rem: R for receptor, mel for melatonin (R-a-
of depression mel-teon)

1015 Poor Therapeutic Index; Profound CNS

depression!! (anesthesia and coma) Pregnancy, pts with liver dz, Rem: Phenobarbital is a Barbiturates; Rem: RC
respiratory depression, abuse potential; pts with porphyria; pts taking PP induces P450 (rifampin, carbamazepine,
induce P450 alcohol or BZD phenobarbital, phenytoin)
1016
1017
1018

Drugs
1019

1020

Schedule II agent - potential for

abuse/dependence.
Some risk of dependence/abuse if ADHD
persists to adulthood
1021 Other predictable toxicities:
Insomnia
Anorexia
Weight loss and growth retardation may HTN, glaucoma, anxiety, seizure Rem: Ethyl was a funny date (Methyl-pheni-
occur with long-term therapy disorders date) cause she was high on her kids ritalin
 D E F
1022

1023
Schedule II agent - potential for
abuse/dependence.
Insomnia!!, reduced weight, emotional
lability (flip flop), significant potential for
diversion (parents, ADHD patient, other
siblings) HIGH ABUSE POTENTIAL
Rem: pommelling the liver (Pemoline,
1024 hepatoxicity), riddling (same as ridalin) your
Less used due to hepatotoxicity but no liver with bruises (no abuse, or can't see
abuse potential (essentially) abuse)

Rem: Adam was an atom bomb of activity in

1025 the class till they gave him an atom of
Dry mouth, then urinary retention ; also Atomoxetine - will inhibit NE-body (NE reuptake
idiosyncratic liver damage Males with BPH, glaucoma inhibitor, effects both child and adult)
1026
Abuse and dependence make this drug
1027
less than optimal

1028

Less abuse potential than other

1029 amphetamines (schedule IV), still get
insomnia, appetite suppresion, etc (less Rem: "the mode to stay awake - finally! A shark
intense however) fin in my butt" (Mod-a-finil)
1030
 D E
Unusual reactivity to sympathomimetics
(amphetamines, E, isoproterenol,
phenylephrine, pseudoephedrine,
terbutaline); dental problems (reduce
salivary flow causing periodontal disease
and other dental problems), insomnia,
1031 increased BP, anxiety, tremor, potential
for abuse (psychosis, dependence) use 4-
6 hours before bedtime (complicates tx of
nighttime hunger).
Overdose: arrhthmia, confusion, diarrhea,
fever (though less than cocaine), assultive
behavior, hallucinations (even small dose
shifts thought to paranoid thinking so high
does can lead to psychosis), circulatory
collapse and coma precede death. No
antidote!!
Class IV associated with blood dyscrasias
1032
(rare); see Benzphetamine
1033 Primary pulmonary HTN, See
Benzphetamine
1034 Lethal SE
1035
Tolerance develops within days or weeks
1036 Dry mouth, headache, constipation,
insomnia, some risk of increased BP
(monitoring required)
1037
Initial flautlence and loose stools which
may occur after high fat meals
(steatorrhea)
1038
Cardiovascular disease
Glaucoma
Moderate or severe HTN
Hyperthyroidism
Psychosis
Alcoholism
History of drug
abuse/dependence
INTERACTIONS: thyroid
hormones (increase stimulant
effects), MAOI (HTN crisis),
anesthetics (esp, halothane
lethal arrythmias)
Benzphetamine (specifically):
Class III CI in pregnancy
(category X)
See Benzphetamine
See Benzphetamine
F
Rem: Ben's feta cheese is so nasty, you'd loss
weight (Benz-pheta-mine) and jack up your
teeth; no antidote for his nasty feta cheeze and
will stimulate sympathomimetics and cause
psychosis. Don't eat he's cheese before
surgery or will die with halothane
Rem: Ethyl will die from her blood diet (Di-
ethyl-proprion, blood dyscrasias)
Rem: it's fun to mine (Phen-ter-mine), cause
you lose weight
Rem: Sir Butt Rammin' (Sibutramine) is taken
Serah (serotonin) in the @$$, (though he can
F&%k NEbody), he's thinking she needs to loss
weight - maybe she will after she fixes the
constipation
 D E F
Rem: Meg wanted to eat, so she eat Mega-
1039 struddles (Meg-e-strol)and gained all sorts of
weight

eatment
1040

1041

1042

Rem: Trex bitting the liver (don't give to pt with

1043 Impaired liver function and pts liver dz); also Trex has been around for a long
being treated with opioids time (long lasting) (Nal-trex-one)

1044 Rem: a camper prostrated himself, asking God

to treat his alcohol problem (and cravings) and
spare his liver (A-cam-prosate)
 D E F

1045

1046
Rem: my piss is foamy from the antifreeze in it
(Fome-piz-ole)
No's
1047

1048
 D E F

1049

1050

1051

Rem: the metabolite of nicotine has the same

letters rearranged - cotinine

1052
 D E F

1053

1054

1055

1056

1057
1058

1059
 D E F

1060
Rem: Flunitrazepam is the flun (fun)
benzodiazepine

1061

1062
Toxicity related to vasodilation -
headache, peripheral pooling of blood, combination of Viagra and
decreased myocardial flow poppers can be deadly
 G H
1 Extra Notes Extra Note

Testosterone analog that blocks production of dihydrotestosterone

7 (growth H resonsible for H-dependent growth of the prostate), Saw palmetto (Serenoa repens): Suggested to inhibit 5-
leads to reduction in size of gland, reduces symptoms, and alpha reductase
can decrease the PSA by up to 50%. No impact on PSA
May get retrograde ejaculation Similar side effects to Finastride

BPH S&S:
More frequent urination, especially at night
Sub sets of alpha1A, B, and D (all three seen in prostate, alpha1A Feeling an urgent need to urinate
9 predominates in prostate; alpha1B predominates with arterials) Having difficulty urinating or straining
both have mosaics of receptors. There is also an alpha2 family (A, Pause/prolonged amount of time before the urine flow starts
B, and D); all of these receptors are most likely expressed on A very weak urinary stream
receptive tissues, but the relative amount changes (eg A urine stream that starts and stops
preponderance of alpha1B in arterials) Feeling of incomplete emptying of the bladder
 G H

10
Relaxation of muscle (Relatively few alpha-1 receptors in the body
of the bladder)
Sympathetic stimulation causes contraction of trigone, therefore Symptomatic improvement
blocking this results in relaxation and hence voiding Does not arrest or reverse the underlying prostatic hyperplasia

11

Mech: Clomiphen occupies hypothalamic and pituitary estrogen

receptors preventing negative feeback effects on LHRH, LH, and
12 FSH. As a result the pituitary continues to release LH and
FSH allowing more follicles to reach maturity together. (Why
does ovulation then occur if cannot respond to E2 surge? - give LH
surge/dose)
13

Phosphodiesterase Type 5 Inhibitors:

14 Increase arteriolar flow - Excess blood engorges the tissue and
compresses veins
Flaccidity is brought about by normal sympathetic tone
Note: many types of PDE, Type 5 is predominant in arterioles of
cavernosa; Some Type 5 also found in arteries and veins
Both male and female cock and clit expand with drug
(increased engorgement); note pt not always ready to hump
just cause of drug, pt must have libido and sexual stimulus
(organ is much more responsive) - see Nitrates in No, No's

15

Tadalafil:
Much longer lasting, with a significantly greater likelihood of
16 priapism
Much less visual disturbance (if any)
Higher incidence of muscle ache complaints (5%)
One advantage with this drug, the mother may change her mind
17
and suckling will usually override the effect.
Bromocriptine and Cabergoline can be taken orally, or
administered intra-vaginally to reduce nausea. Nausea associated
18 with bromocriptine is due to: effect of Dopamine on CTZ
(chemoreceptor trigger zone) via D2 receptors. The CTZ is a
group of cells situated close to the area postrema on the floor of
the fourth ventricle
 G H

19 Better tolerated and considered to be more effective than

bromocriptine

20

21

22 Estradiol (E2): Patch (bipass first pass effect), micronized E2

(oral), Vaginal ring (local administration to vagina, ie vaginal 3 major forms of naturally occurring estrogens (estrogen
dryness) generic term (3 forms):
Ethinyl estradiol ethinyl group reduces first pass effect 1) 17-estradiol made primarily by the
Diethylstilbestrol (DES) non steroidal estrogen, post coital ovary
contraceptive 2) Estrone & Estriol some made in
Conjugated equine estrogens (contains estrone sulfate, equilin ovary, mostly made by conversion from
sulfate, etc.) aka Premoran?, MC post menopausal estrogon androgens in liver and/or adrenal glands
Ethinyl Estradiol is the most commonly used estrogen in OCs
23
(Ovral, Orthotricyclen)
24
 G H

25
The progestagenic component should have low androgenic
activity (ex. Desogestrel)
Reduce free androgens by increasing the amount of plasma
SHBG
The pill does not stop follicular development and when not taken Sequential (E, then P) or E alone oral contraceptives will
for one or more days ovulation may occur. Must be taken faithfully inhibit the H-P-G axis, thus reducing ovarian androgen
(99% effective) production

26

Norplant system:
Injectalbe effective for long-term contraception Also effective for long term contraception - releases much
27 Not good for women who want to get pregnant soon after less steroid as oral agents;
discontinuation of treatment Disadvantages include need for surgical implantation and
Takes awhile for H to be cleared removal, and some irregular bleeding

Sources for progesterone (naturally occurring progestin)

In female:
- produced primarily by ovary (corpus luteum)
Physiological effects of Progesterone: - during pregnancy, placenta produces progesterone
28 Progesterone is involved in the development of the secretory Follicular phase (levels) in women ~ that in males (0.03g/dL)
apparatus in the breast Luteal levels: 0.5 2 g/dL
Causes maturation of the endometrium
Prepare uterus for implantation
Increases body temperature CNS (hypothalamic) effect
Depressant effects, sedative or hypnotic effects (probably
mediated by metabolites of progesterone like Allopregnanolone)

29

Oral contraceptives (containing the not so androgenic

30 Rank order of progestagenic potency: Norgestimate, Desogestrel), influence binding globulin
Desogestrel > norgestrel > norgestimate norethindrone reducing bioavailability, less synthesis of androgens

31
Prodrug: Norgestimate converted to L-norgestrel
 G H

32
Rank order of androgenicity:
Norgestrel >> norgestimate > norethindrone > desogestrel

Drespirenone progestin (Yasmin)

33 have excretion of excess sodium and water
excellent for acne
Similar to spironolactone
Levonorgestrel only (Plan B)
34 0.75 mg ASAP and 2nd dose 12 hrs. later
Due to mechanism of action, is unlikely to work if fertilized egg has preferred formulation, lowest side effects and failure rate
already implanted (this interfers with uterine line formation) Now available OTC for patients 18 and older

35
Sources for testosterone:
In male: Testosterone is principally bound to SHBG (sex H binding
- produced primarily by testis (Leydig cells) globulin) or albumin (only about 2% is free-circulating
- only about 5% produced by adrenals hormone the bioavailable amount). Converted to DHT
Levels in women: ~0.03ug/dL (dihydrotestosterone) by 5-reductase type II (but also by
Levels in men (post-pubertal): 0.6ug/dL type I, especially CNS)
36
Propionate, cypionate esters of testosterone can be administered
37 parenterally. While they have greater activity, they have prolonged
absorption times

38 Alkylation at the 17-position: results in more orally active

androgens (ex. Methyltestosterone, Oxymetholone)

39

40

41
Danazol: Can bind to AR, GR and PR, but not ER;
By binding to SHBG, may increase clearance of hormones
42
43
 G H

44
Rem: hem-abate = blood stop
PGE2 keeps ductus arteriosus open, thus large ingestion of
45 aspirin may cause fetal death

46

47 Chronic hypertension is treated with alpha methyl dopa

(Aldomet), calcium channel blockers, and labetalol

48
49

Females 9-26 years old

Protection against types 6, 11, 16 and 18
3 doses; now and in 1 and 6 months
50 Cost around $500( $120 per dose plus office visits)
Can be given with other vaccines
No need to test before giving vaccine
Non-live vaccine, can be given to immunosuppressed

51
Tell pt to stop taking multi vitamins (for the folate)

52
53

54

55
 G H
Drug Interactions:
Aminoglycosides: Ototoxicity!!
Digitalis (digoxin/digitoxin)!!: Enhanced efficacy of digitalis
56 (mechanism related to hypokalemia) enhanced likelihood of
arrhythmias
Sulfonylureas used for Type II diabetes: Hyperglycemia
Lithium (used in treating bipolar disorder): Na is preferentially
excreted
NSAIDs (e.g., aspirin, ibuprofen): Blunted diuretic response; also
blunts response to loop's ability to reduce pulmonary edema
(mech related to prostaglandins released by the kidneys to cause
vasodilation and rapidly reduce pulmonary edema)
Thiazides: Diuretic synergism - use thiazide and loop diuretic
together to help tx CHF refractory to loops alone (thiazide blocks
distal Na resorption)
57
58
59
60
Normal physiology: Symporter is electrically neutral,
however, net result is excess K+ in the ascending loop cell.
K+ follows concentration gradient back into lumen. Therefore,
the lumen become positively charged. Positive lumen charge
drives divalent cations out of the lumen via paracellular
pathway.
Loop Diuretic: Na+, K+ transport is blocked. Note: Almost
immediately after the (blocked) symporter segment of the thick
ascending loop, a different transporter exists for K+. K+ is
essentially entirely reabsorbed at this site . Net loop diuretic
result across these segments is increased loss of Na+ without
loss of K+; block of Na+, K+ transport leads to a relative loss
of positive charge in the lumen (less driving force for K+ to
back diffuse). This in turn leads to less reabsorption (potential
for greater urinary loss) of Ca++ and Mg++
Remember: torso (torse-mide) of mine sliding down the loop,
blocking function
 G H

61

Note there are 2 sites of action (both are important): Net effect is
reduced HCO3- going back into blood, and less H+ available in Carbonic anhydrase is also present in the eye, where it is
nephron to serve as counter ion for Na+ reabsorption. involved in the production of aqueous humor

62 Thiazides: JNC-7 Virtually unsurpassed in preventing the

Usually prescribe thiazides first, less potential for harm as
compared to loop agents. Satisfactory alone for Stage 1
hypertension
At low doses, side-effects are minimal
Slow onset; long lasting
Less efficacious than loop diuretics
But capable of fluid and electrolyte disturbances
hypokalemia, hyponatremia
Important to note that thiazides do not directly block K+
reabsorption
cardiovascular complications of hypertension
Well tolerated
African Americans respond better to thiazides than do
Caucasians
Although hyperuricemia may occur, gout is uncommon,
particularly when the dose is modest (watch out for Boards,
which will pick on this side-effect)
Although lipid profiles can change unfavorably, this is usually
insignificant when the dose is modest (watch out for Boards,
which will pick on this side-effect)

63
64

65

Resistance occurs to loop agents; if so, add metolazone (thiazide-

66 like diuretic, but it also has a slight efficacy at proximal Na re-
uptake site. This accounts for the greater efficacy of metolazone
vs other thiazides)
 G H

Aldosterone receptor antagonist:

67 Recently demonstrated to improve mortality and morbidity in
patients with severe (NY Class IV) CHF
Spironolactone significantly decreases mortality rates for pt Lends support to hypothesis that aldosterone effects on the
with NY Heart Association class III and IV CHF; does not increase heart are a major contributor to tissue remodeling
clinically significant hyperkalemia Approved for Class 4 CHF

68

69

70

71

ARB Advantages: Excellent efficacy as anti-hypertensives

ARB effects, uses are similar to ACE-inhibitors, but side-effects are
72
even less troubling. Note: ACE-I drugs elevate bradykinin, which
accounts for many of the ACE-I side-effects. In contrast to ACE-I,
ARBs do not elevate bradykinin. ARBs, therefore: do not cause
cough (a frequent side-effect of ACE-I drugs), have significantly
less chance of producing angio-edema (also known as
angioneurotic edema)
Side-effect profile approaches placebo
Blunt the hypokalemia caused by diuretics
Mechanism: decreased aldosterone release
Little orthostatic hypotension
Little reflex activation of SNS
No effect on triglycerides, cholesterol

73
 G H
74
ACE is also the same enzyme as Kininase II, which is the enzyme
that inactivates bradykinin. Note that bradykinin is: Tissue irritant,
vasodilator, a candidate for why ACE-I drugs inhibit cardiac
hypertrophy
ACEI cough: 3-39% of pts
Elevated bradykinin in the lungs produce dry, non-productive,
Irritating cough; dose-related, but seen in the therapeutic range;
not seen with ARBs; elevated bradykinins!! also may rarely
cause angioedema (Remember: Greg Brady entering the vessels
and tissue swells with his offspring abundance)
75
76
Advantages:
Efficacious, particularly for isolated systolic hypertension
77 low incidence of side-effects compared to many older
antihypertensives
Disadvantages:
headache; flushing; orthostatic problems
Mechanism and Effects:
Block conversion of angiotensin I to angiotensin II by inhibiting
Angiotensin Converting Enzyme (ACE):
decrease angiotensin II-mediated release of aldosterone
decrease breakdown of bradykinin
decrease overly active SNS (little reflex tachycardia),
decreasing preload, decreasing afterload which then
decreases BP
Remember: not anal (Enalapril) cause its pro-drug, pril - ACEI
Ca++ is critical for smooth muscle contraction: Myosin light-
chain kinase phosphorylates (activates) myosin, block Ca++
entry and smooth muscle will relax
Nitric oxide (NO) is critical for smooth muscle relaxation: cyclic
GMP promotes dephosphorylation of myosin, NO promotes
cGMP formation, and smooth muscle will relax
 G H

78

Advantages:
Efficacious, particularly for isolated systolic hypertension
low incidence of side-effects compared to many older
antihypertensives Diltiazem and verapamil are relatively selective for cardiac
myocyte Ca channels

Advantages:
79 Efficacious, particularly for isolated systolic hypertension
low incidence of side-effects compared to many older
antihypertensives Not used with pt with CHF (actually accelerates CHF, has
negative inotropic effect)

80
Not associated with AV block (as beta blockers)

81

82

Mechanism is unknown
Decreases systemic vascular resistance (decreases
General effect: afterload), which leads to increased stroke volume
decrease PR, causes compensatory responses (initiated by Has minimal effects on venous capacitance. Therefore, most
baroreceptors) of increased SNS and increased RAS. effective when combined with venodilators
Consequences of SNS and RAS activation: increased SNS with When combined with isosorbide dinitrate, the
arterial block but venous constriction, increased HR and CO, Na+ combination has been shown to decrease mortality in
and H2O retention CHF (but not as effective as ACEIs)
 G H

83

Efficacious, long duration of action (metabolite)

84

85

Hypertensive Crisis: Emergent or urgent

Hypertensive emergencies: acute BP greater than 220/140 with
progressive target organ dysfunction such as myocardial or
cerebral ischemia/infarction, pulmonary edema, renal failure, or
papilledema; tx - gradually decrease BP by 10% in 1st hour then
by 15% over next 3-12 hrs with target of 170/110
86 Hypertensive urgencies: no obvious end-organ damage, blood
pressure control should be achieved within 24 hrs. Get diastolic
pressure to 100-110, then move it to normal over the next few
days; Avoid excessive decrease in BP. Avoid too rapid decrease
in BP; Either can result in cerebral or cardiac hypoperfusion. Use
drugs parenterally in emergencies; Use drugs parenterally and
occasionally orally for urgencies. Overly aggressive therapy is
associated with severe hypotensive problems, including
insufficient circulation to the CNS; Insufficient therapy is
associated with end-organ damage, including stroke.

ORGANIC NITRATES: (ie nitroprusside, NTG, Isosorbide

dinitrate)
Combined with hydralazine, decrease mortality (especially Pharmacodynamics
87 isosorbide dinitrate) - decreases venous return, decreasing Decrease preload
pulmonary edema (esp used for nocturnal dyspnea) Increase exercise capacity
Used by themselves, they decrease congestion Decrease symptoms of congestion
Nitroglycerin is used i.v. in acute HF to decrease ventricular filling Tolerance is a significant issue such that pts must be drug
pressures free 6-8 hrs per day. Drug is given at night to facilitate sleep.
 G H
88
89
90
91
92

93

94

95
Does not work on anaerobes

96
 G H

97

Uncomplicated cystitis: short term therapy (typically 3 days)

includes Trimethoprim-sulfamethoxazole (co-trimoxazole);
amoxicillin or sulfisoxazole are also useful. Fluoroquinolones
are reserved for treatment failure due to multidrug resistant
Most effective against Klebsiella with E. coli bacteria or patients allergic to co-trimoxazole or amoxicillin.

Pharmacokinetics
98 Rapid absorption following oral administration
Oral absorption impaired by divalent cations-antacids
Excellent tissue/fluid distribution
Excreted mainly through kidney by tubular secretion & by
glomerular filtration

99

100
101

Resistance
Mainly due to production of beta-lactamases; Due to reduction of
102 permeability of the outer (porin pores) of gram negative bacteria;
Due to modified penicillin-binding sites
Pharmacokinetics
Excreted rapidly via the urine; 10% glomerular filtration; 90%
tubular excretion; probenecid prevents tubular secretion
Blood level of penicillin can be raised by simultaneous
administration of probenicid, impairs tubular secretion of
penicillin
Susceptible to beta-lactamases, used in combination with
beta-lactamase inhibitors such as clavulanic acid,
sulbactam, and tazobactam
 G H

103

104
105

106

107 Resistance
Plasmid dependent resistance
production of adenylylating, phosphorylating, acetylating enzymes
destroy the drug
P/C open bacteria to allow AMP to reach target

108 Resistance
Plasmid dependent resistance
production of adenylylating, phosphorylating, acetylating enzymes
destroy the drug Antibiotics causing poluria: demeclocycline, methacillin,
gentamicin

109
Note the difference between spectinomycin and streptomycin

110
Resistance
Very similar to penicillin
Degraded by beta-lactamases

111
 G H

112

113
Most effective against Klebsiella (even though first gen are most
effective against gram +)

Resistance
114 Transmitted by plasmids TC affects both pro- and eukaryotic cells
TC resistance genes are closely associated with those of AMG, Mammalian cells have both the uptake and the efflux systems
sulfonamides, CAP for TC
Plasmids usually transmits resistance to multiple drugs rather than Bacteria have only uptake system. Can concentrate TC
TC alone Resistance bacteria have active efflux system

115 Doxycycline less effective than others TCs

Doxycycline is excreted in feces
Other TCs is excreted through kidney

116

117

118

119

120

121
 G H

122

123

124
Resistance
Through alteration in viral thymidin kinase
Through alteration in viral DNA polymerase
Pharmacokinetics
Used orally or intravenously for treating genital herpes
Cleared by glomerular filtration
Safe during pregnancy
125

126

Mechanism of Action: The ultimate mediator of acid secretion is

the H+, K+-ATPase proton pump of the apical membrane of
the parietal cell. This pump is unique to parietal cells. PPIs
irreversibly inhibit the activity of the proton pump. PPIs are
considered prodrugs. At neutral pH, they are chemically stable,
lipid soluble, and are devoid of inhibitory activity. These neutral
weak bases reach parietal cells indirectly, by first being absorbed
into the blood, diffusing into the secretory canaliculi, where they
127
become protonated and thus trapped. The protonated drug
chemically rearranges and covalently modifies sulfhydryl
groups on the proton pump protein, irreversibly inactivating it.
These drugs produce a profound inhibition of acid secretion and
inhibition persists after the drug disappears from the plasma. The
specificity of these drugs derives from the selective distribution of
the H+, K+ATPase, from the requirement for acidic conditions to
generate active drug, and from the trapping of the drug at sites
adjacent to its target enzyme. PPIs may also have antimicrobial
activity against H. pylori.
Pharmacological Properties: PPIs are unstable at a low pH.
The oral dosage forms (delayed release) are supplied as
enteric-coated granules encapsulated in a gelatin shell
(esomeprazole, omeprazole and lansoprazole) or as enteric-
coated tablets (pantoprazole and rabeprazole). It is clinically
important to note that these drugs are destroyed by acidic
conditions. Therefore, if their microencapsulation is
destroyed before swallowing - for example, if the patient
breaks open or chews the gelatin-coated capsule before
swallowing - the neutral pH in the mouth and esophagus
will break down the microencapsulation, and the drug will
be exposed to degradation in the acidic contents of the
stomach. When taken properly, the drug is released after
the granules have left the stomach and is rapidly
absorbed from the intestine. Co-administration of H2
blockers may also diminish the efficacy of the PPIs.

128
 G H
129

130

131

Enterochromaffin cells (ECL cell) release histamine, the

primary stimulus for acid production from the gastric parietal
cell.
Histamine activates the H2 histamine receptor, causing
elevation of cAMP levels, that leads to recruitment of the H+,K+
ATPase (the Proton Pump) to the membrane surface and activates
secretion of protons (acid) into the gastric lumen.
132 Acetylcholine (ACh) released from the vagus nerve or from
interneurons activates at muscarinic receptors (M1, M2, M3). M3
receptors on parietal cells directly stimulate acid production via a
Ca++-dependent pathway. ACh also acts indirectly by stimulating
histamine release from ECL cells. The superficial epithelial cells secrete cytoprotective factors,
Gastrin released from G cells of the gastric antrum acts at mucus, and bicarbonate. Prostaglandin I2 and ACh stimulate
gastrin receptors (G, cholecystokinin, CCK2) on the ECL cell production of these factors. Prostaglandin I2 and E2 inhibit
stimulating histamine release and also stimulates parietal cell acid cAMP formation in the parietal cell and inhibit acid production.
production directly via a Ca++-dependent pathway. Prostaglandins also enhance mucosal blood flow.

133

134

135

136

Antacids should be prescribed on an as-needed-basis for
symptom relief, but only if the patient reports symptomatic relief
after antacid administration. Drawbacks include: lack of patient
compliance, nocturnal acid secretion, and interaction of antacids
with other medications. Antacids typically only provide short-term
symptom relief but act rapidly.
During anesthesia, coma, cesarean section, or
endoscopy, aspiration of gastric contents can cause
aspiration pneumonitis - sodium citrate (Bicitra, a clear liquid
antacid) is used prophylactically to neutralize gastric contents
in these situations. Oral or IV administration of H2 blockers is
also used for this purpose.
 G H

137

138

139

140

141
Misoprostol and H2 antagonists are the only agents with proved
efficacy in preventing NSAID-induced mucosal injury.
Pirenzepine is an antagonist relatively selective for the M1 receptor subtype in the stomach and is being tested as a potential
antisecretory drug. Other, older compounds, particularly quaternary amines with few CNS side effects find limited use as GI
142 antispasmodic agents, e.g. dicyclomine (Bentyl). Other available cholinergic antagonists such as hyoscyamine sulfate (Levsin,
IB-Stat) glycopyrrolate (Robinul) are still used occasionally for their GI antispasmodic activity but are associated with typical
anticholinergic side effects such as dry mouth, urinary retention, and tachycardia. Muscarinic agonists, such as bethanechol, find
some limited use for stimulating GI motility.
 G H

The neural regulation of gastric motility involves stimulation

by cholinergic neurons, inhibition by adrenergic neurons, and
the complex modulatory influence of the enteric nervous
system in which dopamine and serotonin play a role.
143
Metoclopramide is a central and peripheral dopamine (D2) Antagonists of D2 and 5-HT3 receptors and agonists of 5-
receptor antagonist; a serotonin (5-HT4) agonist; a serotonin HT4 receptors can stimulate gastric motility, frequently in
(5-HT3) antagonist (at high doses); and a cholinesterase ways that depend on cholinergic neurotransmission. In
inhibitor. Metoclopramide is used during cancer chemotherapy as addition, the GI peptide, motilin, has potential as a prokinetic
an antiemetic in combination with other drugs. Metaclopramide is agent and derivatives of the antibiotic erythromycin act as
the drug of choice for treating diabetic gastroparesis. agonists at motilin receptors in the antrum and duodenum.

144

Does not interfere with treatment of Parkinsons disease, so is

useful for counteracting the GI effects of levodopa and
bromocriptine. However, this drug does elevate serum prolactin.
145 Used for nausea and vomiting associated with gastric stasis, may
be used in reflux esophagitis if hypomotility is prominent and
omeprazole treatment is insufficient. Not FDA approved in the
USA

146

Prochlorperazine, thiethylperazine, and chlorpromazine are

among the most commonly used general purpose antinauseants
147 and antiemetics. Compared to ondansetron or metoclopramide,
these drugs are not uniformly effective in cancer chemotherapy-
induced emesis. However, they also possess antihistaminic and
anticholinergic activities, which are of value in other forms of
nausea such as motion sickness.

148

149
 G H

SE - By initiating a phase III contraction in the digestive rather

than interdigestive period, erythromycin may
inappropriately cause the delivery of large undigested
particles into the small bowel. Subsequently,
150
malabsorption or a dumping syndrome may result.
Erythromycin is a macrolide antibiotic that binds to motilin Erythromycin may cause QT prolongation, cardiac depression,
receptors. Motilin receptors are G protein-coupled receptors and and possibly torsades de pointes. These cardiac toxicities are
are located throughout the enteric nervous system. As a motilin usually seen at higher intravenous dosages. Furthermore, the
agonist, erythromycin increases the frequency and amplitude of chronic use of erythromycin may result in tachyphylaxis or the
antral contractions and initiates gastric phase III contractions. down-regulation of motilin receptors.

These opiodes penetrate into the CNS poorly and can inhibit
151 diarrhea at doses that produce few central effects.
Atropine is added to diphenoxylate and difenoxin preparations,
primarily so that the unpleasant anticholinergic side effects will Agents Used to Treat Diarrhea - General Considerations:
discourage abuse. Atropine may have some capacity to slow Excessive fecal loss of fluid and electrolytes that characterizes
motility, but usually much higher doses are required to achieve this diarrhea is an important aspect of many infectious and non-
effect. Loperamide alone or in combination with antibiotics infectious GI diseases. Although nonspecific drug therapy for
(trimethoprim, trimethoprim-sulfamethoxazole, or a diarrhea is the norm clinically, knowledge of the types of
fluoroquinolone) has been effective in controlling the symptoms of diarrhea can help determine when to use nonspecific agents
travelers diarrhea. or more specific agents.
Atropine is added to diphenoxylate and difenoxin preparations,
152 primarily so that the unpleasant anticholinergic side effects will
discourage abuse.
Atropine is added to diphenoxylate and difenoxin preparations,
153 primarily so that the unpleasant anticholinergic side effects will
discourage abuse.

154

peptide must be given parenterally (SQ); useful for treating the symptoms of tumors of the GI tract (carcinoid, VIPoma,
glucagonoma, gastrinoma, insulinoma), AIDS-related diarrhea, and various motility disorders. Octreotide can inhibit the secretion
of hormones involved in vasodilation. This property makes octreotide useful in treating variceal bleeding and orthostatic
155 hypotension. Octreotide increases splanchnic arteriolar resistance and decreases gastrointestinal blood flow, hepatic-vein
wedge pressure, hepatic blood flow, portal vein pressure, and intravariceal pressure. Decreased blood flow to the portal vein
reduces portal venous pressure in patients with cirrhosis or portal hypertension. A majority of patients with portal hypertension
have a reduction in variceal bleeding when given octreotide.
 G H

GI Water Flux and Motility - Approximately 9 liters of fluid

Dietary Fiber and Bulk Forming Laxatives
a) Dietary fiber is plant cell wall that is resistant to digestion. Usual
sources are whole grains, bran, vegetables, and fruits. These bind
water and ions, soften stools, increase stool bulk, and promote
colonic bacteria.
156 b) A variety of dietary supplements are available containing wheat
bran, psyllium (e.g., Metamucil), methylcellulose (e.g., Citrucel),
or carboxymethylcellulose. Polycarbophil compounds (e.g.,
FiberCon) are non-absorbed, hydrophilic polyacrylic resins.
c) Bulk-forming laxatives are effective within 2-3 days, are well
tolerated, and are safe for long-term use in conjunction with
increased dietary fiber.
d) Choice of product depends on the patients acceptance of
texture, taste, other ingredients (sugar free, low sodium, etc.), and
cost.
enter the small intestine daily, but normally only 0.1 liter is
passed with the stool. The small intestine absorbs about 8
liters per day. Any reduction in this absorption adds to the
burden of the colon, which can absorb from 4-5 liters per day.
The presentation to the colon of fluid in excess of this amount
or of a load of non-absorbable solutes will increase the
passage of fluid and produce diarrhea. Conversely, excessive
reabsorption of water will result in desiccated feces and
constipation. Intestinal motility dictates the time available
for absorption of solutes and fluid. The extent of
absorption generally parallels transit time, such that altered
motility contributes to either diarrhea or constipation. GI
motility also is an important component of vomiting and
enhanced gastric emptying is a significant aspect of the
actions of some antiemetic agents.

Stimulant Laxatives
1) Diphenylmethane derivatives: phenolphthalein (Modane, Ex-Lax, Feen-a-Mint, Correctol, etc.) and bisacodyl (Dulcolax,
157 Carters Little Pill). Effective doses vary widely among patients. Soft or semiliquid stool occurs within 6-24 hours.
Phenolphthalein causes pink to red colored urine and feces. Can cause gastric irritation, electrolyte imbalance, and allergic
reactions are possible. Use of these agents should be limited to 7 days at most.
2) Anthraquinone derivatives: senna, cascara, rheum (rhubarb), and aloe. Produce laxation after about 6 hours. These agents
may produce an excessive laxative effect and abdominal pain and yellowish brown to red urine. May cause nephritis.

Saline laxatives:
Magnesium sulfate (Epsom salt) - intensely bitter taste may
produce nausea; magnesium hydroxide (Milk of Magnesia)
liquid suspension of Mg(OH)2 or as tablets; magnesium citrate
oral solution, or sodium phosphates oral solution (FLEET
158
PHOSPHO-SODA) is relatively pleasant tasting
Sodium phosphate (FLEET) enema is the DOC for fecal
impaction.
Saline laxatives produce laxation with a delay of 6 to 8 hours in
lower laxative doses and a thorough fluid evacuation in less than
3 hrs when administered at higher cathartic doses.
 G H

Osmotic laxatives
a) are not absorbed and are resistant to digestion, increase osmotic pressure in lumen and water content of stools.
b) Lactulose is a disaccharide broken down by bacteria in the GI to fructose and galactose. These metabolites are only partially
absorbed and increase osmotic pressure in the GI lumen. Used to lower blood ammonia levels in patients with portal
hypertension and hepatic encephalopathy.
159
c) Glycerin administered as a rectal suppository softens and lubricates the passage of hard stool.
d) Sorbitol and mannitol are sugars administered rectally, orally, or as an enema.
e) Polyethylene glycol-electrolyte solutions (Colyte, GoLYTELY) are the drug of choice for bowel preparation for colonoscopy,
barium enema, or colorectal surgery. These preparations are mixtures of sodium sulfate, bicarbonate, and chloride, and
potassium chloride in an isotonic solution containing ethylene glycol. Patient drinks four liters of solution over 3-5 hours. Causes
most complete evacuation of GI tract; copious, watery diarrhea.

Surfactant Laxatives: act primarily as stool-wetting and stool-

softening agents.
Docusate salts: produce minimal softening of the feces in 1-3
days; Poloxamers: anionic surfactant and mild stool softener;
160
Dehydrocholic acid: a bile acid, safe and effective as an oral
laxative; Caster Oil: has been used for ages as a cathartic
laxative; from oil of the castor bean, contains ricinoleic acid, has
very bitter taste; adult dose 15-60 ml on empty stomach produces
one or two copious and semi-fluid stools within 1-6 hours. Too
strong a cathartic effect to be used for common constipation.

161

The 5-HT3 subtype of serotonin receptors mediate

neurotransmission at several sites in afferent pathways
controlling emesis, including in the chemoreceptor trigger zone
(CTZ), in the stomach and small intestine, and in the solitary
162 tract nucleus. Blockade of these receptors by selective
antagonists, such as ondansetron, very effectively inhibits emesis, Emesis is a complex process coordinated by the vomiting
even emesis due to high doses of chemotherapeutic drugs or center in the lateral reticular formation of the medulla.
radiation therapy. These drugs are given orally or IV, have plasma The vomiting center receives input from a number of different
half-life of 3-4 hours, and are generally well tolerated. Used neural pathways that utilize various neurotransmitters,
primarily for cancer chemotherapy- and irradiation-induced nausea including dopamine, acetylcholine, histamine, and serotonin.
and vomiting (N&V), but also some post-operative nausea and Therefore, a wide variety of drugs that block receptors for
vomiting (PONV). these neurotransmitters have antiemetic properties.
163
164
165
 G H
Some H1 antagonists are useful for suppressing vertigo. Used
alone, these agents have only very modest efficacy against
166 chemotherapy-induced emesis but are included in combination
regimens to reduce the extrapyramidal side effects of D2
antagonists.

167

168

169

170

171

172

173

174

175

176

Unlike cisapride, which also has 5HT4 agonist activity, tegaserod

has not demonstrated any significant adverse
electrocardiographic effects. Tegaserod has also shown positive
177 effects in the treatment of gastroesophageal reflux disease
(GERD), but confirmatory studies are needed. While not approved
for chronic constipation, tegaserod has shown positive results in a
randomized, controlled trial for this use.
Tegaserod, as a selective serotonin (5HT4) partial agonist, stimulates the peristaltic reflex. Intestin
involved in motor, sensory and secretory functions. Peristalsis occurs due to release of inhibitory and
neurotransmitters via activation of the intrinsic afferent neurons in the GI mucosa. Additionally, increa
and water secretion produce a softer stool. In animal models, tegaserod has also been shown to red
firing (i.e., through the spinal cord) and thus visceral pain sensation. These actions result in the
and altered stool form associated with constipation-predominant IBS.
 G H

Alosetron (Lotronex) is a 5-HT3 antagonist that has been

approved with limiting indications for the treatment of patients with
178 severe IBS with diarrhea. Only patients who have failed on
conventional treatments and who have severe disease are
candidates for alosetron treatment. This drug was previously
withdrawn due to very serious adverse effects, including ischemic
colitis and serious complications of constipation.

In addition to their mood-elevating effects, antidepressant

medications have several physiological effects that may be
beneficial in IBS. In diarrhea-predominant IBS patients, the
179 tricyclic antidepressants, such as imipramine and desipramine,
slow gut transit time and also may alter visceral afferent
neural function. Newer trials with selective serotonin reuptake
inhibitors (SSRIs) have also demonstrated symptomatic
improvement.

180
181

The principal drugs used in the treatment of chronic

inflammatory bowel disease (IBD: ulcerative colitis [UC] and
The mainstay of therapy for mild to moderate UC and CD are the Crohns disease [CD]) are salicylate derivatives (5-ASA),
anti-inflammatory derivatives of the non-absorbed salicylate, 5- corticosteroids, other anti-inflammatory/immunosuppressive
aminosalicylic acid (5-ASA). 5-ASA (mesalamine) can affect agents, and, when indicated, metronidazole (+ ciprofloxacin).
182 multiple sites in the arachidonic acid pathway critical in the UC is an inflammation of the mucosal layer of the colon and
pathogenesis of inflammation, including inhibition of the rectum that leads to chronic diarrhea, rectal bleeding, and
cyclooxygenase pathway and leukotriene formation. However, 5- abdominal pain. CD is a granulomatous inflammatory process
ASA itself is too toxic to the upper GI tract to be taken directly that may involve any part of the GI tract from the mouth to the
unless coated in special resins (Pentasa, Asacol, Rowasa). anus. Unlike UC, the inflammation of CD involves multiple
These formulations of 5-ASA release drug slowly throughout the tissues layers (transmural) and this leads to deep ulcerations,
GI tract or only in the terminal ileum and colon. Alternatively, the adhesions, and fistula formation. Both diseases are
drug is linked to other chemical moieties such that the active drug characteristically chronic and episodic with a clinical course of
is released in the lower GI tract by action of bacterial enzymes. exacerbations and remissions.

Sulfasalazine (Azulfidine), olsalazine, and balsalazide combine 5-

183 ASA linked to sulfapyridine, another 5-ASA molecule, or an inert
carrier, respectively. These 5-ASA compounds have been shown Notice: steroid the DOC for acute flare ups of IBS -
to induce and maintain remission in up to 75% of patients. predinose for CD, Hydrocortisone suppositories for UC

184
 G H

Of active CD patients refractory to glucocorticoids, 6-MP, or 5-

ASA, 65% will respond to intravenous infliximab; one-third will
185 Tumor necrosis factor (TNF) is a key inflammatory cytokine and enter complete remission. Patients who experience an initial
mediator of intestinal inflammation. The expression of TNF is response will respond again to repeated infusions of infliximab
increased in inflammatory bowel disease. Infliximab is a every 8 weeks up to 44 weeks. Thus infliximab may also be
chimeric mouse-human monoclonal antibody against TNF that is efficacious in maintaining remission. However, more trials
extremely effective in Crohns Disease. It blocks TNF in the serum need to be completed on remission maintenance after
and at the cell surface and likely lyses TNF-producing infliximab therapy. Infliximab is also effective in CD patients
macrophages and T cells through complement fixation and with refractory perianal and enterocutaneous fistulas, with a
antibody-dependent cytotoxicity. 68% response rate and a 50% complete remission rate.

186

187
188
189
190
191
192
193
194

195
196
197

198
 G H

Interferons (IFNs) are potent cytokines that possess antiviral,

immunomodulating, and antiproliferative actions. There are
three major classes of IFNs, alpha, beta, and gamma. Clinically
used IFNs are recombinant proteins of the alpha class.
Endogenous alpha-interferons are secreted by leukocytes (e.g.,
macrophages, B lymphocytes, and non-B non-T lymphocytes) in
response to viral infection or various synthetic and biological
inducers. All alpha-IFNs share common biologic activities
199
generated by the binding of interferon to the cell-surface receptor.
Interferon binding to the cell surface receptor is followed by
activation of the JAK-STAT tyrosine kinase signal transduction
pathway and leads to the nuclear translocation of a cellular
protein complex that binds to genes containing an interferon-
specific response element. This in turn leads to synthesis of IFN stimulates the production of several enzymes such as 2'-
over two dozen proteins that contribute to antiviral effects, 5'-oligoadenylate synthetase (2'-5'-OAS) and beta2-
such as inhibition of viral penetration or uncoating, synthesis microglobulin. Expression of major histocompatibility antigens
of mRNA, translation of viral proteins, and/or viral assembly by IFNs may also contribute to antiviral activity by enhancing
or release. the lytic effects of cytotoxic T lymphocytes.

Oral ribavirin combined with injected interferon is effective for

treatment of chronic hepatitis C!! Aerosolized ribavirin is
200 approved for treatment of RSV bronchiolitis and pneumonia in
hospitalized children. Ribavirin is teratogenic, embryotoxic,
oncogenic, and gonadotoxic. Pregnant women should not directly
care for patients receiving ribavirin aerosol.
201

202

203

204

Peg interferon plus ribavirin is the treatment of choice for

205 chronic hepatitis C; it provides sustained viral responses of 54%
to 63%. When used as monotherapy, peg interferons once weekly
are more effective than standard preparations.
 G H

IFN-a and lamivudine are quite comparable in efficacy as first-line

therapy for chronic hepatitis B. Interferon requires only brief-
duration therapy, too limited in duration to support viral variants,
206 but requires subcutaneous injections and is associated with a high
level of intolerability. Lamivudine requires long-term therapy in
most patients and, when used alone, fosters the emergence of
viral variants. On the other hand, lamivudine is taken orally, is SE are negligible, indistinguishable from those observed in
very well tolerated, leads to symptom improvement and is placebo recipients. Long-term monotherapy with lamivudine is
effective even in patients who fail to respond to interferon. associated with mutations in a key motif of HBV DNA
Although some prefer to begin with interferon, most physicians and polymerase, analogous to mutations that occur in patients with
patients prefer lamivudine as first-line therapy. HIV infection treated with this drug.

Adverse effects: Doses of adefovir used for HBV are

207
Some experts recommend adefovir over lamivudine for long-term
treatment of HBeAg-negative or cirrhotic patients because of the
high risk of emergence of lamivudine resistance.
generally well tolerated but may be associated with asthenia,
headache, diarrhea and abdominal pain. Higher than
recommended doses (30-60 mg/d) and pre-existing renal
impairment are risk factors for azotemia and renal tubular
dysfunction. Hepatitis flares may occur after adefovir is
stopped.

At prescribed doses: Acetaminophen may be converted in

the liver by cytochrome P450 to a quinone type of reactive
A single dose of 10-15 g, or occasionally less, may produce clinical intermediate that is rapidly transformed to a glutathione-
evidence of liver injury. Ingestion of 25 g or more usually, but not type conjugate (mercapturate), when the levels of
208 always, causes fatal fulminant disease. Nausea, vomiting, glutathione are not limiting. With normal levels of the drug,
diarrhea, abdominal pain, and shock are early manifestations this pathway is only of minor significance. However, with
occurring 4-12 hours after ingestion. Then 24 to 24 hr later, when massive drug overdose, glutathione becomes depleted
these manifestations are decreasing, hepatic injury begins to and the quinone reactive intermediate may reach
become apparent. Hepatic failure may not be evident until 4-6 sufficient concentrations to react with nucleophilic
days after ingestion, and aminotransferase levels approaching groups of tissue constituents. Hepatic and renal necrosis
10,000 units are not uncommon. Renal failure and myocardial can result. An antidote, N-acetylcysteine (Mucomyst), take
injury may also be present. the place of the depleted glutathione in the reaction.

209

210

211
 G H
212
Generally well absorbed
Gut bacteria (Eubacterium lentum) in 10% of population rapidly
metabolize digoxin to inactive metabolites
Likely accounts for variability in dosing
Digoxin
Excreted unchanged by kidney
213 Metabolized in liver, then excreted in bile
Enterohaptic circulation creates long elimination t1/2
May be useful in kidney failure pts
214
Treatment strategies for Acute Decompensated HF:
Although pts are edematous, monotherapy with a loop diuretic
is inappropriate - activates Renin-Angiotensin-Aldosterone and
sympathetic nervous system - vasoconstriction is increased, so
much so that GFR declines.
Pts must receive a diuretic and vasodilation (nesiritide)
An inverse relationship exists between extracellular K+ and
phosphorylation of the cardiac ATPase
Elevated K+ decreases the affinity of the ATPase for cardiac
glycosides
Low levels of K+ increases the affinity of the ATPase for
cardiac glycosides!!
Watch out for hypokalemia!
These drugs have a low therapeutic index
Because longer acting drugs manifest toxicity for longer
periods of time, there are significant disadvantages in using
digitoxin.
Nesiritide is particularly useful for short-term vasodilating
actions
Hx: natriuretic peptides were first discovered as products
released from the atrium (ANP). In the hunt for similar
substance, a compound was isolated from brain (BNP) that
was even more efficacious in causing vasodilation. (Note this
is not beta-natriuretic peptide, it is B-natriuretic peptide.)
 G H

215 In healthy subjects, nitric oxide (NO) dilates coronary

NO (from nitrates or endothelium) causes endothelial cells to
activate Guanylyl cyclase to convert GTP to cGMP, causing
dephosphorylation of Myosin Light Chain causing relaxation
arteries
Old hypothesis was that NO improved perfusion to hypoxic
areas of heart. This hypothesis is incorrect
In angina of effort, direct infusion of NTG into heart does not
relieve angina, but sublingual NTG does. Thus, heart is not
the critical site of action.

216

217

218

219

220

221

Class 1A:
222 1. Reduce automaticity (phase 4, reduce slope of upstroke,
AP becomes broader)
Rarely used;has a vasodilator effect so can be used in reduced 2. Prolong action potential duration
vent function or HF; also has a indirect anticholinergic effect that 3. Reduce conduction velocity (phase 0, slope also reduced)
will decrease vagal tone and may facilitate condion in the AV node Note: (phase 3 affected, not 4, according to Lange)
 G H

Antiarrhythmic Class III: prolong duration of cardiac action

223
Absorbed rapidly and is 100% orally bioaviable; i.v. loading
dose must be given slowly, so limited to clinical situations with
adequate time available; Does not increase digoxin levels;
cimetidine and ranitidine decrease clearance 10-50%
potential (AP) and refractoriness;most potent class of
antiarrhythmic drugs, effective for rhythm disturbances in all
tissues; combo of blocker, Ca channel blocker and Na
Channel blocker along with primary effect on repolarization
current (basically does everything the other classes do put
together)

224 Loading dose not recommented, risk of HF or anticholinergic SE;

rapid fluctuations in plasma concentration; Phenytoin, rifampicin,
and phenobarbital increase hepatic metabolism (elimination); Antiarrhythmic Class IA include quinidine, procainamide,
depression of contractility from co-admin with beta-adrenergic of and disopyramide - increase venticular refractoriness and
CCB prolong the QT inverval

Class 1B
Reduce automaticity
Shorten APD (narrow QRS)
225 Slow conduction velocity
Have little or no effect on atrial tissue Antiarrhythmic Class Class IB include lidocain, mexiletine,
all other classes work above ventricles and tocainide - modest Na channel blockers that shorten
Moderately effective for ventricular arrhythmia the action potential duration (APD) and refractoriness with
only used for V!! little effect on PR, QRS, or QT intervals

226 Typically hepatic metabolism (CYP2D6), can be increased with

phenobarbital, phenytoin, or rifampicin; Pts with hepatic CYP2D6
deficiency are dependent on renal excretion. (notice, quinidine
inhibits the CYP2D6 Ez)

227

228
 G H

Antiarrhythmic Class Class IC include flecainide and

229 propalenone - potent Na channel blockers that slow
eliminated by the liver (CYP2D6) and kidney(so not effected by conduction velocity, little effect on repolarization, and increase
CYP2D6 deficiency except in renal insufficiency) PR and QRS intervals, little change on QT interval

230

231
eliminated by the liver CYP2D6; if CYP2D6 deficiency have slow
elimination of propafenone and develop significant receptor
antagonism at low doses

232

Antiarrhythmic Class II: beta adrenergic antagonist, effective

233 for supraventricular arrhythmias and tachyarrhythmias caused
by excessive sympathetic activity; limited efficacy for severe,
life-threatening ventricular arrhythmias; mech unknown; only
esmolol, ultra short half life=9min, used for atrial fibrillation and drugs effective in preventing sudden cardiac death with
atrial flutter after surgery MI survivors

Most potent class of antiarrhythmic agents (meaning Class III)

234 Effective for rhythm disturbance in all tissues
Agents possess combination of mild beta blocker, calcium
almost as good as amiodarone; eliminated by the kidney w half life channel blocker and sodium channel blocker activity along
of 12hrs with primary effect on repolarization current (K current)
 G H

Amiodarone:
prolonged half-life of 30 days - makes difficult to use to
reach steady state (4-5 half lives) requires half a year (3
months for effect), and if make a mistake, takes 5 half lives to
get ride of , must follow pt closely (have foresight)
235
Rapid effect when given IV
Side Effects
Hepatotoxicity
Hypo and hyperthyroidism
metabolized to desethyl metabolite (DEA) in the liver; half life of Corneal deposits
5hrs to 30days (Cecil says 103days); IV HAS A RAPID EFFECT Irreversible pulmonary fibrosis (permanent)

236
oxidative hepatic metabolism and cleared by the kidney

237
eliminated by liver (CYP3A4) and kidney; half life=8-10 hrs but
12% to 18% lower in women
Antiarrhythmic Class IV: Ca channel antagonists; dont
affect the Phase2 plateau???; poor effect as direct
238 antiarrhythmic for atrial or vent arrhythmias, most effective
on slowing conduction velocity (Phase 0) in nodal
tissues; useful for the control of vent rate in SVT

239 CCB and beta blockers have ~same effect in heart - slow
conduction velocity in the AV node (prevent SVT from getting
to V)

240

241

derived from digitalis

 G H
242
Half life of 1.5 to 10 sec (shortest half life of any drug);
metabolized in the plasma
243
Absorbed rapidly and is 100% orally bioaviable; i.v. loading
dose must be given slowly, so limited to clinical situations with
adequate time available; Does not increase digoxin levels;
cimetidine and ranitidine decrease clearance 10-50%
244
245
246 Activated Partial Thromboplastin Time (aPTT) is used to
monitor heparin anticoagulant therapy:
Normal = 35-45 sec; aPTT = 1.5 to 2.5 times control
(theraputic goal with heparin); Ca++ ion, "partial
thromboplastin", and a charged surface contact are added to
plasma and clotting time is compared to a control plasma sample.
The aPTT measures the activity of the intrinsic coagulation
pathway including the factors deficient in the two forms of
hemophilia, hemophilia A (factor VIII deficiency) and hemophilia
B (factor IX deficiency). The aPTT is used to monitor
anticoagulant therapy with unfractionated heparin.
247
Longer duration, simpler kinetics, clotting tests not usually
required
248
Used diagnostically to determine whether ventriclar
tachycardia was induced supraventricularly or
ventricularly
Antiarrhythmic Class III: prolong duration of cardiac action
potential (AP) and refractoriness
Thrombin Time: Dilute thrombin is added to the patients
plasma and a control plasma and the clotting time are
compared. Since no Ca++ is added to the plasma, clotting
time is independent of reactions involved in the
generation of thrombin and depends only upon the
reactions initiated by adding the weak exogenous
thrombin. A long thrombin time may be caused by increased
antithrombin activity, for example when plasma contains
heparin. Dilute thrombin is added to the patients plasma and
a control plasma and the clotting time are compared. Heparin
prolongs both the aPTT and the thrombin time; at higher
doses can also prolong the PT time
LMWH preparations have been developed with the goal of
decreasing bleeding episodes while still retaining
anticoagulant activity, especially for the prevention of deep
venous thrombosis (DVT) in surgical patients.
 G H

Prothrombin Time (PT): Plasma will clot in 12 to 14 seconds

249 after addition of calcium ion and "thromboplastin" (a saline
extract of rabbit or human brain that contains tissue factor and
phospholipids). Warfarin anticoagulant therapy leads to
inactivation of several clotting factors (especially VII, X, and
thrombin) and prolongs the clotting time in the PT test. The INR
(see below) is used to normalize PT test results and monitor
warfarin therapy. The International Normalized Ratio (INR): is a Monitor therapy with INR (PT test); PT time (corrected to an
format for reporting prothrombin times of patients on warfarin. INR) INR = 2.0 to 3.0

250

Clopidogrel:
Alternate to, or additive with, aspirin Approved for the prophylaxis of stroke, MI, peripheral arterial
Inhibits ADP pathway in platelets disease, and acute coronary syndrome. This drug
251 Reduces platelet aggregation irreversibly inhibits platelet fibrinogen binding. Clopidogrel
NO EFFECT ON PROSTAGLANDINS preferred over aspirin: selectively inhibits the binding of adenosine diphosphate
if loop diuretic is being used (ADP) to its platelet receptor and the subsequent ADP-
if kidney disease is present mediated activation of the glycoprotein GPIIb/IIIa
Particularly useful in unstable angina complex, thereby inhibiting platelet aggregation.

Inhibits platelet function by increasing cyclic AMP levels (inhibits

phosphodiesterase and raises adenosine levels which stimulates
cyclic AMP synthesis). It has coronary vasodilator activity as well,
252 but has been mostly disappointing in clinical trials. Dipyridamole is
now indicated in patients with prosthetic heart values and as an
alternative to aspirin for secondary prevention of acute myocardial
infarction, to prevent stroke in patients with transient ischemic
attacks, and to maintain potency of coronary bypass grafts.

253
Ticlopidine (Ticlid) inhibits the platelet ADP receptor and inhibits
the binding of fibrinogen to activated platelets, and thus blocks
platelet aggregation and clot retraction. The effect on platelet
function is irreversible for the life of the platelet.
 G H

inhibits cyclic AMP phosphodiesterase III, suppresses cyclic AMP

degradation, and the resultant increase in cAMP in platelets and
blood vessels leads to inhibition of platelet aggregation and
254 vasodilation. Cilostazol is indicated for the reduction of
symptoms of intermittent claudication, as indicated by an
increased walking distance. The use of this drug is
contraindicated in patients with CHF of any severity.

Glanzmann Thrombasthenia: congenitally deficient or

Monoclonal Ab that prevents clot formation by binding the
glycoprotein IIb/IIIa receptor, thus inhibiting platelet aggregation.
255 The drug has greater antithrombotic activity than aspirin or
heparin. Abciximab is used as an adjunct in high-risk angioplasty
and in acute coronary syndromes. During angioplasty procedures,
the balloon device can cause formation of blood clots that can
cause restenosis of the artery and lead to cardiac arrest.
Eptifibatide and tirofiban, are small peptide analogs of critical
domains of fibrinogen that inhibit platelet aggregation by
256 blocking ligand binding to the IIb/IIIa receptor. These two drugs
are also used to percutaneous transluminal coronary angioplasty
(PTCA).
inactive GpIIb-IIIa platelet surface receptors (noncleaved
fibrinogen is an important cofactor), ADP induces a
confromational change of the GpIIb-IIIa platelet surface
receptors so that they can bind fibrinogen. Fibrogen then acts
to connect multiple platelets together to form large aggregates
(during platelet aggregation phase, after adhesion and
secretion)
Combined antiplatelet and antithrombotic therapy (ie
heparin plus platelet glycoprotein Iib/IIIa inhibitor) is
superior to heparin alone in reducing morbidity and
mortality in pts with acute coronary syndromes

257

258

Derived form the saliva of the medicinal leach (Hirudo

259 medicinalis), does not require cofactors and is not inactivted by
platelet factor 4 or plasma proteins. Monitor therapy PTT

260

Heparin-induced Thrombocytopenia unfractionated heparin

261 induces formation of Ab that activate platelets (HIT II, antibody
mediated), endothelial injury, and prothrombin state. Use low
molecular weight heparin to prevent.
 G H
262
The direct thrombin inhibitor bivalirudin has been recommended
as an improvement over heparin during angioplasty and is the
agent of choice in patients with heparin-induced
thrombocytopenia.
263
264 t-PA is the natural protease activator of plasminogen. It has been
purified and is now produced by recombinant DNA technology.
Three forms of recombinant t-PA are now available, alteplase (rt-
PA), the full-length form, reteplase (r-PA), a shorter, genetically
engineered mutant form, and tenecteplase (TNK-tPA), a mutated
form with a prolonged half-life, increased fibrin specificity, and
increased resistance to inhibition by plasminogen activator
inhibitors.
Reteplase does not bind fibrin so tightly, allowing the drug to
diffuse more freely through the clot rather than binding only to
265 the surface the way t-PA does. Also, this redesigned t-PA in high
concentrations does not compete with plasminogen for fibrin-
binding sites, thus allowing plasminogen at the site of the clot to be
transformed into clot-dissolving plasmin.
266
Bivalirudin is a short-acting, synthetic direct thrombin binding
inhibitor approved for patients with unstable angina
undergoing coronary angioplasty. Most patients in the USA
with acute coronary syndromes undergoing angioplasty are
now treated with platelet glycoprotein IIb/IIIa receptor
antagonists (eptifibatide, tirofiban, or abciximab) plus aspirin
and low doses of unfractionated heparin. This drug is very
expensive compared to more conventional treatments.
($456.00 versus $68.00 Lovenox or $1.20 for UFH)
Intravascular clots dissolve as a result of the action of
plasmin, an enzyme that digests fibrin. Plasminogen, an
inactive precursor, is converted to plasmin by cleavage of a
single peptide bond by tissue plasminogen activator (t-PA),
a protease released from endothelial cells. The normal
fibrinolytic system is regulated such that unwanted fibrin
thrombi are removed, while fibrin in wounds persists to
maintain hemostasis. A major factor in this regulation involves
greater fibrinolytic activity when plasmin is bound to the fibrin
in a clot than to fibrinogen free in circulation. t-PA is rapidly
cleared from blood and/or inhibited by circulating inhibitors
(such as 2-antiplasmin) and thus does not normally effect
circulating plasminogen.
 G H

Streptokinase has been shown to be effective when given IV for

dissolution of intracoronary thrombi in myocardial infarction.
267 Therapy is most beneficial when instituted early (within 90
min) after the onset of symptoms. Streptokinase has also been
used to treat pulmonary embolism, deep venous thrombosis, and
peripheral vascular disease. Bleeding (especially cerebrovascular)
is a serious adverse reaction.
Nonenzymatic activator of plasminogen extracted from
beta hemolytic streptococci. It forms a complex with
plasminogen and accelerates conversion to plasmin. Most
patients have antibodies to streptokinase resulting from
previous exposure to streptococci.

268

(Anisoylated Plasminogen Streptokinase Activator Complex;

APSAC) is the inactive form of the plasminogen streptokinase
activated complex that becomes activated once in the blood.
269 This preparation can be given by rapid IV injection and has greater
selectivity for plasminogen associated with clots, i.e., has less
effect on free plasminogen in plasma and thus less chance of a
generalized fibrinolytic state. It has been shown to have beneficial
thrombolytic effects especially when administer early after an
ischemic attack in myocardial infarction.

270

271
Also give broad spectrum Abx and Xigris for sepsis and DIC
272
273
 G H

274

Mechanism causing rhabdomyolysis is not entirely clear

HMG-CoA inhibitors also inhibit Q10 (ubiquinone), and this
mechanism is most likely. Various statins do so differentially, and
those most efficacious in inhibiting Q10 are also most likely
offenders
Mevalonic acid is a constituent of cell wall molecules, and HMG-CoA reductase inhibitors, cholesterol uptake inhibitors,
blockade of their formation is also implicated, although this and bile acid binding resins primarily used for
hypothesis is losing favor hypercholesterolemia

275

276
 G H
277
278

279 Fibric acid derivatives: Used for hypertriglyceridemia in which

VLDL is elevated
Bile Acid-Binding Resins: Used for hypercholesterolemia with
normal triglycerides
Cholesterol uptake inhibitors: Block cholesterol absorption in
intestine

280

281

282

Taking with food, or aspirin or anithistamine 30 min before can

minimize SE

283
 G H

Phase I and Phase II reactions are biotransformations of

chemicals that occur during drug metabolism.
Phase I metabolism usually precedes Phase II, though not
necessarily. During these reactions, polar bodies are either
introduced or unmasked, which results in (more) polar
metabolites of the original chemicals. Phase I reactions may
284 occur by oxidation, reduction or hydrolysis reactions. If the
metabolites of phase I reactions are sufficiently polar, they
may be readily excreted at this point. However, many phase I
products are not eliminated rapidly and undergo a subsequent
reaction in which an endogenous substrate combines with the
newly incorporated functional group to form a highly polar
Note: unlike bile acid binders, this drug does not decrease conjugate.
absorption of other fatty substances Phase II reactions usually known as conjugation
Well tolerated reactions (e.g., with glucuronic acid, sulfates, glutathione or
No inhibition of cholesterol synthesis in the liver or increase amino acids) are usually detoxication in nature, and involve
in bile acid secretion. the interactions of the polar functional groups of phase I
metabolites.

285

286
 G H
287
Treatment of Iron Deficiency Anemia
The severity and cause will determine the appropriate approach
to treatment.
Symptomatic elderly patients with severe iron deficiency anemia
and cardiovascular instability may require red cell transfusions.
For the majority of cases, oral iron therapy is sufficient.
All dividing cells are undergoing DNA synthesis and require the
precursors and cofactors necessary for synthesizing the purine
and pyrimidine bases in DNA. Two of these essential factors are
288 vitamin B12 and folic acid. Deficiencies in either of these two
substances lead to impaired DNA synthesis and abnormal
maturation and functioning of cells. These changes occur in
any dividing cells, but tissues which normally undergo rapid cell
division, i.e., hemopoietic cells and GI epithelium, are the most
susceptible. Anemia is the chief finding in patients with Vitamin
B12 or folic acid deficiency; GI symptoms may also occur.
Neurological abnormalities may also occur in Vitamin B12
deficiency, but not usually in folic acid deficiency.
Prophylaxis: Generally, prophylactic use of iron preparations
should be reserved for individuals at high risk; pregnant and
lactating women, low birth weight infants and infants
maintained on unsupplemented milk formulas. Other
patients at high risk include rapidly growing children (low
meat diets) and in adults with chronic blood loss.
Megaloblastic anemia: In vitamin B12 or folic acid deficiency
there is decreased DNA synthesis, but continued RNA and
protein synthesis which leads to a characteristic production of
large (macrocytic) red blood cell precursors (megaloblasts)
that do not mature properly into circulating red cells. The
bone marrow is hypercellular and the red cells formed are
more susceptible to destruction.
 G H

Folates are readily absorbed (50-200 ug/day) from ingested

food. Folic acid is stored (5-20 mg) in numerous tissues,
Sources: Richest sources are yeast, liver, kidney, green especially the liver. Folates are excreted in the urine and stool
289 vegetables. Folic acid deficiency, unlike B12 deficiency, is often and are also destroyed by catabolism. Folates are unlike
caused by inadequate dietary intake of folates. Elderly people, vitamin B12 in that there is more breakdown, less storage,
poor people, food faddists, and alcoholics are groups of patients and greater demand, and therefore, folic acid deficiency can
who are prone to diets lacking in fresh vegetables, eggs, and develop within 1-6 months after adequate intake stops.
meat. Deficiency may also occur in pregnant women and patients Certain drugs interfere with folate absorption or metabolism
with intestinal disease, cancer, or undergoing dialysis. (phenytoin, isoniazid, methotrexate, trimethoprim).

Colony stimulating factors (CSFs) have only been recently purified and their physiologic functions and mechanisms of action are
incompletely understood, but these molecules hold great promise for treating anemias and myelodysplastic disorders.
a. SCF (Multi CSF): stimulates bone marrow production of RBCs, granulocytes, macrophages, and platelets.
290
b. GM CSF: stimulates production of granulocytes and macrophages.
c. G CSF: stimulates granulocyte proliferation and differentiation.
d. M CSF: stimulates monocyte macrophage proliferation.
e. Other cytokines: numerous other factors influence bone marrow derived cell proliferation, differentiation, and function
including the interferons (alpha, beta, gamma), the interleukins (1-12), and other factors.

When an increase in EPO levels in the circulation occurs in

291
Erythropoietin: a glycoprotein synthesized by the kidneys in
response to hypoxia and stimulates the division and
differentiation of erythroid progenitors in the bone marrow. It has
been purified, cloned, and the recombinant human hormone is
being produced by genetic engineering techniques.
The human G-CSF gene has been inserted into E. coli which
produce the protein. Endogenous G-CSF is produced by
292 monocytes, fibroblasts and endothelial cells. It is a lineage-
specific stimulator of the proliferation, differentiation, and end-cell
function of the neutrophil line.
response to acute onset of anemia, new proerythroblasts
and normoblasts appear in the bone marrow within 2 to 4
days, and new reticulocytes begin to appear in the
peripheral blood within 3 to 7 days. Reestablishment of
normal numbers of circulating erythrocytes and normal tissue
oxygenation results in reduced production of EPO and a
reduced rate of production of erythrocytes back to the normal
basal level.

293

Sargramostim increases the cytotoxity of monocytes toward

certain neoplastic cell lines and activates polymorphonuclear
neutrophils to inhibit the growth of tumor cells.
 G H

Oprelvekin has been shown to have non-hematopoietic

properties. The drug enhances healing of gastrointestinal
294 lesions and currently in clinical trials for the treatment of Crohn's
disease. Oprelvekin also has been shown to induce protein
synthesis, inhibit adipogenesis, inhibit pro-inflammatory
cytokine production by macrophages, increase production of
osteoclasts, and stimulate neurogenesis.

Mech: Inhibits ribonucleotide diphosphate reductase, the

enzyme that converts ribonucleotides to
deoxyribonucleotides and is a crucial and probably rate-
limiting step in biosynthesis of DNA. Hydroxyurea causes an
immediate inhibition of DNA synthesis without interfering with the
295 synthesis of ribonucleic acid or of protein. The drug is specific
for the S phase of the cell cycle. It causes cells to arrest at
the G1-S interface. Since cells are highly sensitive to irradiation
in the G1 phase of the cycle, combinations of hydroxyurea and
irradiation cause synergistic toxicity. Hydroxyurea also potentiates
the antiproliferative effects of other cancer chemotherapeutic
agents such as cisplatin, alkylating agents, topoisomerase
inhibitors, and antimetabolites.
296
Hydroxyurea is approved for treating adults with sickle cell
disease. The drug reduces the number of painful crises, the
frequency of acute chest syndrome and hospitalization, and
the need for blood transfusions. Known pharmacologic
effects of hydroxyurea that may contribute to its beneficial
effects include increasing hemoglobin F levels in RBCs,
decreasing neutrophils, increasing the water content of
RBCs, increasing deformability of sickled cells, and
altering the adhesion of RBCs to endothelium.

297

298
First-generation sulfonylureas vary considerably in their half lives,
299
duration of action, and extent of metabolism

300
301
302
 G H

Sulfonylureas: Mechanism of Action

303
Type 2 DM patients often fail to respond adequately to a single
agent and are then treated with a combination of oral drugs or are channel. Blockade of this channel reduces K+ conductance
switched to intensive therapy with insulin. Patients with Type 1
diabetes are treated with insulin and do not respond to oral
hypoglycemic agents.
A. lower blood glucose levels by stimulating insulin
release from pancreatic cells. Initially (first few months of
treatment), fasting plasma insulin levels and insulin responses
to oral glucose are increased. With chronic administration,
circulating insulin levels decline to those that existed before
treatment, but, reduced plasma glucose levels are maintained.
B. Sulfonylureas bind to and block an ATP-sensitive K+
causing membrane depolarization and influx of Ca2+ through
voltage-sensitive Ca2+ channels. Ca2+ influx leads to insulin
secretion.

304

305

Repaglinide & nateglinide are structurally different from
sulfonylurea drugs; they are meglitinides. Meglitinides binds to the
ATP-sensitive potassium channel on pancreatic beta cells at a
different site than sulfonylureas. The subsequent
306
depolarization of the beta cell opens the Ca channel and rapidly
increases insulin secretion. Thus, these drugs are sometimes
called non-sulfonylurea secretagogues. Both of these drugs are
well absorbed and reach peak levels within 30 to 60 minutes.
These drugs are rapidly metabolized by the liver to inactive
metabolites that are excreted in the bile or urine.
Repaglinide and nateglinide were developed to manage meal
related glucose loads. The rapid action of these drugs
(taken right before a meal) makes them useful for patients
who are erratic eaters. For example, if a meal is skipped so is
that dose of drug and hypoglycemia is avoided. Only the first
phase of insulin secretion is stimulated because of the rapid
metabolism of the drugs. These drugs are approved for
monotherapy or combined with metformin. Adverse effects
are comparable to sulfonylureas but these drugs should be
used cautiously in the elderly and those with liver dysfunction.

307
 G H

Metformin has been used as sole therapy to treat Type 2 DM

Metformin has an antihyperglycemic action; not a
hypoglycemic action. Unlike the sulfonylurea drugs, It does not
directly effect insulin release. It does not cause hypoglycemia
308 even at high doses. Metformin appears to produce the following
effects:
reduce hepatic glucose output by inhibiting gluconeogenesis.
increase insulin action in peripheral tissues (increases anaerobic
glycolysis), i.e., decreases insulin resistance;
increase glucose uptake and utilization by muscle;
reduces intestinal absorption of glucose
or can be added to sulfonylurea or TZD treatment if only
partial reductions of plasma glucose have been achieved.
Metformin is most often prescribed for patients with
refractory obesity whose hyperglycemia is due to "insulin
resistance". Because metformin is an insulin sparing
agent and does not cause weight gain or provoke
hypoglycemia, it offers advantages over sulfonylureas and
insulin in treating obese, insulin-resistant patients. It also has
a a significant lipid-lowering effect, i.e., it decreases total
cholesterol, LDL, and triglycerides.

309

The most common side effects are flatulence, diarrhea and GI

upset due to undigested carbohydrate. These adverse effects
lead to poor patient compliance.
310

311

TZDs increases glucose uptake and glucose oxidation in both

muscle and adipose tissue, while reducing hepatic glucose
output and lipid synthesis in muscle and fat cells. Insulin Free fatty acids (FFA) increased insulin resistance (FFA
release is not directly stimulated. increased in obesity)

312

313
 G H

The identified metabolic effects of pramlintide are:

suppression of endogenous glucagon production, especially in
314 the postprandial state.
reduction of postprandial hepatic glucose production.
reduction of gastric emptying time. Pramlintide is delivered by subcutaneous injection before
centrally-mediated induction of satiety meals and cannot be mixed with insulin. Thus, use of
reduction of postprandial glucose levels pramlintide requires an additional 2 to 3 injections per day.

Among GLP-1 and Exenatides (and Dipeptidyl Peptidase

Inhibitors) proposed effects are:
glucose-dependent enhancement of endogenous insulin
secretion and perhaps insulin sensitivity.
315 inhibition of endogenous glucagon secretion.
possible appetite suppression and satiety induction. Glucagon-like peptide 1 (GLP-1) is a peptide hormone
reduction in speed of gastric emptying. produced by the cleavage of the proglucagon precursor. It is
possible stimulation of islet growth, differentiation and secreted by intestinal L cells. The analog Exenatide was first
regeneration. discovered in the salivary secretions of the Gila monster.
316

Among GLP-1 and Exenatides (and Dipeptidyl Peptidase

Inhibitors) proposed effects are:
glucose-dependent enhancement of endogenous insulin
317 secretion and perhaps insulin sensitivity.
inhibition of endogenous glucagon secretion.
possible appetite suppression and satiety induction.
reduction in speed of gastric emptying.
possible stimulation of islet growth, differentiation and
regeneration.
318
319
 G H

In solution, insulin can exist as a monomer, a dimer, or as a

320
hexamer (six molecules).The various insulin preparations
crystallize differently. This is an important determinant of how
fast the hormone crystals dissolve after subcutaneous
injection. Since only insulin free in solution can be
Insulin is a protein hormone. cells of the pancreatic islet absorbed, the rate of dissolution of injected insulin
synthesize insulin from a single chain precursor = preproinsulin crystals along with local blood flow determines the rate of
that is further shortened to form proinsulin. Proinsulin folds and onset and duration of action of the preparation. When the
disulfide bonds form. In the Golgi complex, proinsulin is packaged hormone is absorbed and the local concentrations fall, the
in secretory granules along with the enzymes that remove the hormone dissociates into monomers, the active state of the
connecting peptide (C peptide) to form insulin. molecule.

321

322

323

Regular Insulin is short - acting insulin and is simply a solution

of regular crystalline zinc insulin dissolved in a buffer at neutral pH.
Regular insulin has a fairly rapid onset of action (30-45 min) and a
324 short duration of action (4-8 hr). Regular and aspart are the only
types of insulin that can be administered as IV infusions.
Regular, aspart, glulisine, and lispro insulin can be used in
subcutaneous infusion pumps.
Intermediate-Acting Insulins are formulated so that they dissolve
more gradually when give S.C., their duration of action is therefore
325 longer.
NPH insulin is a suspension (not dissolved) of insulin in a
complex with protamine (a highly charged protein) and zinc in a
phosphate buffer.
326
 G H

Glargine (or Detemir or Ultralente) [Basal-Bolus] Regimen: A

pre-breakfast dose of Glargine (or detemir or ultralente) and
ultrashort or regular insulins is taken along with additional
doses of ultrashort or regular insulin at lunchtime and
327 dinnertime. Glargine insulin provides a basal requirement for
insulin, while the rapid acting insulin meets the postprandial
Ultra-Long-Acting Insulins are formulated to dissolve very slowly demand. To achieve more uniform basal levels, the dose of
when injected SQ and thus, these insulins have a very slow onset basal insulin is sometimes divided into morning and evening
and prolonged, relatively flat peak of action. doses.
328
329
330

331 Thyroid hormone receptors belong to the superfamily of

hormone-responsive nuclear transcription factors that are
similar in structure and mechanism of action. Other members
of this family include receptors for steroid hormones, vitamin
Thyroid Hormones: The thyroid gland is the source of the thyroid D, and retinoids. These receptors are activated by hormone
hormones, thyroxine (T4) and triiodothyronine (T3). Normally 80 binding and bind to specific sites on DNA (hormone
100 microg of thyroxine and 30 microg or triiodothyronine are response elements, HRE) in the promoter/regulator regions
produced within 24 hrs, released into the blood stream, and taken of genes. Activation of the receptor results in either activation
up by all tissues. or repression of specific genes.

Indications: The thioamide antithyroid drugs are the preferred

treatment for children, pregnant women, and young adults with
uncomplicated hyperthyroidism. These patients have some
332 chance of spontaneous remission and this is the only treatment
modality that leaves the thyroid gland intact and does not carry
the added risk of hypothyroidism that often accompanies
radioactive iodine treatment and surgery. Treatment for Hyperthyroid states: Exophthalmic goiter, Grave's Disease
uncomplicated Grave's disease typically lasts several years. (diffuse toxic goiter) - The clinical state of thyrotoxicosis is
These drugs are also used to hasten recovery while awaiting the characterized by: nervousness; weight loss; hyperphagia;
effects of radioactive iodine or to control the disorder in heat intolerance; increased pulse pressure; fine tremor of
preparation for surgery. Unfortunately, with antithyroid drug outstretched fingers; elevated BMR; exophthalmos; lowered
treatment alone, there is a 60-70% incidence of relapse. peripheral vascular resistance; increased cardiac output.
 G H

333

334

335

Iodides are rarely used as sole therapy. The most important

Iodides: (1) inhibit thyroid hormone release; (2) block iodotyrosine
and iodothyronine synthesis by blocking organification; (3)
336 decrease the vascularity of the thyroid gland. The inhibitory effect
on hormone synthesis is known as the Wolff Chaikoff effect. This
represents an inherent autoregulatory function of the gland to
prevent excessive synthesis of hormone. However, the thyroid can
"escape" from this block even with continued iodide use.
pharmacological effect of the iodides is their ability to promptly
inhibit thyroid hormone release. Therefore, iodide therapy is
useful in the management of thyroid storm (sudden, intense
exacerbation of the symptoms of thyrotoxicosis) and when
relatively short-term control of hyperthyroidism is
necessary. Beta adrenergic blockers, such as propranolol, are
also useful for the management of thyrotoxic symptoms.

131I is rapidly taken up by the thyroid, incorporated into

337 iodoamino acids and is deposited in the colloid of the follicles.
The beta radiation destroys the surrounding parenchymal
cells. The x-rays can be detected externally and allow for
Physical properties - 131I emits beta particles and x-rays, with estimation of quantity of 131I in the thyroid. When small
a decay half life of 8 days. doses of 131I enter the thyroid, function is not affected.

Beta-blockers (except those with sympathomimetic activity)

decrease symptoms of increased adrenergic tone such as heat
intolerance, profuse sweating, tremors, and palpitations that are
338 associated with hyperthyroid states. Due to their relatively rapid
onset of action, they can be used to alleviate symptoms until a
thioamide takes effect. The most common indications for using a
beta-blocker are palpitations and tachycardia. At high doses, beta-
blockers may inhibit conversion of T4 to T3.
Propranolol, which is dosed t.i.d. or q.i.d. is more suited to
use in inpatients. Outpatients can be treated with either
atenolol or metoprolol, both of which are more beta-1
receptor selective. Patients with hyperthyroidism may require
twice the usual doses of beta-blockers to control symptoms
and heart rate. As the biochemical hyperthyroidism resolves,
beta-blocker doses can be tapered down.

339

340

341 Technesium scan: Pertechnetate (T1/2 = 6hrs) radioisotope

concentrated by the thyroid, can be used to visualize the functional
anatomy of the thyroid
342
 G H

343

344

345

346 dopamine antagonists may produce hyperprolactinemia and

inappropriate lactogenic effects.
347

348
Osteoprosis Tx: Combination of estrogen-calcium or estrogen-
BPs; Statins also prevent fractures and enhance bone formation in
rodents
Combination of estrogen-calcitonin or estrogen-BPs appears to
have additive effects in increasing BMD.

349

Analogues of pyrophosphate (P-O-P) in which oxygen has been

replaced by carbon (P-C-P) with various side chains.
Concentrate in bones and they are to date the most effective
350 inhibitors of osteoclasts and bone resorption. They inhibit
farnesyl diphosphate synthase which leads to decreased
prenylation of small G proteins essential for osteoclast activity and
survival.
351
352
353
354
 G H

355

356

357

358

Pagets Disease: Etiology unknown but a slow virus is suspected;

characterized by uncontrolled osteoclastic bone resorption
359 with secondary increases in bone formation. The new bone is
poorly organized. Goal of treatment is to reduce bone pain, and
stabilize or prevent other problems such as deformity, hearing loss,
hypercalcemia and high out put cardiac failure.
Rx. Calcitonin (SQ or IV) and bisphosphonates are used to reduce
osteoclast activity. Patients may become refractory to calcitonin.

Vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol)

360 Hypocalcemia Tx:
- IV: calcium gluconate infused slowly to prevent arrythmias
- Oral: calcium carbonate (TUMS)
- 1,25(OH)D for rapid effect. Raises serum calcium in 24-48 hrs
- Carefully monitor Ca and PO4 to avoid ectopic calcification
are found in diet.
Vitamin D derivatives are also formed from a prohormone that
is produced in the skin after exposure to UV irradiation.
Vit D3 is converted to metabolites in the liver (25 hydroxy-D3)
and kidney (1,25 and 24, 25 dihydroxy D3).
25 (OH)-D3 and 1,25 (OH)2-D3 (active metabolite) are
available for clinical use.

361

362
363

364
Monitoring required the following: pregnancy test, CBC, liver tests,
lipid panel and psychiatric symptoms
 G H
365

366

367

Benefits of Aerosol Delivery

1. The pathophysiology of asthma appears to involve the
respiratory tract alone. So, ideally, effective treatment could
be achieved if drug administration was restricted to the lungs.
2. Aerosol application of drugs to the lungs can produce a high
local concentration in the lungs with a low systemic
KEY FEATURES OF ASTHMA absorption, thereby significantly improving the therapeutic
1. Mast cell activation associated with early bronchospasm ratio by minimizing side effects. 3. Both 2-agonists and
2. Inflammatory cell infiltration with subsequently mediator cortocosteroids have potentially serious side effects when
release delivered systemically.
3. Epithelial cell damage 4. Probably more than 90% of asthmatic patients who are
368 4. Increased responsiveness of the airways to a variety of non capable of manipulating inhaler devices can be managed by
specific stimuli aerosol treatments alone.
The initial burst of mast cell activity leads to a generalized 5. Factors that determine effective deposition of drug in the
activation of leukocytes in the peripheral circulation. The release lung a. Particle size: >10 microm deposit in mouth and
of mediators from these activated cells contributes to the oropharynx; <0.5 microm are inhaled and then exhaled; 1-5
bronchoconstriction, mucosal edema, and increased mucus microm deposit in small airway and are most effective. b.
secretion associated with late phase responses. Enzyme release rate of breathing and breath holding c. recommendation is
from inflammatory cells can also contribute to bronchial that a slow, deep breath be taken and held for 5 - 10 sec. 6.
hyperresponsiveness by damaging the respiratory epithelium, Even under ideal conditions only 2 - 10 % of drug is deposited
enhancing neuropeptide release, and exposing afferent nerve in lungs; most of the remainder (90%) is swallowed.
endings that can evoke enhanced vagal responses. Other Therefore, to have minimal systemic side effects, an
iInflammatory cells other than mast cells implicated in the aerosolized drug should be either poorly absorbed from the GI
pathogenesis of asthma include eosinophils, neutrophils, tract or be rapidly inactivated by first-pass liver metabolism.
macrophages, lymphocytes, and platelets. Hint: Consider Ipratropium
Levalbuterol is the R-isomer of racemic (R+S) albuterol available
369
only as a nebulized solution.
370

371
Terbutaline can also be given orally, or as subcutaneous injection,
or IV infusion.
 G H

Inhaled steroids are not effective with pts who have a

372 dramatically low FEV1, or FEV1/FVC, as their inhalation
Children appear to have more cholinergic receptors - more capacity is most likely inhibited as well (would have SE with no
responsive to parasympathetic stimualtion than adults theraputic effect)
Bitolterol may produce a longer period of useful
373 bronchodilation (3-6 hrs) than the 2 to 3 hours provided by the
other drugs, perhaps because it is a prodrug that must be
converted to colterol, the active compound, in the lung.

374
Over use may lead to tolerance, some data suggests overuse of
beta agonist may worsen condition, still debated

375

376

377

378
MAO breaks E down very rapidly, short acting
379

380

381
 G H

Ipratropium bromide and tiotropium are quaternary amine

muscarinic receptor antagonists. If given parenterally, these
drugs would have peripheral effects similar to atropine
(tachycardia, bronchodilation, inhibition of salivary secretion),
382 but would lack significant CNS effects because the quaternary
ammonium structure precludes CNS access. By the
inhalation route, the effects are confined to the mouth and
airways. These drugs produces little or no change in
heart rate, blood pressure, bladder function, intraocular
pressure, or pupillary diameter. This selectivity results from
inefficient absorption from the lung or GI tract.

383 Tiotropium is supplied as dry powder capsules for inhalation with

an inhaler device.

384 Cellular Actions of Methylxanthines

a. Adenosine receptor antagonists
b. Inhibit cyclic nucleotide (cyclic AMP and cyclic GMP)
Methylxanthines are alkaloids that occur in plants widely phosphodiesterases and thereby elevate the cellular
distributed geographically and members of this group of agents concentrations of these second messengers. However, the
have been widely used for centuries. Important methylxanthines concentrations required to inhibit these enzymes is probably
include theophylline, caffeine, and theobromine. Tea, coffee, not achieved with therapeutic doses.
cocoa, chocolate, and cola-flavored drinks contain caffeine and/or b. Lower intracellular calcium ion concentrations.
other related alkaloids. c. Hyperpolarize cell membranes

385

386
 G H

387
1. The development of aerosol formulations or aqueous
intranasal sprays significantly improved the safety of
corticosteroid treatment for moderate asthma or other respiratory
disease. 2. Asthmatics who require inhaled -adrenergic
agonists four or more times weekly are viewed as candidates
for inhaled corticosteroid. 3. Available preparations are viewed Asthmatic patients maintained on inhaled corticosteroids show
as being equivalent in efficacy and potential adverse effects, but improvement of symptoms and lowered requirements for
vary considerably in amount of drug aerosolized per inhaler rescue with -adrenergic agonists. Improvement may be
activation. Therefore, the dose of inhaled steroid must be seen within one week, may continue for up 2 years or longer,
empirically determined for each patient. and reductions in dose over time are often possible.

388

389 Inhaled steroids are the DOC for allergic rhinitis, especially
with nasal symptoms including nasal obstruction (mucosal edema)
from inflammed turbinantes (anti-histamines do not)

390

391 Inhaled steroids are the DOC for allergic rhinitis, especially
with nasal symptoms including nasal obstruction (mucosal edema) All inhaled glucocorticoids are effective give twice a day
from inflammed turbinantes (anti-histamines do not) (budesonide can be given once a day for mild asthma)

392

393
 G H

Systemic (parenteral or oral) steroid therapy is used in severe

asthmatic attacks requiring hospitalization and sometimes in less
severe, acute exacerbations of asthma or in patients who fail to
respond to other therapies. Parenteral therapy is also used for
394 some COPD patients and to control other inflammatory pulmonary
disorders, e.g., infiltrative pulmonary diseases. For severe
asthma (hospital), prednisone or methylprednisolone is given
i.v., followed by oral doses and gradual tapering of doses. For
acute exacerbations, oral prednisone is administered for 1-2
weeks. Longer treatment requires gradual tapering of dose Longer treatments require tapering of the dose to account
because of hypothalamic-pituitary-adrenal axis suppression. for hypothalamic-pituitary-adrenal suppression.
395
396

397

398

399 Cromolyn and nedocromil are generally less effective than

inhaled glucocorticoids in controlling asthma. These agents
are useful in mild to moderate asthma as added therapy or as
an alternative to regularly administered oral or inhaled -agonists
and oral methylxanthines. Some studies suggest that nedocromil
used in combination with inhaled corticosteroids produces no
further benefit, but modest reduction in steroid doses may be
possible.
Seasonal allergic rhinitis (hay fever) is caused by deposition
of allergens on the nasal mucosa resulting in immediate
hypersensitivity reactions. This reaction is different from
asthma in that larger particles are usually involved that do not
become inhaled into the lower airways.

400

401
 G H

402
Nasal decongestants that are -adrenergic agonists that cause
vasoconstriction via activation of 1-adrenergic receptors are
found in many, many over-the-counter preparations.
Stimulate vasoconstriction in the nasal mucosa, primarily
on venous sinusoids, resulting reduced edema, i.e.,
decongestions; They are effective only for relief of nasal
congestion and (not?) for sneezing, itching, or discharge.

403

404

1. Role of leukotrienes in airway inflammation: Considerable

evidence shows that the leukotriene (LT) autocoids are important
mediators of inflammatory reactions and anaphylaxis.
405 Leukotrienes are lipid mediators derived from arachidonic acid in
the 5-lipoxogenase pathway. LTs are synthesized by eosinophils,
mast cells, macrophages, and basophils. LTB4 is a potent
neutrophil chemoattractant. LTC4 and LTD4 exert many
effects known to occur in asthma including
bronchoconstriction, increased bronchial reactivity, mucosal
edema, and mucus hypersecretion.
Zafirlukast and montelukast are selective LTD4 receptor
antagonists and drugs have the advantage of being taken
orally. They are rapidly absorbed with peak plasma levels
obtained in 1-3 hours. The drugs are metabolized in the liver
with metabolites excreted in the urine. Plasma t1/2 values are
approximately 2.5 hours. Thus, they must be taken QID
(montelukast BID).

406
Inhibits P450

407

Guaifenesin (Glyceryl Guaiacolate): is claimed to enhance

408
Therapeutic Rationale: Stimulation of secretion in the respiratory
tract is of theoretic value in the treatment of chronic irritating
cough.
the output of respiratory tract fluid by reducing adhesiveness
and surface tension facilitating the removal of viscous mucus.
As a result, nonproductive coughs become more productive
and less frequent. There is a lack of convincing studies to
document efficacy.

Iodides enhance the secretion of respiratory fluids, thus

409 decreasing the mucus viscosity. In addition, iodides may stimulate
breakdown of fibrinoid material in inflammatory exudates.
Objective evidence of clinical efficacy is lacking. Because of the
potential for adverse effects, other agents are usually preferred.
 G H

410 Therapeutic Rationale: Stimulation of secretion in the respiratory

tract is of theoretic value in the treatment of chronic irritating
cough.

Recombinant DNase available as a nebulizer solution for

treatment of cystic fibrosis. In CF, inspissated secretions
containing large numbers of inflammatory cells lodge in the smaller
airways, causing obstruction. A substantial portion of the purulent
411 material is due to the DNA from the nuclei of lysed cells. Inhaled
DNase has been shown to aid in clearing these secretions.
Clinical trials are underway to assess DNAse treatment in adult
COPD exacerbations, where purulent bronchial secretions also
contribute to airway obstruction.

Cough is a nonspecific sign of upper or lower airway irritation or

inflammation and is mediated through reflex vagal pathways.
412
Nonproductive cough that is irritating to the throat and self
perpetuating or exhausting to the patient is an indication for
antitussive therapy. Multiple factors may cause cough, such as
airway hyperactivity, smoking, infection, neoplasms, foreign
bodies, "postnasal drip", esophageal reflux, or irritation of the Opioids are orally active, metabolized in the liver and renally
sinuses, upper airway and eardrum. excreted.

413
Opioids are orally active, metabolized in the liver and renally
excreted.

414

415 Unlike in asthma, antihistamines (H1 histamine receptor

antagonists) produce considerable, though incomplete, symptom
relief of cough

416
 G H
417
418

419

420

421 Chantix, prescription medication, tablet form. Generally prescribed

for 12 weeks. May prescribe Chantix for another 12 weeks to Researchers found Chantix to be more effective than a
enhance long-term success. placebo in helping people quit smoking.

422

Mycobacterium tuberculosis
Tuberculosis still the leading cause of death by infectious disease
throughout the world
Increasing incidence in USA, AIDS patients, homeless, immigrants
423 Difficult to stain & acid-fast
Grows slowly and are relatively resistant to most antibiotics,
therefore must treat for months - years
Lipid-rich cell wall impermeable to many agents
Substantial portion of organisms are intracellular, so inaccessible Treatment divided into:
to drugs which penetrate poorly 1. treatment of latent infection diagnosed by a positive PPD
Many resistant strains so use multiple drug therapy 2. treatment of active clinical TB

424 For patients who cannot tolerate rifampin: 9-12 months of INH
+ ethambutol + pyrazinamide +/- a fluoroquinolone (levofloxacin,
moxifloxacin, gatifloxacin)
Rifabutin has been substituted for rifampin in some patients who
could not take rifampin because of drug interactions (HIV patients Resistance to rifampin: isoniazid + ethambutol for 18mo or
on multiple drugs) isoniazid + pyrazinamide + streptomycin for 9mo

425
Do not use rifobutin with ritonavir or delaviridine (protease inhibitor
and NNRTI respectfully)
 G H
426

427 MDRTB multi-drug resistant TB (Latent): regimens may

include two drugs, e.g., pyrazinamide + ethambutol or a
fluoroquinolone for 9-12 months but are poorly tolerated
Pyrazinamide bacteriacidal for slowly growing intracellular (in M0)
428
at acid pH

429
Other second line drugs include: Ethionamide, Aminosalicylic Acid, Streptomycin bacteriacidal for actively growing extracellular
Capreomycin, Cycloserine organism
430
431
432

433

434
Conventional amphotericin deoxycholate (Fungizone) older, non-
lipid formulation, least expensive - Better tolerated, new
formulations replacing this drug
Lipid Formulations: three lipid formulations are available; generally
better tolerated, nephrotoxicity is less severe than with
conventional Ampho B

435

436

437

438
 G H
439

440

441
442

443
444

445

446

447

448

449

450

451
Resistance
Through alteration in viral thymidin kinase
Through alteration in viral DNA polymerase
Pharmacokinetics
Used orally or intravenously for treating genital herpes
Cleared by glomerular filtration
 G H
452
453

454

455

456

457

458
H1 receptors activation results in:
bronchoconstriction
Storage location of Histamine: exocrine excretion (?)
1. mast cells major source of stored histamine in mammalian increase capillary permeability
tissues contraction of intestinal smooth muscle
2. basophils basophilic leucocytes of the blood contain stored stimulation of sensory nerve endings
histamine Cellular signaling mechanism
3. CNS and peripheral nerves - increase phosphoinositol hydrolysis, increase intracellular
Histamine Receptors- H1, H2, and (H3 not relevant clinically); all Ca++
are G protein-coupled receptors Distribution: smooth muscle, endothelial cells, brain

459

460

461
 G H

462

Azelastine hydrochloride (Astelin), 0.1% nasal spray approved for

treatment of seasonal allergic rhinitis; Clinical trials indicate it is as
effective or more so than Seldane or Cetirizine in relieving
symptoms of seasonal or perennial allergic rhinitis; Metabolized to
463 desmethylazelastine, which is also active. Half-life of 22 and 54
hrs, respectively. Recommended dosing is 2 sprays per nostril
b.i.d.; Does not have effects on cardiac conduction, or dangerous
drug interactions seen with some others; Cost is comparable to
2nd generation anti-H1s.

464

465

466

Second-Generation Antihistamines: These drugs penetrate
poorly into the brain and are much less likely than 1st-gens to
have adverse effects on the CNS; The oral drugs loratadine
(generic [$21.30], Claritin [$27.30], Alavert [$16.50]) and
467 desloratadine Clarinex [$63.29] are non-sedating in recommended
doses; with higher doses, sedation may occur; Fexofenadine
(Allegra [$84.62]) has been free of sedative effects; Cetirizine
(Zyrtec [$63.29]) is sedating in some patients but has a better
established safety record in young children than the other drugs;
No well-controlled trials have convincingly established that any one
of the 2nd-generation drugs is more effective than the others.
Allergic Conjunctivitis: the most common form of ocular allergy, is usually associated with allergi
seasonal or perennial. An oral antihistamine, a 2nd generation, relatively non-sedating drug such as
fexofenadine, or loratadine is recommended to relieve the main symptom, itching. Antihistamines fo
also available.
Topical decongestants reduce erythema, congestion, and eyelid edema; their adverse effects includ
rebound hyperemia and conjunctivitis medicamentosa.
Antihistamine/decongestant combinations such as pheniramine/naphazoline (Visine A, and others)
antazoline/naphazoline (Vasocon-A) available OTC may be more effective than either agent alone, b
of action and may cause rebound vasodilation with continued use.
Topical corticosteroids should only be used as a last resort because they are associated wit
pressure, cataract formation and complications with viral infections.

468

469

Cetirizine is sedating in some patients but has a better

470 established safety record in young children than the other
drugs;
 G H

471

H2 receptor antagonists pharmacokinetics:

Cimetidine inhibits the P 450 oxidative drug metabolism system - elimination via kidney
monitor when coadministered with P-450 metabolized drugs t1/2 = 1-4 hr.

472

473

474
475

476

477
Alpha1 Receptor Distribution and Effects of Stimulation:
Arterioles/Veins Constricts
Eye (Radial Muscle of the Iris) - Contracts (leads to pupil dilation Alpha2 Receptor Distribution and Effects of Stimulation:
mydriasis) NE Nerve Terminals - Decreases NE outflow (autoreceptor)
Intestine- Constricts sphincters, Decreases motility CNS - Decreases sympathetic outflow
(hyperpolarization leads to relaxation), Also : Inhibit release of insulin
Prostate (note: this is an 1A receptor; vascular alpha receptors Relaxes intestinal smooth muscle
are likely 1B) - Contraction, Promotes tissue growth
Urinary bladder sphincters - Constricts
 G H

478

Because E at low dose does not raise mean blood pressure, no

vagal reflexes are activated. Potency slightly greater for beta
than alpha receptors, but clinically (when given at pharmacologic
doses) see alpha and beta stimulation simultaneously. The
concept of net effect requires knowledge of which receptor
response will prevail (what type of receptors does the tissue
possess?) (if the dose of E is raised, only 1 agonist effects will be
seen because E has more efficacy at 1 than 2 receptors),
Alpha1 Receptors Second Messenger Excitation:
Gq second message is amplified by activation of
phospholipase, which leads sequentially to:
Increased levels of IP3
Increased levels of intracellular Ca++ (notice, Caffery's cell
Signaling shows Gp, not Gq)

479
Net effect: Positive inotropic effect, but reflex bradycardia
because of increased systolic and diastolic blood pressure.
 G H

Direct Acting Non-Catecholamines (notice, isoproterenol

is a catecholamine): Synthetic agents, lacking the catechol
480 moiety. Analogues of NE or EPI.
Non-catecholamines are metabolized more slowly (they are
not acted upon as readily by monoamine oxidase [MAO],
notice that isoproterenol, a pure 1/2 agonist, has a greater and often they are not stored in vesicles). Therefore they
vasodilating effect than E are generally longer acting; some are effective p.o.

481
2 Selective Adrenergic Agonists: As a group, 5-10X more
potent at 2 than 1 adrenergic receptors.
Therefore more selective for smooth than cardiac muscle.
Longer acting than catecholamines.
COMBIVENT = albuterol + Ipratropium bromide Tolerance may develop.

482

483

The effect of tyramine and NE on BP is negated in the presence of

cocaine. Note that initially both drugs are given in doses to
produce approximately equal effect. Tyramine is an indirect agonist
485 (it releases NE). Following cocaine, the effect of tyramine is
abolished because tyramine cannot gain access to the inside of
the NE nerve terminal. The effect of NE is enhanced because it is
not removed into nerves.
 G H

486 dopamine (DA) vs dobutamine (DB): both agents have positive

inotropic effects. At higher doses of DA, an increase in systemic
vascular resistance (SVR) limits cardiac output and worsens
congestion (PCP). The inotropic effect of DB occurs with little
change in heart rate (HR).

487

488
As non-catecholamines, they are metabolized slowly and are
effective p.o.; They are non-polar and penetrate the CNS;
Generally display a higher ratio of CNS to peripheral CV effects.
However, vasoconstriction and a positive inotropic effect are
present.

489
Relatively insensitive to degradation by MAO and COMT. Effective
p.o.

Note: psuedoephedrine is so polar it penetrates the CNS poorly

490 and thus has much less abuse potential). This drug is in the news
because it is a one-step synthesis to produce methamphetamine
from it. Still a very popular component of nasal decongestants.
 G H

491

492

493

494

Central Adrenergic Agonists Clonidine:

Not first-line because of side-effects and withdrawal hypertension
(CNS upregulation?)
Give with diuretic (to reduce Na+ retention)
Useful in opioid withdrawal (calms sympathetic component of the Alpha-2 agonists directly inhibit the pancreas from releasing
withdrawal) insulin

495

496

497

Adrenergic neuronal depleting agents. These should only be of

historical interest, but they still show up on Boards.
 G H

498
Adrenergic neuronal depleting agents. These should only be of Does NOT get into CNS (highly polar)
historical interest, but they still show up on Boards. Basis of Board questions concerning this agent vs. reserpine;

499

500

501

502

Alpha Adrenergic Blockers:

Blockade of 2 leads to even greater quantities of NE in the
synapse. In the heart, 1 effects of NE are not blocked, so
tachycardia is profound.
They block the effects of any compound acting at a receptors
(whether that compound acts directly or indirectly)
Endogenous agonists (epinephrine; norepinephrine). Note:
sympathetic tone explains why antagonists produce effects.
Exogenously applied drugs (e.g. norepinephrine,
phenylephrine, tyramine)
 G H

503
 G H

Note: In the absence of reflexes, beta blocking effects should

lead to decreased BP. In reality, if CO falls, sympathetic tone
504 is increased. In the presence of a beta-blocker sympathetic
activation doesnt do much to cardiac function; however,
through alpha-receptors, peripheral resistance increases.
Propranolol is a competitive blocker of beta receptors. It shifts the Peripheral Resistance (complicated phenomena): block of
NE dose-effect curve to the right. It also shifts the Isoproterenol b2 can lead to increased in BP (usually does not); block of
dose-effect curve to the right. Note that the full effect NE or renin release decreases peripheral resistance (usual effect).
Isoproterenol can be re-obtained with higher NE or Isoproterenol Control of Renin release (beta1): under the control of cAMP
dose. (predominate control is exerted by sodium concentration);
Propranolol Sudden Withdrawl: May see rebound hypertension high Na+ inhibits renin release (adenosine, produced in
and/or anginal attacks. Example of receptor up-regulation. Beta macula densa, stimulates Gi second message, inhibits renin
blocker use leads to increased beta receptor synthesis. Sudden release from juxtaglomerular cells); low Na+ increases
termination of beta-blocker uncovers greater density of receptors prostaglandin synthesis, produced in macula densa cell, which
for endogenous agonists. then stimulates cAMP and thus renin release from
Propranolol is very lipid-soluble and is almost completely absorbed juxtaglomerular cells
from the GI tract after an oral dose. However, extensively Lesser control, but still important, is exerted by b1 receptor
metabolized by its first pass through the liver that only about 25% stimulation (stimulates cAMP production)
of the drug reaches the systemic circulation

505

506
 G H

Dramatically decrease mortality in Class II and III CHF pts

507
(class IV is less clear may worsen)
Adverse effects
Symptomatic hypotension common initially
Fluid retention: may have to increase diuretics
Bronchospasm danger in asthmatics
Heart failure may worsen initially
All 1-selective drugs lose selectivity at high doses - use
very cautiously if at all in patients with reactive (asthma)
airways. Benefit may outweigh risk for serious conditions
(e.g., myocardial infarction) in pts with COPD. May also be
preferable in diabetics.

508
use very cautiously if at all in patients with reactive (asthma)
airways.

509

510

511

Partial agonist effects are selective for beta2

receptors,marketed as a vasodilating beta-blocker because
512 of beta2 partial agonist effects, No evidence based medicine
data to show that it is more efficacious or has fewer side-
No documented benefits over pure antagonists effects than other beta-blockers
 G H

ISA = Intrinsic Sympathomimetic Activity - this term is used to

describe an agent that blocks the effects of a full agonist such as
epinephrine, but that also causes some modest beta-adrenergic
stimulation. ISA actually means that the agent is a partial
agonist. Occupancy of beta receptors shields them from the
513 effects of full agonists, thus it looks like a beta blocker. Weak
efficacy appears as a slight beta stimulation. Partial agonist drugs
exist that are either non-selective (beta1/beta2) or cardio selective
(beta1)
In theory, these agents should be preferred because of less
bronchospasm, less bradycardia, less negative inotropic features,
and a better lipid profile. However, no clinical therapeutic
advantages have been documented Do not use for angina - may exacerbate (partial agonist)

514

Advantages: dont adversely affect serum lipids; May be

515 particularly useful when also treating benign prostatic hypertrophy
Disadvantages:
increased risk for aggravating or causing congestive heart failure
(CHF, ALLHAT trial)
first-dose hypotension (can be severe)
nasal congestion An enlarged prostate known as benign prostatic
salt and water retention (must use diuretic) hyperplasia or BPH is caused by an overgrowth of prostate
Orthostatic hypotension, including chronic fatigue and light cells. This enlargement constricts the urethra so the flow of
headedness urine is reduced, making it increasingly difficult to empty the
bladder

516
 G H
Sub sets of alpha1A, B, and D (all three seen in prostate, alpha1A
517 predominates in prostate; alpha1B predominates with arterials)
both have mosaics of receptors.

518

520

Notice the RAS system and sympathetic tone is very high during
521 HF, so to give Carvedilol in the face of high sympathetic (acute
heart failure) are contraindicated because already high
sympathetic with poor heart function, would percipitate acute HF.
Beta blocker improve mortality once HF is undercontrol.
522
Approved for class II and III heart failure
Use results in decreased hospitalizations and all-cause
mortality
Improves symptoms and slows progression

523

524
TOXICITY (controlled by atropine)
Syncope (caused by asystole) or orthostatic hypotension
Cardiac dysrhythmias (decreases refractory period in atria)
Gut or urinary urgency
Flushing, sweating, epigastric distress, abdominal cramps,
salivation.
Muscarinic Cholinergic Receptors
Contract smooth muscle.
Apparent discrepancy ACh & muscarinic agonists given IV
cause vasodilation, due to release of nitric oxide (NO)
Smooth muscle sphincters can be relaxed by parasympathetic
stimulation, this is due to release of NO or other non-
adrenergic, non-cholinergic neurotransmitters (NANC) like
ATP
 G H

525
see muscarine other effects

526
Although not normally evident, nicotinic effects of
acetylcholine can be observed when muscarinic receptors are
blocked by atropine ("unmasking" of nicotinic effect). In this
The choline esters are quaternary ammonium compounds; they do case, the effect of acetylcholine is to stimulate sympathetic
not penetrate the blood-brain-barrier and have little or no direct activity (via stimulation of nicotinic receptors at ganglia and
CNS actions following systemic administration. the adrenal medulla).

527
The choline esters are quaternary ammonium compounds; they do
not penetrate the blood-brain-barrier and have little or no direct
CNS actions following systemic administration.
The choline esters are quaternary ammonium compounds; they do
528 not penetrate the blood-brain-barrier and have little or no direct
CNS actions following systemic administration.

529

530

see muscarine other effects

methacholine very slowly is broken down by cholineesterase, very

effective on muscarinic receptors, used to get M without (very little)
531 N.
The choline esters are quaternary ammonium compounds; they do
not penetrate the blood-brain-barrier and have little or no direct
CNS actions following systemic administration.
532

533
 G H

534

Atropine t1/2 = 2 hours

60% unchanged in urine
Effects in eye can last >72 hrs
Order of appearance of physiological effects with increasing
dosage: The actions of these drugs upon peripheral tissue/organ
1. decrease Salivary, bronchial, sweat secretions activity are (with a few exceptions) similar to that which would
2. decrease Micturition occur following reduction of activity in postganglionic
3. Tachycardia, mydriasis, cycloplegia parasympathetic and postganglionic cholinergic sympathetic
4. decrease Intestinal motility nerves. However, atropine and scopolamine also block CNS
5. decrease Gastric secretion muscarinic receptors.

535

scopolamine can be absorbed through skin

Absorption. Quaternary compounds are less well absorbed and

lack CNS actions
536 Nicotinic actions. Quaternary compounds can block nicotinic
receptors and may have ganglion or neuromuscular blocking
action
COMBIVENT = albuterol + Ipratropium bromide
 G H

537

538

539

540

541

542

543

544

545
 G H

546

547

548

anticholinesterase drugs may produce a variety of signs and

symptoms. In overdose, initial signs usually relate to
parasympathetic overactivity. If the dose is high enough, death
occurs via asphyxiation due to muscle paralysis. If the victim
survives these initial insults, a variety of CNS and ANS signs may
occur until recovery or death.
549 Cholinesterase inhibiting drugs are not used extensively for
therapeutic purposes because of insufficient selectivity and toxic
potential. Their clinical importance is based upon:
(i) reversal of non-depolarizing neuromuscular blockade
(ii) ophthalmologic applications
(iii) use in the diagnosis and treatment of myasthenia gravis
(iv) use in treatment of atropine and curare type poisoning
(v) some of these chemicals (from agricultural or military sources)
are themselves
significant sources of poisoning.
ACh organ effect:
i) CNS: restlessness, apprehension, convulsions
ii) Neuroeffector Sites: eye - miosis, accommodation;
bronchioles - constriction, increased secretions; glands -
increase lacrimation, salivation, sweating; GIT - increase tone
and motility; bladder - increase tone; spontaneous micturation;
cardiovascular - (effects variable) low doses decrease heart
rate (muscarinic) whereas higher doses increase heart rate
and blood pressure (nicotinic)
iii) Neuromuscular junction: initially fasciculations and
tremor, higher doses cause paralysis by producing
depolarizing blockade.

550
 G H

551 Myasthenia gravis (MG) is a relatively rare autoimmune disorder

of peripheral nerves in which antibodies form against acetylcholine
(ACh) nicotinic postsynaptic receptors at the myoneural junction. A
reduction in the number of ACh receptors results in a characteristic
pattern of progressively reduced muscle strength with repeated
use of the muscle and recovery of muscle strength following a
period of rest

552

The nerve agents are all liquids at room temperature and are
divided into two major categories. Those that are volatile and
nonpersistent are the G-agents. Those that are nonvolatile and
persistent - being VX. The G-agents, being volatile, represent
more of a vapor threat but also a liquid threat. If left over time they
553 will eventually evaporate and dissipate in an open environment
and therefore are considered nonpersisent. VX, on the other
hand, is more the consistency of cooking oil and is nonvolatile. It
does represent a vapor threat but represents a significant liquid
threat. The risk of secondary contamination exists with G and VX butyrylcholinesterase (major Plasma cholinesterase aka
agents but more so with VX. Both of these agents will produce pseudocholinesterase) preferentially binds many of the
vapor that is heavier than air and therefore should be taken into organophosphorous anti-AChE drugs and thus analysis of
account when at a scene to insure that there are not populations in plasma cholinesterase activity can be used to detect low-
danger in down-hill areas grade poisoning from this class of insecticides

554

Selectivity: most effective at the NMJ (neuromuscular junction);

does not penetrate the CNS; not effective after "aging" has
occurred.
 G H
555

556
Note: Leber's Heriditary Optic Neuopathy is a genetic mutation Note: Piericidin A is a more potent inhibitor and is a close
of complex I - a mitochondrial inheritance dz structural homologue of ubiquinone.

557

558

559
Note: CO and Cyanide act at same point - Complex IV Cyanide poisoning may have "bitter almond" scented breath

560
Treat with Dimercaprol and penicillamine - treats both lead and
arsenic Arsenic poisoning may have "garlic" scented breath

561
F0 "stalk" of ATP synthase (F1F0 ATPase) complex V, F1 is the
562
catalytic site, or "sphere" Causes increased H+ gradient, but no ATP is produced

563

564
565 Treat with Deferoxamine

566
Treat with Calcium EDTA, dimercaprol, or penicillamine. Note: Diagnose by blood lead levesl and free erythrocyte
Dimercaprol is also known as BAL (British Anti-Lewisite) protporphyrin
567 Treat with Penicillamine
568

569
 G H

Major Use is by anesthetists to relax voluntary muscle.

570
Preferable to deep anesthesia.
Minimizes risk of cardio or respiratory collapse
shortens recovery period
Facilitates tracheal intubation, laryngoscopy
Orthopedic Surgery
All neuromuscular blocking compounds are polar: they are inactive correction of dislocations, fracture alignment
orally and do not penetrate the CNS. All are administered minimize potential trauma of convulsions
intravenously. A muscarinic drug cannot be block by tubocarine, Electroconvulsive Shock Therapy
but can by atropine. Epilepsy
All neuromuscular blocking compounds are polar: they are
inactive orally and do not penetrate the CNS. All are administered
571 intravenously. Mivacurium is a poor substrates for true
cholinesterase but hydrolyzed rapidly by plasma cholinesterase.
Have relatively short duration of action

572

573

574
 G H

575

All neuromuscular blocking compounds are polar: they are inactive

orally and do not penetrate the CNS. All are administered
intravenously. Succinylcholine is a poor substrates for true
cholinesterase but hydrolyzed rapidly by plasma cholinesterase,
has a relatively short duration of action (5-10 min).
Succinylcholine is metabolized only half as rapidly in persons
with a genetically-determined defect in the enzyme
pseudocholinesterase. (see extra note for organophosphate )
Malingnant hyperthermia: Succinylcholine and/or general
anesthesia may lead to fulminant and often fatal hyperthermia
and muscle rigidity (mendelian disorder, autosomal dominant,
in pregnant women) - also occurs with Halothane treat with
dantrolene

576

577 Generally, if pt is allergic to one of the classes of local anesthetics

(amide or ester) than they will be allergeic t all drugs of that callss
(MC allergic to ester, so switch to other class.
578
579
580
581
582

583

584
 G H
585
586
587
588

589

590
591
592

593

594
Causes flaccid descending paralysis

595

596

597

598
599

Malignant hyperthermia - AD, symptoms of hyperthermia,,

600 muscle spasm, autonomic electrolyte distubances during general
anesthesia; disorder due to a mutation in the ryanodine receptor-
gated Ca channel of the SR of skeletal muscles leads to
increased sensitivity to halothane and depolarizing agents
601

602
 G H

603 Definitions
Analgesia: Attenuation of pain perception without the loss of
consciousness.
Narcotic: Archaic term, more legal than medical, referring to
any substance producing stupor associated with analgesia
(usually associated with derivatives of opium).
Pain has sensory and reactive components: Opiates: Natural products and derivatives obtained from the
Sensory - Pain is perceived as a result of direct stimulation of pain opium poppy (e.g., opium, morphine, heroin, codeine).
receptors and/or by the pattern of neural input from the periphery. Opioids: The class of compounds that bind to opioid
Reactive - Intensity of pain is dramatically altered by the level of receptors. Includes agonists, antagonists, partial agonists and
anxiety and the stress response related to the original insult. mixed agonist/antagonists. This is the preferred term.
Delta receptors may be more associated with euphoria than mu
604 receptors. No clinically useful drugs are selective for these Preproenkephalin gives 6 met enkephalin, 1 copy of
receptors leuenkephalin

605

Causes hyperalgesia mechanism unknown but may involve NMDA

606 activation rather than kappa receptors. Kappa receptors
dynorphins>>all others Prodynorphin derived
Kappa receptors less involvement in abuse potential, and
important for effects of some of the mixed agonist-antagonist
607 opioids including dysphoria, psychotomimetic
(depersonalization or dissorientation), analgesia, less miosis
and respiratory depression than mu agonists, sedation,
vasodilation, increased urinary output Prodynorphin derived
 G H

Opioid Effects: Vascular System:
Vasodilation - Morphine is by far the most efficacious opioid in
this regard (non-mu/non-kappa mediation), useful in pulmonary
edema - 2 factors come together very nicely in this regard: (1)
608
morphine-induced vasodilation shifts fluid from the central to the
peripheral compartment; (2) opioids make the brainstem less
responsive to pCO2, which results in reduced sympathetic tone
(patients dont care as much about difficulty breathing/SOB). With
relaxation of the sympathetics comes easier movement of fluid
from central to peripheral compartment
Clinical Uses: Acute Pulmonary Edema (morphine)
Relief from dyspnea associated with left ventricular failure is
due to:
reduced perception of shortness of breath
anxiolytic effects (this effect is noted in many texts, but the
evidence for direct anti-anxiety effects of opioids is nearly non-
existent. By reducing the perception of shortness of breath,
the anxiety accompanying that perception is reduced. This is a
very different phenomenon than anti-anxiety effects per se.)
reduction in cardiac preload and afterload

609 Shorter elimination half life than morphine. Was once given more
frequently for pain than morphine, no longer however due to
negative SE

Methadone: equivalent analgesic dose = 10 mg; maximum

610 efficacy = high; oral:parenteral potency ratio: high; duration of
analgesia = 4-6 hours; has active metabolites;
addiction/abuse liability = high; useful in replacement
treatment of opioid addiction and in treating cancer pain; oral
Very long elimination half life (~24 hrs) solutions, tablets and injection preparations available
Sufentanil is potent/efficacious cousin (5-10 x more potent then
611 fentanyl, used as elephant tranquilizer). Most lipid soluble,
highest potency agents. Very low doses required, transdermal
patch effective (for patients who are vomiting)

612 Heroine enters brain faster than morphine (higher abuse potential) Heroin withdrawal is considered brief lasting 5-10 days, and
where it is rapidly deacetylated to morphine is intense.

613
relatively pure kappa agonist

Drugs Classified as Mixed Agonist-Antagonists - these agents have variable actions at different receptor subtypes, examples:
614 Partial agonists at mu receptors: e.g., buprenorphine
full agonist at one receptor subtype and a partial agonist at another: e.g., pentazocine
agonist at one receptor subtype and an antagonist at another: e.g., nalbuphine
Remember: weak partial agonists act as antagonists when given with a full agonist.
 G H
Opioids with Intermediate Efficacy: Addition of NSAIDs
615 As a general rule, the addition of NSAIDs to an opioid give much
better analgesia than the same dose of either agent alone.
This combination has been used with good success for all opioids
that are not classified as high efficacy
616
Little difference from hydrocodone
617
Would cause withdrawl if given after >7-8 days of morphine use.
618
Efficacy is no better than an NSAID alone and most authorities do
not recommend using this drug
619
Long duration of action, slow to dissacociate from mu
receptors. Ideal drug for preventing access to the receptor by
high efficacy compounds (drug treatment programs)
620
Effects blocked by ondansetron (a 5-HT3 receptor antagonist)
Although classified as intermediate efficacy, literature
suggests it is same efficacy as morphone
Oxycodone: non-equivalent dose = 4.5 mg; maximum efficacy
= moderate; oral:parenteral potency ratio: medium; plasma
half life = ? hours; addiction/abuse liability = medium-very
high! (oxycontin)
Oxycontin is an orally-active, controlled-release formulation of
oxycodone which has significant abuse potential if tablets are
crushed and taken rapidly (i.v., intranasal, etc.)
Buprenorphine is considered an opioid-receptor agonist-
antagonist (actions similar to both methadone and
naltrexone) - at lower doses, like methadone, it decreases
withdrawal symptoms and drug cravings. At the same time,
like naloxone, it occupies receptors and thus blocks the
euphoric action of opioids. At higher doses, it antagonizes its
own opioid-like effects and is thus less likely than other
opioids to cause respiratory depression
 G H

Cytochrome P450: Phase 1 Oxidation

Cytochrome P450 is a family of enzymes located in the
endoplasmic reticulum of liver (Superfamily of heme-thiolate
proteins). When liver is homogenized and biochemically
621 fractionated these enzymes are found in the microsomal fraction
(small closed ER membrane fragments). Thus these enzymes are
called microsomal enzymes. There are several hundred
isoforms of cytochrome P450, with approximately 50 identified in
humans.
Analgesic effects come from the slow conversion of codeine to
morphine by demethylation from CYP2D6. ie P450 family of
which there are 17 families. Family defined as 40% or greater
amino acid homology. Subfamily has 55% or greater
homology

622

Obtained at lower doses than needed for analgesia. Often opioids

chosen that are not well absorbed or combined with atropine
(limits abuse potential)

623
combined with atropine (limits abuse potential)

624
combined with atropine (limits abuse potential)

625

Opioid Overdose: Treatment

626 Opioid Agonist/Antagonists: Antagonist Properties
block the effects of full agonists
precipitate withdrawal symptoms in individuals physically
dependent on mu agonists.
administer opioid antagonist (naloxone is drug of choice)
support of respiration and other vital functions
identify most likely drug
if determined that other drugs were also ingested, treat for the
overdose of these drugs accordingly

627 Antagonist Therapy: primarily use naltrexone (ReVia) - long half Note - naltrexone does not stop runners high, will not stop
life (~10 hr), good oral absorption ; block rewarding effects of pleasure from life activities such as eating, sex, etc
agonists; patients must be highly motivated to remain drug free (theoretically it should, no evidence however that it does)
628
 G H

629

Central Adrenergic Agonists Clonidine:

Not first-line because of side-effects and withdrawal hypertension
(CNS upregulation?)
Give with diuretic (to reduce Na+ retention)
Useful in opioid withdrawal (calms sympathetic component of the
withdrawal) Clonidine does nothing to decrease opioid cravings.

630

Little evidence that dextramethophan actually suppresses cough in

631 children according to FDA; may cause psychotomimeto effects in
children Note: ketamin (special K) and PCP bind NMDA receptors
632

633

634

635 Note that NSAIDs can address symptoms (ie pain) of RA, but do
nothing to slow progression of dz; Corticosteroids can both
decrease pain and slow progression of joint destruction, however,
no longer used on long term treatment do to imminent SE
 G H

636

DMARD=Disease modifying anti-rheumatic drugs. With

exception of methotrexate they are poorly tolerated. Methotrexate Notice: NSAIDs only improve symptoms of RA; glucocorticoid
has a faster onset than other DMARDs, with disease suppression steroids improve symptoms and slow progression of joint
being seen in 2-6 weeks (up to 12 weeks with other agents). destruction (these doses are high and thus lots of SE)

637

638
Sulfasalazine is a poorly absorbed and is metabolized by intestinal
bacteria to sulfapyridine, an active sulfonamide antibiotic, and 5-
aminosalicylate, a salicylate anti-inflammatory agent. Good Sulfasalazine can be given with methotrexate, or as
alternative to methotrexate for patients with liver disease alternative too, and can be given with other DMARD

639

It may be given in combination with methotrexate, but concomitant

use with TNF-alpha inhibitors is not recommended due to an
increased incidence of infections
 G H

640

TNF-is produced by macrophages and activated T-cells and
641 stimulates the release of inflammatory cytokines, including
interleukins and proteases such as collagenase and neutral
metalloproteinases. TNF-effects require activation of specific
membrane bound receptors (TNFR1).
TNF-alpha receptors are expressed on essentially all cells, and TNF-alpha plays an important role
microorganism (Listeria and mycobacteria). It is also important in cell apoptosis. Thus, there is sign
agents may increase susceptibility to intracellular organisms and/or result in increased susceptibility
agents are being watched with particular attention to determine if they are associated with an increas
tubercular and/or fungal infections. Particularly for the murine-derived agents, immunogenicity is a co
proteins that must be injected, and injection site reactions are common. They have good efficacy as

642

A high affinity murine anti-TNF monoclonal antibody was used as a

template for guided selection, which involves complete
643 replacement of the murine heavy and light chains with human
counterparts and subsequent optimization of the antigen-binding
affinity.

IL-1 is found in abundance in the synovial tissue of joints. IL-1 is

644 capable of stimulating its own increased production (positive
feedback loop), resulting in secretion of prostaglandin E2, NO Macrophages release IL-1, but they also release a compound
and metalloproteases, thus promoting joint degradation. IL-1 that binds to the IL-1 receptor and serves as an antagonist
inhibits collagen synthesis, thus suppressing joint repair. (interleukin-1 receptor antagonist; IL-1ra).

645

646
 G H

647 Rem: use a Pen on the Ceiling of the cysteine chapel to draw
lesions on Adam, make him pee blood, and make him pale
(Penacillamine for Pen on Ceiling) is a cysteine analog and can
cause dermatologic probs (skin lesions) nephritis (peeing blood) Give B6 along with D-Penicillamine to prevent neurologic
and aplastic anemia (he is pale) symptoms

648

649

650
Hot peppers

Aurothioglucose and gold sodium thiomalate are water-soluble

compounds rapidly absorbed after intramuscular injection. Weekly
injections of these compounds are given until a cumulative dose of
1 g has been administered. Successive doses lead to
651 accumulation of gold in the tissues and clearance of this gold is
very slow. Aurofin is a more hydrophobic compound that is
administered as daily oral doses for about 6-9 months. Aurofin is
better tolerated that the injectable gold compounds, but is probably
also less efficacious. they cause gradual reduction in symptoms

652

they cause gradual reduction in symptoms

653

they cause gradual reduction in symptoms

654

655
 G H

656 Often given intially with colchicine to minimize acute gout

attacks and once allopurinol has reduced uric acid levels, Urate is freely filtered, secreted (10%) and reabsorbed
colchicine withdrawn (90%)

657 Probenecid was formulated with the objective of blocking the

tubular secretion of the antibiotic and thus maintaining its
Paradoxical effect (like NSAIDS) - at low dose decrease effective plasma concentrations longer. It is still used
excretion, and at high dose they increase excretion occasionally for this purpose

658

Additive effect to probenecid

659

Commonly used with allopurinol

660
Low doses of salicylate NSAIDs (aspirin) must not be used to
treat gout because these drugs inhibit net uric acid excretion
Can also use naproxen; do not use aspirin for gout in the urine
661

662
 G H
663
Chronic aspirin toxicity (salicylism) may develop in persons who
take 3 gm or more daily, the dose required to treat chronic
inflammatory conditions. Chronic salicylism is manifested by
headache, dizziness, ringing in the ears (tinnitus), difficulty in
hearing, mental confusion, drowsiness, nausea, vomiting, and
diarrhea. The central nervous system changes may progress to
convulsions and coma. The morphologic consequences of chronic
salicylism are varied. Most often there is an acute erosive gastritis,
which may produce overt or covert gastrointestinal bleeding and
lead to gastric ulceration. A bleeding tendency may appear
concurrently with chronic toxicity, because aspirin acetylates
platelet cyclooxygenase and blocks the ability to make
thromboxane A2 , an activator of platelet aggregation. Petechial
hemorrhages may appear in the skin and internal viscera, and
bleeding from gastric ulcerations may be exaggerated. - Robbins,
MD consult
664
Cox-2 Inhibitor Controversy: Vioxx (rofecoxib) was voluntarily
withdrawn from the market by Merck in September 2004.
Preliminary data suggested increased risk of serious adverse
CV events compared to placebo. February, 2005: FDA
Review & Congressional Hearings. April 2005: FDA
recommendations. April 2005, Pfizer withdraws Bextra
(valdecoxib). April 2005: FDA calls for boxed warning of
cardiovascular risk for all NSAIDs. The three approved
COX-2 selective NSAIDs are associated with an increased
risk of serious adverse CV events compared to placebo. Data
from large long-term controlled clinical trials that have
included a comparison of COX-2 selective and non-selective
NSAIDs do not clearly demonstrate that the COX-2 selective
agents confer a greater risk of serious adverse CV events
than non-selective NSAIDs. Until other data are available
increased risk of serious CV events is a class effect,
i.e., both selective and non-selective NSAIDs increase risk
 G H

665

666

667

PGE2 keeps ductus arteriosus open following birth.

668

669

670
 G H

671

672

Biotransformation to Drug Toxicity: acetaminophen (Tylenol)

overdose.
1. Acetaminophen may be converted by cytochrome P450 to a
quinone type of reactive intermediate that is rapidly transformed to
a glutathione-type conjugate (mercapturate) when the levels of
673 glutathione are not limiting.
2. With normal levels of the drug, this pathway is only of minor
significance. However, with massive drug overdose, glutathione Pharmacokinetics: Acetaminophen is rapidly and almost
becomes depleted and the quinone reactive intermediate may completely absorbed from the GI tract. Concentrations in the
reach sufficient concentrations to react with nucleophilic groups of plasma peak in 30-60 minutes. The plasma half-life is about 2
tissue constituents. Hepatic and renal necrosis can result. An hours with 20-50% bound to plasma proteins. The drug is
antidote, N-acetylcysteine, take the place of the depleted converted in the liver to several different conjugated
glutathione in the reaction. metabolites.

674 Remember: throw za fur, kast it over the leukotriene receptor

lukast means anti leukotriene for prophylactic treatment of asthma (Zafirlukast)
675
676
677

678
 G H

Therapeutic Regimens:
Alternate Day Therapy
679 Use drug with shorter half-life (e.g., prednisone)
Give drug every other day
Minimizes HPA suppression
Pulse Therapy
life-threatening or serious disease
General Therapeutic Considerations: initial dose large
Individualize therapy always if insufficient benefit quickly, double or triple the dose
Reevaluate frequently Replacement Therapy
Except for replacement therapy, glucocorticoids are neither 1. For primary (adrenal) or secondary (anterior pituitary)
specific nor curative. adrenocortical insufficiency.
A single dose is without harmful side effects! 2. This remains the only application in which chronic
A short course is without harmful side effects. corticosteroid treatment is completely appropriate and
Longer than one week, adverse effects are very likely defensible.
their severity being dependent upon length of treatment and dose 3. When prolonged systemic glucocorticoid treatment is
start low, gradually taper up planned, alternate day therapy is recommended to reduce
taper down slowly toxicity and occurrence of iatrogenic secondary adrenocortical
Cortisol has modest but significant mineralocorticoid activity insufficiency.

680
modest but significant mineralocorticoid activity

681
modest but significant mineralocorticoid activity
682
683
684 methasone ending means long acting steroid
 G H

685

methasone ending means long acting steroid

686

687

688

689

690

691

692

693
694

695
 G H

696

In the normal situation, intercellular Ca++ levels increase when the

T cell receptor on helper T cells binds antigen. Calcium binds a
protein called calmodulin, leading to the activation of phophatases,
calcineurn. Transcriptional activation of nuclear factor of
activated T cells (NF AT) is increased. This, in turn, leads to the
transcription of IL-2. When cyclosporin binds a protein called Development of renal toxicity from use of the calcineurin
cyclophilin, the activity of calcineurin is inhibited. Therefore, T inhibitors, cyclosporine and tacrolimus, continues to plague all
helper cell activation and production of IL-2 is inhibited. transplant recipients treated with this class of drugs.

697

Development of renal toxicity from use of the calcineurin

It appears to me that tacrolimus and OKT3 can both be used even inhibitors, cyclosporine and tacrolimus, continues to plague all
after organ rejeciton transplant recipients treated with this class of drugs.

698

699

Mandatory weekly CD4 T cell count due to apoptosis of T cells

 G H
700
also Remember: azul (blue) Theo from the Cosby show running
around with swollen knees from rheumatoid arthritis and bleeding
from his ass from Chrons dz
701 In vivo, OKT3 binds to most peripheral blood T cells and T cells in
body tissues, but has not been found to react with other
hematopoietic elements or other tissues of the body. A rapid and
concomitant decrease in the number of circulating CD3 positive
cells is observed, including those that are CD2, CD4, or CD8
positive.
702
703
No known drug interactions; given IV
704
705
All patients taking azathioprine require regular blood testing
for blood counts and liver function tests for monitoring.
Other side effects encountered less frequently include fatigue,
hair loss, muscle aches, joint pains, diarrhea, upset stomach
and vomiting.
Azathioprine is transferred to the fetus and must be
avoided in pregnancy. It is also found in breast milk and
therefore should not be used in nursing mothers.
Indicated for the treatment of steroid-resistant acute
allograft rejection in cardiac and hepatic transplant
patients. It is used for acute organ rejection that occurs
suddenly and threatens to destroy an organ quickly. The term
acute means rejection that occurs days to months after
surgery and is primarily a cell mediated immune response. It
may also be used to prevent rejection during the first 10 to 14
days after surgery in patients who have serious side effects
with other immunosuppressive drugs. OKT3 is administered
intravenously.
 G H

706

Mesna (2-mercaptoethane sodium sulfonate) given as a

uroprotectant in patients with hemorrhagic cystitis receiving further
Cyclophosphamide chemotherapy??
707

708
 G H

709
Prolonged use of methylprednisolone can depress the
ability of the body's adrenal glands to produce
Short courses of methylprednisolone usually are well-tolerated corticosteroids. Abruptly stopping methylprednisolone in
with few and mild side effects. Long term, high doses of these individuals can cause symptoms of corticosteroid
methylprednisolone usually will produce predictable and potentially insufficiency, with accompanying nausea, vomiting, and even
serious side effects. Whenever possible, the lowest effective shock. Therefore, withdrawal of methylprednisolone
doses of methylprednisolone should be used for the shortest usually is accomplished by gradual tapering the dose.
length of time to minimize side effects.

Drug interations cont:

Antacids may decrease the absorption of corticosteroids from
the gut.
When taken with carbenoxolone, amphotericin or diuretics
(furosemide) there is an increased risk of hypokalaemia.
DRUG INTERACTIONS When taken with NSAIDs (indomethacin), there is an
The following medicines may increase the effects of increased risk of adverse effects on the gut, such as stomach
710
corticosteroids: ulceration and bleeding.
antifungals (itraconazole and ketoconazole) and oral The blood levels of aspirin are decreased by corticosteroids
contraceptives. and therefore may increase to excessive levels once the
corticosteroid is stopped.
The following medicines may increase the removal of Corticosteroids may oppose the treatment of high blood
corticosteroids from the body, thus reducing their effects:- - pressure and heart failure because they may cause
antiepileptics (carbamazepine and phenytoi) and retention of salt and water.
barbituates (phenobarbitone) - As corticosteroids may increase blood sugar, they can
rifampicin oppose the blood sugar lowering effects of antidiabetic
aminoglutethimide. medicines.
711

712
 G H
713
Mech: Bleomycin is a mixture of cytotoxic glycopeptides that
interact with ferrous iron (Fe2+) and DNA simultaneously.
Bleomycin induces single- and double-stranded DNA breaks
through free radical generation. It is cytotoxic mainly during the G2
and M phases of the cell cycle. Because bleomycin causes little
myelosuppression, it has significant advantages in
combination with other cytotoxic drugs. However, bleomycin
does cause a serious pulmonary toxicity, which begins with a dry
cough, fine rales, and diffuse basilar infiltrates on x-ray and may
progress to life-threatening pulmonary fibrosis. Radiologic
changes may be indistinguishable from interstitial infection or
tumor, but may progress to dense fibrosis, cavitation, atelectasis or
lobar collapse, or even apparent consolidation. Approximately 5%
to 10% of patients receiving bleomycin develop clinically apparent
pulmonary toxicity.
714
715
716
717
Chemotherapy, or treatment with drugs, is only one modality
for cancer treatment. Surgery and radiation therapy are the
other important approaches.
Systemic chemotherapy is the main treatment available
for disseminated malignant disease. Progress in drug
therapy has resulted in the development of curative
chemotherapy regimens for several tumors. Chemotherapy
also has a significant role in palliation, often with improved
survival, in a variety of other tumors. However, chemotherapy
has only minor activity in several common solid tumors. One
of the most important and still evolving roles for systemic
chemotherapy is its use in the adjuvant setting. Adjuvant
chemotherapy is the use of drugs following primary treatment
by either surgery or radiation to treat micrometastases.
Note: Therapeutic regimens that combine several different
agents are now the standard method for treating most
neoplastic diseases, see Cancer Chemotherapy Notes for
details
 G H

718
Cisplatin-induced nephrotoxicity has been largely overcome by the routine use of hydration and diuresis during therapy.
However, ototoxicity caused by cisplatin is unaffected by diuresis and is manifested by tinnitus and hearing loss in the high-
frequency range. The ototoxicity can be unilateral or bilateral, tends to be more frequent and severe with repeated doses, and
may be more pronounced in children. Other adverse effects commonly occur with cisplatin treatment; most notably, marked
nausea and vomiting occur in almost all patients, but usually can be controlled with ondansetron and/or high dose corticosteroids.

All agents alkylate = add alkyl group to DNA, protein, or other

Sterile hemorrhagic cystitis has been reported in 5-10% of cell constituent
719 patients treated with cyclophosphamide. This adverse effect is Alkylation of 7 position on guanine in DNA leads to:
attributed to the accumulation of a metabolite, acrolein. Cystitis Cross-linking of DNA strands!!
can be reduced in intensity or prevented by the parenteral abnormal base pairing
administration of mesna, a sulfhydryl compound that reacts readily Miscoding of RNA & DNA
with and neutralizes the effects of acrolein in the acid environment Inhibition of DNA replication
of the urinary tract. DNA strand breakage
720

721

722

723

724
 G H

725

726

727

728
May cause irreversible dilated cardiomyopathy, the occurrence of which is related to the total dose of the drug. Two types of
cardiomyopathy may occur. (1) An acute form is characterized by abnormal ECG changes and arrhythmias. This is brief and
usually not a serious problem. (2) Chronic, cumulative dose-related toxicity is manifested by CHF that is unresponsive to digitalis.
The mortality rate is >50%. The hazard is attributed to lipid peroxidation of myocyte membranes and nonspecific alterations in the
myocardium have been noted such as a decrease in the number of myofibrils, mitochondrial changes, and cellular degeneration.
Discontinuance of the drug can allow complete resolution of these changes, but there are currently no practical means for early
detection of the toxicity. Cardiac irradiation or administration of high does of cyclophosphamide increase the risk of cardiotoxicity.

729

730

731
 G H

732

733

734

735

736
PRPP = phosphoribosyl pyrophosphate - which is a ribose 5- Allopurinol enhances the retention and potentiation of activity
phosphate from the hexose monophospate shunt activated with of 6-mercaptopurine (xanthine oxidase deactivated) -
addition of pyrophosphate from ATP increases chances of SE (pancytopenia)

737

738

739
 G H

740

The antimetabolites induce cytotoxicity by serving as false

741 substrates in biochemical pathways. They are cell-cycle-active and
are specific mainly for the S phase. Many are nucleoside Fluorouracil (5-FU) simplified mech:
analogues that are incorporated into DNA or RNA and thereby Inhibitor of thymidylate synthase
inhibit nucleic acid synthesis. Other agents in this class inhibit Inhibits DNA synthesis; strand breakage
enzymes involved in nucleotide biosynthesis Inhibits RNA processing and function

742

743

744
High dose regimens of methotrexate combined with co-
administration of a reduced folate, such as leucovorin (folinic acid,
citrovorum factor), that bypasses the block created by
methotrexate can prevent severe gastrointestinal toxicity or
marked bone marrow hypoplasia. This is sometimes called
leucovorin rescue.
Use of very high-dose methotrexate (>1000 mg/m2) requires the monitoring of serum methotrexate l
and schedule of leucovorin rescue. Methotrexate is cleared mainly by renal excretion, and patients w
function require dosage adjustments. High-dose regimens have been associated with acute renal inj
prevented by vigorous hydration and alkalinization of the urine. In the absence of normal renal functi
satisfactory methods (including hemodialysis) to eliminate methotrexate. Acute or chronic administra
been associated with hepatotoxicity and an idiosyncratic pneumonitis.

The principle use of hydroxyurea has been as a

myelosuppressive agent in the myeloproliferative syndromes,
Hydroxyurea inhibits the enzyme ribonucleotide diphosphate particularly chronic granulocytic leukemia, polycythemia vera,
reductase, which converts ribonucleotides to and essential thrombocytosis. The drug is also used in
745
deoxyribonucleotides. This is a critical and rate-limiting step in combination with other drugs to treat some solid tumors.
DNA biosynthesis. The drug is specific for the S phase of the Hydroxyurea is also used to treat sickle cell disease. The
cell cycle; it causes cells to arrest at the G1-S interface. Since drug reduces the number of painful crises, the frequency of
cells are highly sensitive to irradiation in the G1 phase of the cycle, acute chest syndrome and hospitalization, and the need for
combinations of hydroxyurea and irradiation cause blood transfusions. Hydroxyurea is also sometimes used in
synergistic toxicity. combinations to treat HIV/AIDS.
 G H

746 Leuprolide, goserelin, and triptorelin are synthetic GnRH analogs

that suppress FSH/LH release when given continuously as long-
acting depot preparations. This results in reduced testicular
androgen synthesis. These drugs are used to treat metastatic Not a prostatic cancer cure, used to prevent metastatic
carcinoma of the prostate. spread.
Flutamide and others are androgen receptor antagonists used to
747 treat prostate cancer. These agents antagonize residual
androgenic effects after orchiectomy or with leuprolide.

748

749
Adrenal and gonadal synthesis of testosterone are not affected, so
serum levels of T do not decrease, and may actually increase b/c
the dedication blocks the neg feedback in the hypothalamic-
pituitary axis, resulting in increased LH production

750

751

Selective Estrogen Receptor Modulators (SERMs): partial

agonists at the estrogen receptor and can produce either
estrogenic or anti-estrogenic effects depending on the tissue.
752 Tamoxifen is a competitive partial agonist-inhibitor of estrogen
binding to estrogen receptors in estrogen-sensitive tissues and
tumors. It is extremely useful for the treatment of breast
cancer and also has activity against progesterone-resistant Successful if lack endogenous estrogen & have estrogen
endometrial cancer. receptor present (ER-positive)

753
 G H

754

755

Acute Lymphocytic Leukemia:

Vincristine used together with corticosteroids is a treatment
756 of choice to induce remissions in childhood leukemia. It is
also used to treat adults with Hodgkins disease or non-Hodgkins
lymphomas. Vincristine (Oncovin) is a component of the MOPP
and CHOP combination regimens.
Induction: vincristine + prednisone + asparaginase +
daunorubicin + cyclophosphamide
CNS prophylaxis: Intrathecal methotrexate +/- high-dose
systemic methotrexate with leucovorin
Maintenance: Mercaptopurine + methotrexate
High-dose chemo: + bone marrow infusion

757
Topoisomerase I & II introduce and then repair single or double
stranded DNA breaks
Essential during transcription and translation because of twisting
and untwisting of DNA

Cell lines that show MDR are resistant to natural product cytotoxic
agents such as vinca alkaloids, antitumor antibiotics,
epipodophyllotoxins, camptothecins, & taxanes. Mechanism is
758 increased tumor expression of p-glycoprotein, drug efflux pump.
Product of MDR-1 gene.
Another type of MDR is due to expression of a topoisomerase II
with altered drug binding properties resistant to anthracyclines &
epipodophyllotoxins.

759
 G H

Trastuzumab: (Herceptin) is a monoclonal antibody that binds

to Her2/neu, a growth factor receptor expressed on the surface of
about 25 to 30 percent of breast cancers and other epithelial
760 tumors. Her2/neu is a member of the epidermal growth factor
family of receptors and its presence on breast cancer cells is
associated with a more aggressive natural history and poorer
treatment outcome. When cancer cells that over express Her2/neu
are exposed to Herceptin in vitro, cell growth is inhibited.
When promyelocyte counts are high, it induces further maturation
761 of the cells and stabilizes the cells and reduces the typical genetic
translocation of this disease state and improves risk of DIC and
bleeding.

In about half of CML patients, Gleevec treatment is also

associated with cytogenetic remission, in which the Philadelphia
chromosome becomes undetectable.
762 Molecular remission (elimination of CML cells as determined using
a more sensitive molecular method called PCR) occurs in less
than 10 percent of people who receive Gleevec.
Overall, it is estimated that about 80 percent of people receiving Also activity as a tyrosine kinase inhibitor in GI Stromal
Gleevec still have the Philadelphia chromosome, either because it Tumors that are positive for CD117, or c-kit, a tyrosine kinase
was never eliminated or the mutation recurred. similar to bcr/abl fusion protein

763

764

765

When giving LHRH analogs, one must first give adjunct drugs
766 such as bicalutamide for about 2 weeks before to prevent
testosterone storm, which can lead to heart attack and stroke from
malignant hypertension.

767
 G H
768
769

770

771

772

773

774
775
776
777
778
779
780
781
782
783
784
785
786
787
788

Risk of allergic rxn to cephalo among pts with hx of penicillin

789 allergy is ~8%, and the common manifestation is a maculopapular
or morbilliform skin rash, Urticaria and anaphylaxis are less
common, as are serum sickness-like rxns.

790

791

792
793
794
 G H
795
796
797
798
799
800
801
802
803
804
805
806
807
808
Ceftriazone is good for S. pneumonia and H. influenzae, and in
combination with azithromycin (expanded spectrum against gram
809 negatives) which covers Legionella and Moraxella - this
combination is good empiric coverage for community-acquired
pneumonia

810
811
812
Given with Cilistatin - inhibits enzymes in the kidney which
813 break down imipenem and protects kidney from toxicity caused
by imipenem
814
815
816
Considered safe for pregnant or nursing women and infants
817
Streptococcus pyogenes, or Group A b-hemolytic streptococci, can
818 be differentiated from the other b-hemolytic streptococci by its
exquisite sensitivity to bacitracin.

819

820
 G H

Gray baby syndrome: disorder in newborns who have either

received chloramphenicol immediately after birth or whose
mothers have received tit closse to delivery date. S&S - abd
821 distention with and without emeesis > progressive pallid cyanosis
> vasomotor collapse > irregular respiration; death can occur in a
few hours from onnset. Other symptos: loose, greenish stools, a
refusal to suck, ashen color, lactic acidosis
Lung abscesses mandate empiric coverage, due to contaminants
822 and polymicrobial nature (biopsy and bronchoalveolar lavage are
unlikely to provide information that will lead to tx other than
clindamycin)

823
Note: diphtheria toxin also inactivates the eukaryotic elongation
factor (eEF-2) thus preventing translocation

824 Used in combination with ceftriaxone for empiric tx of community

acquired pneumonia
825
826
827

Pseudotumor cerebri is a syndrome disorder defined

828
Do not admin with antacids, milk, or iron-containtin substances -
divalent cations inhibit absorption in SI
clinically by four criteria: (1) elevated intracranial pressure as
demonstrated by lumbar puncture; (2) normal cerebral
anatomy, as demonstrated by neuroradiographic evaluation;
(3) normal cerebrospinal fluid composition; and (4) signs and
symptoms of increased intracranial pressure, including
papilledema.

829

830
831
832
833
834
 G H

835

Require O2 for uptake into the bacterial cell, thus ineffective Aminoglycosides include: tobramycin, gentamicin,
against anaerobes streptomycin, amikacin, and neomycin
836
837
838
839

840

841

842

Do not admin with antacids (binds in GI and prevents absorption) TMP-SMX is MC used for traveler's diarrhea in kids

843

Drugs are secreted in the kidney and stool

844 Used following failure of clarithromycin therapy for bacteremic

pneumococcal pneuonia

845

846

847

848
849
 G H
850

851

Indications - pts in long term care facilities -OR- to all patients

Pneumococcal vaccine is given once at or after age 65yo (pt never older than 65 yrs -OR- younger than 65 yrs with chronic
852 needs another revaccination). If given before 65yo and more than pulmonary diseases, heart disease, diabetes, alcoholism,
5 yrs have passed, then repeat; also repeat every 5 yrs if pt is chronic live disease, heart disease, cerebrospinal fluid leaks,
ICpt. or asplenia.
853 Given annually to pts over 65yo
Given to pts taveling to areas with endemic poliomyelitis and who
plan to stay for prolonged periods. Pt who are unsure of their
854 vaccination hx should be txed as if they are vaccine-nave. If they
were vaccinated as chlidren, they should have a booster dose of
polio vaccine at least 1 mo before leaving the USA

855
Tx travelers to SE Asia or Asian subcontinent
Gives immunity for 10 yrs, travelers to endemic areas should
856
receive a booster after 10yrs
857 Typhoid vaccine requires a booster every 3yrs
Not recommended after age 4-6. Administration of the vaccine is
858 usually during infancy, with four doses being received by age 18
mo
Should be administered every 10 yrs and may be given within that
859 period if quesiton of susceptibility of a person at high risk (ie after
an open trauma, stabbing, or gunshot wound)
860
861

862

863

Drugs for Tension Headaches

Acute Treatment:
864 Three Syndromes to Tx: NSAIDs alone (Aspirin, acetaminophen, ibuprofen, etc)
Tension headaches NSAIDS + caffeine
Migraine headaches NSAIDS + a barbiturate (butalbital)
Cluster headaches NSAIDS + butalbital + caffeine
 G H
Significant dependence potential if doses higher than prescribed
are taken frequently
865 Significant interactions with other sedative-hypnotics alcohol is
contraindicated
Particularly if overused, withdrawal potential may contribute to
rebound headaches

866
Combination products have greater efficacy than NSAIDs
alone:
NSAID + caffeine is more efficacious than either alone
Caffeine mech: Competitive antagonist at adenosine receptors
Caffeine side-effects:
At doses prescribed for headache, caffeine is benign.
However, caffeine is a significant component in the diet of
many patients. Two problems result:
Excess dose. At high doses, caffeine causes palpitations and
anxiety
Termination of taking caffeine in patients who are dependent
on caffeine. This provokes headaches.

Prophylaxis of Tension Headaches Antidepressant Drugs

867 (but not SSRIs): Unclear whether psychological properties
as antidepressants contribute to effect. Most compelling
Note: SSRIs (serotonin selective re-uptake inhibitors) are modern evidence that this is the case is from studies showing that 2-6
antidepressants. They have little efficacy against tension weeks must pass before they are efficacious. This is the same
headaches. time period required for efficacy as antidepressants.
868
869

Tx of Migranes - Agonists at 5-HT1b & 5-HT1d sites:

Triptans: Of the multiple subtypes of 5-HT receptors, many
share overlapping binding sites; there are very few drugs with
870 specific selectivity at these receptor subtypes. Triptan drugs
have roughly equal affinity and efficacy at 5-HT1b and 5-HT1d
sites. Initially thought that 5-HT1d effects were critical (you may
see them referred to on Board exams as 5-HT1d agents), but
actions at 5-HT1b receptor have come to be favored. I will refer to
them as 5-HT1b & 1d agents.
Note, these agents are not active at 5-HT1a sites (those are the
buspirone type drugs, which are anxiolytic) or 5-HT1e sites.
Note: elimination t1/2 with triptans is a complicated issue. For
most of them, the t1/2 is short enough that the headache may
re-emerge. However, long t1/2 does not guarantee best
results. Frovatriptan has a 1-day half-life, but it is one of the
less efficacious agents. (longer active drugs are less
efficacious)!
 G H

As opposed to triptans, they have significant side effects, including

nausea. At higher doses, including those that can be reached with
repeated use for long-lasting migraine, they are dangerous
because of alpha agonist effects.
Triptans and ergots should not be used together because of
871
additive effects to constrict blood vessels
In addition, at high doses they stimulate other tryptamine receptors
- these agents are historically famous for causing hallucinations &
bizarre behavior (5-HT2 receptor stimulation), gangrene (alpha
receptor stimulation) and abortion (receptor mechanism?) in
people who ate moldy rye-bread)

872

873
Most migraine symptoms can be provoked by dopaminergic
agonists. Migraine pts are abnormally reactive to low doses of
dopamine agonists (they show yawning, nausea, vomiting, and
hiccough, all of which are caused by dopamine stimulation of DA
receptors in the brainstem). Hence, it might be expected that
dopamine antagonists would be beneficial.
Antagonists at D2 receptors which are older antipsychotic
drugs - Chlorpromazine (Thorazine), Prochlorperazine
(Compazine), and Metoclopramide (Reglan) (Modern
antipsychotics have fewer side-effects, but the newer agents
are not as efficacious in migraine)

874

875

Virapamil has been shown to be as effective as propranaolol for

876
prophylactic use; Nifedipine (& pines) not effective

877
Do not give to pt with low HR or seasonal allergies/asthma/COPD

878
 G H

Potentially serious complication of long term treatment is

Prophylaxis of Migraine: Methysergide
879 Very sloppy pharmacodynamics
Interacts with numerous 5-HT receptors, including some as
antagonist and some as partial agonist
Therapeutic effects in prophylaxis of migraine appear to relate best
to blockade of 5-HT2a and 5-HT2c receptors
inflammatory fibrosis, including retroperitoneal fibrosis,
pleuropulmonary fibrosis and coronary fibrosis. Usually
reversible on discontinuation, but because of this danger,
other drugs are preferred for prophylaxis. This is so unusual
that it is asked as a Board/Exam question out of proportion to
its importance.

Cluster HA: The predominant form of treatment is prophylaxis.
When a bout occurs, oxygen is most efficacious, and triptans are
880 also a reasonable choice. Effective prophylactic drugs are
prednisone, lithium, methysergide, ergotamine, valproate, and
verapamil. Lithium appears to be particularly useful for the chronic
form of the disorder (note: Li is ineffective in migraine do not
confuse the uses).
Cluster HA characteristics: Worst HA of life may be cluster;
alcohol is a vasodilator, single glass (red or white) can trigger
cluster HA
15min to 5 hrs
cluster very seasonal - common during Winter and Summer
Solstice (hypothalmus associated with cercadian rhythm); also
may occure at the same time of day

881 Lithium Has a Narrow Therapeutic Window; Blood

concentration data:
maintenance ~0.6 - 1.2 meq/L
toxic levels ~ 2.0 meq/L
Toxic levels are easily obtained Lithium has NO effecacy in migranes

882

883

884

Normal output of the indirect pathway depends on a balance

between DA inhibitory & ACh excitatory input. Tremor responds Therapy for Parkinson's can therefore involve increasing DA
well to anticholinergics receptor stimulation or inhibiting cholinergic neurotransmission

885

886
 G H

Inhibits DA metabolism in the striatum (MAO-B) without greatly
affecting degradation of catecholamines in other brain regions or
887 the periphery (by inhibition of MAO-A which would increase NE in
the periphery). Little risk of hypertensive crisis due to
accumulation of peripheral NE as might occur with
nonselective MAOI's (& tyramine)
Selegiline can delay need for aggressive pharmacotherapy,
but does not prove that neurodegenerative process is
delayed, since selegiline also has a direct symptomatic effect
by increasing availability of DA. Best documented use of
selegiline is as an adjunctive agent to improve response to
levodopa.

888

889

890 Behavior change: mood, hallucinations, sleep disturbance, etc.

Limits ability to treat patients with pre-existing psychotic
symptoms, since they will get worse. Behavior disturbances loss of effectiveness after 4-5 years, response fluctuations
induced by L-DOPA cannot be controlled with conventional (dyskinesia/akinesia), less likely with agonist compared to
antipsychotics because of their anti-dopaminergic action; they can levadopa. End dose failure (increasing dose density or use
be controlled with atypical antipsychotics (e.g., olanzapine). Do carbidopa combination prolonged release formula, add COMT
not use MAO-A inhibitors inhibitors, selegine, add agonist. Onn off phenomena most
Do not use with prochlorperazine, promethazine, metoclopromide likely in patients initially showing good therapeutic response.
(D2 receptor antagonists) (Akinesia periods, not related to dose timing)
levodopa converted to DA in CNS where it has therapeutic effect,
but large amount of DA becomes available peripherally and is
891 responsible for toxic effects. carbidopa does not cross BBB; it
inhibits peripheral DA formation, allowing levodopa dose to be
lowered while increasing its availability to the CNS

892

do not use with MAO-A inhibitors (2-wk. wait)

893
Association with cardiac valvulopathy associated with
Ergot alkaloid with similar side effects carcinoid syndrome
 G H

Direct dopamine receptor agonists: Longer duration of

Direct dopamine receptor agonists: Do not depend on
894
functional capacity of DA neurons for their action at receptors and
thus may be more effective than levodopa in late PD, after
substantial degeneration of DA neurons has occurred. Greater
potential for selectivity for receptor subtypes present in striatal DA
system, possibly avoiding side-effects related to other brain DA
systems (this potential is probably not yet realized).
action than levodopa therapy; may prevent dose-related
fluctuations in motor function that tend to worsen in late PD
under levodopa therapy. Reduce endogenous DA release and
reduce need for exogenous levodopa. If DA metabolism
(leading to striatal oxidative damage) contributes to
progression of the PD neurodegenerative process, then
DA agonists (antioxidants??) should retard disease
progression whereas levodopa therapy would tend to
accelerate progression.

895

Body registers more dopamine, which some of it is converted to

896 NE and E, and so upreglates the Ez Catechol-O-Methyltransferase
to eliminate the excessive NE and E. dopa decarboxylase causes
activation of COMT pathway, increasing 3-O-methyldopa (3OMD);
3OMD is associated with poor therapeutic response to levodopa
(competes for absorption into brain with LDOPA) Spasticity does not necessarily respond to analgesic/anti-inflammatory treatment
Typically caused by lesions of descending pathways: corticospinal, reticulospinal, vestibulospinal.
lesion)
Spasmolytics Definitions Peripheral reflex arc is typically intact and can be modulated by drugs to treat spasticity.
Spasm- analgesic/anti-inflammatory agents Normally, intrafusal afferent (Ia) from muscle spindle synapses directly on motor neurons going to the
Spasticity- velocity-dependent increase in tonic stretch reflexes to resist the stretch. Collaterals of the same Ia synapse on inhibitory internuncial neurons which inhi
897 cause hyperactive reflex, spasms, weakness, and loss of dexterity. antagonist muscle. Loss off CNS inhibitory modulation causes hyperreflexia.
Spasm, local trauma or strain, depression of polysynaptic reflex arcs (phenobarbital, other barbiturat
Causes of spasticity: (mephenesin). These would not be desirable for spasticity, because they would also reduce desirab
spinal injury stroke well as excitatory activity.
ALS MS cerebral palsy Disappointing class of drugs because while they are effective against spasticity, they tend to detract
Drug selection determined by type of spasticity mobility.

898

899

900
 G H

901

902

The effects are in the spinal cord dz, acts by increasing gabaergic
mediated presynaptic inhibition of internuncial neurons. Baclofen
by inhibiting release of excitatory transmitters on IA neurons
903 themselves. Excitation of GABA-A receptors causes
hyperpolarization by increased Cl- conductance (gamma subunit
for benzodiazepine facilitation).
Target is intrannuncial (inhibitory interneuron). decrease Ia
(intrafusal afferent) excitation of primary motoneuron.

904
Rem: doc said he would be weak, so they made Dan a bed in
whataburger closet so he didn't have to ambulate; he got liver sick
from eating the food

905

I. Symptomatic
A. Fluid balance, mineralocorticoids
906 (Fludrocortisone, midodrine)
B. Elastic stockings
II. Treatment of underlying disorder
A. Careful manipulation of ANS parameters

907
908
909
910
911
912
913
914
 G H

Phenytoin: Pharmacokinetics
Absorption of oral dose slow and incomplete
70-90% bound; salicylates, phenylbutazone and thyroxine will
displace from albumin
915
Metabolized in liver; therefore, very susceptible to drugs such as
disulfiram and bishydroxycoumarin
t1/2 is 24 hours, but is dose-dependent
At greater than 10 ug/ml = zero-order elimination, therefore
best to measure plasma levels. (relatively low therapeutic index)
SE: megaloblastic anemia - check for low folate
!!All antiepileptic drugs can cause idiosyncratic rxns (not
dose related, no lab test to predict): rash, Stevens-Johnson
syndrome, agranulocytosis, thrombocytopenia, aplastic
anemia, hyponatremia, and hepatic failure!!
Seizure:
A transient loss of cerebral function caused by abnormal
synchronous electrical discharges from cortex.
10% of population has had a seizure.
Epilepsy:
A symptom complex characterized by recurrent paroxysmal
aberrations of brain function, usually brief and self-limited.
Note: Two million Americans have some form of epilepsy
(about 1 in 100).

916

917

Very effective against complex partial when other drugs are

ineffective

918

919

Reduction of Ca2+ Entry: Molecular Actions via T-type (low
threshold) calcium channels:
Ca2+ is necessary for neurotransmitter release.
920 Concentration of Ca2+ is related to number of vesicles/packets of
neurotransmitter released.
Reduced amounts of neurotransmitter release leads to less
conduction.
Absence Seizures:
Effects on Brain Activity - failure to inactivate T-type
channels produces the rhythmic oscillations seen in absence
seizures, increased glutamate release, increased excitation
and reduced inhibition of thalamic cells results in feedback
loop -- T-type Calcium channel blockers decrease
glutamate release in thalamus
 G H

Reduction of Ca2+ Entry:

921 Indications
prevents and reverses absence seizures
Valproate is preferable drug if generalized tonic-clonic seizures eg Ethosuximide (Zarontin) & Valproic Acid (Depakene,
coexist with petit mal Depakote)

922

923

GABA Inhibitory Neurotransmission:

924 Global slow-down of brain activity
Effective against all seizure types
Rapid tolerance
inducer of microsomal enzymes (potential for drug interactions) Side effects as expected for global slow-down:
oral dose slowly but completely absorbed; long duration of action difficulty concentrating
(t1/2 is approximately 96 hours) sedation
ataxia

925
Benzodiazepines: Pharmacokinetics
Rapid onset, short duration
Highly bound (drug interactions)
Diazepam is relatively ineffective when given p.o.

Notice: all status epilepticus drugs must be given at weight

926 based dose at no faster than 20min (rate) (or pt will go into Intubate as necessary. Children under the age of 18 months
arrhythmia or hypovolemia)!! See Epilepsy Orr ppt for algorhthm should receive pyridoxine (B6)
(which is from Harrison's)
 G H
927

928

929

930

931

Infantile Spasms (Wests syndrome)

932 Corticosteroids: corticotropin, prednisone, dexamethasone
Benzodiazepines: clonazepam
Vigabatrin: irreversible inhibitor of GABA-transaminase.
Wests syndrome and adjunctive for partial seizures
933

Neutralizing Antibodies to IFN:
Antibodies (neutralizing antibodies NAb) to -interferon (IFN)
may occur during treatment
934 Presence of NAb may be associated with a reduction in clinical
effectiveness of IFN treatment
The rate of NAb production is probably less with IFN-1a
treatment than with IFN-1b treatment
Clinical utility of measuring NAb in an individual on IFN therapy is
uncertain
The possibility of viral infection as a causative agent raised
the possibility that gamma interferon, one of the body's natural
weapons against viruses, might help MS sufferers. In 1984,
researchers first administered gamma interferon to humans.
Unfortunately, the patients' symptoms became even worse.
This made researchers wonder if gamma interferon might be
directly involved in MS. Research showed that gamma
interferon levels shot up just before and during MS
attacks.
 G H
935
Originally intended to induce an animal model of multiple sclerosis
(experimental autoimmune encephalomyelitis [EAE]) by sensitizing
the immune system to a key component of myelin basic protein. To
the contrary, glatiramer reduces EAE severity.
936
937
A 3-5 day course of high-dose I.V. steroids is the treatment of
938 choice for an acute MS attack. This treatment may require
hospitalization, although it is possible to have I.V. treatment on an
outpatient basis. The I.V. steroids may be followed by a one- to
two-week tapering dose of oral steroids.
939
Efficacious in MG
Often used in MS, but evidence-based medicine is lacking
940
Inhibits the production of helper T-cells.
Works more quickly than azathioprine, usually within one or two
months.
Glatiramer - A random chain of 4 amino acids in a particular
stoichiometery (the stoichiometry is shown below, and only
FYI), which mimic myelin basic protein.
Alanine (5), Lysine (3), Glutamic Acid (1.5), Tyrosine (1)
With this type of acute use (MS), corticosteroids are relatively
benign in terms of toxicities. No evidence supports
continuous use of these drugs in MS.
They are used chronically in other conditions, but long-term
use of corticosteroids has well-documented adverse effects,
including adrenal suppression, altered metabolism, ulcers,
and osteoporosis.
Commonly used in conjunction with thymectomy and
corticosteroids. The clinical benefits may not be observed for
several months, and treatment can continue for up to two
years after benefits are initially observed. In most patients
with severe myasthenia gravis, therapeutic effects and
the best results are noted in late-onset, rapidly
progressive myasthenia gravis in older patients, or in
patients of all age groups with thymoma.
 G H

941

Plasma exchange is usually followed by 3-5 weeks of improved

942 strength.
No better than immunosuppression in reducing circulating levels of
the anti-Acetylcholine-Receptor Ab or in inducing clinical
improvement. Plasmapheresis is, however, faster in onset of
action.

primary diagnosis with circulating antibodies, emg, or CT or

MRI for thymoma.
Differentiate myasthenia g. from lambert eaton syndrome.
select specific muscle gorup (e.g., ptosis, drooping of upper
943 eyelid) for the diagnostic.

Cholinergic crisis: normal muscarinic signs may not be seen

(because of tolerance) in myesthenic patient, so weakness is
Penetrate ganglia poorly, so little effects on blood pressure the only thing observed.

944
Penetrate ganglia poorly, so little effects on blood pressure

Tensilon Test cont:

Tensilon Test Differentiation of myasthenic crisis from
cholinergic crisis; scenario: MG patients being treated with an
anti-cholinesterase drug (e.g. pyridostigmine) presents with
945
profound weakness. Is the weakness the result of too little
anticholinesterase drug (a flare-up of the disease), or too much
anticholinesterase drug (depolarizing blockade)? Muscle
receptors for ACh are nicotinic type, and too much ACh will cause
a depolarizing blockade at nicotinic receptors (Review ANS
pharmacology)
946
Alzheimer's dz - Degeneration of cerebral cholinergic
947 system,especially in the basal nucles of Meyner (projects to the
neocortex and involved ni memory and learning)
If the problem is too little ACh getting to the receptor
(myasthenic crisis), edrophonium will dramatically improve
strength
If the problem is too much ACh getting to the receptor
(cholinergic crisis), edrophonium will either have no effect or
will actually make the problem worse (nicotinic depolarization)
Toxicities in this test are limited because of brief duration of
action of edrophonium. Muscarinic signs and symptoms can
be blocked with atropine-type drugs.
 G H
948
949

950

951
SSRIs: Fluoxetine
longest half life!! (implications when switching to an MAOI) Selective Serotonin Reuptake Inhibitors (SSRIs):
t ~ 48 hr after a single dose newest generation of antidepressants
t ~ 84 hr after multiple doses selectively block serotonin reuptake
Steady state plasma levels not achieved for 4-5 weeks fewer side effects
Active Metabolite - Norfluoxetine much safer in overdose
t ~ 146 hr may be the first-choice for treatment of depression

SSRIs: Sertraline
952 long half life: t ~ 24 hr
Side effects: most likely of the SSRIs to produce GI disturbances
(diarrhea)
Low potential for drug interactions due to P450 interactions.

SSRIs: Paroxetine
long half life: t ~ 26 hr
953 One of the most serotonin selective of the SSRIs
Side effects: more weight gain, sexual dysfunction and
discontinuation symptoms than other SSRIs.
Potential for many drug interactions due to potent inhibition of 2D6.

SSRIs: Citalopram/Escitalopram
long half lives: t ~ 35 hr
citalopram is a racemic drug mixture (S-enantiomer, escitalopram,
954 is active)
Reportedly less likely to produce mania if given to a bipolar,
depressed patient.
Many reports in the literature where escitalopram treatment
induced mania

955
Escitalopram is the most serotonin selective of the SSRIs
 G H

956 Tx OCD with SSRI (usually takes 4-6 wks for effect, but with
long half life: t ~ 22 hr OCD, SSRIs work in 4-6mo and must use aggressive doses)

957

Negligible actions on NE & 5-HT reuptake - so lower incidence of

sexual side effects

958

2nd & Subsequent Generation Antidepressants

959 Sometimes called atypical antidepressants
heterogeneous in number and composition of ring structures
most block monoamine reuptake
some have (less?) side effects than TCAs
some are safer than TCAs in overdose
2nd & Subsequent Generation Antidepressants:
Most have actions on monoamine reuptake, but some do not;
hence some are called Atypicals (Bupropion & Mirtazapine)

960
Not associated with cardiovascular SE, nor sexual
dysfunction or weght gain!!

961

Duloxetine: A fairly new SSNRI (approved in Oct 2004) that Lilly is

962 marketing as being particularly useful in the treatment of painful
physical symptoms of depression. It has received FDA
approval for treating diabetic neuropathic pain.
 G H

963

Tricyclic Antidepressants
964 first generation antidepressants - 3-ring structure
block monoamine reuptake (NE, 5-HT, DA)
down-regulate NE and/or 5-HT receptors
lots of side effects
high toxicity in overdose
SE:
Antimuscarinic: blurred vision, dry mouth, constipation,
urinary hesitancy, confusion,
Metabolic/Endocrine: weight gain, sexual disturbances
SEDATION
Sympathomimetic: tremor and insomnia
Cardiovascular: orthostatic hypotension, conduction defects,
arrythmias

965
966
967

Monoamine Oxidase Inhibitors (MAOIs)

968 First used about the time of the TCAs (mid 1950s)
inhibit MAO which metabolizes monoamines
multiple side effects
adverse interactions with tyramine in food MAOIs:
high toxicity in overdose Generally as effective as other antidepressants

969
970
971

972

Less abuse liability than methylphenidate and amphetamine

 G H

973

A depletion of PIP2 may lead to a decreased

responsiveness to synaptic transmission for those
receptors which utilize phosphoinositide 2nd messenger
signaling (eg -adrenergic and muscarinic receptors). A
depletion of PIP2 sufficient enough to produce decreased
responsiveness may not occur until lithium has been
974 administered for 2-3 weeks, a time course consistent with the
Enzymes inhibited are responsible for the conversion of IP2 to latency to clinical improvement (Li takes several weeks to
IP1 and IP1 to inositol. With chronic lithium treatment there is a work).
depletion of phosphatidylinositol-4,5-bisphosphate (PIP2) - the Other 2nd messenger effects - Inhibits norepinephrine
source of the second messengers inositol triphosphate (IP3) and sensitive adenylyl cyclase and may uncouple receptors
diacylglycerol (DAG) . Inhibits NE sensitive adenylyl cyclase and from their G proteins (e.g., vasopressin and TSH receptors)
may uncouple receptors from their G protein. Some forms of Specific isoforms of protein kinase C may be affected by
protein kinase may be affected leading to alterations in gene lithium, this, in turn, can lead to alterations in gene
expression which may be involved in mood stabilization expression which may be involved in mood stabilization.

Start a mood stabilizer before antidepressants, TCA

975 and Venlafaxine most likely to cause switch to mania,
Escitalopram and paroxetine have low probability of
Wider therapeutic window and faster onset than lithium (4-5 days) switching to mania

976
99% is processed in the liver, adjunctive or 2nd line treatment.
Increasingly used as first line agent. Well tolerated in the elderly,
effective against absence seizures through calcium channel
mechanism) May have to withdraw immediately if they get a rash

977

MFO inducer; self inducing (???)

 G H

978

979

980

981

982 Psychosis and Schizophrenia: disorder of thought,

perception and mood
Positive Symptoms (incomplete list)
delusions
hallucinations
Negative Symptoms
Affective flattening
Atypical Antipsychotics Anhedonia (a psychological condition characterized by
All atypical antipsychotics are better than typical antipsychotics in inability to experience pleasure in acts which normally produce
terms of greater efficacy against negative symptoms it )
Less likely to cause tardive dyskinesia Little voluntary movement
Remember that in addition to blocking D2 receptors, atypicals Disorganized speech and behavior, and poor attention
block 5-HT2 receptors which likely accounts for both phenomena

983
 G H

984

985

986

987
Will not cause weight gain in therapeutic does.
 G H

988
Can give IV (or PO/IM) for acute aggitation (or violent
behavior - straight jacket effect), no recognized ceiling dose
(keep increasing until aggitation deminishes) - more
commonly give atypicial with a BZD now; note that the
aggitation can be addressed within a few hous, but the
delusional thought/psychosis will take the typical 1-3wks
Half-life of approximately 20 hours before drug effect.

989

990

991

992

993

994

995

996

997
 G H

998
Diazepam terminates status epilepticus, given i.v. - second
choice agent behind lorazepam. Diazepam is much more lipid
soluble than lorazepam; so much so that diazepam requires a
special vehicle it precipitates from aqueous solution unless the
concentration is very dilute. These physicochemical properties
have caused the more water-soluble agent (lorazepam) to take
over this function. Not used as long-term therapy for seizures.
Profound tolerance that develops rapidly
Definitions:
Anxiety: Signs and symptoms of anxiety can be useful for
meeting difficult situations; anxiety inhibits unwise action; in
the case of true danger, anxiety can be life saving
In the absence of an appropriate threat, or if the anxiety is
out of proportion to the threat, it can impair the individuals
ability to function
Sedative:
diminish awareness
cause drowsiness
diminish motor activity
Note: sedatives are generally anxiolytic, but sedation is not a
desirable property of an anxiolytic
Hypnotic: an agent that promotes sleep and inhibits
wakefulness

999

1000 Perhaps less sedative than other BZDs, yet also effective for
hypnosis (pt is less anxious)
Relatively short half-life (12-15 hr)

Status epilepticus tx with lorazepam (muscle relaxant

1001 well correlated with antiseizure activity) (phenobarbital can
No active metabolites; because of better water solubility, cause respiratory collapse as dose is rapidly increased, much
lorazepam is more rapid to administer than diazepam less likely to occur with lorazepam)

Final common pathway for diazepam and chlordiazepoxide

metabolism in the liver (which both form Desmethyldiazepam,
common 'active' metabolite, that is further converted to
oxazepam). More reliable pharmacokinetics in elderly for
1002 oxazepam as compared to diazepam and chlordiazepoxide.
Little change in Phase 2 metabolism with aging (e.g. glucuronide Note on drug elimination: with liver dz get a greater
conjugation) reduction in phase 1 reactions than phase 2 - reduction in
Significant changes in Phase 1 metabolism with aging (e.g., P450 everything metabolised by livers P450.
oxidations)
 G H
1003

BZDs as hypnotics are effective but hangover (morning

grogginess) is problem for long acters, rebound insomnia and
1004 Removed in UK because of rebound anxiety/insomnia, high dose anxiety are problems for short acters, morning awakening is
formulation removed in the US, much less problem with current problem for short and intermediate acting, and
formulation tolerance/dependence/withdrawal of course
Water solubility and short duration of action are significant
positive feature for pre-operation. Used at high doses to
1005 produce significant amnesia (anterograde) from time of
administration to when drug wears off. Patients not left fearful of
procedures especially repetetive ones (colonoscopy, bladder
exams)

Beta-Carbolines (FYI) - BZD-receptor inverse agonists

1006 Final proof that the BZD binding site is the functional
No effects in absence of BZD and watch out for precipitated equivalent of a non-competitive binding site in enzymology.
withdrawal (seizures the big issue in BZD dependence/withdrawal) These compounds cause: seizures, anxiety

1007

If SSRI are ineffective in controlling anxiety, buspirone is often tried

alone or with SSRIs Slow onset-1 week onset, 2-4 weeks max effect

1008

1009

1010 Triazolam problems:

Removed from the market in the UK because of rebound Insomnia - two types:
anxiety/insomnia Getting to sleep
High dose formulation removed from the market in the U.S. Staying asleep (usually more troubling)
Much less problem with current formulation Incidence increases with age
 G H

1011 Compared to BZDs, selective alpha1 subunit agonits is very Short half life 3-5 hours, less hangover than long acting BZDs,
hypnotic (nearly as efficacious at producing sleep) and much less no rebound insomnia even after 30 days of use. Abuse
anxiolytic, anticonvulsant, muscle relaxant dependence potential much lower than BZDs!!

1012
Shorter half-life than zolpidem (approx 1hr)
Argued that Ramelteon (melatonin agonist) is regulated by
FDA so consistent formula and thus can more accurately
1013 correct pts sleep schedule (as compare to OTC melatonin)
through strategic timing of administration (take at night) and
Works well, no probs with dependence, safetey standards not set have pt stay awake and be outside in sun to set internal clock
by FDA for travel/jet lag.

1014

No dependence of abuse, no rebound insomnia or withdrawal

BZDs vs Barbiturates Barbituates, alcohol, phenothiazines, and MAOI decrease the

Both facilitate GABAs effects amount of REM sleep while the pt is taking them. Withdrawal
1015 Neither bind directly at the GABA binding site on the receptor of the agent then allows the body to compensate for "missed"
At high doses, barbiturates directly increase Cl- flux REM sleep, and REM rebound develops. Characterized by
In contrast, no dose of BZDs ever directly affects Cl- flux. BZDs increase in the number and intensity of dreams for several
only facilitate GABA. days after discontinuation of the drug
1016
1017
1018

1019

1020

Effects in adults are euphoria, insomnia, appetite suppression,

1021 and shift to paranoid thinking
Effects in children are calming of hyperactive behavior
A so called paradoxical effect Hepatic metabolism, half life is 2.5 hours so requires in
Mechanism is presumably DA morning and in school. Penetration to CNS slower compared
to cocaine or amphetamines (lower abuse potential)
 G H
1022

1023

Allderall combination includes: d-amphetamine saccharate,

amphetamine aspartate, amphetamine sulfate, d-amphetamine
sulfate. These different salts make a more sustained effects CNS stimulate that for unknown reason calm hyperactive
as they have different rates of going into solution in the GI disorder (in children) in the first dose
tract (provides all day coverage)

1024

Related to TCA (remember that amitriptyline has

1025 anticholinergic and antihistaminergic SE) - Atomoxetine -
Single MC SE is dry mouth, then urinary retention (ContraI in
Less abuse liability than methylphenidate and amphetamine males with BPH, glaucoma); also idiosyncratic liver damage
1026

1027

1028

1029

1030
 G H

1031

Anorexiant medication - as adjunct only, never as

monotherapy!
Anorexia = without appetite (this type of drug reduces appetite;
another class produces a sensation of fullness)
Exercise is critical to proper maintenance. These are anorexiant
medications (takes away appetite) where as others produce
fullness
Inclusion for anorexiant medication criteria BMI>30 or
BMI > 27 plus risk (HTN, diabetes, hyperlipidemia).
Amphetamines can not be used in a weight control
program (sched II can not be prescribed)

1032

Fen-Phen associated with valvulopathy typically invovling the

1033 aortic and mitral valves; pulmonary HTN also rarely
fenfluramine (increased serotonin (satiety) but had lethal SE) associated.
1034
Note: agents that increase NE (and DA) cause loss of
1035 appetite; agents that increase serotonin increase satiety
Note: Weight control is not an FDA-approved indication. dont feel like eating, wears off in a few days

1036

1037

Not systemically absorbed, supplementation of fat soluble

nutrients recommended
Hydroxy citric acid (appetite supressant from Garcinia cambogia
1038 CITRIMAX), fat binding fiber, gingko biloba, Vit E, etc NONE HAVE
BEEN SHOWN EFFECTIVE
 G H

1039

1040

1041

1042
EtOH: Pharmacokinetics Oral Absorption
absorbed rapidly and completely
One Drink ~ 14 g EtOH Peak BEC seen at ~30 min (longer if taken with food)
1.5 oz 80 proof whiskey Primary site of absorption is in the small intestine
12 oz beer EtOH: Pharmacokinetics Distribution
4 oz glass of wine Rapid
note: some use 10 g as the definition of a drink Passes easily through membranes
Blood Ethanol Concentration Distributes with total body water
BEC = BAC = BEL = BAL Females on average have a higher fat composition, and,
Units: % (g/dL) or mg % (mg/dL) therefore, a smaller volume of distribution and a higher BEC
1-2 drinks produces a BEC of ~0.025 g/dL than males

1043 use in conjunction with counseling and other psychosocial

therapies

1044 may be useful in combination with naltrexone

use in conjunction with counseling and other psychosocial
therapies Note: acamprosate has the same mechanism as alcohol
 G H

After alcohol intake under the influence of disulfiram, the

concentration of acetaldehyde in the blood may be 5 to 10
times higher than that found during metabolism of the same
amount of alcohol alone. As acetaldehyde is one of the major
causes of the symptoms of a "hangover" this produces
1045
Under normal metabolism, alcohol is broken down in the liver by immediate and severe negative reaction to alcohol intake.
alcohol dehydrogenase to acetaldehyde, which is then Some 5-10 minutes after alcohol intake, the patient may
converted by acetaldehyde dehydrogenase to the harmless experience the effects of a severe hangover for a period of 30
acetic acid. Disulfiram blocks this reaction at the intermediate minutes up to several hours. Symptoms include flushing of the
stage by blocking the enzyme acetaldehyde dehydrogenase (note: skin, accelerated heart rate, shortness of breath, nausea, and
fomepizole blocks alcohol dehydrogenase). vomiting.

1046

1047

Cocaine: Mechanisms
1048 Reinforcing effects correlated best with blocking DA transporter.
One of the most reinforcing substances identified in both humans
and animals. It is thus powerfully addictive.
20% of recreational users go on to serious heavy usage with
negative consequences. NIDA estimates 25+ million Americans
have used cocaine. Use has declined considerably from early 80s
to the 90s. Availability of free-base form (i.e., crack) has Cocaine: Neural Targets: Reward pathways (VTA and NA)
influenced use. (mesolimbic and mesocortical DA pathways); Arousal
Also binds NE and 5-HT transporters systems (NE pathways; Locus Ceruleus, dorsal bundle);
Reinforcing effects similar to i.v. amphetamines Autonomic nervous system (Potentiates the actions of NE in
Cocaine also has a local anesthetic action, which accounts the periphery. Particular concern for blood pressure and
for its convulsant effects in overdose. arrhythmias)
 G H

1049 Amphetamine: Mechanism: Reinforcing effects correlate best

with presynaptic release of DA (amphetamine runs the re-uptake Amphetamine: Neural Targets
transporter in reverse); some stimulants may have direct receptor Reward pathways (VTA/NA) (mesolimbic and mesocortical
effects and/or inhibit MAO, but for amphetamine and DA pathways)
methamphetamine, these are minor actions. No local anesthetic Arousal systems (NE pathways; LC, dorsal bundle)
effect (in contrast to cocaine); thus, seizure potential is less with Autonomic nervous system
amphetamines (although still a possibility)
1050

Nicotine: Mechanisms/Neural targets

1051 Agonist at CNS & peripheral nicotinic sites; Rewarding effects:
activation of VTA accumbens DA pathways (Much less so than
with amphetamine or cocaine); half-life of nicotine 2 hours; Fast
onset, within 7 seconds. Each puff produces a discreet
reinforcement; 10 puffs per cigarette, smoker is typically reinforced
over 200 times a day.; Associational and timing effects become
extremely strong. Both stimulant and depressant, so person
may become more alert and at the same time experience muscle
relaxation.
Nicotine withdrawal syndrome: Irritability, etc., Anxiety,
Dysphoria, Difficulty concentrating, Restlessness, Decreased
HR, Increased appetite and/or weight gain
Factors maintaining smoking behavior : urge to smoke is
correlated with low blood nicotine level, psychological craving,
avoidance of withdrawal

Hallucinogens: Classification
Indoleamine-like:
Lysergic acid diethylamide (LSD)
Dimethyltryptamine (DMT)
1052 psilocybin (magic mushrooms)
Phenethylamine-like:
Dimethoxymethylamphetamine (DOM) (STP)
MDMA derivatives (Ecstasy, Eve) (mixed
stimulant/psychedelic)
Mescaline
 G H

Phencyclidine (aka PCP, angel dust, ozone, rocket fuel)

Dissociative anesthetic, chemically related to ketamine with similar
effects. No therapeutic application in humans.
1053 Mechanism: non-competitive blocker of NMDA receptors Phencyclidine: Effects: Euphoria, staggering, disorientation,
Route: smoking (marijuana laced with PCP), snorting, oral. paresthesia, nystagmus, slurred speech, distortion of body
Tobacco cigarette laced with liquid (dip). image; Strength, power, invulnerability (insensitive to pain);
Psychotomimetic effects; profound tolerance anger, rage; Depression; paranoid ideas; hostility
12-24 h half life; in overdosage may be prolonged to 72-h

Ketamine (aka Special K, vitamin K, cat valium (club/rave

use)): Dissociative anesthetic, chemically related to phencyclidine
with similar effects. Extensive veterinary use; not popular as
1054 human anesthetic in USA.
Mechanism: non-competitive blocker of NMDA receptors
Powder/liquid; Snorted or smoked with marijuana or tobacco
products.
disorientation, sensory illusions, hallucinations

MDA/MDMA: Modest stimulant and hallucinogen properties;

1055
MDA/MDMA - Methamphetamine analogs (schedule I)
MDA- methylene-dioxyamphetamine (love drug)
MDMA- methylene-dioxymethamphetamine (Ecstasy, E)
Initial sedative/dysphoria (30-60 m); Both shown to be
neurotoxic in animals (destroy serotonin-containing cells in the
CNS); Became popular on college campuses in 80s.
Purported to increase insight and self-knowledge. Both have
been tried as aid to psychotherapy. Very popular club drugs

1056
Marijuana: Mechanism Most commonly used nonlegal drug in US,
Binding to cannabinoid receptors Usage peaked in 1970s 60% tried, 11% regular users
Diverse Physiological functions 40%, 2% in mid 90s
Anandamide endocannabinoids Use has leveled off as of 1998-2000
1057
1058 Detectable 12-36 hrs in plasma

Alcohol-like effects; anabolic steroid-like effects; aphrodisiac

1059 Gamma hydroxybutyric acid (GHB) Club drug; popular at rave parties on college campuses
Grievous bodily harm, liquid ecstasy Synergistic interaction with alcohol; produces coma-like
Marketed outside USA as anesthetic sedation (date rape)
Related to GABA, but mechanism not known Extensive illicit synthesis, popular in Texas
 G H
Flunitrazepam (Rohypnol) - Rapid onset benzodiazepine
(roofies)
1060 Sedative-hypnotic
Profound amnestic effect; used as means of date rape
Club drug; popular at rave parties on college campuses
Causes profound amnesia -- forget me pill
Inhalants: Organic solvents - Glue sniffing; gasoline sniffing; nail
polish sniffing
1061 organic hydrocarbons - benzene; toluene
aliphatic hydrocarbons - hexane
halogenated hydrocarbons - trichloroethylene
alcohols, esters, ketones - methanol, ethylacetate
Inhalants: Nitrates/Nitrites
Systemic vasodilators (amyl nitrate, butyl nitrite)
1062 Less toxic than organic solvents
Abuse associated with enhancement of sexual sensations
Toxicity related to vasodilation - headache, peripheral pooling of
blood, decreased myocardial flow
Marketed abroad, extensive illegal importation
Popular in southwest
Significant medical consequences: Damage to neurons,
kidney and liver
Intoxication-excitation followed by drowsiness, disinhibition,
staggering, agitation
Aficionado description: "You open the little brown bottle, stick
it under your nose, and inhale. A few seconds later, your heart
starts pounding, your consciousness changes, and you
become utterly absorbed by sex. Instead of being 'me having
sex,' I become sex itself, and the experience can be
overwhelming. Poppers can make mediocre sex good, and
good sex spectacular."
 I J
1

Usually see approximately a 25% reduction in size of

7 prostate
Safe and Efficacious. See improvement in urine flow and
Finasteride SE = Dutasteride SE, the type I and type II have retention problems
no clinical significance Slow onset often need 6 months to see a full effect

8
Problems to Address:
Prostate size is a function of age + androgens!!
Obstruction-induced detrusor dysfunction
Neural alterations in the bladder and the prostate
Tx Options:
9 BPH age: Watchful Waiting
Rarely occurs <40 Surgery
50% older than 50 Pharmacotherapy (Alpha Blockers, Finasteride or
20 million American men are now over 50 Dutasteride (Anti-Androgen), Saw Palmetto (Anti-
80% older than 70 Androgen + ?))
 I J

Reflex tachycardia may occur; significantly less than with

non-selective blockers. Syncope, particularly when first
administered. (First dose phenomenon). Mechanism (and
10 subsequent tolerance to this phenomenon) not entirely
clear. Some component of orthostatic hypotension, but
CNS-mediated reduction of sympathetic tone also seems
Notice: prazosin is the protype for alpha1 blocker, but is short to be involved. Caution patients to avoid sudden postural
acting and is not used changes

11

12

13

14 NO (vasodilator) stimulates gynylate cyclase which converts

GTP to cGMP prevents dephorylation of light chain kinase,
which ultimately cause smooth muscle to relax and the corpus
cavernosum fills will blood. The phosphodiesterase breaks Small propensity for vasodilation - some systemic
down the cGMP. vasodilation

15

16

17

18
 I J

19

20

21

SOURCES OF ESTROGEN
In female:
- produced primarily by ovary, but some contribution by
adrenals, and local production in such target tissues as the
22 brain
- during pregnancy, fetoplacental unit produces estrogen
(estriol).
- postmenopausally, low levels of estrogen exist (mainly
estrone and estriol from adrenals, adipose tissue)
In male: Estradiol made by testis (Sertoli cells), which
aromatize testosterone (to estradiol) produced by Leydig cells;
also in the adrenals and local production
Physiological Effects of Estrogens:
Female maturation - development of sex organs and
secondary sex characteristics.
Closure of the epiphyseal plates on long bones.
Endometrial effects (proliferative).
Increase in risk of endometrial cancer (with unopposed
estrogen, no progesterone accompaning).
Metabolic and cardiovascular effects - Heart, bone, brain
also require estrongens.
Reduce bone resorption (osteoporosis effect on both
osteoblasts and osteoclasts)

23
24
 I J

SE of OC (estrogen) : Thromboembolism due to effect of

estrogens on clotting factors ( factors II, VII, IX, X;
antithrombin III); Increased risk of stroke in current, but not
past, OC users (Absolute risk: 0.037%); If discontinue, relative
risk returns to base line
Cardiovascular risk Risk of MI is particularly enhanced in
25 smokers [185/100,000 (smokers) vs. 4/100,000(non-
smokers)]; Relative risk increased 50x with smoking and OC
(but still low absolute risk); may be related to the effect of Notice: E increases HDL, decrease LDL, but increase
estrogens on clotting as well as effects of progestagens triglycerides (so P reduces Es enhancement of
(particularly Norethindrone) on HDL) triglycerides, and decrease Es increase of HDL)
Hypertension incidence is ~5% in long term OC users (> If woman has hidden CV dz (eg atherosclerosis), the OC
5yrs); Related to increased levels of renin substrate and may unmask this (ie adding increased thromboembolism),
sodium retention this is associated with age

26

27

28 Some progesterone derivatives (progestins) have androgenic

effects (some 19-nortestosterone derivatives such as
norethindrone)
SE - hirsutism
Progestins that are not as androgenic: Desogestrel,
Norgestimate (can be found in oral contraceptives)
Progesterone half life : approx. 5 min
Like estrogen, huge first pass effect
Metabolized in liver to pregnanediol and conjugated to
glucuronide, excreted in urine

29

30
Prodrug: Desogestrel converted to 3-keto desogestrel

31
 I J

32

33

34

Physiological Effects of Androgens

Testosterone or DHT is responsible for the development of
many secondary sexual characteristics in the male:
Changes in skin, including growth of pubic hair, axillary hair,
beard; Growth of larynx and thickening of vocal chords,
35 leading to deepening of the voice; Sebum secretion (a fatty
secretion of the sebacious glands of the skin)
Liver effect: decrease SHBG (especially oral route) Most of Testosterone is protein bound ~65% to SHBG;
Can stimulate erythropoetin secretion ~30% to Albumin
Increase RBC count (can overproduce) Orally administered testosterone is rapidly absorbed, BUT
Anabolic effects - (increase lean muscle and decrease body only 1/6 of dose is available in active form due to
fat) conversion to inactive metabolites
36

37

38

39

40

41

42
43
 I J

44

45

46

47

48
49

50

51

52
53

54

55
 I J

Loop diuretics, particularly furosemide, acutely increase

systemic venous capacitance (vasodilate), requires intact
56 kidneys: prostaglandin mediation (blocked by prostaglandin
synthesis inhibitors (NSAIDs) or by removal of the kidneys) -
decreases left ventricular filling pressure - useful in
pulmonary edema - happens before significant diuresis
begins
Note: with ascites, Tx improves morbidity but not mortality
Do not give with NSAIDs to CHF pt, because blocks
prostaglandin which dilate afferent arterials (more than
efferent) can cause renal insufficiency (reduction in
filtration) furosemide will actually increase prostaglanin
synthesis in kidney (vasodilatory, esp venous side), Protect against hypokalemia: Add K+ supplement and/or
increasing filtration by increased afferent a. dilation (happens add potassium-sparing diuretic
before observable diuesis effect reducing pulmonary edema)

57

58
59

60
 I J

61

62

JNC-7 recommends starting with a thiazide. In Stage 1

hypertension, thiazides can often be used alone.
In practical experience, Stage 1 hypertension may require the
addition of a second drug to the thiazide regimen.
In Stage 2 hypertension, start with thiazide in combination with
another antihypertensive. hyponatrimia SE distinguishes thiazide from loop

63
64

65

66
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67

CI: renal failure - kidneys can not accommodate K load,

causes hyperkalemia

68

69

70

71

Angiotensin II (Ang II) not only causes vasoconstriction

directly, but indirectly increases sympathetic NS activity
72
ARBs do not improve mortality in CHF. ACE-I do improve and can affect the release of normal dilators such as
mortality in CHF, so ACE-I are mainstay in that condition. prostaglandins and nitric oxide. Furthermore, Ang II
This is a big point of separation of ARBs and ACE-I mediates arteriolar remodeling, resulting in permanent
Note some studies show significat reductions in long-term increases in peripheral resistance, including major
mortality rates in CHF using ARBs compared to placebo contributions to atherosclerosis, renal disease and cardiac
(contradictory) hypertrophy.

73
 I J

74 ACEI Indication: Diabetic nephropathy: Diabetes causes

increased pressure in the glomerulus capillaries (PGC),
causing glomerular hypertrophy. ACE-I (and ARBs) dilate
efferent arteriole. (Note: Ca++ channel blockers selectively
dilate afferent arteriole and are contraindicated with diabetes.)
Indication: non-diabetic renal insufficiency: Elevated
serum creatinine (1.5-3.0 mg/dL); Strong association of
progression to end-stage renal failure with worsening
hypertension (Tx hypertension slows this progression)
2 most common causes of RI 90% of CHF pts have hypertension -- Prils (ACEIs) slow
1. Diabetic glomerulosclerosis (30% of diabetics) the rate of cardiac remodelling, resulting in improved
2. Hypertensive nephrosclerosis mortality. Note: ARBs do not share this effect.
Indication: heart failure

75

76

77
ipine drugs are relatively selective for vascular smooth Dihydorpyridines are more potent antihypertensive agents
muscle Ca channels (than non) but any direct negative chronotropic or inotropic
effects are offset by reflex sympatheitc activation.
 I J

CCB Pharmacodynamics: block Ca entry through L-type

channels; Increase relaxation of arteriolar smooth muscle,
78 decreasing afterload and decreasing O2 demand; Also,
increase supply due to dilation of coronaries
Ca++ Role in Vascular Smooth Muscle Contraction:
Intracellular Ca++ Increases by 3 Mechanisms: Voltage Ca activates calmodulin which activates Myosin light chain
Gated Channels (L, N and T); Receptor Mediated Activation of kinase (MLCK) to phosphorylate Myosin Light Chain which
Internal Stores (e.g., alpha1); Receptor Mediated Influx of Ca+ activates it to Myosin-LC-PO4 which binds to Actin and
+ - all mechanisms lead to cell contraction contracts

79

80

81

82
Bioavailability Issues: Fast and slow acetylators
Acetylated in bowel and liver
Acetylation inactivates
Dose necessary is much larger in fast acetylators
Indications
Typically used with isosorbide dinitrate after a failure of
ACEIs (most commonly because ACEIs produced
intolerable cough)
 I J

83

84

85

86

87

Slow-release isosorbide mononitrate, orally once daily (8hr

duration), is most likely to provide long-term symptomatic relief
of angina without developing tolerance (14 hrs free)
 I J
88
89
90
91
92

93

94

95

96
 I J

97

Prostatitis: Co-trimoxazole and ciprofloxacin show good

penetration into prostate.
Acute pyelonephritis: Parenteral therapy with ampicillin, a In pregnancy, ampicillin and cephalosporins are
cephalosporin (eg ceftriaxone), an aminoglycoside, or co- potentially less toxic than co-trimoxazole and
trimoxazole is usually effective. aminoglycosides.

98

99

100
101

102
 I J

103

104
105

106

107

Requires 02 to work (mech?)

108

109

Four generations:
First generation--very active against gram (+) cocci
Modestly active against gram (-) organisms
110 Second generation---have extended gram (-) coverage.
Moderate gram (+) activity
Third & Fourth generation--- very active against gram (-)
organisms. Less active against gram (+) activity.

111
 I J

112

113

Pharmacokinetics
Oral administration
114 Forms chelate with Ca, Mg, Al ions, thus prevents TC
absorption
Not to be taken with antacids, laxatives
Doxycycline less effective than others
Doxycycline is excreted in feces
Other TCs is excreted through kidney

115

116

117

118

119

120

121
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122

123

124

125

126

Combination Therapy for Eradication of Helicobacter

pylori in Peptic Ulcer Disease and Chronic Gastritis: Triple
therapies consisting of a PPI (proton pump inhibitor) or RBC
(ranitidine bismuth citrate) plus 2 antibiotics are
established as effective and well tolerated as first-line
127
regimens. The most effective antibiotics are
clarithromycin and amoxicillin. Once the first H. pylori
treatment regimen has failed, it is important to consider
regimens that contain different antibiotics according to the
probability of resistance, to increase dosage and duration of
treatment, and to include bismuth compounds in the second
line regimen. An alternative option after failed triple therapies NSAIDs block prostaglandin production that leads to
may be a high-dose, prolonged dual regimen with a PPI and greater acid production, less mucus and bicarbonate
amoxicillin or quadruple therapy consisting of a PPI, bismuth production, and diminished blood flow to the gastric
subcitrate, tetracycline, and metronidazole. mucosa.

128
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129

130

131

Although, H2 receptors are present in other tissues, i.e.,

vascular and bronchial smooth muscle, H2 blockers
interfere remarkably little with physiological functions
other than gastric acid secretion. These drugs are
132 Gastrin and acetylcholine stimulate histamine release from highly selective for the H2 receptor subtype and do not
enterochromaffin-like cells (ECL cells). Histamine binds to H2 interact with H1 receptors at normal doses. Thus, side
histamine receptors on parietal cells and stimulates H+, K+- effects are usually minimal.
ATPase activity and acid secretion into the gastric lumen. H2 H2 antagonists inhibit both basal (fasting) and
antagonists competitively block histamine-mediated acid nocturnal acid secretion, and inhibit acid secretion
secretion and also blunt the response to both gastrin and stimulated by food. This contributes in a major way to
acetylcholine. Antagonists at the other histamine receptor their clinical efficacy. These drugs reduce both the volume
subtype, i.e., H1 receptor antagonists (classic and H+ concentration of gastric secretions. Pepsin levels
antihistamines) do not inhibit acid secretion. fall in parallel.

133

134

135

Chemical Composition and Properties of antacids:

136
Mech: Antacids are weak bases that react with gastric
hydrochloric acid to form a salt and water, neutralizing the
acid, and raising the pH of the gastric contents. The goal of
therapy with antacids is to raise the pH to > 4. Besides
decreasing the corrosive effect of acid, pepsin becomes
increasingly inactive as the pH is increased above pH 4.
Aluminum hydroxides: low solubility, slow acting, high neutralizing capacity, causes constipation.
Magnesium hydroxides: low solubility, slow-to-moderate acting, high neutralizing capacity; causes diar
Calcium carbonate: moderate solubility, very fact acting, moderate neutralizing capacity; releases CO2
and belching with acid reflux; can cause exaggerated and sustained rebound acid secretion.
Sodium bicarbonate: very soluble, fast acting, high neutralizing capacity; rapidly cleared from the stom
both an alkali and sodium load; can cause systemic alkalosis; releases CO2.
Simethicone: a surfactant present in some formulations to decrease foaming and reflux.
Gaviscon: contains antacid mixed with alginic acid; forms a foam that floats on the gastric contents and
during reflux.
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Gastric hypomotility with delayed emptying of gastric

contents is a component of a number of GI disorders, leading
to such symptoms as nausea, vomiting, heartburn,
postprandial discomfort, indigestion, and gastroesophageal
143
reflux. Diabetic gastroparesis is a common finding in type
2 diabetics.
Some antiemetic phenothiazines or the muscarinic cholinergic
agonist bethanechol may provide some relief of these
symptoms, but do not accelerate gastric emptying and often
produce unacceptable side effects.

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150
In clinical studies, erythromycin accelerates gastric emptying,
particularly in the acute setting. The chronic use of
erythromycin is limited by its side effects. Intravenous
erythromycin may be useful short-term for an acute
exacerbation of diabetic gastroparesis.

Diarrheas can be separated into pathophysiologic

151 Diarrhea - From a mechanistic perspective, diarrhea can be
caused by: (1) an increased osmotic load within the intestine
resulting in retention of water within the lumen; (2) excessive
secretion of electrolytes and water into the intestinal lumen;
(3) exudation of protein and fluid from the mucosa; and (4)
altered intestinal motility, resulting in rapid transit. In most
instances, multiple processes are simultaneously affected,
leading to a net increase in stool volume and weight
accompanied by changes in percent water content.
categories: infection/inflammation, osmotic
diarrheas/malabsorption, and secretory diarrheas.
Treatment of infectious diarrheas may first involve
antimicrobial drugs and chronic inflammatory bowel
disease first involves anti-inflammatory agents. Only then
might the use of nonspecific antidiarrheal agents be
appropriate. Treatment of osmotic diarrheas first involves
avoidance of the offending osmotic agent (e.g., lactose in
lactose intolerance, laxative abuse) or correction of the
underlying malabsorptive process (e.g., pancreatic
enzymes for pancreatic insufficiency, gluten-free diet for
gluten-sensitive enteropathy). Secretory diarrheas (e.g.,
carcinoid syndrome, VIP-secreting tumor, AIDS-related
diarrhea) are likely to required hormonal therapy (e.g.,
octreotide).

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Many people have misconceptions about what constitutes

normal bowel function and seek a daily passage of stool
often without any medical reason to do so. After taking
laxatives daily for some period, a laxative habit becomes
established for the following reasons. (1) After complete
156 evacuation of the colon, several days may be required in order
to accumulate sufficient bulk to initiate a physiological
defecatory reflex - the patient interprets this lag as more
constipation and takes additional laxatives, thus a vicious Laxative Use and Abuse: The self-prescribing public
cycle is established. (2) After the GI tract has been stimulated purchases and overuses an enormous quantity and variety
repeatedly with irritant drugs, the smooth muscle reaches the of over-the-counter laxative medications. Only in a small
point where it will not respond to physiological stimulation. percentage of cases are the drugs really needed. The
With continuing laxative abuse, there is a danger of most satisfactory prophylactic and treatment for functional
dehydration and electrolyte imbalance, especially in the constipation is a diet rich in fiber (20-60 grams daily),
elderly and in children. coupled with proper daily exercise and bowel training.

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Routine prophylaxis or treatment of nausea and

Indications for Use of Antiemetic Drugs vomiting during pregnancy is not recommended
162 Prophylaxis and/or treatment of nausea and vomiting unless severe and protracted vomiting occurs or if non-
associated with: drug measures fail. If treatment is called for, pyridoxine
1) motion sickness and vertigo (vitamin B6), is often administered since it may be
2) postoperative recovery from anesthesia effective and is the agent least likely to be toxic. Meclizine
3) pregnancy is used if pyridoxine is ineffective. Promethazine,
4) cancer chemotherapy prochlorperazine, and metoclopramide are also used but
5) migraine there is not enough information as to the safety (to the
6) gastric stasis fetus) of these compounds.
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gonist, stimulates the peristaltic reflex. Intestinal 5HT4 receptors are

Peristalsis occurs due to release of inhibitory and excitatory
177 in the GI mucosa. Additionally, increases in colonic sodium
nt neurons
models, tegaserod has also been shown to reduce extrinsic afferent
eral pain sensation. These actions result in the relief of pain, discomfort
predominant IBS.
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181
Corticosteroids: Oral (prednisone and controlled release
budesonide) and parenteral (hydrocortisone and
182 methylprednisolone) are used to treat moderate to severe UC
and CD. The anti-inflammatory properties of these
glucocorticoids allow induction of clinical remission during
flare-ups of the inflammatory disease. However, the serious
side effects of glucocorticoids prevent their use for
maintenance therapy and limit their chronic use. Once clinical
remission is achieved, the dose of the steroid must be slowly
tapered down over several months before it can be
discontinued altogether.
183
184
Immunosuppressants: azathioprine and 6-mercaptopurine (6-MP) are purine analog immunosuppress
employed in the management of glucocorticoid-dependent IBD. Azathioprine is converted to 6-MP after
converted to a metabolite that inhibits purine ribonucleotide synthesis and thus cell proliferation. Use of
many patients to be weaned from glucocorticoids. These drugs are usually well tolerated, but rarely
(4%). Other side effects include nausea, fever, rash, and hepatitis. Leukopenia which is dose-related an
so CBC should be regularly monitored. Methotrexate (MTX), an inhibitor of dihydrofolate reductase that
DNA synthesis is sometimes used when either 6-MP or azathioprine are ineffective or poorly tolerated. C
potent inhibitor of cell-mediated immune responses. It inhibits interleukin-2 production from T helper cell
recruitment of cytotoxic T cells and blocks other cytokines, including IL-3, IL-4, interferon , and TNF. Cy
used to treat severe UC that is unresponsive to IV glucocorticoids. Cyclosporine may save the patient fro
the potential for significant toxicity.
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TB (frequently disseminated or extrapulmonary at clinical

presentation), invasive fungal infections, and other
opportunistic infections, have been observed in patients
receiving infliximab. Some of these infections have been
185 fatal. Patients should be evaluated for latent tuberculosis
infection with a tuberculin skin test. Treatment of latent
tuberculosis infection should be initiated prior to therapy with
infliximab. The incidence of antibodies to infliximab (25% of
the molecule is from mouse) is 13%. One side effect is a
lupus-like syndrome, which is rare and reversible after
stopping the drug. Anti-double-stranded DNA antibodies occur
in 9% but are not associated with clinical lupus.
Among more than 1000 patients treated with infliximab,
four developed lymphoma: one patient with CD, two with
rheumatoid arthritis, and one with AIDS. Since the risk of
lymphoma is already increased in these conditions, it is
unclear whether infliximab is the cause. Thus, infliximab is
extremely effective in refractory inflammatory and fistulous
CD, but should be used only when necessary. Results on
the efficacy of infliximab in ulcerative colitis are mixed.

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199
Treatment of Hepatitis: In about one third of adults and
children with chronic hepatitis B, treatment with interferon alfa-
2b leads to loss of HBeAg, return to normal aminotransferase
activity, sustained histological improvement and, in adults, a
lower risk of progressive liver disease. However, AIDS
patients co-infected with hepatitis B virus (HBV) generally
respond poorly to interferon. Hepatitis D (hepatitis delta
virus), which occurs only in patients infected with HBV, may
respond to treatment with high doses of interferon alfa, but Interferon- is usually combinated with ribavirin is more
relapse is common. effective than therapy with either agent alone.

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206

207 Resistance: Adefovir-resistant variants emerge at a low

frequency (3.9% of patients after 3 years of use) and have
been associated with a rebound in HBV DNA levels; these
variants may remain susceptible to lamivudine.

Why should acetaminophen be avoided in patients

208
Treatment: gastric lavage, supportive measures, oral
activated charcoal or cholestyramine (if within 30 min), oral N- results, occasionally even modest amounts of
acetylcysteine, and call local poison control center.
with alcoholic liver disease? Chronic alcohol intake
increases the activity of the cytochrome P450 system,
pathway of acetaminophen metabolism. In this setting, a
larger fraction of the acetaminophen is metabolized
through the P450 system, resulting in increased
amounts of the metabolites that need to be detoxified
by glutathione. Alcoholics also have low amounts of
glutathione in the liver because of concomitant poor
nutrition. As a result, the increased levels of toxic
metabolites cannot be detoxified, and hepatocyte necrosis
acetaminophen (3-6 gm/day) can induce this damage.

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1. Mechanical effects of glycosides on the heart: Increases

intensity of actin-myosin interaction - increased
myocardial contractile force (positive inotropic effect),
increased velocity of contraction, decreased duration of
systole (small effect)
2. Electrical effects of glycosides the heart: Effects are both
direct and indirect (indirect are due to vagal stimulation)
and include actions on myocardial impulse conduction &
myocardial automaticity. Indirect effects are generally
212 predominant at therapeutic doses
3. Myocardial impulse conduction: Sinoatrial node - Slowing
of sinus rate (Through indirect vagal effects (?by decreasing
SNS?)); AV node (high propensity to block the AV node) -
Indirect effects (predominant) - Increase in effective refractory
periods (ERP); Decrease in conduction velocity (Direct effects,
same as indirect). Purkinje fibers, ventricle - Indirect effects
negligible (no PSN innvervation); Direct effects (high doses)
- Decrease in ERP, Decrease action potential duration -
Increase in conduction velocity
4. Myocardial automaticity: Glycosides increase cardiac
automaticity, increase in rate of rise of phase 4 depolarization,
may also be caused by delayed after depolarizations
Extra-cardiac effects:
Gastrointestinal - most common complaint!! Occur with
therapeutic and particularly with toxicity
Anorexia (common)
Diarrhea, abdominal discomfort
Direct irritant effect
Nausea, vomiting (most common side effect)
Mediated via excitation of chemoreceptor trigger zone
Salivation
Vascular effects: Initially, an increase in SM tone due to
increase intracellular Ca, generally, however, net effect of
cardiac glycosides is a decrease in vascular tone
(decrease sympathetic activity).

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Drugs for erectile dysfunction -- sildenafil, tadalafil &

vardenafil (the afil class)
215 Inhibit phosphodiesterase-5 enzymes, Leads to reduced
breakdown of cyclic GMP, Nitrates enhance production of
cyclic GMP = dramatically enhanced vascular effects,
including severe hypotension. Therefore, afils are
contraindicated with nitrates. Notice: selectivity is relative, will
effect other phosphodiesterase in the body
NTG - large first-pass effect if taken p.o.; sublingual =
short onset, short-acting
Amyl nitrite - inhalational (poppers, snappers), most rapid
onset
Isosorbide dinitrate - slower, less potent than NTG, short
and long-acting preparations

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218

219

220

221

222 ALL Antiarrhythmic drugs have narrow therapeutic

index, variable metabolism and clearance; many
Drug interactions: increases digoxin level and warfarin (especially class I) inhibit Cytochrome P-450 (which is
effect;heparin, verapamil, cimetidine increases its levels; absent in 7% caucasians and 2% blacks); many drug
phenobarbital, phenytoin, rifampin decreases its level interactions
 I J
223 Class 1A effects also (procainamide is a mixed class drug)
Reduce automaticity (phase 4, reduce slope of upstroke, AP
becomes broader)
Prolong action potential duration
Reduce conduction velocity (phase 0, slope also reduced)
224 Antiarrhythmics: limited usefulness because of toxicity and
lack of efficacy; may worsen mortality. Every agent has
potential for serious toxicity. Classified according to
electrophysiology (see Cecil 341) for Vaughan William s Class
(I, II, III, & IV)
225
Synergistic depression of myocardial function with combo of
other antiarrhythmic agents (especially propranolol). Pts with
heart failure (HF) achieve lidocaine levels that are double
the levels of normal pts (reduce dose by half)
226
227
228
WPW syndrome is best txed with a class IA agent which increase refractoriness of the bypass track an
tachyarrhythmia. Other agents (adenosine, BB, and digoxin (&CCB?) should be avoided in a wide comp
syndrome such as WPW because they may accelerate the ventricular rate and cause the rhythm to dege
agents act by inhibiting the AV node and thus increase conduction down accessory pathway; also class IB
repolarization by decreasing the AP duration and thus also can increase the ventricular response to an S
evidence of WPW on ECG and is hemodynamically unstable, DC cardioversion should be first-line thera
Antiarrhythmic Class I (A, B, & C): local anesthetic or
membrane-stabilizing activity; block fast inward Na
channel, decreasing maximum depolarization rate, Vmax,
of the AP (phase 0); basically Na Channel Blockers
Lidocaine works on slightly depolarrized or ischemic tissue
more so than normal tissue, due to its state-dependent
blocking. Therefore, use lidocaine (IV) to suppress acute
MI-associated ventricular arrhythmias
 I J
Class 1C
Reduce automaticity and conduction velocity in atria and Class IC do same thing as class1A, but more powerful
229 ventricles very powerful side effects, the worst SE is accutally
Prolong action potential duration worsening arrhythmia
Major side effect is proarrhythmia

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232

Benefits of IV BB therapy early in acute infarction

233 Premature ventricular contraction (PVC) - common in pts
with and without HD (found in 60% of adults on Holter
monitoring), do no specifically suggest any underlying dz,
usually requires no tx; beta blocker would be DOC if it effects
daily life of pt
reduces myocardial O2 consumption (negative
inotropic and chronotropic actions) and has a direct
antiarrhythmic effect. Do not withhold in pts with sinus
bradycardia, diabetes, or well-controlled asthma (all
relavite contraindications) - rhythm disturbances tend to be
reversibble and are easily treated with temoproary pacing
if symptomatic

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When macula densa sense increase NaCl, they send signal (via extraglomerular mesanginum) to granula
242 drug interactions: carbamazepine and dipyridamole adenosin which vasoconstricts primarily the afferent a. (know that in most areas of the body adenosin
pretreatment its potency; caffeine and theophylline not so in the kidneys), decreasing GFR (moderate constriction; if severe constriction then GFR decreas
antagonize it flow becomes so stagnent that proteins clog up on exam always assume moderate efferent a. constrict

Procainamide:
Moderately effective for atrial or ventricular arrhythmia
243 Metabolized in liver to active component NAPA
this metabolite is more effective (acetly group)
must check prodrug and metabolite to prevent toxcity
Reduce automaticity and conduction velocity
effects phase 4 and 0
Universal adverse effect is lupus

244
245

Antithrombin III is a protein synthesized by the liver and

which circulates in the plasma. It rapidly inhibits thrombin but
only in the presence of heparin or naturally occurring
substances similar to heparin. It inhibits activated coagulation
factors of the intrinsic and common pathways, including
thrombin, Xa, IXa, XIa, XIIa, and kallikrein. However, it has
246 little or no activity against factor VIIa (extrinsic pathway).
Inhibition of thrombin and factor Xa are most important in the
anticoagulant effect. The principal inhibitory effect of
heparin on coagulation is probably via the inhibition of
thrombin-induced activation of factor V and factor VIII.
(Cecil407) Heparin increases the rate of the thrombin Never given orally or IM: Because heparin is a large
antithrombin reaction by serving as a catalytic template to molecule and is destroyed in the GI tract, it can only be
which both the antithrombin and thrombin (or other administered intravenously or subcutaneously.
protease) bind. Heparin prolongs both the aPTT and the Intramuscular injection is contraindicated because of the
thrombin time; the PT is less effected, but at high plasma likelihood of hematoma formation. (IM contraindicated
concentrations will also prolong the PT. because of hematoma formation)

247
No protein or endothelial binding of LMWH (as UFH), effects
kenetics - more predictable
248
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Vitamin K dependent mechanism: converts glutamic acid

residues in several clotting factor proteins (II, VII, IX, X and
proteins C and S) to gamma carboxyglutamic acid
249 residues. This transformation is required to give these
clotting proteins high affinity for Ca++ and phospholipid;
without undergoing this post-translational modification they are
basically inactive. Vitamin K undergoes a cycle of oxidation Treatment of overdosage: Anticoagulant effects can be
and reduction in the liver to produce the active form of the reversed by withdrawal of drug (but remember-effects are
vitamin. Warfarin prevent the reduction of vitamin K once it quite prolonged), the administration of vitamin K1, and if
is oxidized by inhibiting the enzyme vitamin K epoxide necessary, the infusion of fresh-frozen plasma or plasma
reductase. concentrates rich in II, VII, X.

250

Biotransformation of clopidogrel is necessary to produce

inhibition of platelet aggregation. Clopidogrel also inhibits
platelet aggregation induced by agonists other than ADP by
251 blocking the amplification of platelet activation by released
ADP. Clopidogrel does not inhibit phosphodiesterase activity.
Clopidogrel acts by irreversibly modifying the platelet ADP
receptor. Consequently, platelets exposed to clopidogrel are
affected for the remainder of their lifespan (~7 days)
Clopidogrel has supplanted ticlopidine because of its
more rapid onset of action, lower incidence of serious
adverse events, and stronger clinical trial data.
Clopidogrel increases the risk of bleeding during
coronary bypass surgery, so this drug usually is not started
if the patient is considered to be a surgical candidate.

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263

Thrombolytic Therapy Objective: dissolve pathological

264 Alteplase binds to fibrin in a thrombus and converts the blood clots by injecting a fibrinolytic enzyme or an activator
entrapped plasminogen to plasmin. This initiates local of endogenous fibrinolysis without causing uncontrolled
fibrinolysis with limited systemic proteolysis. rt-PA bound to bleeding. Indications:
fibrin is 100 fold more active in stimulating plasminogen than Acute myocardial infarction
when free in solution. This fact explains why normal Pulmonary embolism
fibrinolytic activity is limited, but to achieve a therapeutic Deep venous thrombosis
effect, levels of rt-PA are much higher than normal in vivo Ischemic stroke (special circumstances only, CAT scan,
levels. MRI first)

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There is a higher risk of intracranial bleeding with tPA when

compared with streptokinase therapy (especially in pts over
70yo or who have HTN at time of presentation). However,
267 accelerated tPA with IV heparin may produce lower mortality
than streptokinase only in pts who are treated within the first 4
hrs after onset of symptoms. Heparin does not provide any Cardiac emergencies: Thrombolysis is indicated only for
advantage when streptokinase is thrombolytic drug (unless LV pts who have acute coronary syndromes with ST-segment
thrombosis which would indicate additional heparin usage) elevation

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Anything that competes for liver metabolism of these

Watch being too aggressive with therapy
Abrupt drop in circulating cholesterol and/or direct cellular
impairment of cholesterol metabolism may impair ability to
maintain cell wall structure
drugs can increase their levels, which has been
associated with muscle problems: verapamil, diltiazem &
grapefruit juice (current recommendation is that
simvastatin or atorvastatin are contraindicated in pts
consuming 1 or more qts of grapefruit juice)

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Cytochrome P-450 - a family of heme-containing Ez, found in Major Cytochrome P-450 inhibitors: FREaCKI
the liver and intestinal tract and are involved in phase I Grapefruit - Ketoconazole, Isoniazid, Cimetidine,
metabolism. Fluoxetine, Ritonavir, Erthyromycin, Grapefruit

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287

Pathology - iron deficiency develops as:

1. storage iron (hemosiderin) decreases
2. then, serum ferritin decreases (isnt this in BM etc, not
serum??????)
Diagnosis: the serum ferritin level is the most convenient 3. next, serum iron decreases and iron binding capacity
laboratory test to estimate iron stores. A ratio of serum iron to (amount of transferrin) increases resulting in a decrease in
total iron binding capacity (TIBC) decreased to 15% or less or the degree of transferrin saturation.
absent hemosiderin staining in liver or bone marrow biopsy 4. Following this, anemia develops; red cells become
samples. increasingly more microcytic and hypochromic.

Absorption: Vitamin B12 is sometimes called extrinsic

factor to distinguish it from intrinsic factor, a glycoprotein
Sources: Vitamin B12 is not synthesized de novo by secreted by the parietal cells of the gastric mucosa that
animals or plants. The vitamin is synthesized by combines with the vitamin and allows its uptake in the
288 microorganisms that grow in soil, sewage, water, or the distal ileum by a specific receptor mechanism. Vitamin
intestinal lumen of animals. Vegetable products are free of B12 deficiency in humans is most often due either to
vitamin B12 unless they are contaminated with such bacteria. lack of intrinsic factor or malfunction of the specific
Animals are dependent on synthesis by bacteria in their own uptake mechanism. The most common causes are
GI tract or the ingestion of animal products containing vitamin pernicious anemia (a syndrome characterized by gastric
B12. Dietary sources include meat (especially liver), eggs, atrophy, failure to secrete HCl and intrinsic factor),
and dairy products. Humans must receive adequate amounts partial or total gastrectomy, inflammatory bowel
in their diet; average American diet 5-30 microg/day, 1-5 diseases, and small bowel resection. Dietary deficiency
microg is absorbed. is not common but may occur in strict vegetarians.
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Megaloblastic anemia is usually the principal clinical

Folic acid occurs in cells in multiple oxidation states,
(oxidized dihydrotetrahydrofolate) and folate cofactors
289 bearing methyl, methenyl, methylene, and formyl groups
(1 C units) on the 5 and/or 10 N position are formed.
Folate cofactors serve as one carbon donors in various
biosynthetic reactions leading to the formation of purine
rings (adenine, guanine) and the synthesis of thymidylic
acid (dTMP) essential precursors for DNA synthesis.
feature of folic acid deficiency.
Folic acid supplementation should only be initiated
after vitamin B12 status has also been ascertained.
Folic acid therapy to prevent deficiency should be
considered in high risk patients, including pregnant
women, alcoholics, and patients with hemolytic anemia,
liver disease, chronic skin diseases, and patients on renal
dialysis.

Other Cytokines:
Stem Cell Factor (SCF), Interleukins (IL1-12), Monocyte-
Macrophage Colony Stimulating Factor (M-CSF, CSF-1),
P1XY321 (GM-CSF/IL-3 fusion protein), Tumor Necrosis
290
Factor (TNF), Transforming Growth Factor (TGF-2) are all
cytokines with stimulatory activity on marrow precursor cells.
The clinical utility of many of these agents is already being
tested in clinical trials. It is likely that future research on these
compounds will yield important therapeutic agents.

Hypoxia caused by: decreased ambient oxygen

concentration; impaired delivery of oxygen through the lungs
and to hemoglobin molecules in erythrocytes; venous-to-
291 arterial shunting of blood; hemoglobin mutants with increased
oxygen affinity and decreased ability to release oxygen in the
tissues; localized renal disease that the renal sensor cannot
distinguish from generalized hypoxemia - then the increase in
EPO results in increased erythropoiesis, erythrocytosis, and
secondary polycythemia.

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295

Hydroxyurea is generally administered orally, although

intravenous regimens are currently being sometimes used.

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303
D. Sulfonylureas have extrapancreatic effects such as
increased numbers of insulin receptors, increased glucose
transporters, and purported enhanced tissue
responsiveness to insulin. Hepatic gluconeogenesis is
suppressed. Whether these are direct effects of the
sulfonylurea drugs or a result of lower blood glucose levels is
controversial.
304
305
306
Meglitinides very fast acting, short half life (dont get into
trouble with low sugars over time)
307
All sulfonylureas are effectively absorbed from the GI tract,
but the drugs with short half lives should be given 30
minutes before eating because GI motility slows their
absorption. Sulfonylureas in plasma are largely (90%-
99%) protein bound.
E. The second-generation drugs are approximately 100
times more potent than the first-generation sulfonylureas.
Although their half-lives are short (~1.5-5 hours), their
hypoglycemic effects last for 12 to 24 hours, and it is often
possible to administer these drugs once daily.
F. All of the sulfonylureas are metabolized by the liver
and the metabolites are excreted in the urine. These
drugs should be administered with caution in patients
with either renal or hepatic insufficiency.
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308

Drugs for Hirsutism and Other Disorders of Androgen

Advantages of metformin: Excess: Agents that increase insulin sensitivity!! Elevated
no weight gain insulin can cause an increase in ovarian androgen
no hypoglycemia production, Ex. Metformin, thiazolidinediones (Troglitazone
favorable lipid profile but watch out for liver toxicity!)

309

310

Rosiglitazone and pioglitazone:

reduce insulin resistance
improve peripheral action of insulin
311
reduce hyperglycemia by increasing glucose uptake (may increase insulin responsive genes and increa
GLUT-4 transport proteins).
reduce hepatic glucose production
produce a small improvement in serum lipids, decrease triglycerides, FFA, increase HDL, in increase la
Pt who need TZDs and metformin the most (HD, obese usually take several weeks to produce a clinical effect.
pts) are the pts who are contraindicated When taken with insulin, allow reduction in insulin dose or facilitate discontinuation of insulin.

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315

The biggest drawback is the need for additional twice-daily

subcutaneous injections.
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319
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The pancreatic islets of Langerhans ( cells) are capable of
sensing the plasma concentration of glucose. As glucose
concentrations rise following a meal, insulin secretion is
stimulated. Glucose is the principal stimulus of insulin
320
secretion. Insulin secretion is a tightly regulated process
involving the coordinated interplay of nutrients, GI hormones,
pancreatic hormones, and autonomic neurotransmitters.
Glucose, amino acids, fatty acids, and ketone bodies
promote insulin secretion. Stimulation of 2-adrenergic
receptors inhibits insulin secretion, whereas activation of
2-adrenergic receptors and vagal nerve activity stimulate
insulin secretion. In general, activation of the autonomic
nervous system leads to inhibition of insulin secretion via 2-
adrenergic receptors.
321
322
323
324
325
326
Regulation of insulin release. Glucose is transported
into the -cell by a specific glucose transporter protein
(GLUT-2 - on liver, pancreatic beta cells, and basolateral
surface of the SI) on the cell surface. The glucokinase
phosphorylates glucose, forming glucose-6-P in the first
step of glycolysis. The generation of ATP by glycolysis and
the Krebs cycle leads to inhibition and closure of the
ATP-sensitive potassium channels (the target of
sulfonylurea drugs), depolarization of the plasma
membrane, and opening of the voltage-dependent Ca
channels. The influx of extracellular Ca and mobilization
of Ca from intracellular stores lead to the fusion of insulin-
containing secretory granules with the plasma membrane
and the release of insulin into the circulation.
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328
329
330

Thyroid hormones are required for optimal growth,

331
T3/T4 are important determinants of genetically coded
developmental programs. These hormones are critically
important for normal development of the nervous system.
Thyroid deprivation during the prenatal or early postnatal
period results in mental retardation and dwarfism (congenital these effects are especially important for temperature
cretinism).
development, function, and maintenance of all tissues.
They stimulate growth by influencing the metabolism
of carbohydrates, fats, protein, and vitamins. The
important effects on intermediary metabolism include a
calorigenic action due to increased O2 consumption,
increased lipolysis, hypocholesteremia, absorption of
carbohydrates in gut, and accelerated glycolysis. Thyroid
hormones increase the basal metabolic rate, oxygen
consumption, and lead to the production of heat;
regulation.

332

Grave's disease is an autoimmune disorder leading to
synthesis of antibodies to thyroidal antigens. One of these
antibodies, Thyroid stimulating immunoglobulin (TSI) binds
directly to the TSH receptor on the thyroid cell. TSI binding to
the receptor activates the cell just as TSH does, but this
activation is much more prolonged leading to excessive T3/T4
output and hyperplasia/hypertrophy (goiter) of the gland.
Hyperthyroid diagnosis: High circulating levels of T3
and T4 (bound and free) and low TSH, also TSI and
antithyroglobulin antibodies present.
Management of hyperthyroidism: the three primary
methods are antithyroid drug therapy, surgical removal of
the thyroid, and destruction of the gland with radioactive
iodine.
 I J

333

334

335

The advantages of iodide therapy are that it is simple,

336 Large doses of iodides are used two weeks prior to thyroid
surgery to increase the firmness of the thyroid gland by
decreasing its size, vascularity, and friability. Iodides facilitate
a smoother, less complicated surgery and decrease
postoperative complications.
inexpensive, relatively nontoxic, and there is no glandular
destruction. Disadvantages include, "escape",
accentuation of thyrotoxicosis, allergic reactions, relapse
after discontinuation, and subsequent interference with
radioactive iodine therapy if used before treatment.

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PTH secretion is regulation by serum [Ca++]; low Ca++

stimulates PTH secretion; increased ionized serum Ca
360 and decreased PO4 lead to decreased release of PTH.
High serum Ca and PO4 reduce synthesis of calcitriol and
The net effect of PTH is to raise serum calcium and increase synthesis of 24,25 (OH)2D. 1,25(OH)2D (and
reduce serum phosphate; the net effect of Vit D is to raise high Ca) inhibits expression of PTH. PTH stimulates
both. synthesis of 1,25(OH)2D.

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365
366
367
368 1. Metered dose inhalers (MDI): a pressurized canister with a
metering valve that delivers drug with CFC propellant,
cosolvents, and/or surfactants. Advantages of MDIs are low
cost and portability; disadvantages include need for hand-lung
coordination making it more difficult for young children and the
elderly to use. Spacer devices that attach to the MDI
markedly improve the ratio of inhaled to swallowed drug and
reduce need for coordination. 2. Nebulizers: preferred for
severe asthma exacerbations with poor inspiratory ability; do
not require hand-lung coordination. Nebulizer therapy can be
delivered by face mask to young children or older patients who
are confused. 3. Dry powder inhalers: require relatively high
air flow to suspend the powder and can be irritating when
inhaled.
369
370
371
Rapid acting 2-selective agonists:
Albuterol, levalbuterol, terbutaline, pirbuterol, or
bitolterol - all are 2-selective, and produce equivalent
bronchodilation when inhaled with an onset of action of
<15 min and a duration of action ranging from 2 to 6
hours.
Albuterol and terbutaline are available in nebulizer
solutions in addition to metered dose inhalers.
Albuterol is also available as a powder inhaler, and as
syrup, tablets, or extended release tablets for oral
administration. Terbutaline can also be given orally, or
as subcutaneous injection, or IV infusion. Levalbuterol
is the R-isomer of racemic (R+S) albuterol available only
as a nebulized solution.
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2. Parasympathetic-mediated bronchospasm is an important component is some asthmatics and COPD patients.

Parasympathetic tone and degree of reflex activation of cholinergic pathways differs from patient to patient. 3. A
particularly good response to ipratropium is seen in a subgroup of COPD/asthmatic patients who experience
382 psychogenic exacerbations. The principal clinical use of ipratropium is in the treatment of COPD. 4. Bronchodilation
with ipratropium develops more slowly and is usually less intense than that produced by -agonists. 5. A useful
bronchodilation response may last up to 6 hours. 6. Combined treatment with ipratropium and 2-adrenergic agonists
results in a slightly greater and more prolonged bronchodilation than therapy with either agent alone. Combined therapy
can be considered if severe asthma exacerbations exist. (Albuterol + ipratropium bromide combination = Combivent) 7.
Ipratropium is also used intranasally to reduce secretion in both the upper and lower respiratory tract in allergic
rhinitis and chronic postnasal drip syndrome (vasomotor rhinitis).

383

384
Bronchodilation (smooth muscle relaxation) is a clinically relevant effect of theophylline. Other effects of theophylline
and some methylxanthines include CNS stimulation, cardiac stimulation, modest peripheral vasodilation, improved
skeletal muscle contractility, and a thiazide-like diuresis.
Theophylline was formerly a first-line therapy for asthma. It now has a far less prominent role in therapy because its
benefits are modest, it has a narrow therapeutic window, there is considerable variation in absorption and
elimination between patients, and monitoring of plasma drug levels is often required.
Nocturnal asthma can be improved with slow-release theophylline preparations (Theo-Dur, Slow-Bid), but inhaled
corticosteroids or salmeterol are probably more effective.

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387

High dose inhaled steroid preparations require the use of
a spacer device to limit side effects.
Asthmatic patients maintained on inhaled corticosteroids show
improvement of symptoms and lower requirements for
rescue with a bronchodilator.
Beclomethasone and triamcinolone are initially given 3 to
4 times daily; flunisolide is used twice daily. With high-
dose inhaled corticosteroids, use of a spacer device
will reduce the risk of adverse side effects and should
be considered mandatory.

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394 Steroids are the most important treatment for status

asthmaticus. Status asthmaticus pt must be treated with
high dose corticosteroid!! Breaks refractoriness, only
treatment which may prevent death. Typical SE only seen
with prolonged use, little or no SE with large dose over breif
period. (Prednisone shown to be more effective vs budesonide
in status asmaticus children when nebulized)
395
396
Steroid treatment for acute asthma is essential - however,
serum glucose must be monitored - insulin can be
administered on a sliding scale if needed. Monitoring pt's
electrolyte levels, esp K, is essential. Hypokalemia can
cause muscle weakness, which may worsen respiratory
distress and cause cardiac arrhythmias

397

398

399
Cromolyn compounds do not directly relax smooth
muscle, therefore they are not useful for control of
Treatment of allergic rhinitis is similar to that for asthma. acute bronchospasm.
Topical corticosteroids delivered as an aqueous nasal spray Cromolyn compounds are primarily prophylactic. When
(beclamethasone, budesonide, flunisolide, fluticasone, inhaled several times daily, they inhibit both the
monetasone, triamcinolone) or cromolyn sodium can be highly immediate and late asthmatic responses to antigenic
effective with minimal side effects. challenge or exercise.

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401
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o Intranasal decongestants should not be used for more
than 3 days in order to avoid rebound congestion, and with
prolonged use, rhinitis medicamentosa. Rhinitis
402 medicamentosa is a complication of chronic use of
vasoconstrictor nasal sprays or intranasal cocaine abuse.
Chronic nasal obstruction and nasal inflammation develop and
are manifest as beefy red nasal membranes on physical
examination.
403
404
Trials have shown these drugs to be modestly effective for
405 maintenance therapy. They are not as effective as inhaled
steroids and are not recommended for acute asthma
attacks (only chronic). However, clinical trials have shown
that leukotriene inhibitors are especially useful for patients
who experience aspirin-induced asthma attacks. Aspirin in
these patients shifts arachidonic acid metabolism from
prostaglandin production to leukotriene production.
406
407
408
409
These drugs are often given in combination with an H1-antihistamine, analgesics, cough suppressants, o
common OTC medications.
Actifed = pseudoephedrine + triprolidine HCl (H1 antihistamine)
Alka-Seltzer Plus Cold & Cough Liqui-Gels = Pseudoephedrine +Acetaminophen (analgesic) + Dex
(cough suppressant) + Chlorpheniramine (H1 antihistamine)
Robitussin Cold & Congestion Liqui-Gels Caplets = Pseudoephedrine + Guaifenesin (expectorant
Dextromethorphan (cough suppressant)
Sudafed Cold and Cough Liquid Caps = Pseudoephedrine + acetaminophen + guaifenesin + dextr
Aspirin-induced asthma (sensitivity), aka Samter's triad: The triad of asthma, aspirin sensitivity, a
affects 5-10% of patients with asthma. Most patients experience symptoms during the third to fourth deca
can provoke an acute asthma exacerbation, accompanied by rhinorrhea, conjunctival irritation, and flushi
neck. It can also occur with other nonsteroidal anti-inflammatory drugs and is caused by an increase in e
cysteinyl leukotrienes after exposure (prostaglandin mediated). Primary treatment is avoidance of these
leukotriene antagonists have shown promise in treatment, allowing these patients to take daily aspirin for
disease.
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417
418

419

420

421

422

Risk of developing clinical TB (from latent) greatest for

those infected with HIV or who are receiving
immunosuppressive therapy. Includes patients receiving
423 cancer chemotherapy or TNF- inhibitors like infliximab,
etanercept, and adalimumab.
Others at high risk: persons in close contact with patient
with recent pulmonary TB, those with radiographic evidence of INH is biotransformed (metabolized) by acetylation in
prior TB, during first 2 years after positive tuberculin test, liver, fast acetylators have lower levels of active drug,
recent immigrants, DM, silicosis, organ transplantation, IV slow acetylators may reach toxic levels. Classic example
drug use, chronic renal failure, and head or neck cancer of pharmacogenetics differences between patients

424

Ripampin is rapidly bactericidal to TB that exist in any of

the three population present in the body: actively growing
extracellular organism, slowly growing intracellular (in M0) at
acid pH, and slowly growing extracellular organism

425
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426

427

428

429 Also used for P.aeruginosa, endocarditis caused by enterocci

or viridans (especially in combination with penicillin G), treat
tetracyclin resitant gonorrhea
430
431
432

433

Coccidioides immitis
Pneumocystis carinii (P. jiroveci) desert SW USA, Valley fever, fungal pneumonia
Approximately 15-30% of HIV-infected people develop P. carinii pneumonia Aspergillus spp.
434 Interstitial pneumonia with ground glass appearance Allergic bronchopulmonary aspergillosis, fungus balls, invasive
Candida albicans Aspergillosis pneumonia
Oral thrush, esophageal, tracheal, or pulmonary Blastomyces dermatitidis
Histoplasma capsulatum fungal pneumonia
Bird and bat-enriched soil, Ohio, Mississippi, & Missouri River beds, caves Histoplasma, Coccidiodes, & Blastomyces
and chicken coops Inhalation of spores cause asymptomatic or acute self-resolving fungal
Cryptococcus neoformans pneumonias (if not immunocompromised)
in pigeon droppings, also meningitis in AIDS patients Mucor, Rhizopus, Absidia
Rhinocerebral infections in ketoacidotic diabetics & cancer patients

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457

H2 receptors
458
Predominant effect of H2 activation is an increase in
gastric secretion
cardiac effects Pharmacological Effects of Histamine (next 2 slides
vasodilatory effects also)
Cellular signaling mechanism: 1. Role in allergy, anaphylaxis and inflammation -
stimulation of adenylate cyclase, increasing cAMP contributes to hypersensitivity phenomena and includes
Distribution: gastric mucosa, heart, mast cells, brain urticaria (e.g. hives), pruritis, allergic rhinitis (e.g. the runny
H3 receptors nose in hay fever); anaphylactic shock; inflammation -
Presynaptic auto-receptors on histamine-containing neurons, mast cells release histamine, causing local dilation and
produce feedback inhibition of histamine release increase blood flow in inflamed area

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462

463

464

465

466

ocular allergy, is usually associated with allergic rhinitis and may be

generation, relatively non-sedating drug such as cetirizine, desloratadine,
ve the main symptom, itching. Antihistamines for topical ocular use are

n, and467
eyelid edema; their adverse effects include burning, stinging,
sa.
pheniramine/naphazoline (Visine A, and others) and
may be more effective than either agent alone, but have a short duration
ontinued use.
a last resort because they are associated with increased intraocular
with viral infections.

468

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470
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Zollinger-Ellison syndrome (ZES) is caused by a nonbeta

islet cell, gastrin-secreting tumor of the pancreas that
stimulates the acid-secreting cells of the stomach to maximal
activity, with consequent gastrointestinal mucosal
471
ulceration. ZES may occur sporadically or as part of an
autosomal dominant familial syndrome called multiple
endocrine neoplasia type 1 (MEN 1). The primary tumor is
usually located in the duodenum, the pancreas, and
abdominal lymph nodes, but ectopic locations have also been
described (eg, heart, ovary, gall bladder, liver, kidney).
Pathophysiology: The symptoms of ZES are secondary to hypergastrinemia, which causes hypertroph
mucosa, leading to increased numbers of parietal cells and increased maximal acid output. Gastrin by its
acid secretion, resulting in increased basal acid secretion. The large quantity of acid produced leads to g
mucosal ulceration. It also leads to diarrhea and malabsorption. Malabsorption in ZES usually is multifa
by direct mucosal damage by acid, inactivation of pancreatic enzymes, and precipitation of bile salts. ZES
of patients, while in the other 25% it is associated with MEN 1, an autosomal dominant condition charact
hyperparathyroidism, pancreatic endocrine tumors, and pituitary tumors.

472

473

474
475

476

Beta Adrenergic:
Heart:
positive inotropic 1
positive chronotropic 1
increase AV node conduction
477 increase electrical excitability of the heart
Stimulate release of renin 1
Relaxation of certain blood vessels (skeletal muscle arterioles, Baroreceptor Control of BP (vagal acts like
coronary arterioles) 2 parasympathetic)
Lungs relaxation of bronchioles 2 Blood pressure increases suddenly:
Metabolic effects (glycogenolysis, 2) (lipolysis, 3) Sympathetic tone decreased & Vagal tone to the SA node
Stimulate release of insulin 2 increased
Relaxation of the uterus 2 Blood pressure decreases suddenly:
Relaxation of detrusor (bladder) 2 Sympathetic tone increased & Vagal tone to the SA node
Relaxation of intestinal smooth muscle 2 decreased
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478

-Receptor 2nd Messenger:

All receptors use Gs proteins as second messengers.
Alpha2 Receptor 2nd Messenger Relaxation: Activation of this second message regulates increased
Gi second message is amplified by down regulation of activity of adenylyl cyclase
adenylyl cyclase activity, with less production of cAMP Production of cAMP is increased

479
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480

other 2 Selective Adrenergic Agonists:

Metaproterenol (Metaprel, Alupent)
Terbutaline (Brethine) - aerosol and sc; sc for emergency tx
of asthma; only 2 agent available sc; iv. and p.o. to delay
delivery.
481
Isoethrine (Bronkosol)
Salmeterol (Serevent). Once a day agent for chronic but not
acute treatment of asthma. Has slow onset of action
Bitolterol (Tornalate)
pirbuterol
ritodrine

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499
500
501
Essential hypertension: a common form of hypertension that
occurs in the absence of any evident cause, is marked
hemodynamically by elevated peripheral vascular resistance,
and has multiple risk factors (as family history of hypertension,
high dietary sodium intake, obesity, sedentary lifestyle, and
emotional stress) -- called also idiopathic hypertension,
502 primary hypertension...Some causes of hypertension can now
be identified, and some may even be curable. By definition,
these are designated "secondary hypertension." the
pathophysiologic mechanism in approximately 90% of the
hypertensive population resists precise description. Members
of this group are classified as having "primary hypertension" or
"essential hypertension," signifying that no cause for their
disorder has been found. (usu a young persons disease, both
high systole and diastole, 80 yr olds get isolated
hypertension?)
Pheochromocytomas are tumors of the adrenal gland
which produce excess adrenaline. Pheochromocytomas
arise from the central portion of the adrenal gland which is
called the adrenal medulla. The adrenal medulla is
responsible for the normal production of adrenaline which
our body requires to help maintain blood pressure and to
help cope with stressful situations. A tumor which arises
from the adrenal medulla and overproduces adrenaline
can be a deadly tumor because of the severe elevation in
blood pressure it causes.The classical symptoms of pheos
are those attributable to excess adrenaline production.
Often these patients will have recurring episodes of
sweating, headache, and a feeling of high anxiety.
Notice: always give alpha blocker first, then beta
blocker second when surgically removing tumor
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503
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504
Beta-Blockers in Chronic Stable Angina:
Indications:
monotherapy for mild to moderate angina of effort (not
for Prinzmetals)
combination therapy (angina of effort)
after MI
Limitations
bradyarrhythmias
Systolic BP x HR = Cardiac Output = Pressure-Rate congestive heart failure
Product (imprecise measure of CO, but close enough) extracardiac effects
Note that increasing doses of beta-blocker does nothing to In the acute stages of CHF, beta blockers are
the final level of CO that can be obtained (angina occurs at the contraindicated - sympathetics are highly active in acute
same CO). However, by decreasing HR and contractility, the HF - Beta-blocker poses a significant danger of reducing
beta-blocker facilitates exercise in a dose-related fashion. cardiac output to intolerable levels

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506
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507
Approved drugs for HF (not all beta-blockers are
efficacious):
Carvedilol
Bisoprolol Metoprolol may cause dyslipidemia (elevated total
Sustained release metoprolol (metoprolol succinate) cholesterol, LDL, and triglyceride levels, and low HDL)

508

509

510

511

512

Do not use for angina - may exacerbate (partial agonist)

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517

518

520

521

522

523

SLUDGE pneumonic for muscarinic type

poisionings/overdoses
Salivation
Lacrimation
Urination
Deffication
Gastrointetinal cramping
524 Emesis
or DUMBBELLS
Diarrhea
Urination
Miosis
Bradycardia, Bronchoconstriction, Bronchorrhea
Emesis
Lacrimation
Salivations, Secretions, Sweating
 I J

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531

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534

Classic symptoms of belladonna (atropine) poisoning:

1. Hot as a hare (hyperthermia from inhibition of sweating)
2. Dry as a bone (inhibition of secretions)
3. Red as a beet (dilation of cutaneous vessels)
4. Blind as a bat (cycloplegia, blurred vision)
5. Mad as a hatter (CNS excitement, hallucinations, etc.) Atropa belladonna (deadly nightshade) contains atropine
6. Bloated as a toad (inhibition of GI smooth muscle) (dl-hyoscyamine); Dautura stramonium (Jimson weed)
controlled with physostigmine contains atropine

535 Atropa belladonna (deadly nightshade) also contains

scopolamine (1-hyoscine) (see atropine extra note);
Hyosacyamus niger (1-hyoscine) contains scopolamine

536
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541

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546

547

548

SE:
SLUDGE mneumonic for muscarinic type
poisionings/overdoses
Salivation
Lacrimation
Urination
Deffication
549 Gastrointetinal cramping
Emesis
or DUMBBELLS
Diarrhea
Urination
Miosis
Bradycardia, Bronchoconstriction, Bronchorrhea
Emesis
Lacrimation
Salivations, Secretions, Sweating

550
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551

552

SLUDGE mneumonic for muscarinic type

poisionings/overdoses
Salivation
Lacrimation
Urination
Deffication
Gastrointetinal cramping
553 Emesis
or DUMBBELLS
Diarrhea Nerve Agent Symptoms: Nicotinic - Mnemonic for the
Urination days of the week
Miosis M: mydriasis (pupil dilation)
Bradycardia, Bronchoconstriction, Bronchorrhea T: tachycardia
Emesis W: weakness
Lacrimation tH: hypertension
Salivations, Secretions, Sweating F: fasciculations

554
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555

556
Note: can add succinate to chain which donates electrons
down stream from complex I (at complex II)

557

558

559
Tx cyanide poisoning with nitrite

560

561

562

563

564
565

566 Inhibition of ALA dehydrase and ferrochelatase - impaired

heme synthese. S&S: lethargy, HA, memory loss, n, d, abd
pain; high levels - lines in gums and in bones on x-ray
567
568

569
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570

NMJ paralysis in order of:

muscles of eyelids
swallowing and speech
limbs and trunk
respiratory muscles; 4-30 min i.v.

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Opioid Receptors and Endogenous Ligands: Overview
603 Comments
Families of endogenous peptides have been identified that
have varying affinities as agonists for opioid receptors
Attributed (e.g., beta-endorphin) as the euphoric agents in
runners high
More than two decades of intense scientific investigation has
failed to produce meaningful drugs from these peptides. This
is a case where we know a great deal about these peptides,
but it has not translated into clinical impact. (Boards,
particularly USMLE, stress knowledge of this material.)
604
605
606
607
Opioid Receptors - Drugs have varying specificity and
efficacy for different opioid receptor subtypes:
mu () opioid receptors***
kappa () opioid receptors
delta () opioid receptors
Opioid Receptors and Endogenous Ligands
Endorphins usually associated with mu receptor
activation
Enkephalins usually associated with delta/mu receptor
activation (Methionine (met-enkephalin) and leucine (leu-
enkephalin) containing pentapeptides)
Dynorphins usually associated with kappa receptor
activation (Experimentally shown to cause analgesia,
mechanism is unclear, but may involve NMDA activation
rather than kappa receptors)
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608
High Efficacy mu Opioids:
Morphine
Meperidine (Demerol)
Binds to all opioid receptor subtypes, low oral:parenteral Methadone (Dolophine)
potency ratio (Highly polar so slowly and incompletely Fentanyl (Sublimaze; Duragesic)
absorbed orally) Heroin (Schedule 1)

609

Methadone: Its high bioavailability via the oral route and long
610 plasma half life (25-52 hr) renders it useful in replacement
therapy in addiction therapy as well as in opioid detox.
Racemic mix of d- and l-methadone has agonist activity as
well as NMDA and monoaminergic receptor blocking activity
non-opioid effects may enhance analgesic activity Replacement/maintenance therapy: see Buprenorphine

611

612

613

614
Rem: You notice how nice your nails are buffed (Nal-buphine)
while kappin the cows that mu as they drop (kappa agonist,
mu antagonist)
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615

616

617

618

Replacement/maintenance therapy: use methadone or

buprenorphine (initially alone, but then in combination with
naloxone). Levomethadyl acetate (also called L--acetyl-
methadol or LAAM) is FDA approved, but no longer distributed
619 due to cardiac toxicities. Orally absorbed agents get addicts
away from the needle. Long half lives keep opioid levels
stable. High doses are given such that cross-tolerance
develops to the reinforcing properties of other opioids such as
heroin.
Subutex (buprenorphine hydrochloride) and Suboxone
tablets (buprenorphine hydrochloride and naloxone
hydrochloride for outpt) - treatment of opioid dependence.
Suboxone tablets has naloxone is added so that if addict
tries to solubolize the buprenophine and inject it, the
naloxone will block the "high" - note that naloxone has little
oral bioavilability, so no effect on prescribed usage.

620
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CYP2 family responsible for 25% of oxidation reactions (both

therapeutic drugs CYP2D6 and procarcinogens (CYP2A6, B,
and E1). 2D6 is responsible for demethylation reactions
621 (codeine to morphine and metab of beta blockers) and is
missing in 5-10 % of caucasians which results in
unpleasantly high levels of the drug and in the case of codeine
no efficacy as an analgesic (with increased likelyhood for
psychotomimetic effects)
Codeine (LEO) - Cough suppressant effects: As with
most opioids, suppression of cough appears to be by
action at mu receptors. Note: all opioids are
efficacious cough suppressants. The ceiling on abuse
liability, or perhaps historical use, has resulted in codeine
usually selected as the first agent of the opioid drugs that
is prescribed if OTC meds are ineffective.

622

623

624

625

626 Note: no known tolerance to antagonists (by definition they

do not activate receptor, just sit on it and block, it is the
Opioid withdrawal is unpleasant, but never life threatening in second messangers which will bring about effect of
~healthy person. tolerance)

627

628
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629

630

Non-opioid used as an antitussive, (no opioid receptor activity)

631 - the d-stereoisomer of methorphan structurally related to
levorphanol, a narcotic (opioid) analgesic.
632

633

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636

Note: methotrexate used to detect the presence of Fragile X -

culture lymphocytes with folate deficent medium tends to
cause break of chromosomes

637

638

639
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640

l cells, and TNF-alpha plays an important role in killing intracellular

o important in cell apoptosis. Thus, there is significant concern that these
641
ganisms and/or result in increased susceptibility to tumor formation. These
determine if they are associated with an increased incidence of
e murine-derived agents, immunogenicity is a consideration. These are
ctions are common. They have good efficacy as DMARDs.

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656 Thiazides stimulate proximal tubule reabsorption of uric acid Majority of gout sufferers do not secret uric acid effectively
(thiazide inhibits DT reabsorption of NaCl, causes elaboration (as compared to overproduction), though allopurinol is still
of more proteins in the PT) commonly used for chronic gout

Probenecid blocks the tubular secretion of a number of

organic acids, most important of which is uric acid. The
uricosuric action of probenecid is blunted by the
657 administration of salicylates and probenecid inhibits renal
secretion of NSAIDs such as naproxen, ketoprofen, and
indomethacin and increases the plasma concentrations of
these drugs.
With either of these two uricosuric agents (Probenecid and
sulfinpyrazone), increased uric acid excretion eventually
ensues. This increased excretion augments the formation
of renal stones and maintenance of large urine volume is
essential to minimize the possibility of stone
formation.

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663

PGE2 sensitizes pain nerve endings to the action of

bradykinin, histamine, and substance P. Aspirin blocks
PGE2 formation.
NSAIDs are mild analgesics effective against pain of low-to-
moderate intensity.
NSAIDs can be superior to opioids for relief of some forms of
post-operative pain and pain associated with inflammation. COX-1 expressed in most tissues. Constituitively active.
Anagesia: Efficacy of pain relief provided by NSAIDs is lower COX-2 Induced by cytokines and other inflammatory
than opioids; NSAIDs lack opioid effects of respiratory mediators. This enzyme is the real target
depression & development of physical tolerance/dependence. Traditional NSAIDs nonselectively inhibit both COX-1 and
Pain from integumental structures is relieved but not pain from COX-2.
hollow viscera.

664
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665

666

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671

672

Hepatotoxicity - acute overdose - depletion of glutathione

and accumulation of a minor metabolite that produces hepatic
673 necrosis. Initial symptoms (first 2 days) of poisoning consist of
nausea, vomiting, anorexia, and abdominal pain and may not
reflect the seriousness of the intoxication. After 2 to 4 days,
hepatic liver enzymes and bilirubin become elevated and
severe hepatic lesions can progress to fatal liver damage.
Treatment - gastric lavage within 4 hours of ingestion,
supportive measures, and administration of N-acetylcysteine,
a drug that restores liver glutathione levels.

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Primary Adrenocortical Insufficiency

a. Due to pathology of adrenal cortex decreased
adrenocorticosteroids in the presence of normal circulating
679 ACTH levels.
Corticosteroid Hyperfunction: Cushing's Syndrome b. Addison's disease: atrophy or bilateral tuberculosis of
a. Etiology includes primary (adrenal hyperplasia or tumor) adrenals.
and secondary (ectopic ACTH secreting neoplasm) sources. c. Symptoms: hypotension, decreased renal Na+
Iatrogenic (induced inadvertently by a physician or surgeon or reabsorption, decreased cardiac function, and
by medical treatment or diagnostic procedures) Cushing's cardiovascular collapse, decreased work capacity,
Syndrome can result from chronic glucocorticoid therapy. hypoglycemia, depression/psychosis.
b. Symptoms result from abnormally high circulating levels of d. Treatment: mineralocorticoid and glucocorticoid
ACTH and/or corticosteroids. replacement therapy
c. Symptoms: high incidence of neurosis and psychosis, Secondary Adrenocortical Insufficiency
poor wound healing, changes in formed elements of a. Due to decreased circulating ACTH levels resulting in
blood, positive Na+ balance, expanded extracellular adrenal atrophy and low levels of circulating
volume, hypertension, osteoporosis, hirsutism, glucocorticoids (generally, levels of mineralocorticoids are
amenorrhea, impotency, Cushing's habitus, muscle not effected - renin is trophic).
wasting, hyperglycemia and glucosuria. b. Etiology: pituitary hypothalamic insufficiency or
d. Treatment depends on exact etiology; surgery; iatrogenic due to prolonged glucocorticoid treatment
pharmacological therapy. c. Treatment: glucocorticoid replacement therapy

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Substrates of p450:
cyclosporine
696 warfarin
phenytoin
tricyclic anti-depressants
theophlline
carbamazepine
beta-blockers
calcium channel blockers
haloperidol
benodiazepines
oral contraceptives

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DRUG INTERACTIONS:
Azathioprine can cause an increase in cancer risk when
used long-term. This particular risk increases in patients with a
prior history of treatment with other immunosuppressants. It
also increases the risk of serious infections.
700 Azathioprine can impair fertility by reducing sperm counts in
males.
Azathioprine's toxicity increases when taken with the gout
medication allopurinol, therefore its dose is reduced with
simultaneous use.
Severely low white blood counts can occur when taken
with other drugs that can affect the bone marrow or with patients with thiopurine methyltransferase (TPMT)
ACE-inhibitor class drugs used to treat elevated blood deficiency are at greater risk for developing
pressure. haematopoietic toxicity from therapy with azathioprine

701 To reduce the side effects, patients may be given a) an
antihistamine to reduce the allergic reaction, b) Tylenol to
prevent fever, and c) steroids such as to diminish the allergic
response. These drugs are generally given 30 to 60 minutes
before the OKT3.
OKT3 is usually given once a day in a very fast
intravenous dose. It usually must be given in a hospital for
the first three or four days and always requires close
medical supervision. The patient can form antibodies
against OKT3. Therefore, blood tests are done during
treatment to watch for signs of antibodies.

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DRUG INTERACTIONS:
Troleandomycin, a macrolide antibiotic, reduces the liver's
ability to metabolize methylprednisolone. This interaction can
result in higher blood levels of methylprednisolone and a
higher probability of side effects. Erythromycin and
709 clarithromycin and ketoconazole also inhibits the
metabolism of methylprednisolone. Estrogens, including birth
control pills, can increase the effect of corticosteroids by 50%
by mechanisms that are not completely understood.
Phenobarbital can increase the metabolism of Methylprednisolone and other corticosteroids do not
methylprednisolone and other corticosteroids, resulting in appear to pose a risk to the developing fetus. The
lower blood levels and reduced effects. Therefore, the dose of amounts of methylprednisolone in mother's milk after
methylprednisolone may need to be increased if treatment consumption of standard doses are lower than the infants
with phenobarbital is begun. adrenal glands produce.

710

Drug Interactions cont: Live vaccines should not be

administered to people taking corticosteroids, because their
normal immune response is reduced and giving a live vaccine
may therefore result in infection rather than the production of
antibodies. As corticosteroids reduce the normal response of
the immune system to attack by micro-organisms, it should be
ensured that if antibiotics are required, that they are given in
effective doses.
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713
Curable by chemotherapy
Acute lymphoblastic leukemia
Acute myeloid leukemia
Ewing's sarcoma
Gestational trophoblastic carcinoma
Hodgkin's disease
Non-Hodgkin's lymphoma
Burkitt's lymphoma
Diffuse large cell lymphoma
Follicular mixed lymphoma
Lymphoblastic lymphoma
Rhabdomyosarcoma
Testicular carcinoma
Wilms's tumor
Chemotherapy has significant activity
Anal carcinoma
Bladder carcinoma
Breast carcinoma
Chronic lymphocytic leukemia
Chronic myelogenous leukemia
Hairy cell leukemia
Head and neck carcinoma
Lung (small cell) carcinoma
Multiple myeloma
Non-Hodgkin's lymphoma
Follicular lymphoma
Ovarian carcinoma

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Alkylating Agents: These compounds are chemically related to the mustard gases used in WWI. In general, these drugs
718 are highly reactive and spontaneously transfer their alkyl groups to DNA, protein, or other cell constituents producing
cytotoxic effects. The most important reaction is the alkylation of the "7 position" nitrogen of guanine in DNA. This
reaction leads to (a) cross linking with a second guanine residue, i.e., the two DNA strands become cross-linked (b)
abnormal base pairing; G instead of pairing with C, pairs with T, i.e., genetic code misread. Most of the alkylating agents
also modify adenine, cytosine, phosphates, or protein in DNA. Overall, these chemical defects lead to abnormal base
pairing, miscoding of DNA, RNA, and protein, inhibition of DNA replication, and can lead to DNA strand breakage.

Common treatment for aggressive Non-Hodgkin's

Lymphoma: Chemotherapy is initiated with the CHOP
719 Broad spectrum alkylating agent regimen (cyclophosphamide, doxorubicin, vincristine,
Can be given orally or IV prednisone). A potential for multidrug resistance to
Prodrug activated by cytochrome P450 develop exists.
In combinations like: An alternative treatment for a lymphoma patient is high-
CMF: cyclophosphamide, methotrexate, flurouracil for breast dose methotrexate with leucovorin rescue, which
CA would be unaffected by the MDR gene product.
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728
Doxorubicin has a broad spectrum of activity and is often
synergistic with other agents. It is used in combination
regimens against Hodgkin's and non-Hodgkin's lymphomas
(ABVD regimen); carcinomas of the breast (CAF regimen),
ovary (PAC regimen), endometrium, ovary, testicle, lung,
prostate, cervix, head and neck; and osteogenic and soft-
tissue sarcomas.
Hodgkins Lymphoma:
ABVD Regimen - Doxorubicin (Adriamycin), bleomycin,
vinblastine, dacarbazine
In Hodgkins disease, combo chemo results in long-term,
disease-free survival in >60% of patients.

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740

Mechanism of Action: Fluorouracil is activated intracellularly

to one of several metabolites. Fluorodeoxyuridine
monophosphate (F-dUMP) is a potent inhibitor of
thymidylate synthase, an enzyme necessary for the
741 synthesis of dTTP and ultimately DNA; fluorouridine
triphosphate (FUTP) is incorporated into RNA and interferes
with its processing and function. Fluorodeoxyuridine
triphosphate (FdUTP) is incorporated into DNA and eventually
leads to DNA strand breakage.
The interference of FdUMP with thymidylate synthesis
requires the presence of reduced folates. Leucovorin,
a folate analogue, has been administered with fluorouracil
in an attempt to increase antitumor activity. Extensive
first-pass hepatic metabolism for fluorouracil has led to
direct hepatic artery infusions for the treatment of
hepatic metastases. The fluorouracil analogue floxuridine,
(FUDR) is also available for intrahepatic infusion.

742

743

744
requires the monitoring of serum methotrexate levels to adjust the dose
cleared mainly by renal excretion, and patients with impaired renal
mens have been associated with acute renal injury, which may be High-dose methotrexate with leucovorin rescue is an
the urine. In the absence of normal renal function, there are no alternative treatment for aggressive NHLs.
minate methotrexate. Acute or chronic administration of methotrexate has This treatment would be unaffected by the MDR gene
ratic pneumonitis. product.

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841

Fluoroquinolone is first line choice for any complicated

842 UTI (ie, a better choice than TMP-SMX for a pt with DM,
multiple past UTI, and given the increased resistance of
common pathogens to TMP-SMX)

843

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863

Tx of migraine - three major pharmacologic classes:

1. Anti-inflammatory agents (Note: if NSAIDs are to be
864 effective in migraine, they usually must be taken very early in
the attack. In general they are not particularly efficacious.)
2. 5-HT1 agonists & ergotamines
3. Dopamine antagonists Tx of cluster HA - see Oxygen
 I J

865

866

867

868
869

Perhaps more important than elimination half-life is the data

concerning time/speed to onset of effect. The slowest onset
870 agent, naratriptan, is also the least efficacious. General rule
of thumb in treating migraine is that faster onset
medications are more efficacious!!
Because the route of administration dramatically impacts
speed of onset, this variable similarly impacts maximum
efficacy. Put another way, the maximum efficacy possible
for a triptan given orally is always less than the maximum
efficacy that can be obtained for that same drug given i.v.
Triptans: Route of Administration
mild migraine: oral
moderate migraine: oral, intranasal or parenteral (s.c.)
Severe migraine: parenteral (s.c., i.m. or i.v.) - IV
(parentral) are much faster onset and thus more
effective than oral
Note the need to change to routes of faster onset to gain
efficacy against more severe forms of the disease.
 I J

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872

873
Dystonias I - Defined by body region affected:
1. Torticollis (muscle contractions leading to twisting of the
neck with an unnatural position of the head)
2. Facial distortion
3. Tongue protrusion
4. Dysarthria (imperfect articulation of speech)
Dystonias II:
Opisthotonus -- whole body spasm
Scoliosis -- bending of the spine
Oculogyric crisis -- rapid eye movements
Akathisia (Inability to sit; patient is constantly pacing,
restlessness; MC after about a week of treatment)

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879

Retroperitoneal fibrosis may encase renal arteries and cause

HTN; may also incase abd aorta, IVC and other
retroperitoneal structures.

Cluster cont: Male 4:1 cluster HA; aka suicidal HA (feels like
hot poker pt bangs head into tree to distract from HA)
880 HA comes on rapidly (little warning, little/no prodrome) by
time oral med works (if can be held down from vomiting) HA
may have remitted and med no good Cluster cont: accompanied by ipsilateral lacrimation,
Prophylactic agents reduce frequency (# of attacks) but if nasal congestion or discharge,and facial flushing (mixture
attack occurs, severity not decreased of para and sympathetic activation)

881

882

883

Anticholinergics improve tremor and rigidity, but not

884
Ach>DA=akinesia, rigidity, tremor
DA>Ach=dyskinesia, choreiform movements
bradykinesia. Will make dementia worse (CNS-acting
anticholinergics by themselves can produce amnesia in
healthy persons (interfer with memory aquisition, learing,
etc); in patients compromised with age- or Parkinsons-
related dementia, this effect will be pronounced;
Harrisons, medicine text say not in patients over 60)

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Note: Nonselective MAOIs (block both MAO-A and MAO-

B) should not be used in Parkinsonism since they would
887 Interactions: meperidine, tricylic antidepressants, SSRIs lead to hypertensive crisis when combined with levodopa
(Meperidine is in a class of medications called narcotic therapy. (Meperidine is used to relieve moderate to severe
analgesics, a group of pain medications similar to morphine. It pain. Also: MAOI with tyramine causes HTN crisis
works by changing the way the body senses pain.) (from excessive NE release)

888

889

890 Parkinson's Dz: Defect in extrapyramidal system that controls
involuntary movement, muscle tone and postural reflexes; 1%
of adults over 65
paralysis agitans (shaking palsy) James parkinson, 1817
Extrapyramidal is literally all CNS but corticosplinal. In
practice, means Basal ganglia coordinate large muscle
movements, initiating and terminating them."
Bradykinesia- slowness of movement
Tremor mostly at rest when patient sits quietly.
Parkinson's Dz cont:
Difficulty initiating movement is overcome in emergency;
i.e., by potent stimuli.
Festinations: short, accelerating steps, festinating gait.
Dyskinesias: (in TD, HC, or PD at peak levodopa dose):
Choreiform: involuntary, complex movements
Athetosis: slow writhing movements of the hands Athetoid
Dyskinesia: impaired movement, fragmentary or
incomplete

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Advanced Parkinson's Dz:

894
(often requires combinations)
Levodopa/Carbidopa
DA agonist
Amantadine
Selegiline
Notice: bradykinesia is ~the most debilitating effect of PD

895

896

esic/anti-inflammatory treatment
ys: corticospinal, reticulospinal, vestibulospinal. (i.e., upper motor neuron

odulated by drugs to treat spasticity.

synapses directly on motor neurons going to the muscle to excite muscle
pse on inhibitory internuncial neurons which inhibit contraction of the
ation897
causes hyperreflexia.
aptic reflex arcs (phenobarbital, other barbiturates, glycerol ethers Baclofen: Implantable osmotic pump available for
asticity, because they would also reduce desirable inhibitory activity as continuous intrathecal administration. Allows patient to
tolerate higher doses (little egress from cerebrospinal
effective against spasticity, they tend to detract from, or fail to improve fluid)

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Primary neurologic disorders:

915
brain tumor
cerebrovascular accident
toxic agents
head trauma What makes a seizure happen?
Metabolic & systemic disorders: Molecular changes in normal neural function:
electrolyte imbalances Neural conductance
uremia (excess nitrogen in blood) Synaptic events
infection Alterations in connectivity:
fever Increased excitation
drug overdose or withdrawal Decreased inhibition

916

917

918

919

920 Ethosuximide: Pharmacokinetics
Completely absorbed after oral dose
Not significantly bound
t1/2 is 30 hours in children and 40-60 hours in adults
A patient can have true petit mal and be treated with ethosuximide, but then one day have a grand mal (G
part of the idiopathic epileptic syndrome (but now it is atypical), and you would have to change the AED t
DOC, for petit mal with GTCS. Alternatively, you could have treated the patient in the first place with valpr
though they had never had a GTCS.
GTCS can occur with petit mal, but it is the atypical presentation.
 I J

921

922

923

Facilitation of GABA
924 Directly: Enhancing Receptor Activity
BZD allosteric site
Barb allosteric site
Indirectly: Increasing GABA Levels
Uptake inhibition
Inhibit degradation
GABA(A) drugs
Direct:
Barbiturates: phenobarbital
generalized tonic-clonic seizures
Alternative for febrile convulsions in children <5 years
Benzodiazepines
diazepam (Valium), lorazepam (Ativan)
status epilepticus
clonazepam (Klonopin)
absence; myoclonic, akinetic, atonic seizures

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930

931

932

933

Definitive mechanism for efficacy of beta interferon in MS

The outcome of the gamma interferon experiments:
934 1. Showed that gamma interferon can play a key role in MS
relapses.
2. Provided evidence that attacks of MS are triggered by
immune system growth-factors.
3. Suggested that beta interferon, which inhibits the action
of gamma interferon, could be a treatment for MS.
is not established.
Most interesting suggestion is that the immune system is
modulated from TH1 activity to TH2 activity; thus, the
inflammatory potential of the disease is reduced. (Note:
this immune shift takes place during pregnancy, and
pregnancy is a protective factor against MS attacks.)
However, efficacy is very clear
 I J

In the first stage of CNS myelination, the axon at a particular site is enclosed by the process of the myelin-forming
oligodendrocyte. The process completely envelopes the axon and its lips come together to form a mesaxon. With
increased myelination (oligodendrocyte process elongation), cytoplasmic faces of most portions of the plasma membrane
of each side of the process become positioned very close together forming the major dense line (MDL). The process of
935 MDL formation is called compaction. Formation of MDL is essential for myelination. If MDL does not form (dysfunctional
or lacking myelin basic protein (MBP)), myelin becomes loosely wrapped around the axon. Close apposition of the outer
faces of the plasma membrane of two adjacent oligodendrocyte processes forms the intraperiod line (IPL).
In humans with multiple sclerosis (MS), many nerve fibers become devoid of myelin. There is evidence that MS is an
autoimmune disease. The myelin has been observed to be stripped from the axons by M0. The space created by the
loss of myelin is taken up by astrocytic processes (astrocytic hyperplasia or hypertrophy).
This region is referred to as an MS plaque. MBP is 30-35% of total myelin protein and MBP is located in the MDL.

936

937

938

Blast acute MS pt with steroid (Single dose has little risk

associated) - 1000mg of solumedrial (sp?)

939 Allopurinol increases 6-mercaptopurine levels - xanthine

oxidase metabolizes 6-mercaptopurine, allopurinol inhibits
xanthine oxidase, thereby increasing the levels of 6-
mercaptopurine, can cause pancytopenia (if must continue
both drugs, decrease azathioprine to 1/3 dose)

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950

Biological Basis of Depression Receptor & Post-

951 Biological Basis of Depression Amine Hypothesis
Depression is caused by a decrease in biogenic amines
(primarily NE and 5-HT).
Depletion of biogenic amines with reserpine can induce
depression in normal individuals.
Drugs with antidepressant properties increase levels of
biogenic amines (at least acutely)
Receptor Hypotheses
That antidepressants must be taken chronically before
clinical effect is seen implies that something downstream
of receptor (transporter) blockade are responsible for
clinical efficacy.
Some antidepressants decrease NE and/or 5-HT
receptors or decrease the sensitivity of these receptors.
Intracellular changes, including phosphorylation) of
receptors or intranuclear regulatory elements, may be
involved.
Changes in neurotrophic factors may be involved

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956 Cingulate gyrus (basal ganglia) is linked to OCD, torrets

also located here, the two are commonly comorbid

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963

TCAs: Amitriptyline & Nortriptyline

TCAs: Dangerous in Overdose! - A patient may overdose on
964 as little as a 4 day supply of TCAs (depressed patients are at
risk for suicide). The pharmacokinetics of TCAs hinder
treatment of overdose (large volume of distribution and high
plasma protein binding make dialysis ineffective in removing
ingested drug).
Amitriptyline has the most sedative and strongest
antimuscarinic side effects of all the TCAs (useful in
enuresis)
Nortriptyline has somewhat lesser antimuscarinic and
sedative effects.
Both block 5-HT (+++) and NE (++) reuptake.

965
966
967

968 MAOIs: Interactions with Tyramine

MAOIs block deamination of dietary tyramine. At
noradrenergic nerve terminals tyramine produces the release Foods to Avoid: aged cheeses, pickled herring, beers
of NE which in turn results in a potentially fatal increase in and wine, liver, yeast extract, dry sausages, fava beans
blood pressure

969
970
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972
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973

Diuretics (e.g., thiazides) can reduce lithium clearance by

as much as 25%.
Newer NSAIDs can reduce lithium clearance.
974 Lithium worsens extrapyramidal syndromes produced by older
antipsychotic drugs.
In kidneys lose ADH effects decrease (nephrogenic diabetes
insipidus) resistant to vasopressin and responds to amiloride.
Chronic interstitial nephritis, minimal change glomerulopathy
(decreased GFR), no renal failure, and patients should avoid
dehydration! Renal clearance increases and returns to If OD it is usally from change in clearance and not due
normal immediately after delivery, and it is present in breast to deliberate ingestion Dialysis is effective in removing the
milk. Most data suggests low risk of teratogenic effects drug

975

976 notes on other anticonvulsants

both gabapentin and topiramate have been studied for efficacy
in treating mania
most controlled studies do not suggest these drugs are useful
in treating mania

977
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978

979

980

981

Dopamine Hypothesis of Schizophrenia

Too much dopaminergic activity in the mesolimbic
pathway (positive symptoms) & too little in the
mesocortical pathway

Dopamine and Positive Symptoms of Schizophrenia

Excess dopamine in the mesolimbic system is a likely
site accounting for positive symptoms in schizophrenia.
982 Positive symptoms - hallucinations, delusions, distured
DA Receptors: All Antipsychotics Block Dopamine Receptors thinking, bizarre behavior, agitation
- 2 Major Families (D1 family and D2 family). Family subtypes
include: Dopamine and Negative Symptoms of Schizophrenia
D1a and D1b (sometimes referred to as D1 and D5) Decreased dopamine in the prefrontal cortex
D2, D3 and D4 (the D2-like receptors), which share (mesocortical pathway) as well as the mesolimbic
comparable binding affinities for most D2 drugs system likely involved in negative symptoms in
schizophrenia.
Most important DA tract related to Schizophrenia - Negative symptoms - lack of emotions, impaired
Mesolimbic tract, with cell body location in the ventral spontaneity, passivity/apathy, social withdrawal, lack of
tegmental area, having terminal fields in the nucleus pleasure
accumbens and prefrontal cortex - function euphoria, Serotonin may also be involved
reinforcers, and psychosis Burnt out schizophrenics

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989

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 I J

SSRI, Venlafaxine, Tricyclics

998 Efficacious for treating obsessive-compulsive disorder
(SSRI), panic disorder (SSRI) and generalized anxiety
disorder (venlafaxine, tricyclics SSRI?)
Preferred because of no potential for
dependence/abuse
Treatment of Anxiety: Slow onset (2-4 weeks)
SSRIs, venlafaxine, tricyclics - some studies estimate as Must be taken continuously
much as 85% co-morbidity between anxiety-disorders and Always consider these agents first for treatment of
depression anxiety
Benzodiazepines See antidepressant above for detail
Buspirone These agents are superceding BZD-type drugs

999

1000

1001
Lorazepam used short term, tremendous tolerance within
48hrs, usually switched to phenobarbial)

1002
 I J
1003

1004

1005

1006

1007

No dependence or tolerance, no cross tolerancce with other Buspirone - clear consciousness, no dependence or
BZDs, does not alleviate BZD or EtOH withdrawal withdrawal - but its efficacy as an anxiolylitic is poor.

1008

1009

Ideal Hypnotic: Benzodiazepines as Sedative-Hypnotics:

Produces sleep rapidly Effective, however, "hangover (morning grogginess) is
Does not alter sleep pattern a problem for long-acting BZDs
1010 No early morning awakening Rebound insomnia & anxiety are problems for short-
No rebound insomnia acting BZDs
No hangover Early morning awakening is a problem for short and
No tolerance or dependence intermediate-acting BZDs
Has a high Theraputic index (TI) Tolerance/dependence/withdrawal
 I J
Binds a subset of BZD receptors (BZD1) note, the
manufacturers of zolpidem have been on a long quest to
1011 get this receptor reclassified as an omega1 subtype based
upon the rationale that structurally, zolpidem is not a
Alpha-subunit of BZD receptor has at least 6 subtypes benzodiazepine.

1012

1013

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1015

1016
1017
1018

1019

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1021
 I J
1022

1023 Basic amphetamine structure looks exactly like tyramine

(uptaken into synapse then causes release of
catecholamines) except it does not have a hydroxly group
and has a methyl group hanging off of the alpha carbon
(sterically inhibits binding), this protects the structure
from deamination from MAO (tyramine is chewed up this
Ez in seconds), so amphetamines are active for 4-6hrs.
Amphetamine is a schedule 2 (high abuse) so drug
companies put lots of side chains on it to decrease it
effeciacy and thus reduce its scheduling (less abuse
potential).

1024

1025

Children have increased suicidal thoughts with atomoxetine 2/3 of ADHD kids continue with it to adults
1026

1027

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1029

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 I J

1031 Amphetamine-related anorexiants - Mechanism of action:

Modification of norepinephrine and dopamine
neurotransmission
Critical effect for anorexia is on appetite-control areas of the
hypothalamus.
Likely a norepinephrine mechanism; dopamine is underlined
because of the role of this neurotransmitter in abuse
High-abuse liability amphetamines cannot be used in weight
control programs (amphetamine, methamphetamine,
phenmetrazine Schedule II agents cannot be prescribed for
weight control)
Amphetamine-related anorexiants - Effectiveness:
Amphetamine related anorexiants effectiveness limited by
tolerance (2-3 weeks), discontinue after tolerance, initial
weight loss then plateau (some weight gain likely
thereafter regardless of continuation of medications).
Usefull ness should be considered against risk of side
effects and or abuse potential

1032

1033

1034

1035

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1038
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1039

1040

1041

1042
Ethanol Metabolism: first step - primary route
ADH = Alcohol Dehydrogenase
EtOH: Pharmacokinetics Metabolism and Elimination ADH is inhibited by 4-methylpyrazole (Fomepizole)
Small, predictable amounts excreted through the lungs, urine First step in EtOH metabolism (90-98% of ingested
and sweat (2-10%), basis of breathalyzer tests EtOH), occurs in the cytosol
Primarily metabolized by oxidation in the liver (>90%) Acetaldehyde may be partly responsible for headache
EtOH elimination follows - ZERO ORDER KINETICS - which is characteristic of hangovers
Independent of concentration nicotinamide adenine dinucleotide (NAD) is a cofactor,
Elimination rate is dependent on body weight or liver weight availability of NAD may be rate limiting
An average adult metabolizes 7-10 g/hr (~0.7 drinks/hr) some ADH activity in the stomach (higher for men than
for women)

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1044
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1045

non-toxic in absence of ethanol (?)

Aldehyde Syndrome: flushing, throbbing headache, use in conjunction with counseling and other psychosocial
sweating, nausea, vomiting, confusion therapies

1046

1047

Cocaine: Sources/availability: Coca plant Erythroxylon coca

(up to 1% weight); Cultivation in Peru, Bolivia, Colombia,
1048 Argentina, Brazil and Ecuador, exported to US; Used to help
workers adapt to working in thin air; high profit
Cocaine: Forms of Abuse
Chewing leaf
Powder (cocaine HCl - 10-90% pure on the streets)
Snorting (20-100 mg)
Oral (poor absorption)
Intravenous, 5-25 mg
smoked: free base method; crack In these methods,
cocaine is neutralized to get rid of the HCl. The resulting free
base is more amenable to pyrolysis by flame than is the HCl
salt form of cocaine.
Cocaine: Pharmacokinetics: Half life is 50-min; drug-
seeking occurs after 10-30 min in users of alkaloid form
(crack, free base); declining plasma concentration
related to termination of high (NOT the absolute drug
level per se, but the decline in drug level is critical for the
loss of the high. Cocaine is toxic by a mechanism that
is separate from the dopamine system [seizures
induced by its local anesthetic actions], and this fatality
mechanism is directly related to plasma concentration.
Leads to overdose potential.)
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Amphetamines: Acute effects Amphetamines: Toxicity

1049 Alertness/anti-fatigue (NE in RAS) Low acute toxicity
Euphoria Paranoid psychosis and violence in high dose and/or
Anorexia prolonged use
Emotionality ANS effects: sympathetic arousal (mild for
Toxic psychosis with chronic use amphetamines; severe for cocaine)
Responds to antipsychotics Not convulsant

1050

1051 Smoking/Nicotine: Treatment

Nicotine replacement - Suppression of symptoms of
withdrawal is primary benefit. People get little positive
reinforcement from patch or gum, but are less likely to initiate
smoking in response to emergence of withdrawal during
smoking cessation (gum, patch, cigarette inhaler, nasal spray).
Gum and patch do not achieve same peak levels as
cigarettes; suppress symptoms of withdrawal; concurrent
smoking may produce adverse effects
Nicotine Tx: Nicotine polacrilex delivers nicotine within a pressure sensitive resin, to minimize the risk o
poisoning. Released slowly and chewing is necessary for activation. Mildly unpleasant tasting (to reduce
poisoning by a child. Delivery across buccal mucosa. Take every 1-2 hours. Dont chew constantly. Softe
chew intermittently. Nicotine is lost if swallowed, plus this leads to upset stomach, nausea, etc. Large firs
swallowed.
Acidic foods & beverages will prevent absorption (weak base)
Patch has better compliance; gum may not have sufficiently high dose of nicotine. 24-h and 16-h system
stepped down dosages (i.e., 21, 14, or 7 mg of nicotine)

1052
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Phencyclidine: Effects cont:

Moderate dose: Sympathomimetic effects: tachycardia, PCP Overdosage:
1053 increased BP, mydriasis, xerostomia anxiety, agitation, aggression, hallucinations
High dose: Analgesia, anesthesia, decreased BP and dysphoria, catatonia, muscle rigidity, convulsions
respiration. Combined horizontal and vertical nystagmus is tachycardia, diaphoresis, salivation, lacrimation,
specific to PCP; horizontal seen in ethanol and sedative hypertensive crisis
hypnotics.

1054

1055

Marijuana: Pharmacokinetics
Rapid absorption following inhalation
Euphoria onset after 10-30 minutes lasting 3-4 h
1056 Delta-9-THC is highly lipid soluble; accumulation in fatty
tissue
In some states, marijuana is legal for appetite stimulation Active and inactive metabolites
among AIDs patients. 10-15% urinary excretion- detectable up to 30 days after
use.
1057
1058

1059
Similar S&S to opioid OD - respirtory depression, coma, and
brandycardia; no response to naloxone or flumazenil
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1060

1061

1062
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1

7 Decreases PSA about 50%. PSA test is still valid, but data have to
be interpreted differently. Get a PSA before starting.
Get base line, so when on 5a reductase blocker, would double Notice: alpha blockers have fast onset, 5a reductase
PSA score to correct inhibitors have slow onset

Watchful Waiting
If no signs, or if minimally disrupting, simply wait. Patient training
to: Tamsulosin:
9 Restrict caffeine at night Competitive alpha blocker; binds a1A (and a1D) with
Phosphodiesterase inhibitor little a1B binding
Stimulants cardiac output (more fluid to glomeruli) Highly efficacious in benign prostatic hyperplasia.
Restrict fluid at night Very limited (if any) vascular effects, Well tolerated,
Do not delay voiding Effectiveness is maintained for years (little tolerance)
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10

Asthenia loss of strength, pt will complain of weakness, but Notice: Terazosin SE similar to doxazosin, but side-
strenght tests will be normal effect profile is perhaps more severe.

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12

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14

Priapism: an abnormal, more or less persistent, and often painful

erection of the penis; especially - one caused by disease rather 5 questions to ask ED pt: alcohol use, smoking Hx, DM,
than sexual desire marital conflict, and work related stress

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20
21
Physiology cont:
Liver effects* (increase in CBG, TBG, SHBG, transferrin;
*Particularly relevant for oral estrogens)
22 CBG = transcortin = cortisol binding globulin; TBG = thyroid
binding globulin; SHBG = sex H binding globulin
Transdermal delivery of estrogen bypasses first pass effect
Increase HDL and triglycerides, decrease LDL (modest)
Enhance coagulative ability of blood (SE - thromboembolism)
Induce progesterone receptors (especially hypothalamus, but not
everywhere)
Behavioral effects (mood, specific cognitive domains, libido)
23
24
Mechanisms of action for Estrogens, Progestins &
Androgens (classic): Genomic effects are mediated by
the intracellular (nuclear receptor) transcriptional
modulation (H/receptor complex binds to H
response element of DNA), this takes time (not
seconds). Metabolites (such as DHEA, for androgens;
Allopregnanolone for progesterone) can elicit effects via
other receptor systems as well (Allopregnanolone at
GABA(A) receptor) Another major metabolite of
testosterone is estradiol (about 80% of the
developmental effects of testosterone in the brain are
mediated by prior conversion to estrogen).
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OC (Estrogen) SE cont
Nausea related to amount of estrogen; Heightened sense of
smell (sickenly sweet to woman)
Headache or worsening of migraine has been suggested to
be related to the influence of estrogen on tryptophan metabolism
(tryptophan has been used to treat migranes)
25 Edema (Bloating) associated with estrogens ability to promote
sodium retention
Breast tenderness or fullness
Cancer (?, depends on type) more likely with the higher
concentration and/or alternate preparation of hormone used in HT
or ET; Reduced exposure and dose helps
OC may improve risks for ovarian cancer (higher the dose of
progestin, the lower the ovarian cancer)
Side effects of OCs associated with progestin
Cardiovascular disease: depends on age of subject
and genetic factors (thromboembolic factors, liver Ez)
Stroke (thromboembolic factors)
Increased appetite may be a result of the glucose
intolerance, and consequent increase in the amount of
insulin which influences satiety centers in the brain.
Weight gain may be more prevalent with the
androgenic progestins (they are anabolic)
Fatigue
Depression may be related to the ratio of
Progesterone to Estrogen
Breast regression

26

27

28
Medroxyprogesterone acetate (MPA): Progestoren Challenge test: progestoren which will
t of 38-46hrs (long half life) stimulate the endometrium to change from proliferative
Elimination: phase to secretory phase and then slough off (+
Renal (minor) withdrawl bleed). Give for 7 days then stop (mimics
Fecal (major) corpus luteum) woman should have menstruation if
she has sufficient estrogen and vaginal patency.

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General Notes for Diuretics: increases loss of Na+ and H2O,

leads to decrease in blood volume, decreased CO, decreased BP
(however, reflex sympathetic activity offsets BP effect); chronic
effects (the critical event for hypertension control): Na+ loss
causes decreased responsiveness of arterioles to NE and
decreased arteriolar resistance Remember: piss through the TEF(lon) loop (torsemide,
ethacrynic acid, furosemide)

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62

DIURETICS: USES IN CHF: Should seldom be used alone,

even if symptoms are well-controlled. Monotherapy with a
diuretic may cause adverse neurohormonal activation (renin
system) due to volume depletion. Mortality is improved by other
drugs

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Competitive blockers, but blockade by most of these

72
AT1 (receptor): responsible for the effects of angiotensin II that
must be diminished in CHF. Sartan drugs block this receptor.
AT2: Role of these receptors is less clear. Some evidence that
their activation opposes effects of AT1
drugs is insurmountable (Mechanism unclear)
Capable of more effective reduction of angiotensin II at
AT1 receptor than can be achieved with ACEI
(Angiontensin II is still generated by chymase pathway in
presence of ACEI). Increase activation of AT2 receptors
(Body tries to overcome AT1 blockade by releasing
higher amounts of renin, which leads to more
angiotensin II available at AT2 receptors)

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ACEI advantages: Predictable, typically mild, dose-related side-
effects
Blunt the hypokalemia caused by diuretics
Decrease aldosterone release
Little orthostatic hypotension or SNS activation
No effect on triglycerides, cholesterol
Contraindication: ACEI with renal a. stenosis
(bilateral, eg atherosclerosis or fibromuscular
dysplasia): Stenosis must be removed by surgery; renin
levels are high in this condition; ACE-I will further dilate
the efferent arteriole, resulting in even less pressure in
the glomerulus (rise in serum creatinine).

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76

Do not use short acting dihydropyridines to treat HTN (rapid

bp drop and large SNS response), may tirgger MI, infaction,
77 stoke,and death. Dihydropyridine should not be used as first-line
therapy for HTN in pts wit proteinuric renal dz but may be used as
adjunctive therapy once the dose of the ACEI or ARB has beeen Remember: pine trees are for slow growing sinus
maximized in combination with an appropriate diuretic bradycardia, AV dysjunction
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Mechanism of Beneficial Effects of Ca Channel Blockers in

Angina:
Decreases excitability of vascular smooth muscle (decreases
78 propensity of arteries to spasm (helpful in Prinzmetals))
Decreases tone of vascular smooth muscle (decreases afterload
(helpful in angina of effort))
In addition to their vascular effects, verapamil and diltiazem
decrease SA and AV node function and decrease cardiac
contractility - both effects lead to less cardiac work (useful in
angina of effort)
Ca Channel Blockers as Monotherapy
1. Angina with historical features suggesting dynamic
coronary vasoconstriction (Prinzmetals)
2. Patients with sinus bradycardia, AV dysfunction
(block, verapamil and diltiazem will worsen block)
use a pine
3. Patients with atrial fib/flutter use verapamil
4. Patients resistant/tolerant to nitrates or blockers

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General note: Community-acquired infections

(uncomplicated UTI)
Most UTI are caused by gram negative aerobic bacilli
97
from intestinal tract
80% to 90% noninstitutionally acquired,
uncomplicated UTI is due to E. coli infection
Resistance Rest are due to:
Mediated by plasmid Proteus mirabilis
The mechanism of resistance includes Klebsiella pneumoniae
1. increased production of PABA overcomes sulfas--most common Enterococcus faecalis
2. increased capacity to destroy or inactivate drug Staphylococcus saprophyticus (10-15%)
3. alternate pathways for nucleic acid synthesis Notice: UTI in adult men are always considered
complicated

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NSAIDs are ulcerogenic. NSAIDs aggravate mucosal damage,
delay healing, and predispose to bleeding. Prolonged ingestion of
NSAIDs is one of the primary causes of gastric ulcer and, to a
lesser extent, duodenal ulcers. NSAIDs should either be avoided
or reduced in dose in ulcer patients. COX-2 selective NSAIDS
(e.g., celecoxib), have a lesser incidence of ulcer formation than
nonselective NSAIDs. However, recent reports of increased risk
of adverse cardiovascular events with these agents have
significantly limited their use. Rofecoxib, valdecoxib have been
withdrawn from the market.

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Absorption, Fate, and Excretion: Rapidly and well absorbed after

oral dose. Half-time for elimination is approximately 2-3 hours.
These drugs are subject to hepatic metabolism, but are largely
excreted unchanged in the urine; renal impairment requires
adjustment of dosage. Hepatic metabolism of ranitidine
contributes enough to clearance that dosage must be adjusted in
patients with hepatic dysfunction.
Adverse Effects and Drug Interactions: Adverse side
effects are infrequent and mild.
All agents that inhibit gastric acid secretion may alter
the bioavailability or rate of absorption of certain drugs
secondary to changes in gastric pH.

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s:
ng, high136
neutralizing capacity, causes constipation.
moderate acting, high neutralizing capacity; causes diarrhea.
act acting, moderate neutralizing capacity; releases CO2 causing distention SINCE ALUMINA COMPOUNDS DECREASE
ated and sustained rebound acid secretion. MOTILITY AND CAUSE CONSTIPATION, AND
high neutralizing capacity; rapidly cleared from the stomach and presents MAGNESIUM COMPOUNDS INCREASE MOBILITY
mic alkalosis; releases CO2. AND CAUSE DIARRHEA, MOST COMMERCIAL
mulations to decrease foaming and reflux. PRODUCTS CONTAIN A COMBINATION OF THE TWO
cid; forms a foam that floats on the gastric contents and protects the mucosa INGREDIENTS TO MINIMIZE EFFECTS ON BOWEL
MOTILITY.
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Travelers Diarrhea: The most common cause of

travelers diarrhea is infection with noninvasive
enterotoxigenic (ETEC) or enteroaggregative (EAEC)
strains of E. coli. Less common pathogens include
Shigella, Salmonella, Campylobacter, Aeromonas,
viruses and parasites. Mild to moderate diarrhea is
151 usually treated with loperamide or bismuth subsalicylate
alone or in combination with antibiotics (trimethoprim,
Acute-onset infectious diarrhea is usually self-limited, and trimethoprim-sulfamethoxazole, or a fluoroquinolone).
specific chemotherapy is seldom warranted or effective unless When diarrhea is severe or associated with fever or
there is evidence of GI erosion or systemic disease. Therefore, bloody stools, self-treatment with a 3-day course of
the treatment of diarrhea is generally nonspecific and is ciprofloxacin, levofloxacin, norfloxacin, or ofloxacin is
usually aimed at reducing the discomfort and inconvenience usually recommended. Azithromycin is an alternative for
of frequent bowel movements. Occasionally, the replenishment travelers to areas with fluoroquinolone-resistant
of fluid and electrolytes may be necessary or even lifesaving. Campylobacter, such as Thailand.

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Chemotherapeutic agents are regarded as having low,

moderate, or high emetogenic potential. Nausea and vomiting
associated with cancer chemotherapy can be quite severe and
prolonged and can prevent effective treatment. Patients may
refuse to continue treatment because of nausea and vomiting.
162 Ondansetron, and other 5HT3 antagonists, are expensive,
but are the most effective agents available for preventing
nausea and vomiting from chemotherapy. Dexamethasone,
added to ondansetron, improves effectiveness. Prochlorperazine,
perphenazine, or thiethylperazine are added for breakthrough
nausea and vomiting. Antihistamines may decrease the
toxicity of the primary agent. Metoclopramide and lorazepam
(to reduce anxiety) are also used in combination regimens.
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captopurine (6-MP) are purine analog immunosuppressants commonly

ependent IBD. Azathioprine is converted to 6-MP after absorption; 6-MP is
nucleotide
182 synthesis and thus cell proliferation. Use of these drugs allows
oids. These drugs are usually well tolerated, but rarely pancreatitis occurs
ash, and hepatitis. Leukopenia which is dose-related and delayed can occur,
exate (MTX), an inhibitor of dihydrofolate reductase that results in impaired
-MP or azathioprine are ineffective or poorly tolerated. Cyclosporine is a
ses. It inhibits interleukin-2 production from T helper cells, decreases
cytokines, including IL-3, IL-4, interferon , and TNF. Cyclosporine can be
V glucocorticoids. Cyclosporine may save the patient from colectomy but has
Antibiotics: Metronidazole (Flagyl) and ciprofloxacin
have been shown to significantly decrease recurrence
after ileal resection in patients with active inflammatory,
fistulous, and perianal Crohns disease. However, in
patients with ulcerative colitis, metronidazole and
ciprofloxacin are only useful to treat infections
associated with pouchitis after colectomy and ileal
pouch-anal anastomosis.

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SE - The most frequently reported adverse reactions

were "flu-like" symptoms, particularly fever,
headache, chills, myalgia, and fatigue. More severe
toxicities are observed generally at higher doses and
199
may be difficult for patients to tolerate. In addition, the
following spontaneous adverse experiences have been
reported during the marketing surveillance of interferon
alfa-2b, recombinant for injection: nephrotic syndrome,
pancreatitis, psychosis, including hallucinations, renal
Interferon must be given as an IM, IV, or SQ injection. IFN failure, and renal insufficiency. Very rarely, interferon
proteins are connected to large inert polyethylene glycol (PEG) alfa-2b, recombinant used alone or in combination with
molecules (pegylation) to decrease the clearance. Plasma ribavirin capsules may be associated with aplastic
concentrations of pegylated IFNs are prolonged and the extended anemia. Very rarely sarcoidosis or exacerbation of
duration of action allows for once-weekly dosing. sarcoidosis has been reported.

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212 Extra-cardiac effects cont:
Central nervous system: HA, fatigue, malaise and drowsiness
(Occur early in digitalis intoxication)
Neuralgic pain (involving the lower third of the face, Tends to
occur early in therapy, and if it occurs, it often is severe)
Mental symptoms: Disorientation, confusion, delirium,
hallucinations (digitalis delirium), nightmares, depression
(elderly); Mechanism unclear
Vision: Blurred vision, White vision, White halos on dark
objects (classic Board question), Color vision, Chromotopsia (a
disturbance of vision which is sometimes caused by drugs and in
which colorless objects appear colored): yellow and green
common (classic Board question)
213
214
Treatment of glycoside toxicity: Depends on severity
(Standard or Fab fragments):
Standard: stop glycoside, monitor ECG; minimize
aggravating circumstances:
Electrolyte abnormalities the most common factor
precipitating glycoside toxicity if hypokalemia
Acid base disturbances: low PO2
Avoid catecholamines, avoid beta blockers in AV block
Treat ventricular arrhythmias
Treat bradyarrhythmias (atropine)
Avoid cardioversion: may cause arrhythmias
Extracellular K+ elevated (severe toxicity) - Elevated
K+ reduce the effects of cardiac glycosides. If glycoside
toxicity is occurring in the face of elevated K+, this can
only be happening because a massive dose of the
glycoside has been taken. The elevated K+ in the
plasma is occurring because of massive poisoning of the
ATPase. Requires use of Fab fragments: antibodies
to digoxin (antibodies also recognizes digitoxin) - Very
effective, Rapid effect
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215
Nitrate therapy in chronic stable angina
Short-acting: Relief during acute episodes, Prophylaxis of acute
episodes,
Long-acting: monotherapy for mild angina, adjunctive for more
severe angina
Limitations: side-effects & tolerance
NTG primarily works on venous side (dilation),
however, large enough dose will dilate arterials also.
Venodilator drugs reduce preload by redistributing blood
away from the chest into peripheral viens
Arteriodilators decrease afterload (eg Hydralazine)
Venodilators decrease preload (eg Organic nitrates)

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220

221

Action Potential
Electrolyte shifts create electrical activity
222 Four phase action potential demonstrates the various
stages of activity
Electrolytes associated with each phase differ in nodal
eliminated mainly by the liver and some by the kidney; elderly vs. non-nodal tissue
requires lower dose due to reduced clearance
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ent which
223 increase refractoriness of the bypass track and "break" the reentry
and digoxin (&CCB?) should be avoided in a wide complex preexcitation
elerate the ventricular rate and cause the rhythm to degenerate to Vfib (these
rease conduction down accessory pathway; also class IB agents shorten the
thus also can increase the ventricular response to an SVT). If a pt has
ally unstable, DC cardioversion should be first-line therapy

Disopyramide:
Moderately effective for atrial arrhythmia and poorly effective for
224 ventricular arrhythmia
Reduces automaticity and conduction velocity
Side effects include decreased contractility and urinary retention
has anticholinergic effects - stops peeing, pooping, salivating

225
Note: Infiltration of inflammation mediators and necrotic materials
lower tissue pH (eg abcess) and render lidocain anestheic less
effective (lidocaine is a weak base, does not work when
protonated)

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Class IC kills people; thus, they are not used as first line agents

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233
BB are beneficial in longterm tx of pts follwing MI if they have
evidence of recurrent ischemia or have sustained a Q-wave MI
(give BB, ACEI and ASA). Howevere, BB have no benefit in pts
with small or non-Q-wave MI (give ACEI and ASA)

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send signal (via extraglomerular mesanginum) to granular cells to secret

ent a.242
(know that in most areas of the body adenosin is a vasodialator,
ate constriction; if severe constriction then GFR decreases because blood
on exam always assume moderate efferent a. constriction)

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244
245

246 Heparin-induced thrombocytopenia (HIT) type II syndrome is

uncommon, but due to the formation of antibodies (IgG) directed
against the heparin-platelet factor 4 complexes. These
antigen-antibody complexes bind to Fc receptors on adjacent
platelets causing aggregation, platelet activation and
paradoxical thrombosis, causing venous/artial thrombosis,
"White Clot Syndrome". HIT with thrombosis can be treated with
direct thrombin inhibitors(ie lepirudin, agatroban, or danaproid).
Occurs 4-14 days following administration. Type I HIT occurs 1-2 Recommended treatment during acute MI is: aspirin
days followinng initiation, a non-immune type and less severe; therapy immediately (+O2, nitroglycerin, and morphine),
occurs in ~30% followed by thrombolytic therapy, followed by heparin IV.

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Drug-Drug interactions: Some drugs increase the effect of oral

249 anticoagulants by inhibiting anticoagulants hepatic metabolism,
cause displacement from plasma binding sites, interfer with Vit K ,
effect platelet function; decreased effect may be due to increased
hepatic metabolism, reduced absorption, increased synthesis of
clotting factors, hemoconcentration of clotting factors, or
bypassing the site of action. Warfarin is 99% bound to prt, so
with only 1% free, any drug that causes displacement can
increase its levels.
Drug-Drug interactions cont: Warfarin interacts with
most drugs used to tx UTI, inclucing TMP-SMX and all of
the fluoroquinolones (though ciprofloxacin is probably
the worst and moxifloxacin probably has the least
interaction)

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251

Pt presenting with unstable angina should be txed

withantithrombotic therapy (IV heparin or SQ LMWH) with
additional antiplatelet therapy using clopidogrel

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Thrombolytic drugs are reserved for emergency. Would not give

for DVT as might cause clots in body to break down and cause
bleed (this contradicts the indication for thrombolytic thereapy??)

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Absorption - Iron is available in a wide variety of foods,

but is especially abundant in meat protein. Also, iron
from meat protein is more readily and efficiently
absorbed since it is absorbed as intact hemin without
first being broken down to elemental iron. Nonheme
287 iron from other foods must be converted to the ferrous
ion before it can be absorbed. Absorption occurs
Iron Deficiencies: The most common cause of iron deficiency primarily by mucosal cells of the duodenum and
in adults is blood loss. Menstruating women lose approximately jejunum by a facilitated or active transport
30 mg of iron with each period. The most common site of mechanism. The normal diet contains approximately 14
unrecognized blood loss is in the GI tract (ulcers, GI cancer), mg/day; only 10% of this is absorbed, according to
and occult blood loss should always be evaluated as a possible need. Absorption is increased in iron deficiency,
cause of anemia. Iron deficiency is common in infants and hydrochloric acid (in the stomach), and vitamin C.
children during rapid growth periods. Iron deficiency also Absorption is decreased when stored and circulating iron
occurs following gastrectomy and in patients with severe small levels are elevated, and also in the presence of
bowel disease that results in generalized malabsorption. Iron chelating substances in the GI tract. Iron balance is
deficiency due to inadequate dietary iron intake is rare in adults. controlled by changes in absorption.

Two important reactions require vitamin B12 as a

cofactor: First, in the synthesis of fatty acids required
for the formation of cell membranes. This role is
especially important in the CNS tissue. Severe vitamin
288 B12 deficiency leads to neurological manifestations
(myelin degeneration in spinal cord, loss of vibratory
senses, abnormal sensations, etc.). It is important to
properly diagnose the cause of megaloblastic anemia
(B12 or folic acid deficiency), since replacement therapy
Storage and transport: Vitamin B12 is transported in the plasma with folic acid may initially reverse the anemia
bound to a glycoprotein, transcobalamin II. It is avidly stored, without improving the B12 deficit. If not properly
especially in the liver; about 5 years of B12 deficit are required to treated, the neurological damage may progress and
deplete the stored pool. Very little B12 is excreted. become irreversible.
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Pregnant women have increased folic acid requirements and

289 may become folic acid-deficient, especially if their diets are
marginal. Recent evidence implicates maternal folic acid
deficiency in the occurrence of neural tube defects, e.g., spina
bifida, anencephaly. Nutrition should be a prime consideration for Alcoholics have a tendency to become folate deficient
pregnant women and folic acid supplementation should be because of the rapid half life in the body (5mo) and their
considered if dietary intake is questionable. general malnutrition

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If severe hyperglycemia or contraindications for

sulfonylurea drugs are present, then insulin may be the
drug of choice with the ultimate goal being incremental
Patients most likely to respond to sulfonylureas are recently decreases in insulin requirements once euglycemic
diagnosed, older than 30 years old, are not overtly obese, have control is achieved.
303 residual -cell function, and have a fasting plasma glucose level Approximately 30% of all patients with Type 2 DM
of less than 300 mg/dL. receiving sulfonylureas fail to respond to therapy,
B. Type 2 patients with mild hyperglycemia should be encouraged most often owing to dietary noncompliance. Pts who
to restrict their caloric intake and to start an exercise program. show only a partial response to maximal doses of a
Diet alone can sometimes correct glucose intolerance. sulfonylurea agent may have metformin or exenatide
C. If diet and exercise fail or if more severe hyperglycemic added to the regimen or may be treated with insulin.
conditions are present, sulfonylurea drugs (especially the Replacing one sulfonylurea agent with another
second-generation drugs) are a good choice for initial sulfonylurea is unlikely to produce substantially
treatment. different results and is not recommended.

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ptake (may increase insulin responsive genes and increase GLUT-1 and

ecrease triglycerides, FFA, increase HDL, in increase large fluffy LDL. If pt continues to eat poorly, they will dramatically gain
l effect. weight if they are prescribed TZD!! Do not prescibe if pt
lin dose or facilitate discontinuation of insulin. clearly has no intention of improving diet (and excersize)

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Distribution and Degradation of Insulin

1. Insulin circulates as the free monomer; not protein
bound.
2. Degradation of insulin occurs primarily in the liver
Insulin is released in two phases in response to glucose and kidney. Uptake by muscle is also a significant
administration (or meal), both DM type I & II lack phase 1 (which source of insulin clearance.
shuts off glucagon release by the -cells). It also follow a pulsatile 3. The half-life of insulin in the plasma is about 5 to 8
pattern through out minutes.

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Thyroid hyperactivity or hyperthyroidism (thyrotoxicosis) is

characterized by the following typical findings: warm moist skin,
sweating, heat intolerance; exophthalmos (protruding eyeballs);
increased peripheral resistance, heart rate, cardiac output, and
331 arrhythmias; increased appetite and hypoproteinemia; rapid
mentation, irritability, restlessness, hyperkinesia; weakness and
muscle fatigue, increased deep tendon reflexes; increased renal
blood flow; menstrual irregularity, increased gonadal steroid
metabolism; increased basal metabolic rate. Some of these
manifestations resemble over activity of the sympathetic nervous
system and it is known that T4/T3 can induce increased
expression of beta adrenergic receptors and may enhance
signal amplification by these receptors.
Thyroid hypoactivity or hypothyroidism is
characterized by pale, cool, puffy skin; drooping eyelids;
large tongue; decreased peripheral vascular resistance,
decreased heart rate, and decreased cardiac output;
bradycardia; tendency towards hypercholesterolemia
and arteriosclerosis; decreased appetite; ascites;
lethargy and slow mental processing, sleepy; stiff
muscles, sluggish reflexes; decreased renal blood flow;
hypermenorrhea; decreased gonadal steroid
metabolism; decreased basal metabolic rate.

Causes of Hyperthyroidism:
* Graves' Disease (toxic diffuse goiter)
Hyperthyroid Symptoms: Heat Intolerance, Weight loss * Toxic uninodular goiter (Plummer's disease)
332 common; or weight gain due to increased appetite, increased * Toxic multinodular goiter
sweating, palpitations, Pedal edema, Diarrhea/frequent bowel * Nodular goiter with hyperthyroidism due to exogenous
movements, Amenorrhea/light menses, Tremor, Weakness, iodine (Jod-Basedow)
fatigue * Exogenous thyroid excess through self-administration
Physical Findings: Thinning of hair (fine), Proptosis, lid lag, lid (factitious hyperthyroidism)
retraction, conjunctivitis, stare, periorbital edema, loss of ocular * Tumors (thyroid adenoma, follicular carcinoma,
movements, Diffusely enlarged goiter, bruits, thrills, Wide pulse thyrotropin secreting tumor of the pituitary, and
pressure, Pretibial myxedema!!, Plummer's nails, Flushed, moist hydatiform mole with secretion of a thyroid stimulating
skin, Palmar erythema, increased Deep tendon reflexes substance)
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360 Nutritional Rickets: Treat with Vit D and diet having adequate Ca
and phosphate.
Chronic Renal Disease: Reduced synthesis of 1,25 and 24,25
(OH)2, retention of phosphate and secondary
hyperparathyroidism leading to renal osteodystrophy

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Use of -Agonists in Asthma:
a. 2-adrenergic agonists are the preferred therapy for
bronchoconstriction per se. These are the only agents shown
to be immediately effective for relieving bronchoconstriction during
acute, severe asthma. 2-selective agonists are more potent at
2 compared to 1-adrenergic receptors.
b. Inhalation of a selective 2-agonist usually produces excellent
bronchodilation or short term protection against a challenge
without appreciable cardiac or other systemic side effects,
especially in younger asthmatic patients. Exceeding the
recommended dosage will intensify side effects, but a greater
danger is the tendency of patients to continue self-medication
368 during periods when their symptoms are escalating. To avoid a
medical emergency, patients should be encouraged to seek
medical attention as soon as possible after they detect a
marked decline in the efficacy of their usual therapeutic
regimen. (inappropriate use can kill - paradoxical response of
increased bronchial obstruction and may induce status
asthmaticus)
c. Current emphasis is on the use of 2-selective agonists for
symptomatic relief of bronchoconstriction on an as needed basis
with inhaled corticosteroids as the main treatment for control of
inflammatory processes. 2-agonists are the treatment of choice
for severe, acute bronchospasm and are highly effective and safe
for intermittent, prophylactic treatment of exercise-induced
asthma.
369
370
371
Oral Therapy with -Adrenergic Agonists
a. Oral administration of -adrenergic agonists is not
widely used because of the greater risk of side effects,
especially tremulousness, muscle cramps, cardiac
tachyarrhythmias, and metabolic disturbances.
b. There are two situations where oral therapy is
"appropriate
1) In young children (<5 years old) who cannot
manipulate metered dose inhalers yet have occasional
wheezing with upper respiratory tract infections, brief
courses of oral albuterol or metaproterenol syrups are
well tolerated and effective.
2) In some patients with severe asthma
exacerbations, any aerosol, nebulizer or MDI, can be
irritating and cause a worsening of cough and
bronchospasm. Albuterol or terbutaline tablets can be
an effective oral therapy in these circumstances.
c. The frequency of adverse systemic side effects is
greater with oral therapy and greater in adults than in
children.
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Chronic Obstructive Pulmonary Disease (COPD): Patients with
active inflammation with bronchospasm and excessive mucus
production can obtain relief of symptoms with inhaled ipratropium
382 or a 2-adrenergic agonist. Ipratropium bromide + albuterol is
available as a combination (Combivent). As with asthma,
continuous use of bronchodilators is controversial, with some
studies suggesting worsening of symptoms with overuse of the
drugs. A subgroup of patients may respond to oral or inhaled
corticosteroids, but corticosteroid therapy has given mixed results
in the treatment of COPD.
383
384
Drug interactions: ciprofloxacin, digoxin, and warfarin - decrease
rate of theophylline clearance by intefering with P-450
metabolism. Dilantin and cigarette smoking can increase the
rate of metabolism. Pt who smoke (or did within 6mo) must have
higher loading and maintenance doses
385
386
Allergic Rhinitis Muscarinic Cholinergic Antagonist
Nasal Spray: Ipratropium bromide (generic or Atrovent)
o Given as a nasal spray, it is useful in patients with the
primary symptom of nasal discharge, especially if
triggered by exposure to irritants or cold air.
o Ipratropium does not relieve sneezing, itching or
nasal congestion.
o It may cause dry nose and mouth, pharyngeal
irritation, & urinary retention.
Mech according to Dr. Dubin handout - potentiates
exogenous catecholamines and stimulates endogenous
catecholeamine release and diaphragmatic muscular
relaxation, which, in turn, stimulates bronchodialtion
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387 Intranasal Corticosteroids reduce sneezing, itching,

General note: Many allergens are absorbed through skin,
respirator masks may do little to prevent reactions
discharge, and congestion and most are effective
when given once daily.
o These drugs take at least one week to be maximally
effective.
o Adverse effects are usually mild and include dryness
and irritation or burning of the nasal mucosa, ore throat,
epistaxis, and headache. Growth suppression in
children during one-year treatment has been
detected with beclomethasone (long-term
significance unknown), but not with mometasone or
fluticasone.

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Mechanisms: 1. Cromolyn sodium and the newer compound,

nedocromil, indirectly inhibit antigen-induced bronchospasm and
399 directly inhibit the release of histamine and other autocoids from
sensitized mast cells.
2. Cromolyn may suppress the activating effects of
chemoattractant peptides on eosinophils, neutrophils, and
monocytes.
3. Cromolyn does not directly relax smooth muscle but after long-
term therapy bronchial hyperreactivity to allergens, histamine, and
exercise is significantly diminished.
Cromolyn's effects on Allergic rhinits: applied
topically to the nasal mucosa is minimally absorbed into
the systemic circulation; Given before allergen exposure
it inhibits mast cell degranulation and mediator release,
and prevents early- and late-phase allergic
responses; It has only modest efficacy and is much less
effective than intranasal corticosteroids, but has
essentially no local or systemic toxicity.

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an H1-antihistamine, analgesics, cough suppressants, or expectorants in
(H1 antihistamine)
402
= Pseudoephedrine +Acetaminophen (analgesic) + Dextromethorphan
tihistamine)
Caplets = Pseudoephedrine + Guaifenesin (expectorant) +
seudoephedrine + acetaminophen + guaifenesin + dextromethorphan
Pseudoephedrine and Methamphetamine: Pseudoephedrine obtained OTC is the major ingredien
make methamphetamine (Meth, Ice; see No No's) in illegal labs (cars, motel rooms, basements, g
Meth is a major drug abuse problem. Efforts are underway at both the national and various state legis
to restrict the use and availability of pseudoephedrine. Several states (Oklahoma) restrict sales or no
pharmacies to place medications containing pseudoephedrine behind the counter. Most drug manufa
reformulating their OTC medications to replace pseudoephedrine with phenylephrine. Phenyleph
be easily converted to methamphetamine. Long-term changes in the laws and availability of drugs
determined.

403

404

Early, acute phase of bronchial asthma is trigger by

mter's 405
triad: The triad of asthma, aspirin sensitivity, and nasal polyps
ents experience symptoms during the third to fourth decade. A single dose
ompanied by rhinorrhea, conjunctival irritation, and flushing of the head and
nti-inflammatory drugs and is caused by an increase in eosinophils and
ndin mediated). Primary treatment is avoidance of these medications, but
reatment, allowing these patients to take daily aspirin for cardiac or rheumatic mediator, but far less potent, and antihistaminic agents
release of chemical mediators - leukotriens C4, D4,
and E4 promote intense bronchoconstriction and mucin
production. Montelukast is an agent that binds to
cysteinyl leukotriene (CysLT) receptors on mast cells
and eosinophils to block the lipoxygenase pathway of
arachidonic acid metabolism, which generates the
leukotrienes. Histamine is also an early acute phase
are not useful for treating asthma

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Directly Observed Therapy (DOT): Poor adherence to therapy

is the most importance cause of treatment failure and is
423 associated with emergence of drug resistance. Most experts
recommend a program which requires patients to take drugs
under direct observation (DOT). DOT has been shown to improve
cure rates compared to self-administration of drugs. DOT is Extrapulmonary TB: treat same as pulmonary dz, but
particularly important for patients with MDRTB or patients on recommended 12mo for meningitis in infants and
intermittent regimens. DOT services are available at most local children, miliary TB and bone or joint involvement in any
and state health departments age.

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2. Cardiovascular system: decrease in blood pressure (systolic

and diastolic) and increase in heart rate
458
A. Cardiac - increased force and rate of contraction; physiologic
significance minimal
B. Vasculature - capillary dilatation, particularly in peripheral
capillary beds; local edema; arteriodilation; venodilation;
venoconstriction of large vessels (species specific); histamine
headache; histamine shock
C. Triple response
1. localized red spot, local dilation, appears within seconds
2. "flush" or "flare" Axon reflex
3. wheal, local edema, within 1-2 min.
3. Non-vascular smooth muscle
A. GI tract: contraction causing diarrhea
B. Bronchioles - constriction, not striking in humans
(except asthmatics)
C. Effects on other smooth muscle (uterus, bladder, iris,
etc.) are negligible
4. Exocrine glands - gastric acid secretion
5. Nervous System
A. Peripheral - stimulates sensory nerve endings
causing pain, itching, flare of triple response
B. Central neurotransmitter

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ondary to hypergastrinemia, which causes hypertrophy of the gastric

471
al cells and increased maximal acid output. Gastrin by itself also stimulates
secretion. The large quantity of acid produced leads to gastrointestinal
malabsorption. Malabsorption in ZES usually is multifactorial, being caused
f pancreatic enzymes, and precipitation of bile salts. ZES is sporadic in 75%
d with MEN 1, an autosomal dominant condition characterized by
rs, and pituitary tumors.

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Beta Adrenergic continued:

positive inotropic and chronotropic effects on the heart
beta1
Alpha1 (& 2) Receptor Distribution and Effects of Stimulation relaxation of bronchioles beta2
477 Continued: relaxation of the uterus beta2
Constriction of blood vessels a1 (to lesser extent a2) relaxation of certain blood vessels (skeletal muscle
mydriasis a1 arterioles, coronaries, some mesenteric) beta2
contraction of the spleen a1 metabolic effects (glycogenolysis, beta2) (lipolysis,
contraction of the uterus a1 beta3)
inhibit release of insulin a2 stimulate release of insulin beta2
constrict sphincter of bladder a1 stimulate release of renin beta1
glycogenolysis, - liver a1 (relatively weak compared to b2) relaxation of detrusor (bladder) beta2
ejaculation,vas deferens a1 relaxation of intestinal smooth muscle beta2
relaxation of intestinal smooth muscle a2
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478

renin: Sympathetic stimulation (acting via -adrenoceptors),

renal artery hypotension, and decreased sodium delivery to the
distal tubules stimulate the release of renin by the kidney. Renin is
an enzyme that acts upon a circulating substrate,
angiotensinogen, that undergoes proteolytic cleavage to from the
decapeptide angiotensin I. Vascular endothelium, particularly in
the lungs, has an enzyme, angiotensin converting enzyme (ACE),
that cleaves off two amino acids to form the octapeptide,
angiotensin II (AII).

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503

Raynauds syndrome: This is a condition in which the smallest

arteries that bring blood to the fingers or toes constrict (go into
spasm) when exposed to cold or from an emotional upset.
Smoking cigarettes or working with vibrating machinery also can
cause these episodes. The small veins are usually open, so the
blood drains out of the capillaries. The result is that the fingers or
toes become pale, cold and numb. If there's a spasm in the small
veins and blood is trapped in the capillaries, the fingers or toes
turn blue as the blood loses its oxygen.
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504

Beta-blockers and CHF:

When CHF is under control (ACEI and diuretics), a beta-blocker
is useful in slowing the remodeling of the heart. Mechanism is
not entirely clear: two most likely candidates are 1. High
sympathetic tone in CHF causes beta-receptor down regulation.
Beta-blockers may counteract this effect by inducing receptor
spread & 2. Beta-blockade may directly prevent remodeling
caused by catecholamines.
Not all beta-blockers are efficacious for CHF, only 3 are
approved: Bisoprolol, Carvedilol, and sustained release The combination of either diltiazem or verapamil
metoprolol - these decrease mortality!! with a -blocker is not generally used in patients with
Notice carvidilol will worsen acute HF - inadequate CO with unstable angina because the effect of these calcium
high SNS/RAS already exist, do not want to further decrease SNS channel blockers on heart rate and myocardial
further decompensating contractility are additive to the effects of -blockers.

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552

Because of the stimulation at all of the sites at which acetylcholine

is used as a neurotransmitter, a variety of symptoms are seen on
organophosphate in nerve agent exposure. However, most
commonly these pts will exhibit a toxidrome of symptoms referred
to as dumbells. Because of the characteristics of the sites that
are stimulated by the persistent acetylcholine, the variety of other
553 symptoms may also be seen in nerve agent exposure. The All autonomic ganglia (nicotinic)
nicotinic sites that are stimulated may cause mydriasis or pupil All postganglionic parasympathetic neuroeffector
dilation, tachycardia, weakness, hypertension and fasciculations. junctions (muscarinic)
These symptoms may or may not be seen or may be seen with Postganglionic sympathetic cholinergic sites (sweat
rapid variation between nicotinic and muscarinic symptoms as glands) (muscarinic)
described earlier with the dumbells mnemonic period. For Adrenal medulla (nicotinic)
example, a patient may rapidly alternate between bradycardia and Skeletal neuromuscular junction (Nm)
tachycardia. Fasciculations are commonly seen with skin Central nervous system (M & N)
exposures to nerve agents.

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Endogenous peptid activity:

603 Mu receptor - endorphins > enkephalins > dynorphins
Kappa - dynorphins >> all others

Opioid receptors - G proteins coupled

Opioid Receptors and Endogenous Ligands - These 3 families
of peptides are in turn derived from precursor proteins:
Prepro-opiomelanocortin (POMC) - gives met-enkephalin, beta-
endorphin, ACTH, among others
Preproenkephalin - 6 copies of met-enkephalin, 1 copy of leu-
enkephalin
(Pre)Prodynorphin - dynorphin A, dynorphin B
presynaptically to Ca channels, blocking Ca release,
thereby decreasing NT release. Opioid effects spinal
actions (sensory), however, also have actions in brain
which modulate perception and emotional reception to
pain - most significant analgesia of opioid comes
from action in CNS (when opioid gets to brain, it is
most effective).

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608

Notice: there is point to point rate of abuse to

capacity of substance as an analgesiac (with the
Head injury are usually a contraindication with opioids exception of Nalbuphine and Butorphanol due to
(further decreasing respiratory rate) their negative kappa agonist SE)

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619

Partial agonist action decreases some of the craving for HEO Remember weak partial agonists work as antagonists
opioid when given with a full agonist

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Codeine has less potential for abuse (than morphine)

Clinical Uses: Cough Suppression
621 Preferred drugs are usually Dextromethorphan (Non-opioid
available OTC) - When used with opioids, this drug increases the
cough suppressant effects of the opioid
Codeine - Cough suppression obtained at doses lower than
needed for analgesia. DOC for opioids as cough suppressant.
even though converted to morphine in the liver for two
reasons: first is that it must be converted to morphine in
the liver which takes time (abuse of opioids relative to
rate of drug delivery to brain, faster delivery, greater
abuse potential), second high levels of codeine cause
psychotomimetic and dysphoria effects (non-kappa
related, sigma?) limiting abuse potential

622

623

624

625

Note: naloxone (and other mu blockers) due not prevent

euphorias associated with endogenous NT (eg beta-endorphin
626 with runners high); a dose of a mu blocker has no effect to
person's general feeling of pleasure: eating, sex, etc (dose would
have no effect greater than placebo) - so little evidence that an
opioid system is responsible for persons sense of pleasure Naloxone: near zero oral bioavailability

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656

When using a uricosuric agent in treatment of gout, it is important

to maintian neutral/basic urine pH (notice, in an acidic enviroment
657 the uric acid is noncharged and thus much less soluble/less likely
to be freely filtered; note that the joint, with lactic acid produced
inside from increased anaerobic metabolism/low vasculature, at low doses only inhibit secretion, so verify high enough
cause precipitation of gout due to low pH) dosing to gain reabsorption inhibition

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663
Analgesia: PGE2 sensitizes pain nerve endings to the action of
bradykinin, histamine, substance P and other mediators and thus
blockade of PGE2 synthesis prevents this hyperalgesia.
Antipyresis: Temperature control center in hypothalamus
regulates body temperature. Pyrogens (cytokines) from
lymphocytes lead to higher temperature set point, i.e., fever - heat
generation (metabolism) increases and heat loss (vasodilation)
decreases. NSAIDs (that can cross BBB effectively) suppress this
response but do not effect normal body temperature. Anti- Gastrointestinal Effects: PGI2 inhibits gastric acid
inflammatory: PGE2 and PGI2 (prostacyclin) cause vasodilatation secretion.
and are important mediators of localized erythema and edema in PGE2 and PGF2a stimulate synthesis of bicarbonate and
inflammation. NSAIDs inhibit their formation. Also, it has been mucus.
proposed that NSAIDs directly inhibit activation and function of PGE2 promotes mucosal blood flow.
neutophils, stabilize lysosomal membranes, and inhibit leukocyte NSAIDs inhibit all of these effects which leads to GI
phagocytosis. irritation.

664
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679
Therapeutic Uses and Diagnostic Applications of ACTH
All of the known therapeutic effects of ACTH also can be achieved
with appropriate doses of corticosteroids that are more convenient
to administer. Therefore, ACTH has very limited therapeutic use.
A synthetic analog (Cosyntropin) is available for diagnostic tests
of adrenal function. ACTH plasma concentrations can be
measured by an immunoradiometric assay. Metyrapone
stimulation test is used to test for ACTH deficiency. It works by
inhibiting cortisol synthesis, which should result in an increase in
ACTH levels by reduced negative feedback. It is used to evaluate
the HPA axis and not used for the diagnosis of Cushing syndrome
680
681
682
683
684
Receptor Mechanism:
Steroid hormone receptors are located in the cytoplasm
of cells (they are soluble, mobile proteins; not
membrane-associated). The receptors are associated in
a complex with a number of other proteins (heat shock
proteins; hsp); these proteins dissociate from the
receptor upon binding of the steroid. The activated
receptor moves to the nucleus of the cell where it binds
to specific sequences of DNA. termed glucocorticoid-
responsive elements (GREs). Receptor binding at the
GRE site can either activate or inhibit transcription of
specific genes. The hormone-receptor complex also
can regulate gene transcription by binding to other
nuclear transcription factors (regulatory proteins) or to
their promoter/regulator regions on the DNA.
Because the metabolic and antiinflammatory effects
are mediated by the same receptor, none of
glucocorticoid derivatives have selective anti-
inflammatory activity without also affecting
carbohydrate, protein, and fat metabolism.
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700

Leukopenia is a common problem after kidney transplantation,

with a wide differential diagnosis. Usually it is induced by drugs
(e.g. azathioprine, mycophenolate mofetil, ganciclovir, co-
trimoxazole) or infections (e.g. cytomegalovirus). Rare causes are
post-transplantation lymphoproliferative disease (PTLD) and
recurrence of pre-existing autoimmune disorders like systemic
lupus erythematosus (SLE) or Wegener's granulomatosis.
Allopurinol increases 6-mercaptopurine levels -
xanthine oxidase metabolizes 6-mercaptopurine,
allopurinol inhibits xanthine oxidase, thereby increasing
the levels of 6-mercaptopurine, can cause pancytopenia
(if must continue both drugs, decrease azathioprine to
1/3 dose)

701

OKT3 is powerful and is not suited to maintenance

immunosuppression; it used almost exclusively to treat patients in
the first few weeks after transplant, or to stop acute rejection
episodes.

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Adjuvant chemotherapy is effective

Breast carcinoma
713
Colorectal carcinoma (stage III)
Osteogenic sarcoma
Ovarian carcinoma (stage III)
Testicular carcinoma
Chemotherapy has minor activity
Brain tumors (astrocytoma) CCS Drugs
Cervical carcinoma S Phase specific
Colorectal carcinoma Cytosine arabinoside
Hepatocellular carcinoma Hydroxyurea
Kaposi's sarcoma S Phase specific, Self-limiting
Lung (non-small-cell) carcinoma 6-Mercaptopurine
Melanoma Methotrexate
Pancreatic carcinoma M Phase Specific
Prostate carcinoma Vincristine, vinblastine
Soft tissue sarcoma Paclitaxel

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715

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Cisplatin is toxic to both proximal and distal renal

718
Although alkylation of DNA can occur at any phase of the cell
cycle, cytotoxicity is greatest in cells that are progressing through
the cell cycle. These agents are best regarded as cell-cycle-
active but non-phase-specific.
tubule epithelial cells. Adequate intravenous hydration
with saline diuresis, accompanied by administration of
furosemide or mannitol, can decrease the incidence of
nephrotoxicity. Nausea and vomiting are at times severe.
Sensory neuropathy and high-frequency hearing loss
after several cycles of therapy are not uncommon.
Cisplatin produces modest myelosuppression.

719

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728
Principles defining drug selection:
1. Single agents should have known activity against the tumor
2. all agents in the regimen should have different mechanisms of
action
3. Agents should not have overlapping toxicities so that the
duration of acute and chronic toxicities are minimized.
4. All should be used in their optimal dose and schedule.
Anthracycline Antibiotics mech: planar multi-ring
structures that are active by insertion of the planar ring
between base pairs (G-C sequence) of DNA and
interferes with DNA function. Other minor activities are
TOPOII inhibition, and free radical formation.

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740

741 SE associated with 5-FU, Capecitabine: Palmar-plantar

erythrodysesthesia erythrodysesthesia syndrome: A condition caused
red, painful sensation to touch in palms of the hand and sole of by continuous infusion therapy and resulting in a tingling
the foot sensation of the palms and soles, progressing to severe
pain and tenderness with erythema and edema.

742

743

Methotrexate inhibits dihydrofolate reductase, preventing the

744 reduction of folic acid to produce tetrahydrofolate.
Tetrahydrofolate derivatives are used as a source of one-carbon
moieties in purine nucleotide synthesis and in the methylation of
dUMP to form dTMP. Thus, by inhibiting dihydrofloate reductase,
methotrexate also obstructs one-carbon metabolism, and deprives
DNA polymerase of essential substrates - thus it is an Notice: Trimethoprim (use for prokaryotes) and
antimetabolite that inhibits DNA synthesis in the S phase of the Pyrimethamine (used for protozoa) are the same
cycle mechanism

745
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746

747

748

749

750

751

752

753
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754

755

756

757

758

759
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760

761

762

763

764

765

766

767
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768
769

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771

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773

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775
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777
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779
780
781
782
783
784
785
786
787
788

789

790

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792
793
794
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795
796
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798
799
800
801
802
803
804
805
806
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810
811
812

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815
816
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818

819

820
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821

822

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824

825
826
827

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829

830
831
832
833
834
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835

836
837
838
839

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842

843

844

845

846

847

848
849
 K L
850

851

852

853

854

855

856
857

858

859

860
861

862

863

Recurrence HA: return of episodic headache during the

same attack following acute treatment, For headache
864 recurrence, repeating headache agent used initially is
almost always effective
Rebound HA: recurring headache induced by repetitive
Woman 3:1 migrane (may be associated with menses) and chronic overuse of acute headache medication
 K L

865

866

867

868
869

As opposed to the mechanism of action (1b&1d agonists), the

physiologic mechanisms are less clear. Two effects in particular
870 are attributed to these agents:
Triptans act at presynapatic trigeminal nerve endings to inhibit
the release of vasodilating peptides - substance P &
calcitonin gene-related peptide (CGRP). Triptans, by causing
vasoconstriction, may prevent vasodilation (vasodilation causes
stretching of pain endings). The vasodilation hypothesis of
migraine was very popular for many years, but more recent data
have questioned whether this is the critical mechanism.
GI 5-HT disrupted nausea/vomiting
Hormones modulate 5-HT receptors: menstrual and
pregnancy headaches
Decreased 5-HT receptors with aging
Raphe neurons cease firing during sleep (i.e. sleep often
resolves headache)
 K L

871

872

Neuroleptic malignant syndrome (NMS) is a rare, but life-

threatening, idiosyncratic reaction to a neuroleptic medication.
The syndrome is characterized by fever, muscular rigidity,
altered mental status, and autonomic dysfunction.
873 Although potent neuroleptics (eg, haloperidol, fluphenazine) are
more frequently associated with NMS, all antipsychotic agents,
typical or atypical, may precipitate the syndrome. For example,
these agents have been associated with NMS: prochlorperazine
(Compazine), promethazine (Phenergan), clozapine (Clozaril),
and risperidone (Risperdal). NMS has also been associated with
non-neuroleptic agents that block central dopamine pathways, eg,
metoclopramide (Reglan), amoxapine (Ascendin), & lithium.
Pathophysiology of NMS: All medications implicated in NMS have dopamine D2-receptor antagonis
NMS has also been noted following withdrawal of anti-Parkinson medication. The clinical syndrome is
be secondary to decreased dopamine activity in the central nervous system (CNS), either from blocka
dopamine D2-receptors or decreased availability of dopamine itself, and shares similarities with malig
hyperthermia and the serotonin syndrome. Blockade of dopamine neurotransmission in the nigro
hypothalamus results in muscular rigidity and altered thermoregulation, respectively. There is
sympathetic nervous system activation or dysfunction may play a significant role in the pathogenesis

874

875

876

877

878
 K L

879

880

881

882

883

884 (muscarinic) anticholinergics (useful in early stages) inhibitory

dopaminergic control of cholinergic interneurons in striatum is lost
in PD and blocking muscarinic receptors prevents the overactivity
of the cholinergic interneurons.

885

886
 K L

887 Seleginlin is neuroprotective the intermediate of dopamine

breaking down becomes an aldohyde (condensation reaction with
proteins speeds destruction of the neuron)

888

889

Two striatal pathways modulate the thalamic output via

890
D1 excites the direct pathway
D2 inhibits the indirect pathway
Remember that overall effect of combined D1 and D2 stimulation
by dopamine release has an excitatory effect on the thalamus,
which is driving the cortex and thus enabling the extrapyramidal
loop. Loss of DA neurons disables the loop.
the globus pallidus internal (GPi) in an opposing fashion:
The direct pathway drives the thalamus by inhibiting
GPi (GPi normally inhibits the thalamus)
The indirect pathway, via the globus pallidus externa
(GPe) and subthalamic nucleus (STN), inhibits the
thalamus by exciting GPi.
Notice: the direct pathway is a positive feedback loop (-1
x -1 = 1), and the indirect pathway is a negative
feedback loop (-1 x -1 x -1 = -1)

891

892

893
 K L

894

895

896

The effects of these drugs are primarily in the spinal cord; targets
897 are Ia fibers that excite the primary motorneuron Baclofen inhibits
release of excitatory transmitters from IA neurons themselves.
Excitation of GABA-B receptors causes hyperpolarization by
increased K+ conductance. Baclofen inhibits both monosynaptic
and polysynaptic spinal reflexes

898

899

900
 K L

901

902

903

904

905

906

907
908
909
910
911
912
913
914
 K L

915
Partial Seizures:
Simple Partial (single focus):
no abnormality of consciousness
motor, sensory, autonomic, psychic (??effected or
not??)
Seizure types: Complex Partial (multiple foci):
Partial seizuresBegin locally at some focus quality of consciousness impaired
Generalized seizuresInvolve both hemispheres; no local onset psychomotor
ContinuousNot transient or self-limited Partial seizures secondarily generalized (Spread)

916

917

918

919

with ethosuximide, but then one day have a grand mal (GTCS) that is actually
920
w it is atypical), and you would have to change the AED to valproic acid, the
could have treated the patient in the first place with valproic acid, even

cal presentation.
 K L

921

922

923

924

925

926
 K L
927

928

929

930

931

932

933

Interferon: 1a and1b
Reduce the attack rate in MS, whether measured clinically or by
MRI
934 For relapsing/remitting MS & secondarily progressive MS.
Both of these forms of MS are characterized by relapses
These drugs slow the accumulation of physical disability and
decrease the frequency of clinical exacerbations.
In patients with chronic progressive multiple sclerosis, safety and INF-beta (anti-inflammation) has opposite effect of INF-
efficacy have not been established. gamma (inflammation)
 K L

935 CNS Myelin Proteins:

Myelin basic protein (MBP) 30-40%
In humans, about 30% of myelin is protein, while about 70% is Proteolipid protein (PLP) 40-50% (Xxwhere does
lipid. Myelin protein zero come inxX??)
Typical membranes have an ~1:1 ratio of protein to lipid. Myelin-associated glycoprotein (MAG) <1%
Proteolipid protein (PLP) is ~50% of total myelin protein and found 2,3-cyclic nucleotide 3phospho-
in the IPL of compact myelin. diesterase (CNPase) ~2%

936

937

938

939

940
 K L

941

942

943

944

945

946

947
 K L
948
949

950

Effectiveness of Antidepressant Drugs:

Effective in ~60-70% of patients
951 Drug Induced Depression In a population, no single antidepressant drug is more
reserpine** effective than any other antidepressant drug -
propranolol ANTIDEPRESSANT DRUGS ARE ROUGHLY
methyldopa EQUIVALENT DRUGS
amphetamines Severe depression may respond better to TCAs than
oral contraceptives SSRIs
drugs of abuse Often finding the right drug for the pt must be done
empirically

952

953

954

955
 K L

956

957

958

959

960

961

962
 K L

963

964

Tricyclinics used to treat chronic pain disorders (NE blocking Tricyclics tx of Enuresis: reduce bed-wetting by
effect) reduction of delta sleep (note - this is not a long term
solution, only treats symptom)

965
966
967

Barbituates, alcohol, phenothiazines, and MAOI decrease the

968 amount of REM sleep while the pt is taking them. Withdrawal of
the agent then allows the body to compensate for "missed" REM
sleep, and REM rebound develops. Characterized by increase in
the number and intensity of dreams for several days after
discontinuation of the drug

969
970
971

972
 K L

973

Bipolar Affective Disorder:

Reason for shifts in affect are unknown and usually unrelated to
life events
974 DA, NE, ACh, GLU might be involved.
Strong familial components.
At least 3 putative linkages to different chromosomes
SUICIDE is leading cause of death if untreated.
Treated with lithium or other mood stabilizing drugs.
Start mood stabilizer before antidepressants:
TCA & Venlafaxine most likely to cause switch to mania
Escitalopram and paroxetine have a low probability of a
switch to mania

975

976

977
 K L

978

979

980

981

Evidence Against the Dopamine Hypothesis

Therapeutic effects on delusional thought requires time
(3-6 weeks for typical antipsychotics; somewhat shorter
time for atypical antipsychotics) before antipsychotics
are effective, whereas binding to DA receptors occurs
immediately.
Many schizophrenics get no help from antipsychotics.
982 Evidence in favor of the dopamine hypothesis: Implies a heterogeneity of illness.
Antipsychotics are high affinity, and often selective, antagonists The psychosis seen with amphetamine is invariably
for D2 receptors paranoid in type. Lacks the diversity of signs and
Administration of dopaminergic agonists and drugs that block the symptoms of schizophrenia.
dopamine up-take site (transporters), such as amphetamines, Several laboratories have studied the expression of D2
phencyclidine (PCP) or cocaine, can initiate psychotic episodes in receptors in normal and schizophrenic individuals. The
both psychotic and normal individuals. reports are conflicting as to whether there are
Data concerning amphetamines are particularly compelling. differences in the expression of D1 or D2 receptors in
Clinical studies have shown that high-dose amphetamines cause these populations.
a temporary psychosis in normal individuals. The psychosis can Emerging role for 5-HT2 receptors. Newer (and much
include auditory hallucinations, a symptom that is seldom found in better) antipsychotic drugs are only modest D-2
any disorder other than schizophrenia antagonists, but all of these newer agents also block 5-
HT2 receptors.

983
 K L

984

985

986

987
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988

989

990

991

992

993

994

995

996

997
 K L

GABAa Receptor Complex - A critical receptor complex for the
anxiolytic/sedative-hypnotic effects of
benzodiazepines
barbiturates
ethanol
998 GABAa Structure - 7 families
Receptors containing alpha, beta, gamma, and delta are most
frequent in CNS
15 total subunits
e.g., 6 alpha subunits (alpha1, alpha2, etc)
5 subunits come together to form the receptor complex,
approximately 2000 variants of GABAa receptor possible, several
subtypes exist in the mammalian CNS; Usual stoichiometry is
limited, composition of 2alpha,2beta,1gamma is most frequent.
Within a receptor, the alpha, beta, gamma subunit families are Note - the modulators have no effect on neuron without
identical (e.g., both alpha might be alpha1, or both might be
alpha3, etc)
GABAa Structure
Alpha unit binds GABA
Alpha/beta junction seems to be BZD binding site
gamma unit must be present for BZDs to modulate
GABA
Channel opens to Cl- ions when GABA binds
Increased Cl- conductance inhibits neural firing
Decreased Cl- conductance excites neurons (seizures)
Binding Sites on the GABA Receptor
True Receptor Site - GABA
Sites that Modulate GABA binding:
BZDs
barbiturates (and alcohol)
neurosteroids
picrotoxin (a convulsant you are not responsible for
this agent)
the presence of GABA, they do not have a true receptor
site, only modulate GABA's effect

999

1000

1001

1002
 K L
1003

1004

1005

1006

1007

1008

1009

1010

Primates have been shown to distain marijuana and LSD, but love
everything else.
 K L

Sedative hypnotics are just as likely to potentiate the lethal

1011 effects of alcohol (even though they are not anxiolytics or muscle No dependence develops with sedative hypnotics.
relaxants) drinking in combination with sedative hypnotics is a Note - dependence is manifest as a withdrawal
bad idea syndrome on termination or use of an antagonist

1012

1013

1014

1015

1016
1017
1018

1019

1020

1021
 K L
1022

1023 Mech is still not quit known seems to interfer with active
uptake (at presynaptic neuron membrane as well as at the
transporter into the vessicle) amphetamine interfers with both
processes some claim it actually reverses these transporters Amphetamine enhance both DA (abuse) and NE (so
increases concentration in both cytoplasm (and extracellular increase BP (peripheral) and activate sleep wakefulness
space?) (note: coke only blocks the uptake mech of DA or NE, not in RAS (central))
the vessicular transport).

1024

1025
Note: all drugs of abuse increase DA somehow (either block DA
reuptake or release it) - no DA release with Atomoxetine
1026

1027

1028

1029

1030
 K L

Amphetamine-related anorexiants - Overdose:

Arrhythmia, confusion, diarrhea, fever; however, as
1031 compared to cocaine, which is a CNS stimulant with
similar abuse potential, the likelihood of these type of
toxicities is less
Assaultive behavior, hallucinations; from the lowest
doses, amphetamine shift thought processes towards
Amphetamine-related anorexiants - Therapeutic effects: paranoid thinking. This typically only becomes a
Decrease in appetite problem with higher doses used in abuse, where a frank
Less interest in food paranoid psychosis is possible
Less pleasure from eating Circulatory collapse and coma precede death
Increased satiety with eating No specific antidote; management specific to
Decrease in total energy intake symptoms (e.g., lorazepam, antipsychotic)

1032

1033

1034

1035

1036

1037

1038
 K L
1039
1040
1041
1042
Ethanol Metabolism: first step - secondary route
MEOS = Microsomal Ethanol Oxidizing System
Occurs in microsomes of the smooth endoplasmic reticulum
Important role in EtOH metabolism when: [EtOH] is high
(high km for EtOH) or NAD levels are inadequate
Nicotinamide adenine dinucleotide 3 phosphate (NADPH) is
used as a cofactor
MEOS may be involved in the interaction of EtOH with other
drugs which are metabolized by MEOS
MEOS activity increases with chronic EtOH
1043
1044
Acetaldehyde Metabolism: second step (for both
primary and secondary routes)
via aldehyde dehydrogenase in cytosol and
mitochondria to acetate
also uses NAD as a cofactor
responsible for most of the metabolism of
acetaldehyde (~90%)
acetate converted to acetyl CoA which enters the citric
acid cycle
in alcoholics, excess acetate is converted to
acetoacetate resulting in ketosis
 K L

1045

1046

1047

Cocaine: Withdrawal syndrome

Cocaine: Acute effects - Euphoria (typically, supply used until Dysphoria, depression
gone), Intense arousal, sense of psychic and physical well-being, Sleepiness, fatigue
1048 self confidence, improved vigilance and alertness, Increased HR Cocaine craving
and BP, Cardiovascular effects are much more pronounced Bradycardia
than with amphetamines, Decreased appetite, Delays Cocaine: Toxicity
ejaculation Fatality most likely with i.v. or smoking; possible with
any route
Cocaine: Chronic effects - Dysphoria, Stereotyped behavior, Arrhythmias; seizures, coma, cardiovascular collapse
Anxiety, Sexual dysfunction (impotence, particularly with habitual Euphoric effect relatively short-lived (much shorter than
and/or high dose use), Paranoia, Hyperreflexia, Convulsions; half-life in plasma). Thus, when user attempts to
coma; cardiovascular collapse, Hallucinations maintain euphoric effect over several hours (by repeated
Visual objects whizzing in the periphery of the visual field drug taking), cocaine is likely to accumulate in plasma to
Auditory voices telling user what to do toxic levels.
Tactile sensation of bus crawling under the skin)
 K L

Amphetamine-type drugs:
d-amphetamine (Dexedrine)
methamphetamine (Desoxyn) - favorite of the biker set, and a
drug of abuse that waxes and wanes in popularity among other
folks. Its long duration of action makes profound sleep disruption
1049 more likely than with cocaine, which is a negative for those trying
to maintain work habits. Methamphetamine has become an
epidemic in rural America. Ice is methamphetamine that is
smoked
Methylphenidate (Ritalin) - extremely limited in abuse potential
compared to amphetamines
Phenmetrazine (Preludin) - not readily available
1050
Psychostimulants: Uses
Commercial availability of amphetamines carefully controlled since 1972
Weight control (Not amphetamine or methamphetamine) - derivatives of amphetamine that are sch
IV agents that are used for weight control; they have very little abuse potential compared to d-amphe
methamphetamine.
Anti-fatigue - e.g., military uses amphetamine for this purpose. Penalty is a rebound effect = need t
crash
Enhance Athletic performance - actually, they improve tasks where boredom is a factor, but are no
other tasks.

1051
e within a pressure sensitive resin, to minimize the risk of accidental
essary for activation. Mildly unpleasant tasting (to reduce risk of accidental Nicotine use amoung Mental Illness:
cosa. Take every 1-2 hours. Dont chew constantly. Soften it up and then 50% of all psychiatric patients
plus this leads to upset stomach, nausea, etc. Large first-pass metabolism if 70% of patients with Bipolar Disorder
90% of patients with Schizophrenia
(weak base) (reduces outside sensory stimuli and increase
sufficiently high dose of nicotine. 24-h and 16-h systems. Each comes with concentration)
icotine)

1052
 K L

1053

Serum glutamic-ocaloacetic transaminase level and

creatinine phosphokinase (reflecting muscle damage) found in
plasma greater than 7 days

1054

1055

Marijuana: Chronic effects

Bronchial/pulmonary - irritation, impaired function,
Marijuana: Acute Effects presumably an increased risk of cancer
Increased pulse rate Aggravation of angina pectoris
1056 Decreased exercise tolerance Orthostatic hypotension
Reddening of conjunctiva Decreased testosterone (males)
Euphoria, relaxation Diminished intellectual performance
Impaired memory and motor coordination Amotivational syndrome
Distorted time sense, hunger, dizziness Other reported effects contradictory (??)
1057
1058

1059
 K L

1060

1061

1062
 M N
1

9 Conclusion: Retrograde ejaculation is a consequence of the alpha1

vascular effects of alpha blockers likely mediated by a1B blockers. Seminal fluid is mixed with prostate fluid, and the
receptor rhythmic sympathetic discharge in the process is the
Prostate/bladder-sphincter alpha-receptors are a1A primary driver to expel the fluid. Alpha blockade interferes
subtype with that process.
 M N

Drugs Aggravating BPH:

Adrenergic agonists - Psuedoephedrine (any direct or
indirect alpha agonist)
10 Antimuscarinics - Atropine/scopolamine
Antihistaminics - H1 antagonists, particularly first-
generation drugs (have antimuscarinic effects)
Pt with BPH with cold, recommend local nose spray
(local effect) or just juice and soup

11

12

13

14

15

16

17

18
 M N

19

20

21

Estradiol can be converted in liver to estrone and estriol

(less potent at the ER)
22 Other mechanisms of Gonadal Hormone: Estradiol can also be converted to catechol estrogens that
1. Receptor mediated and genomic (classic) may have neurotransmitter efficacy
2. Receptor mediated and non-genomic Estrogen and its metabolites are excreted in the bile,
3. Receptor mediated, at the plasma membrane (new and can be reabsorbed from the intestine
discovery, potentailly rapid acting) (enterohepatic cycling). Can serve as the basis of drug
4. Non-receptor mediated - membrane fluidity effects (eg interactions - eg broad spectrum antibiotics alter intestinal
estrogen has antioxidant effects, as a membrane flora such that reduced hormone may be reabsorbed,
bound molecule is a potent free radical scavenger) lowering efficacy of oral contraceptives!

23
24
 M N

25
Post-partum depression
Therory: ratio of E:P, P gets converted to
allopregnenolone by 5alpah-reductase, alloP is the
most potent positive allosteric modulator of the GABAa
receptor (sedation/anxiolysis). Enhances GABAa
currents, increasing sedation/depression
Progestins SE cont
Progestins can increase blood pressure in certain
individuals, especially obese (Not a problem unless pt is
obese)
The more androgenic progestins may reduce HDL levels
May increase CV risk
Remember that testosteone (an androgen) decreases HDLs

26

27

Progesterone as birth control:

The progestagenic component of OCs interferes with
28 endometrial structure and consistency of the cervical
mucous
1 alteration in cervical mucous reduces sperm motility
2 alteration in endometrial structure makes the uterus
unreceptive for implantation
The endometrial tissue is now hostile to sperm and Depo-Provera (medroxy progesterone acetate)
implantation 150 mg IM q 11-13 weeks

29

30

31
 M N

32

33

34

35

36

37

38

39

40

41

42
43
 M N

44

45

46

47

48
49

50

51

52
53

54

55
 M N

56

Resistance occurs to loop agents; if so, add metolazone

All diuretics (except ethacrynic acid) contain sulfur (thiazide-like diuretic, but it also has a slight efficacy at
moiety, can cause photosensitibyity, and should be proximal Na re-uptake site. This accounts for the greater
avoided in pts with HS ot sulfa drugs (all diuretics or just efficacy of metolazone vs other thiazides)
loops?, thiazides do, others?)

57

58
59

60
 M N

61

62

63
64

65

66
 M N

67

68

69

70

71

72

Notice: ARBs do not effect (slow) cardiac remodeling

73
 M N

74
If a blockage in an artery to the kidney is suspected, the
captopril test may be done. The captopril test involves
taking a dose of the medication captopril following a
plasma renin activity (PRA) test and baseline blood
pressure measurement. Then follow-up blood pressure
measurements and a PRA test done 60 minutes later
screen for high blood pressure. Deterioration of renal
function in a pt suggests bilateral renal a. stenosis or
stenosis in a single functioning kidney. The increase Note: ACEIs and ARBs selectively dilate the efferent
after captopril of PRA is higher in unilateral significant arterioles, dihydropyridine CCB selectively dilate the
lesions. More commonly MRA imaging is used today. afferent arterioles.

75

76

77
Most dihydropyridine calcium channel blockers (arterial Note: ACEIs and ARBs selectively dilate the efferent
dilation) induce a reflex increase in heart rate in the arterioles, dihydropyridine CCB selectively dilate the
absence of -blockade afferent arterioles.
 M N

Combination therapy of Ca channel blocker and

blocker - More effective in combination than either drug
given individually for angina of effort.
Its reasonable to assume that agents decreasing the
78 afterload and/or preload should be uniformly effective in
angina. They are not. Drugs with these actions but
with no beneficial effects in angina include:
Alpha blockers
ACEIs
ARBs
Hydralazine (worsens angina via coronary steal) Prinzmetal angina should be txed with CCB and nitrates

79

80

81

82
 M N

83

84

85

86

87
 M N
88
89
90
91
92

93

94

95

96
 M N

General note: Hospital-acquired infections (termed

as complicated UTI) and those associated with urinary
tract pathological abnormalities:
Most prevalent etiologic organisms E. coli
UTI due to Staphylococcus aureus are result of
hematogenous spread
Other agents : P. aeruginosa, indole-positive proteus,
97
Enterobacter, Serratia, and Acinetobacter (encountered
more often in hospital-acquired than with community-
acquired infection)
Other causes of complicated UTI: nursing home
acquired; host factors including residual urine in
bladder, GU strictures, foreign bodies (catheters, calculi, Pathogenesis of UTI: begins with heavy and persistent
tumors), Atrophic vagina (postmenopause), vesicourteral colonization of the vaginal vestibule with intestinal bacteria
reflux; Worse prognosis of UTI involving the kidneys in women with recurrent UTIs
include Childhood pyelonephritis, diabetic nephropathy, Colonization of urethra occurs, leads to infection of the
malignant HTN, chronic pyelonephritis bladder

98

99

100
101

102
 M N

103

104
105

106

107

108

109

110

111
 M N

112

113

114

115

116

117

118

119

120

121
 M N

122

123

124

125

126

127

128
 M N
129

130

131

132
Drugs that inhibit P450:
Cimetidine
isoniazid
fluoxetine
erthromycin
ketoconazole
ritonavir
grapefruit juice

133

134

135

136
 M N

137

138

139

140

141

142
 M N

143

144

145

146

147

148

149
 M N

150

151
Drug-induced diarrhea: A number of drugs can cause
diarrhea: reserpine, guanethidine, sulfonamides,
tetracyclines, most broad-spectrum antibiotics,
cholinergic agonists, osmotic and stimulant laxatives,
prokinetic agents (metoclopramide, domperidone),
prostaglandins, quinidine. Adjustment of dosage or
change in medication is preferred to co-
administration of an anti-diarrheal drug.

152

153

154

155
 M N

156

157

158
 M N

159

160

161

162

163
164
165
 M N

166

167

168

169

170

171

172

173

174

175

176

177
 M N

178

179

180
181

182

Notice: steroid the DOC for acute flare ups of IBS -

predinose for CD, Hydrocortisone suppositories for
UC

183

184
 M N

185

186

187
188
189
190
191
192
193
194

195
196
197

198
 M N

IFN-a and lamivudine are quite comparable in efficacy

as first-line therapy for chronic hepatitis B. Interferon
requires only brief-duration therapy, too limited in
199
duration to support viral variants, but requires
subcutaneous injections and is associated with a
high level of intolerability. Lamivudine requires long-
term therapy in most patients and, when used alone,
fosters the emergence of viral variants. On the other
hand, lamivudine is taken orally, is very well tolerated,
leads to symptom improvement and is effective even in
patients who fail to respond to interferon. Although some
prefer to begin with interferon, most physicians and
patients prefer lamivudine as first-line therapy.
What recommendations should you give to persons
traveling to areas endemic for hepatitis?
For hepatitis A: strict sanitation (handwashing, avoiding
local water, peeling fruit); avoiding known vectors (e.g.,
oysters). Immunoglobulin (there is no "hyperimmune"
globulin), and vaccination are indicated when prolonged
stays are planned.
For hepatitis B: vaccination and avoidance of high-risk
activities (any activity that provides exposure to blood or
body fluids). Endemic areas include Southeast Asia.
For hepatitis C: no current recommendations.

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206

207

208

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212
EKG effects of glycosides:
S-T segment depression
Inversion of T wave
Preceding two effects normally first to appear
Prolongs P-R interval
Decease conduction velocity at AV node
Up to 0.25 sec, followed by block as dose increases
Shortens Q-T interval
Due to accelerated ventricular repolarization ADDITIONAL USES OF DIGOXIN
Because of digoxins many effects, many types of Atrial arrhythmias: 1. Fibrillation, flutter (Blocks the AV node,
dysrhythmia are possible Increases contractility of ventricle) 2. Paroxysmal
tachycardia (Make sure it is not caused by digoxin)

213

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215
NTG: reduces preload and afterload and myocardial oxygen consumption. Also, it directly dilates coronary stenoses
and increases oxygen delivery to the ischemic region.
Nitroglycerin increases collateral flow and favorably redistributes regional coronary flow.
In contrast to other vasodilators, it does not induce a coronary steal
Nitroglycerin inhibits platelet aggregation and, in experimental models, reduces platelet thrombus deposition.
The most common adverse effects are headache, nausea, dizziness, hypotension, and reflex tachycardia.

216

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221

All phases common to nodal and non-nodal
Phase 0: Rapid depolarization
222 Phase 1: Depolarization overshoot
Phase 2: Plateau
Phase 3: Repolarization
Phase 4: Instrinsic depolarization
Electrolyte shift in Atrial or Ventricular tissue (non-nodal)
Phase 0: Sodium
Phase 1: Sodium channel closes
Phase 2: Calcium channel open
Phase 3: Potassium rectifier
Phase 4: Sodium leak
 M N

223

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242

243

244
245

Treatment of Heparin Overdose:

1. Immediate withdrawal of heparin if bleeding
246 complications occur.
2. Protamine sulfate: is a strongly basic protein
administered IV that binds and inactivates heparin
because of its strong positive charge. Protamine may
cause transient hypotension if given too rapidly. This
drug must be used cautiously to avoid thrombotic
complications. Occasionally, anaphylactic reactions Heparin is isolated from porcine intestinal mucosa or bovine
occur. Note protamine not used for HIT II (Ab are to lung and is composed of a heterogeneous mixture of
platelet directly (so what?)), use direct thrombin inhibitor complex linear polysaccharide (glycosaminoglycan) chains,
instead (eg lepirudin) the heterogeneous mixture is called regular or
3. Infusion of fresh-frozen plasma unfractionated heparin (UFH).

247

248
 M N

249 Distribution:
rapid and complete absorption
Onset: considerably delayed (36 - 72 hours), delay in highly fat-soluble
onset is due to long t1/2 of warfarin and the fact that pre- 99% bound to plasma albumin
existing clotting factors are slowly cleared from the blood Termination: delayed (2 -5 days)
(t1/2 for VII = 6 hours) liver and kidney metabolism
Duration: prolonged, proportional to the elimination long elimination t1/2
t1/2 (25-60 hours) new, active clotting factor must be synthesized

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277
278

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286
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287
Storage forms: Hemoglobin represents the largest
pool of iron in the body. Iron is also stored in the
intestinal mucosal cells, plasma, and macrophages of
the liver, spleen, and bone marrow in the form of ferritin.
Ferritin is the most readily available stored form of iron.
It consists of a water soluble complex of ferric hydroxide
crystals covered with a shell of the protein apoferritin.
Hemosiderin is the name given to the (insoluble) ferric
core crystals without apoferritin; iron is stored in this
form in macrophages.
288 Second reaction requiring vitamin B12 as a cofactor:
Vitamin B12 is also required in a key reaction of folate
metabolism required for DNA synthesis (conversion
of 5-methyl tetrahydrofolate and homocysteine to
tetrahydro-folate and methionine). This is the
biochemical reaction in which vitamin B12 and folic acid
metabolism are linked and explains why the anemia of
B12 deficiency (but not the neurological abnormalities)
can be partially corrected by folic acid.
Circulating iron-bound transferrin (TF) is bound to
specific receptors on the surface of red blood cell
precursors in the marrow. Most of this iron is incorporated
into hemoglobin; the remainder is stored as ferritin.
Following maturation of the erythroid precursor cell, the
nucleus is shed and the red blood cell emerges from the
marrow into the plasma where it circulates for approximately
120 days. The senescent red blood cell is taken up by the
monomuclear phagocyte system and is destroyed. The
heme iron is initially incorporated into ferritin. This storage
iron is available for transport to the marrow via transferrin.
Malabsorption of B12, the most common cause of the
vitamin deficiency, is a lifelong disease. Other causes
dietary (vegetarian), gastrectomy, fish tapeworms,
bacterial overgrowth of the small bowel, blind loop
syndrome are reversible if the underlying cause is
corrected.
 M N

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300
301
302
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Adverse Reactions: Hypoglycemic reactions,

303 including coma. This adverse reaction is seen most
often in elderly patients with impaired hepatic or renal
function who are taking long-acting sulfonylureas. The
longer the drugs half life the more likely the agent will
induce hypoglycemia (compare chlorpropamide to 2nd
generation drugs). Severe hypoglycemia in the elderly
can present as an acute neurologic emergency that may
mimic a cerebrovascular accident. Treatment is
administration of glucose or glucagon.
Other adverse reactions are infrequently observed including
nausea, vomiting, cholestatic jaundice, hyponatremia,
agranulocytosis, aplastic anemia, generalized
hypersensitivity reactions. About 10-15% of patients
receiving these drugs, particularly chlorpropamide,
develop an alcohol-induced flush, similar to that caused
by disulfiram.

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308

309

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313
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314

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319
 M N

Cellular Actions of Insulin

1. Insulin is the primary hormone controlling the uptake,
utilization, and storage of cellular nutrients, including
glucose, amino acids, and fatty acids. Target tissues for
glucose homeostasis are liver, muscle, and fat. Insulin
exerts potent regulatory effects on all other cell types, as
well.
320
2. Insulin inhibits catabolic processes (and activates
anabolic processes), such as the breakdown of
glycogen, fat and protein.
3. Insulin stimulates the transport of substrates and ions
into cells and promotes the translocation of proteins
between cellular compartments.
4. Insulin alters the transcription of specific genes and
can promote the growth, proliferation, and
differentiation of certain cell types. Probably over 100
genes are regulated by insulin.
The insulin receptor is a member of the superfamily of
tyrosine kinase receptors.
Insulin stimulates glucose transport by promoting the
energy-dependent translocation of intracellular vesicles that
contain GLUT4 (found fat, skeletal muscle, and heart, and
mediates insulin-stimulated gluscose uptake) to the plasma
membrane. This effect is reversible, the transporters return
to the intracellular pool when insulin is removed.
Insulin can regulate the synthesis of GLUT1 and GLUT4
that may be important when there is long-term insulin
resistance, as in DM Type 2 . GLUT2 mediates glucose
uptake into pancreatic cells; defects in GLUT2-mediated
transport may contribute to diminished insulin secretion in
DM Type 2.

321

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327

328
329
330

Iodide Uptake: Iodide is an essential component of the
T3 and T4 molecule. Iodide (I-) is present in the normal
diet (recommended daily adult intake = 150 microg), is
331 rapidly absorbed, and concentrated from the blood by
the thyroid gland by an active uptake mechanism. The
thyroid can concentrate iodide 20 to 50, or even a 100
times over the plasma concentration. TSH (thyrotropin)
stimulates iodide uptake. Cardiac glycosides
(ouabain) can inhibit uptake. Uptake is also controlled
by autoregulatory mechanisms; if stores of iodide
decrease, uptake is stimulated; excess iodide
decreases uptake.
Synthesis: The enzyme peroxidase oxidizes iodide to
oxidized iodine (Io) which rapidly bonds with tyrosine
residues on the large protein thyroglobulin forming
monoiodotyrosine (MIT) and diiodotyrosine (DIT). Two
molecules of DIT combine on the thyroglobulin molecule to
form one molecule of thyroxine (T4). One MIT and one
DIT combine to form T3. This process of synthesizing
iodinated amino acid residues on the protein is sometimes
referred to as "iodide organification and coupling". The
antithyroid thioureylene drugs (propylthiouracil and
methimazole) inhibit peroxidase and thus block synthesis
of T3 and T4.

Propylthiouracil (PTU, Propyl thiocil) & Methimazole

(Tapazole) Mechanism of Action: Inhibits the
peroxidase enzyme and thus interferes with the
incorporation of iodine into tyrosyl residues of
thyroglobulin and with coupling of iodotyrosyl residues
332 (MIT, DIT) to form T3 and T4, i.e., inhibits organification.
These drugs do not inhibit or interfere with the release of
thyroid hormone previously formed and stored in the
gland. Inhibition over time results in depletion of stores
of iodinated thyroglobulin as the protein is hydrolyzed
and hormones are released into the circulation. Clinical
effects only become noticeable after the stored hormone
is depleted and the circulating hormone levels decline (2 Propylthiouracil, but not methimazole, also inhibits
days to 2 weeks). peripheral conversion of T4, to T3.
 M N

333

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343

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348

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354
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357

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359

360

361

362
363

364
 M N
365

366

367

Adverse Effects of -Adrenergic Agonists

a. Inhalation greatly decreases adverse effects
compared to oral or parenteral.
b. Patients with underlying cardiovascular disease
are particularly at risk.
c. Skeletal muscle tremor is the most common adverse
effect.
d. CNS stimulation: restlessness, apprehension,
anxiety, tremors
e. CVS stimulation: tachycardia, especially to
systemic administration (due to 1 stimulation and/or
368 reflex stimulation following 2 vasodilation),
dysrrhythmias possible (especially if also on MAO
inhibitor or tricyclic antidepressant), hyper or
hypotension. Allergen-specific IgE binds to Fc receptors on mast cell -
f. Parenteral administration can cause hypokalemia when allergen comes in contact with IgE, the mast cell is
especially when used in conjunction with non-potassium activated and releases a large number of mediators. The
sparing diuretic or systemic corticosteroid. (used in ED enormous variety of mediators released each have more
for hyperkalemia) than one potent effect on airway inflammation. Thus, a
g. In some diabetic patients, hyperglycemia may be pharmacological blocker of any one mediator, e.g.
worsened and higher doses of insulin may be required. antihistamine, is ineffective in alleviating the symptoms or
Less likely with inhaled compared to oral drug. (used in progression of asthma or the inflammatory component of
ED for hypoglycemia) other respiratory diseases. Corticosteroids, which can
h. Drug interactions potentiation of cardiotoxicity of block many of the key steps in the inflammatory
thyroid, digitalis and methylxanthines process, come closest to this ideal therapy.

369
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372

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374

375

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378
379

380

381
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382

383

384

385

386
 M N

387

All inhaled glucocorticoids are effective give twice a day

(better compliance than 4 times daily; budesonide can
be given once a day for mild asthma)

388

389

390

391

392

393
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394

395
396

397

398

399

400

401
 M N

Pseudoephedrine obtained OTC is the major ingredient used to

o No's) in illegal labs (cars, motel rooms, basements, garages, etc.).
e underway at both the national and various state legislative levels
402Several states (Oklahoma) restrict sales or now require
hedrine.
seudoephedrine behind the counter. Most drug manufacturers are
e pseudoephedrine with phenylephrine. Phenylephrine cannot
Long-term changes in the laws and availability of drugs is yet to be

403

404

Allergic rhinits: Montelukast (Singulair [$87.95]):

Cysteinyl leukotrienes are released in the nasal
mucosa during allergic inflammation and produce nasal
congestion; Montelukast is a reversible D4 leukotriene
405 receptor antagonist, given PO, that has modest
beneficial effect in relieving sneezing, itching, and
discharge, in addition to congestion; Clinical trials show
Montelukasts efficacy to be similar to H1 blocker
loratadine in relieving symptoms of allergic rhinitis; it is
not as effective as nasal corticosteroids; Montelukast
appears to be safe.

406

407

408

409
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410

411

412

413

414

415

416
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417
418

419

420

421

422

423

Multidrug-resistant tuberculosis (MDRT, defined as

resistance to at least isoniazid and rifampin) is curable
even in low-income countries, but the necessary therapy BCG - vaccine given round world which midigates effects of
is complex and should be administered in collaboraton TB. Causes PPD skin tests to be positive (~induration).
with a clinician who has expertise in treating such cases. Treat pt by typical standards (ignore the BCG history)

424

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426

427

428

429

430
431
432

433

434

435

436

437

438
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439

440

441
442

443
444

445

446

447

448

449

450

451
 M N
452
453

454

455

456

457

H1 receptor antagonists - classically referred to as

Histamine Release
A. Immunologic release
B. Drug/chemical induced release - morphine,
tubocurarine, organic bases (eg antibiotics) can cause
release
C. Physical release - mechanical; thermal
458
Uses of Histamines - Histamine itself is seldom used
clinically. Histamine agonists are used for some
diagnostic purposes.
A. Assessment of gastric acid secretion (pentagastrin,
impromidine)
B. Diseases of allergy,desensitize patients, not very
successful (?)
C. Assessment of bronchial reactivity (histamine itself in newer H1 blockers; antiemesis, antinausea; effective in
aerosol form), usually use methacholine challenge
instead
antihistamines
A. Structure activity relationship - several
subclassifications of H1 blockers; most contain a
substituted ethylamine moiety
B. Pharmacokinetics - rapidly absorbed, widely distributed;
newer 2nd generation drugs do not enter CNS;
metabolized in liver; duration of action 4-6 hrs. (12-24 for
long-acting)
C. Pharmacodynamic effects due to H1 blockade -
antagonize most of the pharmacological effects of
histamine; do not block gastric acid secretion (H2 receptor-
mediated) or histamine release
D. Pharmacodynamic effects independent of H1
blockade - sedation; antimuscarinic effect, minimal with
preventing motion sickness; local anesthetic action;
blockade of Na channels

459

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462

463

464

465

466

467

468

469

470
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471

472

473

474
475

476

477
 M N

478

479
 M N

480

481

482

483

485
 M N

486

487

488

489

490
 M N

491

492

493

494

495

496

497
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498

499

500

501

502
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503
 M N

504

-blocker mask many of the symptoms of

hypoglycemia (tremors,sweating, palpitations) that are
mediated by epinephreine - increases DM for prfound
hypoglycemia

505

506
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507

508

509

510

511

512
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513

514

515

516
 M N

517

518

520

521

522

523

524
 M N

525

526

527

528

529

530

531

532

533
 M N

534

535

536
 M N

537

538

539

540

541

542

543

544

545
 M N

546

547

548

549

550
 M N

551

552

553

554
 M N
555

556

557

558

559

560

561

562

563

564
565

566

567
568

569
 M N

570

571

572

573

574
 M N

575

576

577

578
579
580
581
582

583

584
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585
586
587
588

589

590
591
592

593

594

595

596

597

598
599

600

601

602
 M N

Opioid Receptor Subtypes cont:

delta receptors:
May be more associated with euphoria than mu receptors.
No clinically useful drugs are selective for their actions on
this receptor

kappa receptors:
less involvement in abuse potential and physical
603 dependence
important for effects of non-selective and some of the mixed
Opioid Receptor Subtypes: mu receptors agonist-antagonist opioids including:
important for most of the classical effects described for dysphoria
opioids including: psychotomimetic responses (disoriented to
analgesia person/place/time or depersonalized feelings)
euphoria less miosis and respiratory depression than mu agonists
miosis analgesia
respiratory depression sedation
physiological dependence vasodilation
reduced GI motility (constipation) increased urinary output

604

605

606

607
 M N

Morphine:
equivalent analgesic dose = 10 mg
608
maximum efficacy = high
oral: parenteral potency ratio: low
duration of analgesia = 4-5 hours
addiction/abuse liability = high
Abuse potential is decreased by slower rates of infusion oral and suppository preparations available
(eg morphine pump in hospital) - no rush

609

610

611

612

613

614
 M N

615

616

617

618

619

620
 M N

621

622

623

624

625

626

627

628
 M N

629

630

631

632

633

634

635
 M N

636

637

638

639
 M N

640

641

642

643

644

645

646
 M N

647

648

649

650

651

652

653

654

655
 M N

656

657

658

659

660

661

662
 M N

Effects on the Kidney

663 Little effect in normal subjects.
Effects on Platelets and the Cardiovascular System: PGs oppose effect of vasoconstrictors (PGE 2 and PGI2
Platelets have thromboxane synthetase and make TXA 2, cause vasodilatation), maintain renal blood flow, particularly
a potent vasoconstrictor and activator of platelet in the presence of circulating vasoconstrictors.
aggregation and release. Endothelial cells make PGI 2 In situations where there are high levels of circulating
vasoconstrictors, e.g., compensated congestive heart
(prostacyclin) an inhibitor of platelet aggregation and a failure, chronic renal disease, NSAIDs can reduce renal
vasodilator. Low doses of aspirin irreversibly inhibit blood flow.
COX and platelet aggregation for the life of the platelet Retention of sodium and water. Reduced effectiveness of
(8-11 days). Higher doses of aspirin can be counter- hypertensive regimens.
productive, since they lead to inhibition of PGI2 In patients with congestive heart failure, hepatic cirrhosis,
synthesis in endothelial cells; PGI2 is a vasodilator chronic renal disease, or hypovolemia (e.g., high levels of
and inhibitor of platelet aggregation. COX1 is vasoconstrictors) NSAIDs can decrease renal blood flow
abundant in platelets, while COX2 is not. Other and the rate of glomerular filtration. Acute renal failure can
salicylates and NSAIDs inhibit thromboxane synthesis result.
reversibly so their effects on platelet aggregation are Both COX1 and COX2 are expressed constitutively in the
less pronounced and more easily reversed. kidney.

664
 M N

665

666

667

668

669

670
 M N

671

672

673

674

675
676
677

678
 M N
Carbohydrate and Protein Metabolism
Corticosteroids:
1. decrease peripheral glucose uptake ("anti-insulin
effect").
2. stimulate protein breakdown and lipolysis, which
provides amino acids and glycerol for conversion to
glucose.
3. stimulate gluconeogenesis in liver (from AA and
679 glycerol); glucose is deposited in liver as glycogen.
4. net effect is to elevate blood glucose levels.
Glucocorticoids can worsen control with diabetes and
precipitate hyperglycemia in other patients.
5. These peripheral effects are associated with a number
of catabolic actions, including atrophy of lymphoid tissue,
decreased muscle mass, negative nitrogen balance, and
thinning of the skin.
Lipid Metabolism
1. Corticosteroids cause a dramatic redistribution of
body fat with increased fat in the back of the neck,
buffalo hump, and face, moon facies, coupled with a
loss of fat in the extremities.
2. Have a permissive effect, i.e., facilitate lipid
breakdown stimulated by growth hormone and
catecholamines with a resultant increase in free fatty
acids.
680
681
682
683
684
Electrolyte and Water Balance, Mineralocorticoids,
especially aldosterone:
1. act on the distal tubules and collecting ducts of the
kidney to enhance reabsorption of Na+.
2. increase urinary excretion of K+ and H+.
3. These effects on the kidney, combined with similar effects
on the colon, salivary and sweat glands, help maintain Na+,
K+, and water balance.
4. Aldosterone excess causes elevated Na+ expansion of
extracellular fluid volume, hypokalemia, and alkalosis and
chronic excess causes hypertension.
5. Aldosterone deficiency leads to Na+ wasting, contraction
of extracellular fluid volume, hyponatremia, hyperkalemia,
and acidosis; and if chronic, hypotension and vascular
collapse.
6. Glucocorticoids play a permissive role in the excretion of
free water
7. Interfere with Ca2+ uptake in the gut, increase Ca2+
excretion by the kidney, and decrease total body Ca2+
stores.
 M N

685

686

687

688

689

690

691

692

693
694

695
 M N

696

697

698

699
 M N

700

701

702

703

704

705
 M N

706

707

708
 M N

709

710

711

712
 M N
Importance of Cell Cycle Kinetics in Chemotherapy:
Most anticancer drugs are designed to kill rapidly
713 dividing cells, which means cells that are traversing the
cell cycle.
a. Cell cycle specific drugs (CCS) are only effective on
proliferating cells. Cell populations in which a relatively
large proportion of the cells are proliferating are said to
have a large growth fraction. CCS drugs are most
effective in tumors that have a large growth fraction,
such as leukemias and lymphomas. Drugs that are
mostly active during only one particular phase of the cell
cycle, e.g., M phase, are said to be phase specific.
b. Cell cycle nonspecific drugs (CCNS) can kill tumor
cells whether they are dividing or "resting" in Go,
although dividing cells are more vulnerable. CCNS
drugs are useful in both high growth fraction tumors
and in low growth fraction tumors, such as solid
tumors.
714
715
716
717
All cells, whether normal or malignant, demonstrate a
dose-response relationship between the dose of drug
and cell death. The difference between the two curves
(ratio of EC50 values) is the therapeutic index.
CCNS drugs, e.g., alkylating agents
More shallow dose-response curve
Increase dose, increase cell kill
Use single large dose
CCS drugs
Steep dose-response curve
Plateau cell killing capacity
Higher doses do not improve kill rate
Length of time cells exposed important
Schedule-dependent drugs
 M N

718
Cisplatin causes severe n/v. The recommended initial
regimen would be ondansetron (consider the most
effective, or other other 5-HT3 antagonist) plus
dexamethasone plus lorazepam.
The most common drugs that are cycle dependent are the
antimetabolites. The most common drugs that are cycle
Independent are the alkylating agents.

719

720

721

722

723

724
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725

726

727

728

Cardiac toxicity decreased (free radicals) by admin

dexrazoxane

729

730

731
 M N

732

733

734

735

736

737

738

739
 M N

740

741

742

743

744

CBC for anemia and platelet count is mandatory at

baseline and then weekly for pts treated with
methotreaxate until the dose is stabel; LFT are
performed monly, pt may develop elevated
transaminases

745
 M N

746

747

748

749

750

751

752

753
 M N

754

755

756

757

758

759
 M N

760

761

762

763

764

765

766

767
 M N
768
769

770

771

772

773

774
775
776
777
778
779
780
781
782
783
784
785
786
787
788

789

790

791

792
793
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 M N
795
796
797
798
799
800
801
802
803
804
805
806
807
808

809

810
811
812

813

814
815
816
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818

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820
 M N

821

822

823

824

825
826
827

828

829

830
831
832
833
834
 M N

835

836
837
838
839

840

841

842

843

844

845

846

847

848
849
 M N
850

851

852

853

854

855

856
857

858

859

860
861

862

863

864
 M N
865
866
867
868
869
Serotonin is a NT as well as stored in RBC, functions are
unclear; (Notice: n/v drugs use 5HT3 receptor with ion
channel receptor; the rest of the 5HT receptors are G
870 protein coupled (7 transmembrane domains) - 7 families
(70% homology), 16 receptor type); Extracellular domain
for the 5HT receptors are all different, but binding
receptor is very similar for all receptors, so difficult to get
selective agonist (no highly selective agonist for these
receptors), several antagonists. Triptans one of the
first selective (1b/1d receptors). CNS has 5HT1
receptors that are Gi (inhibitory)
Q: Why would you use 5HT1b/d agonist to treat migraines if
problem with migraines are too much serotonin (raphe
nucleus) in the first place? Or am I mistaken that it is an
excess of serotonin? A: I don't think of migraines as a "too
much serotonin" problem per se. Remember that there are
14 subtypes of serotonin receptors, and we don't fully
understand which are pre-sypanptic, which post-synaptic
etc. We came to using the 1B/1D agents through the sloppy
pharmacology of the erogt alkaloids, which have multliple
receptor interactions. Thus, these drugs were not a rational
approach to treating the project, but a refinement of what
was known to work. - Dr. Oglesby
 M N

871

872

873
plicated in NMS have dopamine D2-receptor antagonist properties.
of anti-Parkinson medication. The clinical syndrome is thought to
n the central nervous system (CNS), either from blockade of
ty of dopamine itself, and shares similarities with malignant
ckade of dopamine neurotransmission in the nigrostriatum and
nd altered thermoregulation, respectively. There is evidence that
unction may play a significant role in the pathogenesis of NMS.

874

875

876

877

878
 M N

879

880

881

882

883

884

885

886
 M N

887

888

889

Functional schematic of extrapyramidal system: DA

neurons of the substantia nigra pars compacta (SNc)
enable output of the striatal-thalamic-cortical loop by
890 modulating both direct and indirect pathways in an
opposing fashion:
SNc DA neurons promote activity in the direct pathway
via a D1 receptor mechanism, thus driving the output of
the thalamus.
SNc DA neurons inhibit indirect pathway (that inhibits
thalamus) via a D2 receptor mechanism. Thus, activity at
the D2 receptors ultimately also promotes output of the
thalamus.
Loss of dopamine containing neurons in Parkinsonism
tends to disable output of the whole striatal-thalamic-
cortical loop, by diminishing output of direct and increasing
output of indirect pathways.
Effective therapy for idiopathic Parkinsonism involves
increasing DA receptor stimulation via dopamine
replacement or by direct DA receptor agonists. As
suggested by the anatomical arrangements, either D2, D1,
or nonselective agonists can be effective (although different
side-effects can be associated with selective vs
nonselective).

891

892

893
 M N

894

895

896

897

898

899

900
 M N

901

902

903

904

905

906

907
908
909
910
911
912
913
914
 M N

Generalization (Loss of consciousness): Spread from

915
thalamus to cortex
Primary: Involves whole brain from start
Secondary: starts in focus
Types: Tonic-Clonic Seizure (grand mal):
Absence seizures Petit mal Aura
Tonic-clonic seizures - Grand mal Loss of consciousness
Tonic seizures Tonic phase
Clonic seizures Clonic phase
Myoclonic seizures Post-ictal phase: decreased responsiveness, sleep, coma
Atonic seizures - drop attacks

916

917

918

919

920
 M N

921

922

923

924

925

926
 M N
927

928

929

930

931

932

933

934
 M N

Myelin-associated glycoprotein (MAG) is less than 1%

935 of myelin protein. The role of this protein in CNS myelin
is not completely understood.
The enzyme 2',3'-cyclic nucleotide 3'-
phosphodiesterase (CNPase) comprises about 2% of
CNS myelin protein. This enzyme is not restricted to
nervous tissue and its biological function remains to be
determined.

936

937

938

939

940
 M N

941

942

943

944

945

946

947
 M N
948
949

950

SSRIs: General Notes

little effect at NE or DA uptake sites
951 Antidepressant-induced sexual dysfunction little or no effects at muscarinic, histaminergic or alpha-
(associated with increased monoamine NT in the adrenergic receptors
synaptic cleft): relatively long half lives (care should be taken with hepatic
decreased libido / decreased arousal / anorgasmia or renal impairment)
all three prevalent with TCAs & MAOI fewer or less severe side effects than TCAs and most of the
all three can also be seen with SSRIs, but anorgasmia heterocyclics
most prevalent much safer in overdose than TCAs
fewer sexual side effects with bupropion and nefazodone FIRST CHOICE FOR DEPRESSION

952

953

954

955
 M N

956

957

958

959

960

961

962
 M N

963

964 May precipatate acute or narrrow angle glaucoma

due to anticholinergic actions (muscarinic receptors on
the pupillary constrictor muscle of the iris are blocked) -
this causes pupillary dilation which further "narrows" the
angle in the anterior chamber of the eye

965
966
967

968

969
970
971

972
 M N

973

974

975

976

977
 M N
978
979
980
981
982
Drug Terminology: Antipsychotics as a term refers to
both the entire class of these drugs as well as to an
older set of drugs that should now be seen as a
subclass (a class sometimes described as Neuroleptics
or Typical Antipsychotics, eg Chlorpromazine and
Haloperidol). At one time this subclass comprised scores
of drugs. You should know only some of them. This
subclass is rapidly being supplanted by a new subclass,
the so-called Atypical Antipsychotics (Olanzapine,
Risperidone, Clozapine, Arapiprazole).
983
Mechanism of Action of Typical Antipsychotics
All block DA receptors, particularly the D2 receptor. Their
clinical efficacy against positive symptoms is relatively well
correlated with this action. Not particularly efficacious
against negative symptoms. Many side-effects are well
correlated with this action. Note that drugs do not well-
differentiate the subtypes of the D2-receptor-family (D2, D3
and D4). Within the family, D2 predominates in terms of
number of receptors. Hence, the D2 receptor per se is
usually the one specified for mediating the effects of
antipsychotics.
 M N

984

985

986

987
 M N

988

989

990

991

992

993

994

995

996

997
 M N

998

Note: BZD have a celling/plateau to effect (so much
safer drug), where both alcohol and barbituates do not;
also note that (though considered modultor drugs with
no true receptor) barbiturates and alcohol can directly
increase Cl- flux into cell (where BZD cannot, indirect
effect, also makes safer). A true receptor must have a
binding site and activate a secondary messanger system
of cell
Benzodiazepines (BZDs) - 3 Types of Drugs:
Agonists (therapeutic agents) - facilitate GABA action at
GABAa receptors by increasing the frequency of Cl-
channel openings
Antagonists - competitively antagonize BZD agonists
Inverse Agonists - decrease Cl- conductance; inhibit
GABA in a non-competitive fashion

999

1000

1001

1002
 M N
1003

1004

1005

1006

1007

1008

1009

1010
 M N

1011
FDA reports that pts using hypnotics may develop
amnesia during usage.

1012

1013

1014

1015

1016
1017
1018

1019

1020

1021
 M N
1022

As compared to his behavior before starting the

1023 medicine, child will now be calm, called the
paradoxical effect (note: some companies claim that
they (ADHD kids) become better students can do more
correct problems in a day Bullshit reasoning no data
that shows theyre smarter, they are just more on task
now)
If kid continues on the drug for 4yrs, the effect of the
drug (as compared with initial use) provides about the
same attentiveness in class (however, see tolerance to the
SE: less appetite suppression > little less insomnia > almost
no tolerance to emotional lability (flip flop of emotion (eg
angry aggressive sad happy) but ability to remain calm in
class remains about the same as initial doseing!

1024

1025

1026

1027

1028

1029

1030
 M N

1031

Note that methylphenidate and amphetamine are both

effective anorexians/appetite suppressors (both
schedule II; relain appetite suppression the longest
compared to other agents, but high abuse potential,
cannot be used for weight loss no off label uses for
schedule II drugs!!)

1032

1033

1034

1035

1036

1037

1038
 M N

1039

1040

1041

1042
Ethanol metabolism can produce an excess of
reducing agents - during EtOH metabolism, excess
NADH and NADPH are formed; involved in EtOH-
induced metabolic disorders including:
reduced gluconeogenesis
hypoglycemia
ketoacidosis
increased triglyceride synthesis from free fatty acids
Acute EtOH: liver
Increased oxygen utilization
decreased gluconeogenesis
decreased production of glucose from glycogen
increased lactate production
decreased oxidation of fatty acids
increased fat accumulation
Acute EtOH effects on ion channels - 2 major:
GABA gated Cl- channel is facilitated;
Glutamate gated Ca++ channel is inhibited

1043

1044
 M N

1045

1046

1047

1048
Cocaine: Interactions
Opioids (speedball)
Alcohol, where it condenses covalently to form
cocaethylene - produced by use of alcohol in
combination with abuse of cocaine; covalent linkage of
ethanol and cocaine; this compound has a much longer Cocaine: Tolerance: occurs to euphoric effects; however,
half-life than cocaine. Like cocaine, cocaethylene blocks very little carryover over tolerance from one session of use
the dopamine transporter, which accounts for its to another. Does not result in significant escalation of
euphoric effects dosage across sessions of use
 M N

efully controlled since 1972

1049 - derivatives of amphetamine that are schedule III and
mphetamine)
have very little abuse potential compared to d-amphetamine and

e for this purpose. Penalty is a rebound effect = need to sleep and a Psychostimulants: Uses
Narcolepsy - Legitimate use
ey improve tasks where boredom is a factor, but are not helpful on ADHD - Legitimate use, but watch for diversion

1050

1051

Nicotine Neuropharmacology: Binds to the cell bodies
in the VTA (ventral tegmental area) as well as the
dopaminergic terminal of the nucleus accumbens (Brain
stem to Cortex). Stimulates the release of dopamine
and glutamate. Also releases or causes increases in: B-
endorphin, epinephrine, vasopressin, norepinephrine,
adrencorticotropin, Cortisol, Glutamate
Epidemiological studies have found that smokers have a
reduced risk of developing Parkinson's disease,
Alzheimer's disease, and ulcerative colitis. A nicotine
analogue that stimulates dopamine release is under study
for treatment of Parkinson's disease, and the nicotine
transdermal patch is being studied to counteract the
cognitive impairment caused by treatment with haloperidol.

1052
 M N

1053

1054

1055

Marijuana: Dependence
Tolerance reported
Withdrawal syndrome: anorexia, nausea, vomiting,
1056 diarrhea, irritability, restlessness, insomnia - observed
after sudden discontinuance of prolonged use of high
doses (difficult to demonstrate in clinical populations)
Withdrawal does not appear to be major factor in
maintaining use.
1057
1058
Marijuana: Overdosage
Euphoria, time-space distortion, tachycardia, fever
Psychosis (visual and auditory hallucinations,
depersonalization)
Treatment
haloperidol or diazepam for agitation
propranolol for cardiovascular effects

1059
 M N

1060

1061

1062
 O P Q
1

9 Retrograde ejaculation - orgasm occurs,

nothing comes out - semen acutally stays in
prostate during ejaculation contraction, then with
relaxation moves into the bladder and is
expelled latter with the urine
 O P Q

10

11

12

13

14

15

16

17

18
 O P Q

19

20

21

Equine Estrogens (CEE): t : 10 24 hrs,

Time to peak concentration: 4 10hrs
22 Protein binding mainly to albumin (in contrast,
non-conjugated estrogens bind to both albumin
& SHBG)
Binds to alpha fetoprotein during early
development
Elimination: Ethinyl estradiol - (IV) used to stop emergency
Renal (major route) uterine bleeds (especially anovulation associated
Fecal (minor route) with bleeding)

23
24
 O P
oral contraceptives desired efffects:
The progestagenic component should have low
25 androgenic activity (ex. Desogestrel)
Reduce free androgens by increasing the
amount of plasma SHBG (an effect of estrogen)
Sequential (E, then P) or E alone oral
contraceptives will inhibit the H-P-G axis, thus
reducing ovarian androgen production
Treating disorder associated with high androgen
levels (eg hirsutism)
26
27
28
29
30
31
Advantages of transdermal estradiol versus oral
CEE preparations:
Reduced conversion of estradiol (E2) to estrone (E1)
No effect on SHBG
Little, to no, thromboembolic risks!! (less first
pass effect)
** However, transdermal estradiol may not have the
same benefits on serum lipid profiles as oral
preparations.
But no negative effects of transdermal E2 on lipid
profiiles have been reported
Q
Relative OC contraindications continued:
Uterine fibroids (E makes these grow)
Lactation
Diabetes mellitus
Sickle cell disease (More likely to sickle)
Hypertension (Average bp increase by
7mmHg)
Age 35+ and cigarette smoker (Risk for HD
goes up expenetially after 35 on pill)
Age 40+ and high risk for vascular disease
Hyperlipidemia
 O P Q

32

33

34

35

36

37

38

39

40

41

42
43
 O P Q

44

45

46

47

48
49

50

51

52
53

54

55
 O P Q

56

Hypercalcemia Tx: Note: the NaKCl2 transport of the thick ascending is

- Saline rehydration and loop diuretic the transport used by the macula densa (so loops
(furosemide). (Thiazides cause hypercalcemia) decrease the Na that it registers, causing afferent
- In addition calcitonin and BPs dilation)

57

58
59

60
 O P Q

61

62

63
64

65

66
 O P Q

67

68

69

70

71

72

73
 O P Q

Results of Blocking Angiotensin II Production:

74
angiotensin converting enzyme (ACE, which
is identical to kininase II ACE is associated
with angiotensin; kininase is associated with
bradykinin)
Vasodilation
Decreased Na and H2O retention
Decreased response to sympathetics
Decreased tissue remodeling
Net effect: decreased preload; decreased afterload;
decreased mortality (slower disease progression)
Results of Increasing Bradykinin Levels:
Vasodilator ACEIs: Effects on Morbidity
promotes NO formation relieve dyspnea
increases synthesis of prostacyclin prolong exercise tolerance
Prevents vascular and cardiac cell growth decrease need for emergency care
Stimulates tPA release These effects observed in mild, moderate
Kinin autocoids produce tissue irritation and pain, and severe HF
which likely accounts for a major side-effect of ACEIs

75

76

77
 O P Q

78

79

80

81

82
 O P Q

83

84

85

86

87
 O P Q
88
89
90
91
92

93

94

95

96
 O P Q

Treatment: E. coli is the most common pathogen Treatment of UTIs cont:

causing about 80% to 90% of uncomplicated upper
97
and lower UTI.
Staphylococcus saprophyticus is the second most
Predisposing factors to UTIs: common bacterial pathogen causing UTI.
Age Other common causes include Klebsiella
Female gender pneumoniae and Proteus mirabilis infection. UTI may
Pregnancy be treated with a group of agents called urinary tract
Instrumentation antiseptics. Urinary tract antiseptics are concentrated
Urinary tract obstruction in the urine and as a result, microorganisms at that
Neurologic dysfunction site can be effectively eradicated.
Renal diseases
Uncomplicated cystitis: short term therapy (typically 3 days) incl
sulfisoxazole are also useful. Fluoroquinolones are reserved for
co-trimoxazole or amoxicillin.
Prostatitis: Co-trimoxazole and ciprofloxacin show good penetrat
Acute pyelonephritis: Parenteral therapy with ampicillin, a cepha
usually effective.
In pregnancy, ampicillin and cephalosporins are potentially less t
Acute urethral syndrome: Tetracyclines, such as doxycycline, ar
Chlamydia trachomatis, two common causative agents.
Pregnant women are treated with erythromycin.
Vaginal candidiasis: Topical clotrimazole and miconazole

98

99

100
101

102
 O P Q

103

104
105

106

107

108

109

110

111
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112

113

114

115

116

117

118

119

120

121
 O P Q

122

123

124

125

126

127

128
 O P Q
129

130

131

132

133

134

135

136
 O P Q

137

138

139

140

141

142
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143

144

145

146

147

148

149
 O P Q

150

151

152

153

154

155
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156

157

158
 O P Q

159

160

161

162

163
164
165
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166

167

168

169

170

171

172

173

174

175

176

177
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178

179

180
181

182

183

184
 O P Q

185

186

187
188
189
190
191
192
193
194

195
196
197

198
 O P
How risky is hepatitis B vaccination?
Fewer than O. I % of 43,618 persons immunized
199
for hepatitis B experienced an adverse reaction
other than transient fever or sore arm. Serious
reactions (e.g., Guillain-Barre syndrome) did not
occur, nor did transmission of the human
immunodeficiency virus (HIV). All health care
workers, family members, and sexual
contacts of HbsAg-positive people, prison
guards, and other persons with likelihood of
exposure should be vaccinated.
200
201
202
203
204
205
Q
Who should receive hyperimmune globulin to
prevent hepatitis? Hyperimmune globulin is used
only in the prophylaxis of hepatitis B infection. It
should be given in the following situations:
1. After homoandrewsexual or heterosexual contact
with an HBsAg-positive partner
2. After a percutaneous puncture (e.g., in health
care workers or drug abusers sharing needles)
3. In neonates who are born to HBsAg-positive
mothers. Such offspring (except neonates) also
should be started on hepatitis B vaccine.
4. Patients with cirrhosis due to HBY received after
transplantation
 O P Q

206

207

208

209

210

211
 O P Q

212

Digoxin: Indications in CHF:

Drugs that increase digitalis levels:
Dosing, clinical states that increase or Ca++ channel blockers:
decrease sensitivity: Up to 100% increase
Acute MI Decrease renal clearance
AV nodal disease Erythromycin, tetracycline:
Renal failure (and decreased K+) 40-100% increase
Due to increased absorption
No effect on survival
Improves clinical status
Give in conjunction with diuretic, ACE
inhibitor and beta blocker (watch functioning
of SA and AV nodes)
Indicated for CHF with atrial fibrillation

213

214
 O P Q

215

216

217

218

219

220

221

Electrolyte shift in Nodal Tissue

Phase 0: Calcium and Sodium
222 Phase 1: Sodium channel????????
Phase 2: Calcium channel
Phase 3: Potassium rectifier All class I anti-arrhythmic agents are use-
Phase 4: Sodium leak dependent, meaning that they tend to be more acive
at ion channels that are depolaring more frequently
 O P Q

223

224

225

226

227

228
 O P Q

229

230

231

232

233

234
 O P Q

235

236

237

238

239

240

241
 O P Q

242

243

244
245

246

If prolonged anticoagulation is necessary, the

initial heparin therapy is overlapped with and
then replaced with oral anticoagulant, i.e.,
warfarin
5 days of heparin with Warfarin started at day
one is most effective time span of use
Heparin does not dissolve thrombus or
emboli, however, it allows the fibrinolytic
Sometimes pt will show resistance to heparin, system to proceed unopposed and more
thought to be from clotting process already occuring, readily reduce the size of the thromboembolic
heparin concentration in blood needs to be saturated burden

247

248
 O P Q

Platelet Count:
(Normal Values = 130,000-400,000 per
microliter)
Thrombocytopenia = low platelets (<100,000/
ml, severe < 50,000/ml)
249 Bleeding Time:
Spring-loaded device makes incisions on volar Individual patient variation is very high
surface of the forearm with pressure cuff at 40 Due to differences in absorption, elimination, liver
mm Hg function, and drug-drug interactions.
excess blood is blotted away every 30 sec. Noncompliant and unreliable patients are not good
Normal = 7 min (2-9 min) candidates for warfarin therapy
Measures adequacy of platelet plugs Potential drug-drug interactions are numerous When ever hear Vit K think Warfarin and
Highly variable results vice versa

250

251

252

253
 O P Q

254

255

256

257

258

259

260

261
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262

263

264

265

266
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267

268

269

270

271
272
273
 O P Q

274

275

276
 O P Q
277
278

279

280

281

282

283
 O P Q

284

285

286
 O P Q

Transport: Iron is transported in the plasma

bound to the beta globulin protein,
transferrin. Iron is delivered to the maturing
erythroid cells in the marrow by a specific
receptor endocytosis mechanism (similar to the
LDL receptor mechanism). The iron transferrin
complex is bound at the surface of cells by a
287 specific transferrin receptor, the entire receptor
transferrin iron complex is internalized by
endocytosis, in cytoplasmic vesicles,
(endosomes) low pH causes release of bound
iron, but the iron free transferrin remains bound
to its receptor and is recycled back to the cell
surface to begin the cycle again.
Excretion: Very little excretion of iron occurs;
some is lost through exfoliation of intestinal
mucosal cells and trace amounts are lost in the
bile and urine. Iron balance is achieved through
changes in absorption.
The response to iron therapy varies,
depending upon the erythropoietin stimulus
and the rate of absorption. Typically, the
reticulocyte count should begin to
increase within 4 to 7 days after initiation of
The goal of therapy in individuals with iron deficiency therapy and peak at 1 weeks. The
anemia is not only to repair the anemia, but also to absence of a response may be due to poor
provide stores of at least to 1 g of iron. adsorption, noncompliance (which is
Sustained treatment for a period of 6 to 12 common), or a confounding diagnosis. If iron
months after correction of the anemia will be deficiency persists, it may be necessary to
necessary to achieve this. switch to parenteral iron therapy.

288

Requires intrinsic factor to be absorbed from the

GI tract. If the pt cannot produce intrinsic factor
(eg gastric atropy), pt must receive parenteral
B12 (injections) for life
 O P Q

289

290

291

292

293
 O P Q

294

295

296

297

298

299

300
301
302
 O P Q

Rules for Using Anti-Diabetic Agents:

Oral agents are not used in pregnancy at this
time by endocrinologists
Do not switch from one Rx to another within
the same class!
303 ADD MEDICATIONS TO ACHIEVE GLYCEMIC
CONTROL - Combination therapy is
necessary to achieve control
All agents (except insulin) are at best capable of
decreasing A1c by 1-1.5%
Adding agents gives an additive effect: Add an
agent if the A1c is <1-1.5% above goal!
Insulin can lower any A1c and can always be
used to achieve glycemic control

304

305

306

307
 O P Q

308

309

310

311

312

313
 O P Q

314

315

316

317

318
319
 O P Q

Ultra-Short Acting Insulins: Lispro insulin & aspart

are is human insulin. The onset of action is within 15
min, and the peak action is at 45 min to 2 hours. The
peak of plasma insulin levels is faster, higher, and
320
shorter than regular insulin, and more closely
Subcutaneous Insulin Injections: SQ insulin mimics the normal initial endogenous insulin
differs from physiologic secretion in two main peak. Because of its rapid action, it can be taken
ways: (a) the kinetics of S.C. insulin does not immediately before a meal instead of the current
match the normal rapid rise and decline in recommended waiting period of at least 30 min for
response to ingestion of nutrients, and (b) regular insulin. This property gives the patient more Dawn phenomena: both normal and
injected insulin diffuses into the peripheral flexibility in managing their meals and insulin diabetic patients have an increased
circulation instead of into the portal circulation. injections. Insulin glulisine [Adpidra] is another ultra- requirement for insulin in the early morning,
Thus, the preferential effect of insulin on hepatic short acting insulin that can be taken either 15 min making the kinetics and timing of the evening
metabolic processes is not provided. prior to a meal or within 20 min after starting a meal. dose of insulin extremely important.

321

322

323

324

325

326
 O P Q

327

328
329
330

Storage: Thyroglobulin, with 2-5 T4 and T3

molecules attached, is stored in the follicular
colloid of the thyroid gland. The gland stores
vast amounts of hormone in the colloid and
inhibition of synthesis must be prolonged to
deplete this store of hormone.
Secretion: To release T3 and T4 small
331 quantities of colloid containing thyroglobulin
must be captured from the follicular fluid by
pinocytosis. The pinocytotic vesicle eventually
fuses with lysosomes within the cell exposing
the thyroglobulin to proteolytic enzymes that
degrade it to individual amino acids releasing
T3, T4, MIT, and DIT. DIT and MIT are
deiodinated and recycled. T3 and T4 are
released to the bloodstream.
Circulating Hormone: The ratio of T4 to T3 on
thyroglobulin is typically 5:1, and so most of the
released hormone is thyroxine. Most circulating T3 is
formed in the periphery by deiodination of T4 by the
enzyme 5' deiodinase. As a result 33% of the
circulating T4 is deiodinated to T3. There is also
some conversion to the inactive "reverse T3" or 3, 3',
5' triiodothyronine. T3 is 4 times more potent than
T4.
99.96% of T4 is bound (0.04% is free)
tightly to thyroxine binding globulin (TBG)
and loosely to thyroxine binding
prealbumin (TBPA) and albumin. T3 is
99.6% bound; 0.4% free. Only free
hormone is active. Bound hormone thus
represents a large pool of T4 and T3 that
"buffers" free hormone levels in the plasma.
Depletion of this pool does not occur rapidly.

Both PTU and methimazole cross the

placental barrier and are concentrated by the
fetal thyroid. Thus, high doses of these drugs
332 can lead to fetal hypothyroidism, even though
the mother is hyperthyroid. Of the two drugs,
PTU is preferable in pregnancy because it is
more strongly protein bound and therefore Life threatening SE - drug-induced agranulocytosis
crosses the placenta less readily. In addition, it (0.1-0.2% of pts); requires immediate discontinuation
is not secreted in sufficient quantity in breast of the drug. Agranulocytosis is an immune-mediated
milk to preclude breast feeding. Methimazole disorder; the absolute N0 count is often extremely
treatment can lead to congenital scalp depressed (usually < 100). Generally the N0 count
defects (aplasia cutis). will recover 5 to 7 dayys after drug discontinued
 O P Q

333

334

335

336

337

338

339

340

341

342
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343

344

345

346

347

348

349

350

351
352
353
354
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355

356

357

358

359

360

361

362
363

364
 O P Q
365

366

367

368

Only relieves bronchospasm, not used for beta-blocker induced asthma (seen in eye
treatment of underlying inflammatory Beta-agonist, steroids, and theophylline are drops for glacoma) - contraindication in pt
disease mainstays in the treatment of status asthmaticus with asthma or history of atopy

369
370

371
 O P Q

372

373

374

375

376

377

378
379

380

381
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383

384

385

386
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387

388

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390

391

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393
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397

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399

400

401
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Isoniazid bacteriacidal for actively growing Isoniazid OD - profound metabolic acidosis

extracellular organism and slowly growing associated with high lactate levels. Pt may also
intracellular (in M0) at acid pH present with seizures quickly after acute OD.

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First Generation Antihistamines

o Diphenhydramine (Benadryl)
o Chlorpheniramine (Chlor-Trimeton)
o These drugs are inexpensive, are a predominant
458
Allergic Rhinitis: component of available over-the-counter (OTC)
Characterized by sneezing, nasal itching, combinations, but may cause somnolence,
rhinorrhea (discharge) and congestion, may be interfere with learning, decrease work
seasonal (intermittent) or perennial (persistent). productivity and impair psychomotor Intranasal Corticosteroids: Topical
H1 histamine receptor antagonists performance, and are associated with increased (intranasal spray) corticosteroids are the
(antihistamines) are the drugs most risk of injury. most effective drugs available for
commonly used to treat allergic rhinitis. o Patients should be made aware of these effects, prevention and relief of symptoms of
All of these drugs are more effective in which can persist in the morning after taking the allergic rhinitis. See Pulmonary Anti-
relieving sneezing, itching, and discharge than drug at bedtime and may continue to occur with Inflammatory Agents, Corticosteroids
in relieving nasal congestion. regular use.

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603
As a general rule, the greater the opioid's
efficacy against pain, the greater the abuse
potential
General:
Euphoria - Mu receptors
Dysphoria - Kappa receptors (predom)
Psychotomimetic - Kappa receptors (and
sigma for some drugs)
Notes on Clinical Uses: Analgesia
Best with severe, constant, dull pain (eg bone Opioid Effects - Therapeutic uses and
fracture). Not as effective with sharp, intermittent, side-effects are confined to actions in:
brilliant pain (eg knife pain). CNS
Although dulled, pain is still perceived. Reaction to G.I.
pain is diminished. Vasculature
Match drug to intensity of pain Kidney (kappa agonists)

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Dysmenorrhea
Prostaglandins released by the endometrium during
menstration contribute to severe cramps and pain.
NSAIDs have proven very effective for treatment

Patent Ductus Arteriosus

NSAIDs suppress the clinical signs in rheumatic
disease, but subsequent tissue damage is not
halted.
NSAIDs do not induce remission (a state or
period during which the symptoms of a disease
are abated).
PGE2 keeps ductus arteriosus open following birth.
Indomethacin is the NSAID often used to stimulate
closure of the patent ductus arteriosus.
Preeclampsia and hypertension of pregnancy:
low doses of aspirin are used to treat women at high
risk for hypertension and preeclampsia.
Reyes syndrome is a rare but often fatal
consequence of infection with chicken pox,
varicella and influenza viruses. Liver damage
and encephalopathy (hepatitis and cerebral
edema).

664
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 O P
Cardiovascular System
1. Mineralocorticoid-induced hypertension can
contribute to atherosclerosis, cerebral
hemorrhage, stroke, and cardiomyopathy.
Restriction of dietary Na+ can lower the blood
pressure considerably.
2. Corticosteroids enhance vascular reactivity to
other vasoactive substances. Glucocorticoids
increase expression of adrenergic receptors
in the vascular wall.
G. Skeletal Muscle
1. Permissive concentrations of corticosteroids
are required for normal function of skeletal
muscle; diminished work capacity is a prominent
679 sign of adrenocortical insufficiency.
2. Chronic glucocorticoid excess causes skeletal
muscle wasting.
H. Central Nervous System
1. Indirect effects are important for maintenance
of the CNS, including effects on blood pressure,
glucose levels, and electrolyte concentrations.
2. Clinical administration of glucocorticoids can
induce mood elevation or more pronounced
behavioral changes, such as euphoria,
insomnia, restlessness, and increased motor
activity. A smaller percentage of patients treated
with glucocorticoids become anxious,
depressed, or overtly psychotic.
3. Recent studies suggest that steroids
produced locally in the brain (neurosteroids)
may regulate neuronal excitability.
680
681
682
683
684
Formed Elements of Blood
The administration of glucocorticoids leads to a
decreased number of circulating lymphocytes,
eosinophils, monocytes, and basophils. This effect is
due to redistribution of cells away from the periphery
rather than from increased destruction. In contrast,
glucocorticoids increase circulating PMN leukocytes.
Anti-inflammatory and Immunosuppressive
Actions
1. Corticosteroids profoundly alter the immune
responses of lymphocytes and can prevent or
suppress inflammation in response to any number of
inciting stimuli (radiant, mechanical, chemical,
infectious, and immunological).
2. Glucocorticoids inhibit the production and release
of many different cytokines that normally would
stimulate the proliferation and function of B and T
lymphocytes. Glucocorticoids suppress interferon,
GM-CSF, interleukins, tumor necrosis factor,
prostaglandins and leukotrienes.
3. The HPA axis and the immune system are capable
of bidirectional interactions during the stress
response. Several cytokines, e.g., IL-1, stimulate
release of CRH and ACTH. This centrally mediated
feedback by the immune system stimulates
glucocorticoid release which inhibits the immune /
inflammatory response and helps protect the
organism from the potentially life-threatening
consequences of a full-blown inflammatory reaction.
Q
Transport, Metabolism, and Excretion
1. Following absorption, 90% of cortisol is
bound to protein. The extent of protein
binding varies among different steroid
analogs. Only unbound hormone or drug is
free to enter cells and affect function.
2. Two plasma proteins bind glucocorticoids,
albumin and corticosteroid-binding
globulin (CBG or transcortin).
3. At low steroid levels, most of the hormone
is protein bound; at higher levels, the binding
capacity of albumin and CBG is exceeded
and a much higher fraction of steroid exits in
the free state.
4. CBG has high affinity for cortisol and low
affinity for aldosterone. Corticosteroids
compete with each other for binding to CBG.
5. In general, metabolism of these steroids
involves oxidation or reduction followed by
conjugation in the liver to more water-soluble
metabolites which are excreted in the urine.
 O P Q

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 O P Q

Tumor Resistance to Cytotoxic Drugs - a

major problem in cancer chemotherapy.
Primary resistance is defined as the
absence of response on the first exposure to
Dose-Response and Pharmacokinetic an agent. Acquired resistance develops
Relationships: The concentration range over over time often from a change in the tumor
which the dose-response curve remains linear cells genetic expression of one or more
for a particular drug is an important genes, i.e., amplification or increased
consideration in designing dose-intensive expression of a gene that effects a drugs
regimens. Drugs such as the alkylating agents accumulation, metabolism, or site of action.
(CCNS) characteristically have steep dose- Multidrug-resistant phenotype:
713
response curves: An increase in the drug characterized by resistance to a variety of
concentration by an order of magnitude or Most chemotherapeutic agents are inducers of natural product anticancer drugs of differing
more results in a proportional increase in programmed cell death. structures. This form of resistance is often
tumor cell kill. By contrast, the dose- Drugs such as the alkylating agents, the associated with increased expression of a
response curve of phase-specific agents, purine/pyrimidine analogs, and the topoisomerase normal gene (the MDR-1 gene) for a cell
such as the antimetabolites (CCS), typically inhibitors result in DNA damage. In response to surface glycoprotein (P-glycoprotein)
is linear over only a narrow range. These genotoxic damage, cells can arrest at two identified involved in pumping drugs out of a cell
agents are less suitable for dose escalation. checkpoints: the G1/S and G2/M boundaries. G1 before they can accumulate to toxic
However, increased tumor cell kill is observed arrest is mediated in part by the tumor suppressor levels. Other mechanisms of multidrug
after prolonged exposure to these agents. p53 via activation of the expression of the cyclin- resistance involve overexpression of the
Increasing the exposure time means that a dependent kinase inhibitor p21. G1 arrest may allow MRP protein(s), a family of transmembrane
larger percentage of the tumor cells will enter the cell to repair damage before DNA replication, and transporters, and qualitative or quantitative
the cell cycle and thus become susceptible to G2 arrest permits repair prior to mitosis. If the DNA changes in topoisomerase II, which repairs
the cytotoxic effects of the drugs. These agents damage is irreparable, apoptosis may occur via p53- the lesions created in DNA by antitumor
are often referred to as schedule-dependent. dependent or -independent pathways. drugs.

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Simplified Neurotransmitter Schematic for

Predicting Therapeutic Effects: normal output
890 of the indirect pathway depends on a balance
between DA inhibitory and ACh excitatory input.
Loss of DA inhibition leads to an imbalance
in favor of cholinergic excitation, and this
imbalance yields symptoms of Parkinsonism.
Therefore, effective therapy for idiopathic Notice: D2 (SNc) ultimately inhibits the indirect
Parkinsonism can involve either increasing DA pathway (which ultimately inhibits the thalamus).
receptor stimulation, or inhibiting cholinergic Thus the thalamus is excited (Notice: thee thalamus Notice: D1 (SNc) ultimately excite that
neurotransmission. normal excits the cerebrum) thalamus

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915
Typical Absence Seizure (petit mal):
3/second spike & wave (dome) activity
brief loss of consciousness without loss of
postural tone
blinking, licking lips, head turning
No aura
Abrupt onset, brief duration, prompt recovery
Continuous Seizures:
Generalized status epilepticus:
Absence status epilepticus
Generalized tonic-clonic status epilepticus
Clonic status epilepticus
Tonic status epilepticus
Benign Febrile Convulsion: Myoclonic status epilepticus
brief generalized seizure Partial status epilepticus:
during first day of febrile illness not due to meningitis Epilepsia partialis continua of Kojevnikov
or encephalitis Aura continua
only in children 6 months to 5 years of age Limbic status epilepticus (psychomotor
Good prognosis unless have mutation on SCN2A status)
gene Hemiconvulsive status with hemiparesis

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948
949

950

SSRIs: Drug Interactions

951
Other SE: dizziness, rashes, pruritis, tremor,
sweating, dry mouth, anxiety (acute),
nervousness, headache, tremor, asthenia,
lightheadedness
SSRIs inhibit various drug metabolizing
SSRIs: Discontinuation Syndrome enzymes - leads to potential interactions with
Occurs with abrupt discontinuation after chronic a variety of other drugs
treatment The levels of SSRIs can be increased by
Less pronounced with fluoxetine due to long half-life P450 inhibitors or can be decreased by P450
Most pronounced with paroxetine inducers
The combination of an SSRI with an MAOI
Discontinuation Syndrome Symptoms Include: can be lethal! (SEROTONIN SYNDROME)
agitation, anxiety, anorexia, confusion, impaired Symptoms: Altered mental status, fever,
coordination, diarrhea, headache, insomnia, sensory agitation, tremor, myclonus, hyperreflexia,
disturbances, sweating, tremor, vomiting, shock-like ataxia, incoordination, diaphoresis shivering,
sensations, flu-like illness GI symptoms

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 O P
978
979
980
981
Mechanism of Action of Atypical
982 Antipsychotics:
They do block D2 receptors, but they have
higher affinity as antagonists for 5-HT2
receptors than D2 receptors. Both actions
appear important to their efficacy in
schizophrenia. Efficacious for positive and
negative symptoms!!
Some of these atypical drugs have not been
implicated in the development of tardive
dyskinesia all are less prone to cause
tardive dyskinesia than typical
antipsychotics.
983
General Effects of all Antipsychotics:
Control bizarre behavior and calm agitation (D2
blockade)
Cause psychomotor slowing (this property makes
them first-choice for controlling disruptive behavior)
decrease agitation, aggression and impulsivity
Produce emotional quieting
If the dose is high enough, they do these things in
everyone.
Q
Additional Effects of Antipsychotics in
Schizophrenics
1) Improve the core thought disorders in
about 50-70% of schizophrenics. (D2
blockade); those schizophrenics with
negative symptoms are particularly
resistant to pharmacotherapy. Atypical
antipsychotics are better against negative
symptoms (D2 and 5-HT2 blockade)
2) Tourettes Syndrome (D2 blockade)
3) Hiccups - Brainstem (D2 blockade)
4) Nausea - Chemoreceptor trigger zone in
the floor of the fourth ventricle, D2 blockade
 O P Q

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996

997
 O P Q

BZD Agonists Overview

Anxiolytic
Anti-convulsant*
Hypnotic
Amnestic
Produce confusion
As dose goes up, progression of effects
usually does NOT go on to coma unless very
998 rapid injection
Benzodiazepines: Overview
Efficacious anxiolytics; fast onset
SAFE by themselves
When combined with sedative-hypnotics
such as ethanol or barbiturates, lethality is
enhanced
Dependence is a serious problem
Long half-lives foster drug hangover and
next-day drug interactions
BZD Overdose
If no other drugs are present, this is usually not a
life-threatening problem
If poisoning is mixed, usually with EtOH and/or
opioids, life threatening respiratory depression is
possible
Drug Interactions with BZDs BZD Tolerance:
CNS depressants (additive effects) Differential tolerance to the sedative
EtOH (tiredness) vs. anxiolytic effects of BZDs.
other BZDs Fortunately, less tolerance occurs to
opioids anxiolytic efficacy
antipsychotics Nonetheless, many patients escalate the
tricyclic antidepressants dose to treat anxiety or insomnia
antihistamines BZD Tolerance:
Cimetidine (Tagamet) inhibits liver mixed-function The higher the dose, and
oxidase. Prolongs the action of most BZDs. The more frequently the dose is taken, and
Use alprazolam, lorazepam or oxazepam for The longer the dose is taken, then
patients taking cimetidine. Modern pharmacology is The greater the tolerance
to avoid cimetidine.

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1017
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1020

1021
 O P Q
1022

1023 Never let the pt push you into a diagnosis, and

(note: ADHD kids suffer more physical abuse,
consequence of pissed parents)
definitely do not let them boss you into prescribing a
drug! eg mom trying to get this schedule 2 agent
(high abuse, could be factitous disorder by proxy);
should have warning bells/whistles when someone
comes into the office looking for a schedule II drug!!

1024

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1031

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1035

1036

1037

1038
 O P Q

1039

1040

1041

Acute EtOH in the CNS (NOTE: All effects

at specific BECs are in non-tolerant
individuals)
Acute EtOH: cardiovascular system BEC = 50 - 100 mg/dL
Vasodilation - contributes to hypothermia- sedation
producing effects of EtOH, direct smooth muscle subjective high
relaxation by acetaldehyde, depression of vasomotor increased reaction times
system in CNS 2-4 quick drinks
1042 Depression of myocardial contractility BEC = 100 - 200 mg/dL
Acute EtOH - membrane disordering effects: Acute EtOH: endocrine system impaired motor function
old and somewhat discredited hypothesis of Diuresis - via inhibition of antidiuretic hormone slurred speech
EtOH actions based on the finding that high release ataxia
doses of EtOH can fluidize membranes (similar Acute/Chronic EtOH: CNS BEC = 200 - 300 mg/dL
to volatile anesthetics - Overton & Meyer). Blackouts: episodes of temporary anterograde emesis
Discredited in part because of steric limitations amnesia stupor
on increasing potency with increasing carbon Fragmentation of sleep patterns, also diminishes BEC = 300 - 400 mg/dL
chain length of alcohols REM sleep early in sleep cycles coma
potency increases until carbon chain length too Relaxes muscles in the pharynx - snoring and sleep BEC > 500 mg/dL
long to fit into protein pocket. May disrupt apnea respiratory depression
protein-lipid interface death

1043

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 O P
1045
1046
1047
1048
General Drug Reinforcement: ability of drugs
to increase frequency of drug-taking (e.g.,
euphoric effects)
Abused drugs directly activate neural
reinforcement circuits (e.g., those activated by
food or sex), with no satiety equivalent
associated with natural reinforcers
Most drugs of abuse can increase extracellular
dopamine (DA) in the nucleus accumbens (NA)!:
ethanol, opioids, amphetamine, cocaine, nicotine,
others
Noradrenergic, serotonergic, and opioidergic
mechanisms may also be involved, but all ultimately
resolve to DA in the accumbens
Q
Mesolimbic dopamine pathway: from
ventral tegmental area (VTA) to nucleus
accumbens (Na, lesions to this area ablate
the interest is substances of abuse), to the
amygdala (helps assess whether an
experience is pleasurable or aversive), to the
hippocampus (participates in recording the
memory of the experience) to the frontal
regions of the cerebral cortex to coordinate
and process this information and determine
the ultimate behavior. The VTA, the NA and
the prefrontal cortex are the reward
pathway. The neurons of the VTA contain
the neurotransmitter dopamine which is
released in the NA and in the prefrontal
cortex. This pathway is activated by a
rewarding stimulus.
 O P
1049
1050
1051
Nicotine: Recent evidence has shown that
nicotine increases the strength of synaptic
connections in the hippocampus, the brain
region that supports short-term memory. Several
nicotine-like compounds that stimulate
acetylcholine release are under study as
cognitive enhancers for treatment of Alzheimer's
disease.
1052
Nicotine: Behaviorally, the stimulatory effects of
nicotine produce improved attention, learning,
reaction time, and problem-solving ability.
Tobacco users also report that cigarette smoking lifts CBF. In contrast to its stimulatory CNS
their mood, decreases tension, and lessens
depressive feelings.
Q
Nicotine: In studies of the effects of nicotine
on cerebral blood flow (CBF), results suggest
that short-term nicotine exposure
increases the CBF without changing
cerebral oxygen metabolism but that long-
term nicotine exposure decreases the
effects, nicotine acts as a skeletal muscle
relaxant.
 O P Q

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 R S
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25

Post-pill amenorrhea (2%)

Most serious complication is venous thromboembolus!! usually had irregular (anovulatory) cycles prior to pill use
the most frequent serious side effect in non-smoking healthy women This is more of a SE
3-4 x increased risk These women usually obese, general association with
(Notice: risk is increased 12 x in pregnancy) PCOD (classic women is metabolic syndrome pt)

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 R S

ACE inhibitors Adverse Effects/Contraindications

74
ACE inhibitors: Uses in CHF
ALL patients with left ventricular systolic dysfunction should be on ACE inhibitors (use with In renal hypotension, angiotensin II maintains efferent
diuretic in those with fluid retention)
Patients with left ventricular systolic dysfunction who have no symptoms (slows
remodeling)
Advise patients about side effects, and that improvement may take weeks to months
ACE inhibitors generally NOT to be used in acute failure (use after stabilization)
Acute HF occurs, e.g., following myocardial infarction or valve rupture. Hypotension is
often a problem initially, which contraindicates vasodilators. In addition, RAS is highly
active in acute HF, and sudden reduction of this tone can lead to cardiovascular
collapse.
Dry, persistent cough (bradykinin related often
intolerable)
Severe hypotension in pts who are hypovolemic (watch
out for hypovolemia in pts taking diuretics). Hypotension
is frequently accompanied by azotemia because
perfusion pressure at the glomerulus drops too low to
maintain renal function.
Acute renal failure (particularly in renal artery stenosis)
arterial tone in the glomerulus, which maintains
glomerular filtration (re-visit Dr. Mallets diagrams from
Renal2 to see why this is the case)
Hyperkalemia
Study Guide see Cecils, pp685-687 for mechanism
and importance
Problematic in diabetics (often have renal problems)
Watch for interaction with K sparing diuretics
(spironolactone is used in CHF) and NSAIDs

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 R S

herapy (typically 3 days) includes Trimethoprim-sulfamethoxazole (co-trimoxazole); amoxicillin or

97
oquinolones are reserved for treatment failure due to multidrug resistant bacteria or patients allergic to

ofloxacin show good penetration into prostate.

erapy with ampicillin, a cephalosporin, such as ceftriaxone, an aminoglycoside, or co-trimoxazole is

osporins are potentially less toxic than co-trimoxazole and aminoglycosides.

ines, such as doxycycline, are useful since they are effective against Ureaplasma urealyticum and
on causative agents.
rythromycin.
azole and miconazole

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Drug treatment of acute HF:

Adrenergics are the mainstain - Dobutamine is usually
Step treatment of chronic HF: drug of choice
Restrict sodium Dopamine is preferred in some situations (low blood
Restrict water (rarely required) pressure/shock)
Give ACE Inhibitor (and diuretic if needed) PDE inhibitors
Give beta blocker for Class II, III with LV systolic dysfunction Vasodilators
Give digoxin if atrial fibrillation (unless beta blocker on board) and/or symptoms persist NTG
Give vasodilator (hydralazine/ isosorbide) Nitroprusside
Give newer inotropic agent Diuretics and morphine as needed

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Vitamins, especially vit E, can increase the risk of
bleeding in pt taking warfarin; foods high in vit K (eg
Supratherapeutic INR (eg pt has ecchymoses which is a minor bleeding complication but brussels sprouts, green tea, and spinach, organ meat,
wanting to maintain anticoagulation) - stop the warfarin and give oral vit K and continue to alfalfa, asparagus, broccoli, cabbage, cauliflower, kale,
follow INR to theraputic levels. Warfarin Overdose (ie serious bleeding) - no antedote - turnip greens, and watercress) can reduce the efficacy
can only give back clotting factors (FFP, danger of clotting), stop warfain, oral vit K of warfarin.

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Acute Iron Toxicity - seen almost exclusively in children. Adults can usually tolerate
large doses of oral iron without serious consequences. Consider the following scenario:
excess iron tablets, e.g., prescribed during pregnancy but no longer needed, are left in the
medicine cabinet; curious child sees what looks like M&M candies, child eats tablets and
becomes severely ill.
Ingestion of as few as 10 tablets of the commonly prescribed oral iron preparations can
287 be lethal if ingested by a small child. Large amounts of oral iron cause necrotizing
gastroenteritis, with vomiting, abdominal pain, and bloody diarrhea followed by shock,
lethargy, and dyspnea. Subsequently, improvement is often noted, but may be followed by
severe metabolic acidosis, coma, and death. Urgent treatment of acute iron toxicity is
necessary, especially in young children. Gastric aspiration, followed by lavage with
carbonate solutions to promote formation of insoluble iron compounds is the usual initial
treatment. Deferoxamine (Desferal), a potent and specific iron chelating compound
should be given systemically by intermittent IM injection or by continuous IV infusion to
bind iron that has already been absorbed. Deferoxamine can also be given via gastric
tube to chelate any remaining iron in the GI tract, but this is controversial. General
supportive measures for GI bleeding, metabolic acidosis, and shock must also be
provided.
288
Parenteral iron therapy is used only if oral
preparations cannot be tolerated, absorbed, or if
untoward reactions occur by this route. Iron
dextran complex is usually given IV (less tissue
staining), but also can be injected IM. Parenteral iron
use has been rising rapidly in the last several years with
the recognition that recombinant erythropoietin therapy
induces a large demand for iron that frequently cannot
be met through the physiologic release of iron from
reticuloendothelial sources. Allergic hypersensitivity
reactions and hypotension, vascular collapse,
headache, nausea are adverse reactions. Never
administer concomitantly with oral iron
preparations.
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Hypoglycemia due to 1) inappropriate dose, 2)

320
Measurements of HbA1c: Periodic measurement of HbA1c levels is used as an adjunct
to blood glucose monitoring to determine long-term hyperglycemic control. Normal
values vary from laboratory to laboratory but usually range from 4% to 6% in nondiabetic
patients. Each 1% increase in HbA1c can reflect an increase of 25 to 35 mg/dL in mean
blood glucose concentration. HbA1c < 6.5% is a recommended target.
mismatch of time of injection vs food intake, 3) exercise-
induced increased glucose utilization, or 4) other factors
that increase the sensitivity to insulin (adrenal
insufficiency, pituitary insufficiency). The more rigorous
the attempt to achieve euglycemia, the greater the risk
of hypoglycemia. Dysfunctional Counter-Regulatory
hormones: normally, glucagon is the predominant
counter-regulatory hormone. In Type 1 DM of long
duration, glucagon secretion in response to
hypoglycemia becomes deficient and epinephrine
becomes the dominant glucose-mobilizing hormone.
However, if the patient also suffers from autonomic
neuropathy, the epinephrine response is also deficient
and night-time severe hypoglycemia can result in
convulsions and coma.

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TBG levels may be altered in certain conditions, thus changing the total circulating pool of
thyroid hormones. For example, TBG levels are elevated during pregnancy in
response to high estrogen levels; this increases the serum concentrations of both
protein bound and total T4 and T3 but not the concentrations of free hormones. Biotransformation: T3 and T4 are deiodinated and/or
Since free concentrations are the relevant factor for biological activity and do not change, conjugated to their respective glucuronate and sulfate
thyroid function and action during pregnancy are not normally affected. The opposite conjugates and excreted in the bile. Half-life for T4 is 6
situation occurs during androgen therapy, when TBG levels are reduced. - 7 days; T3 has a much shorter half-life 1.5 days.

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*Terfenadine (Seldane) and Astemizole (Hismanal) were voluntarily withdrawn from the
market in 1998. These drugs produce the potentially fatal torsades de pointes cardiac
arrhythmia is the presence of other drugs that affect their metabolism. These agents
accumulate, usually a consequence of the simultaneous administration of a second agent
that competitively inhibits their metabolic degradation by the cytochrome P-450
isoenzyme 3A4. Other agents metabolized by this isoenzyme include macrolide
antibiotics (except erythromycin and azithromycin), the imidazole antifungals (e.g.,
fluconazole), HIV protease inhibitors (indinavir, ritonavir, saquinavir, and nelfinavir),
serotonin reuptake inhibitors (fluvoxamine, nefazodone, and sertraline), zileuton,
cisapride, sparfloxacin, mibefradil, and grapefruit juice.

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Opioid Effects: CNS

Analgesia mu & kappa receptors both reactive (affective) and sensory components of
pain are diminished, but the reactive component of pain is usually much more
diminished by opioids than is the sensory component! The classic descriptions are
either It doesnt hurt as much or It still hurts as much, but it just doesnt bother me.
Euphoria mu receptors
603 Dysphoria predominantly kappa receptors
Psychotomimetic kappa receptors (and for some drugs, perhaps sigma receptors)
Sedation
Respiratory depression - cause of death in overdose (decreased response of brainstem
to CO2)
Cough suppression - different receptors from those responsible for other opioid actions
(sigma receptors??)
Miosis - due to indirect parasympathetic actions (stimulation of the Edinger-Westphal
nucleus with oculomotor outflow; blocked by atropine). Little or no tolerance
development.
Nausea and vomiting - stimulation of the chemoreceptor trigger zone of the brainstem.
Opioid Effects: Vascular System:
Vasodilation - Morphine is by far the most efficacious
opioid in this regard (non-mu/non-kappa mediation),
useful in pulmonary edema - 2 factors come together
very nicely in this regard: (1) morphine-induced
vasodilation shifts fluid from the central to the peripheral
compartment; (2) opioids make the brainstem less
responsive to pCO2, which results in reduced
sympathetic tone (patients dont care as much about
difficulty breathing). With relaxation of the sympathetics
comes easier movement of fluid from central to
peripheral compartment

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Avoid use during third trimester unless absolutely necessary:
low birth weight, increased perinatal mortality, anemia, antepartum and postpartum
hemorrhage, prolonged gestation, premature closure of ductus arteriosus
664
Aspirin absorption
Since aspirin is an acid, it exists principally as
unionized drug at the low stomach pH and is readily
absorbed by passive diffusion into the mucosal cells of
the stomach. Once it diffuses into the cells it
becomes ionized and trapped. This process may lead
to accumulation of the drug and may contribute to the
toxic effects on the stomach lining. Aspirin should be
taken with food or large volumes of fluid. Enteric coated
tablets (Ecotrin) do not dissolve until reaching the small
intestine; this helps minimize, but does not eliminate, GI
toxicity (toxicity due to prostaglandin inhibition is still a
key factor). Misoprostol, an analog of PGE 1, is
sometimes prescribed for patients who must take
NSAIDs chronically.
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679 Toxicity of Adrenocortical Steroids: Two categories of toxic effects result from the
therapeutic use of corticosteroids: withdrawal of steroid therapy and those resulting
from continued use of supraphysiological doses. The side effects from both of these
categories are potentially life threatening and mandate a careful assessment of the risks
and benefits in each patient.
Withdrawal of Therapy
1. The most frequent problem is flare-up of the underlying disease.
2. The most severe complication of steroid cessation is acute adrenal insufficiency, which
results from too rapid withdrawal of corticosteroids after prolonged therapy has led to
suppression of the HPA axis.
3. Many patients recover from HPA suppression within several weeks or months; others
require a year or longer.
4. Patients who have received supraphysiological doses of glucocorticoids for a period of
2 weeks within the preceding year should be considered to have some degree of HPA
impairment in settings of acute stress and should be treated accordingly.
5. Less severe withdrawal is characterized by fever, myalgias, arthralgias, and malaise.
680
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684
Toxicity Due to Continued Use of Supraphysiological Corticosteroid Do
1. Suppression of HPA axis & life-threatening susceptibility to stress up
2. Fluid and Electrolyte Handling: hypokalemia, edema, hypertension. Hyp
can usually be managed with diet and insulin.
3. Immune Response: Increased susceptibility to infection and reactivati
4. Peptic Ulcers: significant numbers of patients treated with supraphysiolog
develop peptic ulcers with hemorrhage and perforation. Many of these patien
with NSAIDs. Use caution in patients susceptible to peptic ulcers.
5. Myopathy: weakness of proximal muscles; diminished respiratory muscle
important in patients with COPD or asthma. Recovery from steroid myopathi
incomplete.
6. Behavioral Changes: insomnia, nervousness, changes in mood and psyc
Suicidal tendencies are not uncommon.
7. Cataracts: Related to both dose and duration of treatment. Children are
Resolution of opacities may not occur after stopping drug.
8. Osteoporosis: Osteoporosis and vertebral compression fractures are freq
in patients of all ages and are related to both dosage and duration of therapy
inhibit osteoblasts and bone formation; inhibit GI Ca2+ absorption and stimul
which leads to greater osteoclast activity and increased bone resorption. Wh
osteoporosis is an indication for withdrawal of glucocorticoid therapy.
Ca2+ supplements, with or without vitamin D, for patients who must take cort
9. Growth Retardation: in children can occur with prolonged treatment at re
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3. Drugs kill cells by a first-order process, i.e., each

treatment kills a "constant fraction" of the cells, not a
constant number of cells. From our example above,
10E12 tumor cells are reduced by 99.9% by drug
1. Log kill Hypothesis (see cancer chemotherapy notes for graph and example): treatment leaving 10E9 cells. A subsequent treatment
713
Patients with widespread cancer, i.e., acute leukemia, could have 10E12 (1 trillion) tumor would kill 99.9% of the remaining cells, leaving 10E6
cells in the body at the time of diagnosis. Suppose the highest tolerated dose of an cells, and so on.
anticancer drug was effective in killing 99.9% of these tumor cells. This would probably 4. Tumor cells remain. In chemotherapy of bacterial
appear as symptomatic improvement and apparent clinical remission of the disease. infections, a 99.9% reduction in the numbers of bacteria
However, there would still be 10E9 (1 billion) tumor cells remaining in the patient. Some of would likely be curative, since the body's immune
these remaining cells might be inherently resistant to the effects of the drug, or the cells system could then eliminate the remaining invading
might be compartmentalized in areas of the body inaccessible to the drug, e.g., CNS. In cells. With cancer, the immune system is much less
addition, if a cell cycle specific drug was used, some cells might not be in the sensitive effective and many cancer chemotherapeutic
phase of the cell cycle. Therefore, must retreat and/or treat with combination of regimens lead to immune suppression directly
agents (hemopoietic tissues are killed).
2. Total Cell Kill: since, theoretically, cancer can arise from a single mutant cell and a 5. Combination chemotherapy: To overcome the
single cancer cell can give rise to many, many progeny cells (logarithmic growth), the ideal limitation of this log-kill problem, combinations of
is to kill all tumor cells. Sometimes this means taking the patient to the limits of toxicity chemotherapeutic agents with different mechanisms of
and then "rescuing" the patient, allowing normal cell recovery, and then repeating the actions and toxicities are used. A single drug may
sequence. produce regression of the disease, but not a cure.

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890

Simplified Neurotransmitter Schematic for Predicting Therapeutic Effects: In Consider impact of pharmacotherapy in three
Huntingtons chorea, there is primarily a GABAergic loss in the indirect pathway, dopaminergic pathways in relation to their function and
leading to a loss of inhibition of thalamic activity. Cholinergic neurons may also be lost; involvement in different pathology:
that reinforces the effect, and dopamine is left to inhibit whatever is left. Huntingtons Nigrostriatal (motor function; Parkinsonism)
disease symptoms involve increased and dysregulated output of the extrapyramidal Mesolimbic (reward function; schizophrenia)
circuitry and can be viewed as opposite those of Parkinsonism. Mesocortical (reward function; schizophrenia)

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Inhibition of Na+ Conductance:

Sodium ion (Na+) channels: Action potentials
Calcium ion (Ca2+) channels: Neurotransmitter release
GABA receptors: Inhibition
Located on axons - propagation of action potentials
Reduced neural activity - fewer action potentials, elevate
seizure threshold
Good for partial, tonic-clonic

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950

SSRIs: Suicidality in Children (& Adults) SSRIs: Other Clinical Uses

Prominently reported in the popular press. ANXIETY
951 FDA recommends warning for all antidepressant drugs Obsessive compulsive disorder
http://www.fda.gov/cder/drug/antidepressants/SSRIPHA200410.htm Premature ejaculation
Evidence for increased suicidal thought and behavior; however, no completed suicides in Panic disorder
any of the FDA cited studies Premenstrual dysphoric disorder
Note: Controversy as to if antidepressants cause suicidal tendencies/ideations weak Social phobia
evidence, pt who are depressed may have suicidal tendencies, and part of reason why Bulimia nervosa
treat; also very unlikely to effectively kill ones self with SSRI (as opposed to Tricyclics Note: not used in chronic pain
which were (are?) the #1 way depressed pts killed themselves)

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982 Typical Antipsychotics, Two broad classes:

Phenothiazines
Chlorpromazine (Thorazine) original prototype Rapidly Occurring Neurologic Side-Effects - Direct
Prochlorperazine and promethazine (anti-nausea use. All antipsychotics have anti-emetic Result of Blocking DA Receptors in the Basal
properties. These 2 are particularly popular). Ganglia: The extrapyramidal effects of antipsychotics
Butyrophenones are mediated by the basal ganglia (caudate/putamen),
Haloperidol*** (a must know drug as the standard against which all others are judged) while the antipsychotic effects are mediated by the
mesocortical and prefrontal cortex systems.
Critical Points for Typical Antipsychotics Extrapyradmidal effects include:
High affinity D2 receptor antagonists Dystonias
Clinical potency highly correlated with affinity for D2 receptors Parkinsonism
Most of these drugs are very messy in their pharmacology - antagonists at Neuroleptic Malignant Syndrome
dopamine, alpha1, muscarinic and histamine receptors.

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BZD Dependence - Nasty problem:

1. Initial anxiety returns during withdrawal
2. Additional anxiety occurs because of withdrawal
Net effect = intolerable anxiety
998 Symptoms of withdrawal occur before signs of
BZD Physical Dependence = an abstinence syndrome when: drug administration stops withdrawal, and anxiety/insomnia are the first withdrawal
(spontaneous) or an antagonist is given (precipitated) symptoms
The higher the dose, and Cross-dependence with other sedative-hypnotics -
the more frequently the dose is taken, and EtOH & barbiturates; often referred to as dependence
the longer the dose is taken, then of the sedative-hypnotic type. Also appropriate to refer
the greater the physical dependence to it as dependence of the BZD type.
the nastier the withdrawal syndrome So:
Limit the number of pills in a prescription
BZD Abstinence Syndrome - Withdrawal S&S: Counsel the patient to never use them for more than 3
Signs: tremors and seizures successive days
Symptoms: ANXIETY, insomnia, nausea, malaise

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Management of acute alcohol intoxication:
Prevent severe respiratory depression Progress of EtOH Liver Disease
Prevent aspiration of vomitus alcoholic steatosis (fatty liver) - reversible; 90% of
Give thiamine (depleted in alcoholism) heavy consumers of alcohol
May need to treat hypoglycemia and ketosis alcoholic hepatitis and fibrosis (replacement of healthy
If patient is hypoglycemic, give thiamine before glucose - with thiamine deficiency, tissue with scar tissue) - 40% of heavy consumers of
glucose may result in lactate acidosis and Wernickes encephalopathy. alcohol
May need to treat electrolyte and phosphate imbalances cirrhosis and liver failure - 15-30% of heavy consumers
of alcohol
Intoxication is more pronounced when BEC is rising than when falling

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1047

Speed of Onset; Abuse liability is higher for drugs and

modes of administration yielding rapid access to critical
brain sites. Physicochemical properties, e.g., ionization
1048 & lipid solubility may limit or facilitate potential for abuse.
For example, substances that enter the brain slowly
have less abuse potential even though they may
ultimately reach high concentration in the brain.
Other pharmacological actions The most reinforcing effects of drugs occur during
While control of drug self-administration relates to potency/efficacy in neural reward the increase in plasma/brain concentration. Indeed,
circuitry; numerous other pharmacological actions occur independently that mediate even substantial levels of drugs may not be particularly
therapeutic or toxic effects: euphoric during the time when plasma/brain
Autonomic nervous system (e.g., cardiovascular effects of cocaine) concentrations are falling. True for: opioids,
CNS arousal systems psychostimulants, nicotine, ethanol
Respiratory centers (e.g., opioids) Reinforcing effect is thus profoundly influenced by route
of administration
 R S

1049

1050

1051

Nicotine: In operant conditioning, positive reinforcement

Significant genetic influences, definite social link
Research is demonstrating that the mesolimbic dopamine system active in cases of
nicotine addiction is the same system linked to heroin, morphine, amphetamines,
marijuana, and alcohol.
is the process by which certain consequences of a
response increase the probability that the response will
recur. Food, water, praise, and money are positive
reinforcers.
Many substances also appear to be positive reinforcers,
including opium, cocaine, nicotine, and barbiturates.

1052
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Benefits (in addition to contraception) of

combined OC:
Reduction in risk of some cancers
25 (endometrial, ovarian, possibly colon ca), no
proven increased/decreased risk for breast
cancer
Increase in bone density
Improving dysfunctional bleeding Hepatic tumor
Irregular, heavy flow all improved, less painful Hepatoma (associated with long term OC use, may Do not give to pt <16yo because of E effects
Improving acne (decrease by 60%) rupture) on growth (interfers with HPG axis), give Cyclic
Also hot flashes in perimenopausal women medroxyprogesterone acetate

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74

Angioneurotic edema
Rapid swelling in the upper respiratory tract DRUGS THAT REDUCE THE RATE OF CARDIAC
life-threatening REMODELING
0.1-0.2% incidence ACE-I
Typically occurs within first week of therapy, Hydralizine/Isosorbide (in ACEI intolerant Many patients tx with ACEIs show return to
often with the first dose individuals) near baseline levels of angiotensin II, which
Not immune mediated BETA-BLOCKERS occurs by activation of the chymase pathway.
Bradykinin is listed as a culprit, but the evidence ALDOSTERONE ANTAGONISTS Nonetheless, the ACEIs continue to be
is not compelling Remember: triple A HIB (ACEI, Aldosterone efficacious.
Antagonists, hydralizine isosorbide, beta blockers

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212

Digitalis and intravenous inotropes may

eliminatin half life ~ days (1.7) compared to
digitoxins 7 days; therapeutic concentration
is 0.5-2ng/ml compared to digitoxins 14-
21ng/ml; Digitals drugs have a low therapeutic
index
increase O2 demand, provoke serious
Digitalis increase ERP ( the time when additional arrhythmias, and extend infarction. Current
depolarizations are not allowed) & reduce the recommendations support the use of digoxin
possibility for re-entry circuits & hence inselected pts recovering from acute MI who
tachycardias, atrial flutters. This makes them good develop SVT (eg AFib) or HF refractory to ACEI
as an Anti-arrythmic - according to Dr. Olgesby and diuretics.

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Atrial fibrilation - tx with warfain therapeutic

anticoagulation, target INR is generally 2.0-3.0
(2.5-3.5 in pts over 75yo) if INR 5-9, stop dose and give IV vit K

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287 Hemochromatosis: The most common genetic

Chronic iron overload, also known as
hemochromotosis and hemosiderosis,
results when excess iron is deposited in the
heart, liver, pancreas, and other organs. It most gene, called the HFE gene, that regulates the
commonly occurs in patients with an inherited
disorder characterized by excessive iron
absorption (homozygous for HFE gene) or in
individuals who receive many red cell
transfusions. Chronic overload due to
excessive oral iron intake is unlikely.
disease in people whose ancestors came from
northern Europe is hemochromatosis, a disease
that causes the body to absorb too much iron. It is
due to an inherited abnormality in a specific
amount of iron absorbed from the gut. In people
who have two copies of an abnormal form of the
gene, the protein made by the gene cannot tell the Infants, up to two years old, are at greatest
cells in the gut when the body is full of iron, so the risk for iron deficiency because of the
gut keeps on absorbing iron and excess iron demand for growth. Also pregnant women.
damages many different organs. Give both prophylactic iron.

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320
Precautions Against Hypoglycemia: all
patients who receive insulin should:
a. Be aware of symptoms of hypoglycemia.
b. Carry some form of easily digested glucose.
c. Carry a medical ID card or bracelet.
d. Be prepared to measure their own glucose
level.
Treatment of Hypoglycemia: consists of
ingesting glucose. If severe, IV glucose or
glucagon injections can be employed.
321
322
323
324
325
326
V
Ketoacidosis: Diabetic ketoacidosis (DKA) is
a serious condition that often calls for constant
Insulin Allergy and Resistance intravenous infusion of insulin. (Only
1. The availability of human insulin and highly regular or aspart insulin can be given IV). A
purified animal insulins has greatly decreased relatively low dose of insulin (0.1 U/ kg /hr) is
allergic reactions to the hormone. usually sufficient to inhibit lipolysis and
2. The most frequent allergic reactions are IgE- gluconeogenesis completely and to produce
mediated local cutaneous reactions, but near-maximal stimulation of glucose uptake.
occasionally patients may develop a life-threatening Blood glucose levels fall by about 10%/hr; the
anaphylactic reaction or insulin resistance due to acidosis is corrected more slowly. Appropriate
circulating IgG antibodies. replacement of fluid and electrolytes is an
3. Patients who develop allergic reactions to bovine integral part of the therapy. Insulin must be
or bovine/porcine insulin should be switched to administered by SQ injection prior to
human insulin. Desensitization, antihistamines, or discontinuing i.v. infusions because of the short
glucocorticoids are sometimes required treatments. plasma t1/2 of insulin.
 T U
327
328
329
330
Feedback Regulation: The hypothalamus and
pituitary are subject to feedback regulation by
circulating free T3 and T4. High free
concentrations of T3/T4 inhibit TRH and TSH
331 release, i.e., negative feedback. This feedback
loop is important in maintaining normal
(circadian) levels of thyroid hormone activity.
Autoregulation of the Thyroid: The thyroid
also regulates its uptake of iodide and T3/T4
synthesis by intracellular mechanisms
independent of TSH. High iodide
concentrations in the blood inhibit uptake
and organification.
332
See THYROID FUNCTION TESTS at Thyroid Drug
Notes Martin
V
Interference by Drugs and Disease States: Unlike TSH measur
measurements can be influenced by a number of drugs and disea
5 fluorouracil, perphenazine, clofibrate, narcotics, acute hepatitis, a
can increase serum TBG concentrations and cause an elevated to
durgs and disease states may decrease TBG concentrations and r
in serum including androgens, glucocorticoids, 1 asparaginase, da
malnutrition, acromegaly, and nephrotic syndrome. High concentra
salicylates, fenclofenac, furosemide, mitotane, and phenylbutazon
binding proteins. Because of these multiple effects of drugs and n
concentrations, measurement of serum TSH concentrations in a
provides the most accurate assessment of thyroid function in
hypothalamic disease.
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603
Opioid Effects: GI System
Constipation - decreased motility secondary
to increased tone (due to effects both in the
CNS and on the local enteric nervous system).
The tone is sometimes described as spasm it
is not coordinated contraction
Little or no tolerance development
604
605
606
607
Opioids: Excessive Use and Abuse
Tolerance - Occurs even with the lowest
therapeutic doses and increases as dose and
duration of treatment increase
Dependence/Withdrawal
Overdose
Maintenance Treatment
V
Opioid Tolerance
Tolerance, with cross-tolerance, can develop to
all opioid agonists
rate of development varies among agents but
generally develops faster with more potent
drugs and/or higher doses
starts with first dose but doesnt become
clinically relevant for 2-3 weeks (@ normal
therapeutic doses)
there is specificity of tolerance development
tolerance can be profound (as great as 35-fold)
No tolerance develops for constipation nor
miosis! - presence of constipation/miosis
indicates opioid use, but not degree pain nor
dose taken
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663 Mixed order kinetics of aspirin metabolism.
Esterases present in tissues and blood
hydrolyze aspirin to salicylate and acetic acid.
Salicylate is conjugated in the liver to water-
soluble metabolites. At low doses, aspirin
and salicylates are cleared by first-order
kinetics. However, at the high doses used to
treat arthritis patients, the liver conjugation
pathways become saturated and zero-order
kinetics of elimination exist. Under these
conditions, the half-life of the drug is 15 hours
or longer (as opposed to the usual 2-4hr).
Under these zero-order conditions, small
increments in dose produce disproportionate
increases in plasma concentration that can lead
to toxicity. The long half-life allows twice per
day dosing in arthritis patients.
664
Uricosuric Effects of Salicylates: Salicylate is an
organic acid secreted into the urine by a transport
system also responsible for uric acid secretion.
"Paradoxical effect": at low doses of aspirin, renal
tubular uric acid secretion into the urine is
decreased and net retention of uric acid results, at
higher doses of aspirin, proximal tubular
reabsorption of uric acid is inhibited and net
excretion of uric acid in the urine results. These
mechanisms are potentially important in patients
with gout; (low dose) aspirin should not be used
for analgesia in patients with gout. Changes in
urinary pH have significant effects on salicylate
excretion; for example, the clearance of salicylate is
about four times as great at pH 8.0 as at pH 6.0.
V
Respiration: in toxic doses, salicylates cause
respiratory depression and a combination of
uncompensated respiratory and metabolic
acidosis.
Hypersensitivity: as many as 15-20% of
patients experience hypersensitivity reactions
to aspirin. This syndrome is especially
prominent in patients with asthma, nasal
polyps, or chronic urticaria. This aspirin
intolerance manifests symptoms such as acute
profuse watery nasal secretions, angioneurotic
edema, generalized urticaria, and bronchial
asthma that potentially can progress to severe
dyspnea, hypotension, and shock.
Hypersensitivity to aspirin is a
contraindication to therapy with any NSAID.
Patients that are intolerant to aspirin may react
to any of these drugs, despite their chemical
dissimilarity.
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ysiological Corticosteroid Doses:

ng susceptibility to stress upon withdrawal.
a, edema, hypertension. Hyperglycemia with glycosuria

ty to infection and reactivation of latent tuberculosis.

679 with supraphysiological corticosteroid doses
nts treated
rforation. Many of these patients are also being treated
ble to peptic ulcers. Mechanisms of anti inflammatory and
diminished respiratory muscle function is especially immunosuppressive activity:
ecovery from steroid myopathies may be slow and a. Glucocorticoids inhibit both early inflammatory
processes (edema, fibrin deposition, capillary
ss, changes in mood and psyche, and overt psychosis. dilatation, leukocyte migration, phagocytosis) and
later manifestations (capillary and fibroblast
on of treatment. Children are particularly at risk. proliferation, collagen deposition and cicatrization
pping drug. (?)).
compression fractures are frequent, serious complications b. Glucocorticoids induce a family of proteins,
osage and duration of therapy. Glucocorticoids directly lipocortins, which inhibit phospholipase A2
GI Ca2+ absorption and stimulate renal Ca2+ excretion, activity and suppress the release of lipid mediators
ncreased bone resorption. When diagnosed, from cells. Glucocorticoids may also inhibit the
l of glucocorticoid therapy. Many experts advocate oral expression of prostaglandin synthase Except for replacement therapy, glucocorticoids
or patients who must take corticosteroids chronically. (cyclooxygenase), the rate limiting enzyme in the are neither specific nor curative (steroids cure
with prolonged treatment at relative low doses. generation of prostaglandin metabolites. nothing).

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 T U
Note on Toxicities: Initial listing is the primary
acute toxicity usually encountered, i.e., nausea
& vomiting; second listing, i.e., bone marrow
depression, is the delayed toxicity. Note that
713 many more toxicities occur with each class of
agent. Every chemotherapeutic regimen
administered in adequate doses will have some
deleterious side effect on normal tissues. Many
complications can be anticipated, and
considerable expertise has been gained in
treating and preventing them. Since almost all
chemotherapeutic agents target dividing cells, it
is not surprising that the most rapidly
proliferating healthy cell types of the body are
the most susceptible to damage, as well. Thus,
bone marrow stem cells, GI and buccal
mucosa, and hair follicles are killed along with
malignant cells. Myelosuppression, nausea
and vomiting, stomatitis, and alopecia are
the most frequently observed side effects.
714
715
716
717
Chemotherapy-induced bone marrow
suppression, manifested as leukopenia,
thrombocytopenia, and anemia, is the most
common dose-limiting toxicity. Blood counts
usually reach their nadir (low point) between 10 and
14 days after treatment, with recovery noted by day
21 and a return to normal by day 28. Neutropenia
increases the risk of infectious complications.
Thrombocytopenia may occur in patients receiving
chemotherapy but is less often dose-limiting than
leukopenia. Thrombocytopenia of this degree is
usually observed only with very intense
chemotherapeutic regimens, such as those used in
the treatment of acute leukemia. Some degree of
anemia is to be anticipated with chemotherapy.
V
Nausea & vomiting are major side effects of
cancer chemotherapy. Chemotherapy
appears to induce nausea and vomiting
through several pathways. Vomiting is
controlled by two medullary centers, the
vomiting center and the chemoreceptor trigger
zone (CTZ). The CTZ is stimulated directly by
various toxins or drugs to release
neurotransmitters, such as dopamine, which
then interact with the vomiting center. The
vomiting center coordinates the process of
vomiting through multiple efferent tracts.
Cerebral input, especially from visual or
olfactory stimuli, can also stimulate the
vomiting center. (Cisplatin is the worst)
 T U V

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Levodopa metabolized in GI tract (intestinal

mucosa) via dopa decarboxylase to DA l-aromatic
Drugs affecting activity of DA neurons will act in amino acid decarboxylase (ubiquitous enzyme).
all dopamine systems of the brain, even though Most (70%) of the drug is metabolized in the GI,
890 the intended targets in Parkinsonism are 27-29% stays in the periphery (toxic/SE; Do not use in psychotic patients
nigrostriatal, whereas the intended targets in hypovolemic shock pressor), and 1-3% crosses to Do not use with MAO-A inhibitors
schizophrenia are mesolimbic/mesocortical. the brain. Adding carbidopa allows 10% of dopa Do not use with narrow angle glaucoma
Therefore: to get into brain, which would cause more of dopa Side effects: Cardiac dysrhythmia, activate
Antipsychotics that block DA receptors can in the blood stream, but because so much more malignant melanoma (precursor to melanin),
produce Parkinsonism and/or dyskinesia. reaching the brain, can reduce dose and thus nausea, vomiting, dont use phenothiazine
Drugs for Parkinsonism that increase perpherial toxicity is not a problem (also see antiemetic. (chemoreceptor trigger zone)
dopamine or stimulate DA receptors may more of a sustained concentration reducing on/off Do not use with prochlorperazine,
have psychotomimetic effects. phenomenon). promethazine, metoclopromide

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 T U V

915
Old classic drugs still appear to be the most Treatments:
effective Do not have to sedate patient to control
Have adverse effects Pharmacotherapy: seizures
However, newer drugs not as effective and/or Seizure type determines treatment Require careful monitoring of blood levels
adverse effects worse More than one type of seizure may be present of drug and seizure frequency!!
Most newer drugs best used as adjuncts Treat all seizures Never discontinue drug abruptly, and shift
Starting to identify which drugs best for certain Multi-drug therapy may be necessary from one drug to another gradually (Allergic
syndromesmany of which are refractory to Nearly all anti-convulsants make some kind of rxn is the only reason to stop immediately)
standard treatment seizure worse Continue therapy until seizures absent for ~4
years

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948
949

950

Neurotransmittion notes: Homovanillic acid

(HVA, a major metabolite of dopamine) -
elevated in unmedicated schizophrenic pts;
951 decreased HVA in Parkinson's dz, depression,
and medicated schizophrenic pts. Increased
vanillylmandelic acid (VMA, a metabolite of NE)
elevated in pheochromocytoma. Decreased
body fluid concentration of 5-HIAA (metabolite Schizophrenics show increased size of cerebral
of serotonin) seen in depression. HVA and ventricles; decreased size of the hippocamus and
MHPG (metabolites of dopamine and NE limbic structures sucha s the amygdala and
respectfully) decreased in depression. decreased glucose usage in the frontal lobe

952

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 T U V

978

979

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981

Neuroleptic Malignant Syndrome

This syndrome occurs in 0.5-1.0% of patients.
Resembles a severe form of Parkinsonism with
catatonia, congnitive deficiencies, tremors and
Dystonias: defined by body region affected instability of the autonomic system ( i.e.
1 Torticollis -- muscle contractions leading to alterations in blood pressure and pulse rate).
twisting of the neck with an unnatural position of Parkinsons-like Syndrome In severe cases impairment of sweating and
the head Dystonias are one type of extrapyramidal effect of high fever (due to muscle contraction; see
982 2 Facial distortion antipsychotics. A second type is iatrogenic elevated CPK) can ensue with a 10% mortality
3 Tongue protrusion Parkinsons disease, also caused by antipsychotics rate.
4 Dysarthia -- imperfect articulation of speech blocking dopamine receptors in the basal ganglia. Treatment
5 Opisthotonus -- whole body spasm Rigidity or tremor (3 per second) at rest Stop antipsychotic and anticholinergics (Note:
6 Scoliosis -- bending of the spine Facial mask anticholinergics may be co-prescribed to
7 Oculogyric crisis -- rapid eye movements Bradykinesia or akinesia minimize extrapyramidal effects of
8 Akathisia - inability to sit; patient is constantly Treatment of Extrapyramidal Symptoms antipsychotics. As a side-effect,
pacing, restlessness - most common after about Reduce dose of antipsychotic anticholinergics inhibit sweating, which can be
a week of treatment. Do NOT give dopamine agents (e.g., do not deadly in Neuroleptic Malignant Syndrome)
Tx dystonias with anticholinergic or administer L-DOPA, a typical form of therapy in Give antipyretics
antihistamine (BZD (IM)); note akathisia normally occurring Parkinsons disease) Give a dopamine agonist (e.g.,
responds very well to beta blockers (eg Use anticholinergics bromocriptine)
propranolol) Give antispasmatic (eg Dantrolene)

983
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 T U V

998

BZD Dependence
Shorter elimination half-life drugs give nastier
signs and symptoms of withdrawal
Longer half-life drugs give less severe signs
and symptoms of withdrawal, but they are more
protracted.
If withdrawal is threatening to become
intolerable or if seizures are likely, consider
administering a longer acting BZD
Management of EtOH Withdrawal
Benzodiazepines may be administered as a
FDA warning: BZD and BZD alpha 1 subunit drugs substitute for EtOH followed by tapering.
are capable of producing anterograde amnesia Long acting BZDs like diazepam and
(short term memory) in large enough dose (dose to chlorazepate may be used because long half
produce muscle relaxation/hypnosis/surgery, not lives provide a built-in tapering effect.
usually at dose used for anxiety) With liver disease, a short-acting BZD such
as oxazepam or lorazepam may be used

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1038
 T U
1039
1040
1041
Chronic EtOH: Hepatic Effects
15-30% of chronic heavy drinkers develop liver
cirrhosis
A group of chronic diseases characterized by
fibrosis, nodules and loss of normal structure of
the liver tissue accompanied by functional
decline.
1042 women are more susceptible than men
concurrent infection with hepatitis B or C
increases severity
Chronic EtOH: GI & Other Effects
Pancreatitis - 3x higher than general public,
>10% of all cases
Gastritis
Reversible injury to small intestine
(Diarrhea, weight loss, vitamin deficiencies
(malabsorption))
Blood & plasma protein loss
1043
1044
V
Chronic EtOH: Other Effects
Cancer
Alcoholics have a rate of carcinoma ~10x normal Chronic EtOH: Cardiovascular Effects
Cardiovascular Dilated cardiomyopathy with ventricular
dose-dependent hypertension hypertrophy and fibrosis.
cardiomyopathy (~1/3 of all cardiomyopathies) Arrhythmias
Chronic EtOH: Cardiovascular Effects Cellular effects:
*** HYPERTENSION *** membrane disruption
11-30% of hypertension due to heavy alcohol depressed mitochondrial and SR function
consumption (males) intracellular accumulation of phospholipids
In the population at large there is a 50% higher and fatty acids
risk of hypertension among individuals consuming up-regulation of voltage dependent Ca+2
3-4 drinks per day (100% higher w/ 6-7 drinks/day) channels
increased HDL cholesterol
 T U
1045
1046
1047
Route of self-administration: Preferred routes
depend upon physicochemical
properties/limitations of the drug:
Oral (swallowed): slow absorption for many
drugs; rapid for ethanol
Sublingual (chewed): more rapid than oral;
1048 less rapid than inhaling or parenteral
administration. Bitter taste of alkaloids is a
deterrent to using this route.
Nasal (sniffed): e.g., cocaine hydrochloride,
methamphetamine, heroin; readily absorbed
Inhaled (smoked): popular route. Allows heat-
pyrolyzed drug to reach large absorbing
surface; high concentrations reach brain very
quickly: Cocaine (crack), Methamphetamine
(Ice), Nicotine, Marijuana, Opioids (chasing the
dragon), PCP
Intravenous: most direct route
Speed of Termination: Termination of the
reinforcing effect of abused drugs is associated
with declining plasma concentration, not with
absence of concentration. Drug taking tends to
occur more frequently when the high is
terminated rapidly. Withdrawal signs and
symptoms are more likely with a more rapidly
eliminated drug. Abused drugs tend to have short
t of elimination; Note: The reinforcing effect may
be terminated more rapidly than other effects of the
drug (e.g., toxicity, which may occur in direct
proportion to the plasma concentration). Continued
drug taking to achieve a reinforcing effect may thus
lead to accumulation in plasma to a toxic level. e.g.,
cocaine
V
Tolerance: A reduction in the response to a
drug after repeated administrations; may take
form of a reduction in potency, efficacy, or both.
(Graphically: Rightward, downward shift -
decrease in potency, decrease in efficacy,
respectifully)
Tolerance plays a key role in drug abuse and
dependence, because it leads the user to
escalate dosage to achieve equivalent
high. Note: Tolerance may develop more
rapidly to the reinforcing effect than other
effects of the drug related to toxicity. This
effectively decreases the therapeutic index of
the drug in a tolerant individual, leading to
higher probability of accidental fatality (e.g.,
opioids; respiratory depression). Tolerance may
involve a variety of mechanisms. Tolerance is
not limited to drugs of abuse
 T U V

1049

1050

Dependence syndrome cont:

1051 Acute intoxication: There must be
dysfunctional behavior or perceptual
abnormalities, as evidenced by at least one of
the following: insomnia, bizarre dreams, lability
of mood, derealization, interference with
personal functioning (?)
At least one of the following signs must be
present: nausea or vomiting, sweating,
tachycardia, cardiac arrhythmias
Dependence syndrome - Three or more of the
following manifestations should have occurred
together for at least 1 month or, if persisting for
periods of less than 1 month, should have occurred
together repeatedly within a 12-month period:
1) a strong desire or sense of compulsion to take
the substance
2) impaired capacity to control substance-taking
behavior in terms of its onset, termination, or levels
of use, as evidenced by: the substance being often
taken in larger amounts or over a longer period
than intended; or by a persistent desire or
unsuccessful efforts to reduce or control substance
use
3) a physiological withdrawal state when
substance use is reduced or ceased, as
evidenced by the characteristic withdrawal
syndrome for the substance, or by use of the
same (or closely related) substance with the
intention of relieving or avoiding withdrawal
symptoms
4) evidence of tolerance to the effects of the
substance, such that there is a need for
significantly increased amounts of the
substance to achieve intoxication or the
desired effect, or a marked diminished effect
with continued use of the same amount of the
substance;

1052
 T U V

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25
Migrane HA are CI with OC - d/t association of
migrane, OC, and stroke (2 to 4 fold increase).
Greatest risk in pts with aura and and focal
neurologic symptoms. No risk associated with
tension HA
Older combined formulas had 50 micrograms
of estrogen (and had higher incident of MI in
smokers); newer formulations usually have 35
microg (new studies show no increased
incidence of MI in any age, but guide lines
remain that OC should not be given to >35 yo
smokers)

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Hyperkalemia: Problematic in diabetics (often

have renal problems) & Watch for interaction with
K sparing diuretics (spironolactone is used in
CHF) and NSAIDs

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Note: though digoxin may significantly reduce

hospitalization rates and need for other
interventions in pts already receiving diruretics
and ACEI, it has not been shown to increase
survival of CHF pts.

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Drug Interactions and Glucose Metabolism: A

large number of drugs can cause hypoglycemia or
hyperglycemia or may alter the response of
diabetic patients to insulin. The most common
drug-induced hypoglycemic states are those
caused by ethanol, -adrenergic antagonists, and
320
salicylates. Ethanol inhibits gluconeogenesis. -
antagonists pose a risk of hypoglycemia
because of their capacity to inhibit the effects Basal Insulin (Fasting state)
of catecholamines on gluconeogenesis and a. Controls fasting glucose levels
glycogenolysis. These agents also mask the b. Produced at a constant rate because the liver makes
sympathetically mediated symptoms glucose at a constant rate
associated with the fall in blood glucose, e.g., Bolus Insulin (Fed state)
tremors and palpitations. Salicylates enhance a. Controls glucose disposal in the fed state
pancreatic -cell sensitivity to glucose and No role for oral agents in DM type I (only b. Immediate rise and sharp peak at 1 hour
potentiate insulin secretion. insulin and pramlinitide) corresponds with food intake

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328
329
330
States: Unlike TSH measurements, T4 and free T4
a number of drugs and disease states. Estrogens, tamoxifen,
e, narcotics, acute hepatitis, and acute intermittent porphyria
ons and331cause an elevated total T4 concentration. Other
ase TBG concentrations and reduce total concentrations of T4
orticoids, 1 asparaginase, danazol, celestipol niacin,
tic syndrome. High concentrations of phenytoin, barbiturates,
mitotane, and phenylbutazone may displace T4 from serum
multiple effects of drugs and non-thyroidal illness on serum T4
um TSH concentrations in a sensitive assay generally
ment of thyroid function in the absence of pituitary or
332
Y
Hashimoto's Thyroiditis (Chronic Lymphocytic Thyroditis) and Mild Hypothyroidism with Simple
Goiter:
1. In these conditions, there is deficient secretion of thyroid hormone, negative feedback to the
hypothalamus and pituitary are reduced, and consequently excess output of TSH results. Excess TSH
stimulates hypertrophy and hyperplasia of the gland and goiter develops.
2. The therapeutic objective is to replace the T4/T3 levels to normal. Too little thyroid hormone fails to
alleviate the hypothyroidism, while too much can cause cardiac problems and bone demineralization with
osteoporosis. The dosage must be individualized and varies with the size and age of the patient. Mild
hypothyroidism can be treated initially with one half to three quarters the expected maintenance dosage,
with full replacement amounts given after one to two months. Patients with pre existing cardiac problems
must be given gradual increments in dosage and carefully monitored.
 W X Y

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 W X
603
Opioid Dependence (accompanies tolerance
development) - may include both physical and
psychological dependence; withdrawal
syndrome is seen upon cessation of drug use
or upon treatment with opioid antagonists or
mixed agonist/antagonists (precipitated
withdrawal).
604
605
606
607
Y
Opioid Withdrawal - Treatment -Three main
approaches:
Opioid Withdrawal: 1) Do nothing. From a pharmacological standpoint, no
Begins 6-12 hr after the last dose of a short treatment is necessary. Monitor patient. Some
acting opioid and as long as 75 or more hr treatment centers believe it beneficial to allow the addict
after a very long acting opioid to suffer through withdrawal while providing counseling.
Heroin withdrawal is considered brief lasting 2) Detox the patient with methadone or
5-10 days, and is intense. buprenorphine. The idea behind this approach is to
Longer acting agents (e.g., methadone) substitute a longer acting opioid for the abused agent
produce a slower onset, longer lasting and less (usually short acting). Longer acting agents produce a
intense withdrawal. more protracted, but less intense withdrawal syndrome
3) Treat with clonidine (2 agonist). Many opioid
Opioid Withdrawal - Symptoms: rhinorrhea, withdrawal symptoms are due to lack of opioid
lacrimation, yawning, chills, piloerection, suppression of the locus ceruleus, results in excess
hyperventilation, hyperthermia, mydriasis, sympathetic outflow; no consistent effects on cravings;
vomiting, diarrhea, anxiety has analgesic actions
 W X Y

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661

662
 Drug-drug interactions: potential drug-drug
interactions with aspirin, salicylates, and other
NSAIDs are numerous. W Notable examples
include:a. Antacids (given for relief of NSAID-
induced ulceration) delay NSAID absorption. b.
NSAIDs may displace other protein bound
drugs and vice versa, e.g., phenytoin, thyroxine,
thiopental. c. Aspirin increases the risk of
bleeding for patients taking heparin or warfarin
anticoagulants. d. Aspirin and salicylates block
the uricosuric effects (to increase excretion of uric
acid) of probenecid and can worsen the
symptoms of gout.
Toxicity:
a. Salicylism is the term used for mild salicylate
intoxication and is characterized by nausea,
vomiting, tinnitus (ringing in the ears),
hyperventilation, headache, mental confusion,
and dizziness. Tinnitus begins to appear at the
663 top of the therapeutic range and is a reliable
indicator of plasma concentration range.
b. Severe toxicity due to overdose: accidental or
intentional overdose with aspirin is not
uncommon. Under these conditions, the
symptoms listed above are followed by fever,
dehydration, delirium, hallucinations, convulsions,
coma, respiratory and metabolic acidosis, and
death. Children are especially vulnerable to
salicylate induced intoxication and death which
can occur with ingestion of as few as 30 adult
tablets or 4-5 ml of methyl salicylate found in
liniments. Aspirin overdose is an acute medical
emergency. Treatment consists of cardiovascular
and respiratory support, correction of acid-base
imbalance, and enhancement of elimination
(lavage with activated charcoal, i.v. bicarbonate).
664
X Y
Aspirin as a Therapeutic Agent in
Cardiovascular Disease
1. Aspirin therapy confers conclusive benefits
in the acute phase of evolving myocardial
infarction (MI) and should be administered
routinely to virtually all patients with
evolving MI.
2. Secondary prevention of MI and Stroke:
Long-term aspirin therapy confers conclusive
net benefits on risk of subsequent MI, stroke,
and vascular death among patients with a wide
range of manifestations of cardiovascular
disease. Daily aspirin (75-325 mg/d) should be
strongly considered for all patients (men and
women) who have experienced chronic stable
angina, MI, TIA, or occlusive stroke and who
are at elevated risk of subsequent vascular
events.
3. Primary prevention of Cardiovascular
Disease: Currently, the use of aspirin therapy
for primary prevention remains inconclusive.
Additional clinical trials are necessary to firmly
establish the benefit-to-risk ratio of long-term
aspirin in apparently healthy persons. Taking
into account an individual patient's particular
cardiovascular risk profile, aspirin may be NSAIDs inhibit renal Na excretion, and can impair the
warranted. antihypertensive action of diuretics as well as drugs that
4. Additional proven benefits: reduction of block the RAS. Becase a fall in renin & AII levels is a
thromboembolic complications associated with compensatory mech that normally serves to counter
artificial heart valves; decrease in thrombotic volume-dependent HTN, the bp-raising effects of
occlusion of uremic patients undergoing NSAIDs are problematic with ACEI-based therapy
hemodialysis; increased potency of coronary (interruption of mech). Also occurs with asprin > 325mg
bypass grafts. (not with 81mg/d) (Cecil 358)
 W X Y

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Antiemetic regimens always should be given on

a routine schedule, preferably beginning 24 h
before chemotherapy administration. Treatment
on an as-needed basis is generally inappropriate.
The phenothiazines, such as prochlorperazine
713 and chlorpromazine, are the most widely used
antiemetic agents and appear to exert this effect
through their antidopaminergic and anti-
serotoninergic activities. The serotonin
antagonists ondansetron!!, granisetron, and
dolasetron are the newest and among the most
effective antiemetic agents. They selectively block Stomatitis, an inflammation of the oral mucosa, is a
the serotonin receptor 5-HT3, which is present major complication of cancer chemotherapy. Early signs
peripherally on the vagus nerve and centrally in The cannabinoid dronabinol (Marinol) of stomatitis are erythema and edema, which may
the CTZ. contains the principal psychoactive agent in progress to frank, painful ulcerations that persist for from
Common antiemetics: marijuana, -9-THC. It is available only in oral several days to a week or longer. The painful ulcers
Ondansteron (most effective)!! formulation and appears to be most effective result in poor oral intake with subsequent dehydration
Prednisone against mild or moderately emetogenic and malnutrition. The lesion also may become
Diphenhydramine chemotherapeutic regimens. It produces secondarily infected and further complicate patient
Dronabinol significant mood alterations, including management. Virtually all chemotherapeutic agents will
Prochlorperazine dysphoria in some patients. cause stomatitis if given at sufficient dose intensity.

714

715

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Failure of Levodopa Therapy - loss of

effectiveness after 3-8 years!!
Response fluctuations (dyskinesia/akinesia -
less likely with agonist compared with levodopa)
890 End of dose failure - (reemergence of PD
symptoms) & On-off phenomena - severe
diskinesia during off period; associated with falling
plasma levels of levodopa. Can sometimes be
fixed by: adding agonist, dividing dosage, drug
holiday. increase dosing density or use
Levodopa/Carbidopa prolonged-release formula
(Sinemet CR); add COMT-inhibitors, selegiline,
add agonist.
Drug induced Parkinsonism with
Antipsychotic therapy (particularly true for
haloperidol), seen as tremor, rigidity,
bradykinesia.
reduce dose or switch antipsychotic
anticholinergics
amantadine
NEVER l-dopa; be able to explain why??????
Rem: black man (substantia nigra) walking in the park
(parkinsons dz) smoking dope (dopaminergic) walking
the tigers path (to the striatum)
Rem: the tiger (striatum) hunts (huntingtons dz) the
black man (projection to substantia nigra), when the tiger
attacks him, the man screams GABA
Rem: the ballers leaned R on the car seat (hemiballism)
while he bumbed and danced with his L arm to the sub
woffer (subthalamic, contralateral)

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Dangers of combination therapy

Phenytoin level decreased by carbamazepine,
Why use more than 1 drug? phenobarbital.
If adequate control is not achieved with single Carbamazepine level decreased by
drug phenobarbital, phenytoin. Level increased by
915
When two or more seizure types present valproic acid
Potentiate seizure control while reduce adverse Valproic Acid level decreased by
effects?? carbamazepine, phenobarbital, phenytoin
HOWEVER, Recent studies have indicated that Phenobarbital level increased by valproic acid,
in almost all cases, antiepileptic agents are phenytoin.
better tolerated as monotherapy. Lamotrigine level decreased by
Exceptions appear to be if adverse effects are carbamazepine, phenobarbital, phenytoin. Infantile Spasms (Wests Syndrome): generalized,
directly opposite: Level increased by valproic acid. often myoclonic but can be of heterogeneous types;
valproate: weight gain Clonazepam level decreased by epileptic syndrome of unknown cause with onset before
zonisamide: weight loss carbamazepine, phenobarbital 1 year, associated with mental retardation.

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Note that it takes usually 3-4wks before SSRI

have effect (longer for OCD)

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Long Term Neurologic Side Effects - Tardive

dyskinesia is the major long-term side effect
of chronic treatment with typical antipsychotics.
tardive = belated or delayed
dyskinesia = impairment of voluntary
movement
Other Side Effects of Antipsychotics Late appearing, occurs after chronic treatment
Dysphoria - It was once said that no one likes to with antipsychotics (usually > 10 years)
take these drugs. Aversion to taking The more selective as a DA antagonist, the Tardive Dyskinesia: Mechanism
antipsychotics is less with the atypical agents. more likely this side-effect. Haloperidol is the Perhaps up-regulated striatal dopamine receptors
Endocrine Abnormalities - increased secretion most offensive. Atypical antipsychotics show Up regulation of DA receptors does occur when
of prolactin (hyperprolactinemia), which is caused it much less, but some reports of tardive have antipsychotics are administered
by block of dopamine receptors in the pituitary. been linked to risperidone. However, time course correlation between up-regulation
982 (Release of prolactin is under negative regulation Risk increases for pts on higher doses and tardive phenomena is not impressive
by dopamine secreted from cells in the tuber- 15-20% of institutionalized patients on typical Therapy for Tardive Dyskinesia
infundibular system of the hypothalamus). antipsychotics will develop syndrome Decrease the dose of the antipsychotic.
Females - Galactorrhea -- excessive or more prevalent in older patients Initially the dyskinesia will get worse.
spontaneous production of milk. Motor dysfunction - stereotypical, repetitive, Over the next several weeks it may improve.
Males - Gynecomastia enlargement of breasts involuntary movements; Lateral jaw Note: Increasing the dose of the antipsychotic drug will
Decreased Sexuality - Loss of sex drive; movements; Lip smacking; Twisting and temporarily suppress the dyskinesia, but this is
impotence in males protrusion of the tongue. In early stages of contraindicated because at some point the dyskinesia
Weight gain (particularly with some of the the disorder, can see this on physical exam will reappear, and it will be worse.
atypical drugs) by asking the patient to open their mouth. It As a general practitioner, be alert for early signs of this
Hypotension (alpha-blocking effect) will subsequently become obtrusive and disorder in patients on antipsychotic drugs, and alert the
Poikilothermia - failure to regulate body obvious; Purposeless movements of the psychiatrist as soon as they are detected.
temperature extremities

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Consequences of chronic EtOH: Tolerance

Pharmacodynamic: adaptive changes such
that proteins, cells, tissues, organs, systems and
1042 individuals are less affected by EtOH
Pharmacokinetic: slight. due to induction of Ethanol Withdrawal Syndrome
MEOS Amount, rate and duration of alcohol
Behavioral: attenuation of drug effect due to consumption can affect severity
learning Repeated withdrawals can increase the Delirium Tremens
Cross-Tolerance: with other sedative-hypnotic probability of a more severe withdrawal Relatively rare, but life-threatening (5-15% mortality)
drugs (kindling) Mental confusion with fluctuating levels of
Dependence Symptoms include: consciousness
Physical: Characterized by an ethanol hyperexcitability tremor
withdrawal syndrome convulsions agitation
Psychological: characterized by craving and a toxic psychosis autonomic over-activity - marked increases in blood
desire to avoid withdrawal delirium tremens pressure, pulse and respirations

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Tolerance and dependence can suppress parts of
the brains reward circuitry. CREB (cAMP
response element-binding protein) regulates
expression or activity of genes thus the behavior
of the nerve cell. CREB controls the production
of dynorphin in the NA that inhibits neurons in
the VTA. CREB is turned on by cAMP. Once
1048 CREB is turned on it binds to specific genes
causing the production of specific proteins.
Chronic drug use causes sustained activation of
CREB and protein production. Some of the
proteins coded for dampen the reward
circuitry such as dynorphin that tells the VTA
to lighten up on the release of dopamine. Thus
making the same old dose less rewarding.
Because the brain has been reved up by the
dynorphin contributes to dependence because in
the drugs absence the individual is unable to take
pleasure in the past pleasurable activities.
Y
Types of Tolerance:
Innate (preexisting sensitivity)
Acquired (Pharmacokinetic (metabolic),
Pharmacodynamic)
Learned
Behavioral
Conditioned
Acute tolerance
Dopamine signaling also leads to production of Cross-tolerance
the protein FosB. FosB represses Pharmacokinetic Tolerance - changes in distribution or
dynorphin synthesis and activates specific metabolism of a drug after repeated administration, such
genes giving rise to proteins involved in that there is a diminished concentration of drug at the
sensitizing responses to drugs and to site of action. The most common mechanism is
reminders of past drug abuse. induction of hepatic metabolism: alcohol, barbiturates,
benzodiazepines.
 W X
1049
1050
Dependence syndrome cont:
5) preoccupation with substance use, as
manifested by important alternative pleasures or
1051 interests being given up or reduced because of
substance use; or a great deal of time being spent
in activities necessary to obtain, take, or recover
from the effects of the substance
6) persistent substance use despite clear
evidence of harmful consequences, as evidenced
by continued use when the individual is actually
aware, or may be expected to be aware, of the
nature and extent of harm
1052
Nicotine Withdrawal: develops within two
hours and peak within 24 to 48 and can last for
weeks or months
S&S: intense craving, tension, anxiety,
dysphoric mood, irritability or restlessness,
difficulty concentrating, drowsiness, trouble
sleeping, decreased heart rate, decreased
blood pressure, increased appetite and
weight gain, malaise or weakness, decreased
motor performance, increased muscle tension.
Y
Nicotine: Highly toxic alkaloid, 60 mg fatal to adults
(metabolized liver enzymes CYP2A6 to cotinine)
0.5 mg from common cigarette
Signs of overdose: Nausea, vomiting, salivation, pallor
(from vasoconstriction), weakness, abdominal pain
(increased peristalsis), diarrhea, dizziness, headache,
increased blood pressure, tachycardia, tremor, cold
sweats, inability to concentrate, confusion, and sensory
disturbances, decreased REM, and during pregnancy
low birth weight and increase incidence of
persistent pulmonary hypertension.
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Normal individuals have two phases of insulin

320
secretion in response to a meal:
Phase I - rapid rise and fall
Phase II - slower, more gradual increase
Type 1 diabetes mellitus - no insulin secretion
Type 2 DM
initially, Type 2 DM patient may have elevated plasma
insulin levels and tissue insulin resistance, but often 1st
phase of insulin release is dysregulated
years later, beta cells fail and insulin levels are low
GLUT1 - found in RBC, brain microvessels, kidney, colon, and other
cells; part of the BBB; GLUT2 - on liver, pancreatic beta cells, and
basolateral surface of the SI, high capacity low affinity; GLUT3 - found
on neurons, placenta, and testes, has very low Km; GLUT4 - found fat,
skeletal muscle, and heart, and mediates insulin-stimulated gluscose
uptake; GLUT5 found in SI, testes and sperm, low levels are also found
in kidney, skeletal muscle, adipose tissue, and brain, functions a sa
fructose transporter

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Myxedema Coma: is the end stage of untreated
hypothyroidism. Immediate T3 or T4 replacement is
required along with general supportive procedures.
These patients have a large pool of empty TBG binding
sites that must be filled with a loading dose.
Cretinism: Early diagnosis and treatment are essential. Most of
adverse effects of cretinism can be minimized or avoided if treatment is
begun immediately after birth. Treatment initiated after about 1.5
months of age fails to reverse all of the intellectual impairment that has
already occurred but does reverse the physical defects.

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Opioid Overdose: Signs/Symptoms

Primary (triad):
603 lethargy or coma
depressed respiration
pinpoint pupils (normoxic)
(needle marks)

Secondary Opioid Overdose: Treatment

hypotension
hypothermia with cold or clammy skin
pulmonary edema
convulsions (primarily in children)
hypoxia with dilated pupils (harbinger of death)
administer opioid antagonist (naloxone is drug of choice)
support of respiration and other vital functions
identify most likely drug
if determined that other drugs were also ingested, treat for the
overdose of these drugs accordingly

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S&S of salicylate toxicity - GI toxicity, altered mental

status (especially elderly pts), noncardiogenic
pulmonary edema, and acid-base disturbances. The
classic acid-base disturbance is a respiratory
alkalosis from brainstem respiratory center
stimulation and metabolic acidosis, mainly from
lactic acid production. Severe vomiting, however,
may also create a metabolic alkalosis. Acetylsalicylic
acid is converted to salicylic acid, a weak acid. It is
excreted in the kidneys in its anionic form.
Alkalinization of the blood and urine with sodium
bicarbonate helps promote anion formation and
excretion.

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713
Alopecia: chemotherapy-induced hair loss is one of the
most distressing aspects of cancer treatment for some
patients. It is due to the cytotoxic effects of
antineoplastic agents on the hair follicle. The hair loss
tends to be patchy and most severe on the scalp, and it
is usually noticeable 1 to 2 weeks after the beginning of
therapy. After the cessation of chemotherapy, the hair
should eventually return to pretreatment levels,
although it may be different in texture and color.
Cyclophosphamide, dactinomycin, doxorubicin,
paclitaxel, and vincristine generally cause the most
profound alopecia. Scalp-cooling devices, which
apparently decrease scalp perfusion, have been
employed with mixed results.

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Side-Effects of Dopaminergic Drugs - 4 CNS regions:

890
Dopamine reuptake blockers are not used in PD
because of the potential for abuse
Extrapyramidal Tract
Parkinsons (from block DA function)
Dyskinesias (excess DA stimulation)
Meso-Limbic/Prefrontal Cortex (from ventraltegmental area)
Psychiatric symptoms (DA stimulation)!!
Also associated with drugs of abuse
Brain Stem
Vomiting (DA stimulation) (outside BBB, dopamine causes v)
Pituitary
Hyperprolactinemia/Galactorrhea/Gynecomastia (DA block)

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Status Epilepticus:
Most commonly due to cessation of anti-convulsant
915
medication
In infants, likely due to high fever
Initial treatment - IV diazepam or lorazepam (longer-
acting)
Continuing treatment: Teratogens: Drugs for monotherapy of epilepsies are teratogens
IV phenytoin (phenytoin, phenobarbital, carbamazepine, valproic acid)
IV fosphenytoin may be safer Designated FDA category D (benefits outweigh risks) based on
IV phenobarbital may be used if patient unresponsive to considerably greater pregnancy risk associated with uncontrolled
phenytoin seizures

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Olanzapine (and other Atypicals) and Type-2 Diabetes

982
Serotonin atypical antipsychotic affects: negative
symptoms, mood, extrapyramidal symtptoms, appetite,
sexual function
FDA has required a warning for all atypical antipsychotics concerning
their propensity to cause hyperglycemia and diabetes. Label states:
hyperglycemia, in some cases extreme and associated with
ketoacidosis or hyperosmolar coma or death, has been reported in
patients treated with atypical antipsychotics.
The revised labeling recommends that "patients with an established
diagnosis of diabetes mellitus who are started on atypical
antipsychotics should be monitored regularly for worsening of
glucose control. Patients with risk factors for diabetes mellitus (e.g.,
obesity, family history of diabetes) who are starting treatment with
atypical antipsychotics should undergo fasting blood glucose testing at
the beginning of treatment and periodically during treatment."
In addition, all patients treated with atypical antipsychotics should
be monitored for symptoms of hyperglycemia, including
polydipsia, polyuria, polyphagia, and weakness. Patients who
develop symptoms of hyperglycemia during treatment with atypical
antipsychotics should undergo fasting blood glucose testing. In some
cases, hyperglycemia has resolved when the atypical antipsychotic was
discontinued; however, some patients required continuation of anti-
diabetic treatment despite discontinuation of the suspect drug.

983
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 Z AA
1039
1040
1041
Management of EtOH Withdrawal
thiamine (parenteral and oral)!!
glucose, but only after thiamine
prevent seizures - use diazepam or other BZD
(lorazepam or oxazepam with liver disease), often not
1042 used unless history of seizures
potassium, magnesium and phosphate balance should
be restored
Follow-up with psychosocial therapy or
pharmacotherapy for alcoholism
benzodiazepines may be administered as a substitute
for EtOH followed by tapering. (maybe / maybe not)
long acting BZDs like diazepam and chlorazepate may
be used because long half lives provide a built-in
tapering effect.
with liver disease, a short-acting BZD such as
oxazepam or lorazepam may be used
1043
1044
Chronic EtOH: Neurotoxicity
Generalized symmetrical peripheral nerve injury (5-15% of
alcoholics) - usually begins with distal paresthesias of the hands and
feet
Cerebellar degeneration (1% of alcoholics)
Atrophy of the cerebellar vermis
unsteady stance and gait
can be exacerbated by alcoholic myopathy (decrease in skeletal
muscle strength)
Wernicke-Korsakoff syndrome
Wernickes Encephalopathy: confusional state associated with
alcoholic thiamine deficiency - treated with thiamine
Korsakoffs psychosis: long-lasting memory problems
(confabulations)
Rem: COAT RACK: Confusion, Ocular abnormalities, Ataxia, Thiamine
deficiency, Retrograde amnesia, Anterograde amnesia, Confabulation,
Korsakoffs
 Z AA
1045
1046
1047
1048
Pharmacodynamic Tolerance : Adaptive changes in
target tissue occur with repeated use such that there is
a diminished response to the same concentration of
drug. Common mechanisms:
Reduced receptor density at the site of drug action
resulting in deceased agonist sensitivity (e.g., down-
regulation of -opioid receptors with chronic morphine)
Uncoupling of receptor to signal transduction
pathways.
Compensatory changes (e.g. up-regulation) in
systems mediating opposing physiological effects
Learned Tolerance : A reduction in the effects of a drug due to
learned compensatory mechanisms:
Behavioral tolerance: skills developed through experience with drug
(often called learned tolerance). Learning to walk a straight line during
alcohol intoxication is classic example. The same phenomenon has
been shown in simulated driving experiments. Note: the legal system
does not care about learned tolerance.
Conditioned tolerance (situation-specific tolerance): Based on
pairing of drug administration with specific environmental cues related
to drug-taking. A conditioned response that is opposite to the effects of
the drug occurs upon presentation of these environmental cues prior to
drug administration. Mechanism is thought to be Pavlovian learning.
 Z AA

1049

1050

Treatment: VARENICLINE (Chantrix) - is the first treatment that

1051 Nicotine Treatment
Abstinence
First line - Nicotine Patch (21mg x 1 wk, 14mg x 1 wk,
7mg x 1 wk) (15%), Nicotine Gum, Nicotine patch and
gum
Second line - Nicotine Nasal Spray (12%), Nicotine
Inhaler, Medications: Bupropion (Zyban) (150mg
23%, 300mg 33%), Clonidine, fluoxetine, buspirone,
etc.
specifically targets the neurobiological mechanism of nicotine
dependence. Studies show that the drug successfully stimulates
dopamine and blocks nicotine receptors. This reduces nicotine
withdrawal symptoms and cravings, helping to prevent a full relapse.
The drug also blocks the effects of nicotine if patient begins smoking
again. Chantix, prescription medication, tablet form. Generally
prescribed for 12 weeks. May prescribe Chantix for another 12 weeks
to enhance long-term success. Side effects may include nausea,
vomiting, gas, headache and insomnia. Researchers found Chantix to
be more effective than a placebo in helping people quit smoking.

1052
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Thyroid Carcinoma: Patients with papillary or follicular carcinoma of

the thyroid require thyroid hormone replacement therapy. The goal is to
administer the minimum amount of hormone that will completely
suppress pituitary TSH secretion. These tumors are stimulated by TSH
and regress when TSH levels are decreased. Such patients may also
require surgery and / or ablative radioiodine therapy.
Thyroid replacement therapy is not indicated for abnormalities of
reproductive function (amenorrhea, sterility, etc.), obesity, or
"metabolic insufficiency" unless hypothyroidism is definitively
diagnosed as a causative factor in these conditions.

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 AB AC

Opioid Receptors: Distribution

603
Pain is an antidote to the opioids!! (eg bang around OD pt to
increase pain and off set the respiration depression). If pt (with
profound pain) is taking high levels of opioids suddenly has the pain
source eliminated (eg laminectomy) then pt goes into respiratory
depression (pain receptors no longer stimulated and pt essentially is in
OD state) - this was not tolerance, the pain balanced the opioid
stimulation
All three opioid subtypes are expressed in high concentrations in
the dorsal horn of the spinal cord, both on primary pain afferents
and on pain transmission neurons
Supraspinal sites in the rostral ventral medulla, the locus ceruleus
and midbrain periaqueductal gray area
Mu receptors are selectively expressed on GABAergic
neurons in the ventral tegmental area (VTA). Inhibition of GABA
activity in the VTA increases dopaminergic neuronal activity with
increased dopamine release into the nucleus accumbens
(reward center of brain)
Kappa receptors are selectively expressed on dopaminergic
neurons in the VTA. Inhibition of dopaminergic neurons in the VTA
may be the basis for the dysphoria-producing effects of kappa
agonists.

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Potentially cause arrhythmias from sympathetic stimulation

Cogwheel movement in endstage parkinsons (beta1, aplha 1, D1) if dose high enough

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915

All seizure drugs can effect Bone Marrow and Liver!! Also: Dose-dependent - Nystagmus, ataxia, dizziness!

916

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Other SE - all antipsychotics lower the seizure threshhold - must Note: anxiolytic drugs have no effect on schizophrenia, only causes
consider if Hx of seizures an intoxicated crazy person (does not calm aggitated behavior)

983
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1041

Alcoholism:
No standard definition.
pharmacological definition: 1 pint of hard liquor daily for at least 30
days.
1042 dependence
LOSS OF CONTROL
Fetal Alcohol Syndrome societal problems
Greatest preventable cause of mental retardation CHRONIC/RELAPSING DISORDER
Symptoms: AA is still the treatment of choice
midfacial abnormalities
retarded body growth Alcoholism: Genetics & Prevalence
microcephaly higher concordance for monozygotic versus dizygotic twins
poor coordination Four fold increased risk in children of alcoholics even if adopted at
minor joint anomalies birth.
heart & kidney defects Prevalence is about 20% even in affluent areas

1043

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1047

1048 Cross-Tolerance: Tolerance conferred upon one or more other

drugs as a result of repeated use of a given drug. Involves drugs in
the same structural and/or mechanistic category
Can be based on similarity of pharmacologic actions, target tissue
Acute Tolerance : Rapid tolerance developing with repeated use on effects, or metabolic sources of the tolerance:
single occasion (e.g., cocaine binge). Cocaine is often self-administered Tolerance to a naturally-occurring or synthetic opioid results in
in a binge pattern, with repeated doses over one to several hours (often cross-tolerance to other opioids.
limited only by supply). There is a decrease in euphoric response to Tolerance to ethanol can produce tolerance to other sedatives and
subsequent doses of cocaine during the binge. In contrast, there is general anesthetics
little tolerance retained from one binge session to the next. Occurs Cross-tolerance pattern is important in detoxification of persons
with cocaine, methamphetamine, nicotine dependent on a drug
 AB AC

1049

1050

Behavioral Therapy
1051 discover high-risk relapse situations,
create an aversion to smoking,
develop self-monitoring of smoking behavior, and
establish competing coping responses
The most effective behavioral support programs address such issues
as how to perform common daily activities (such as eating, driving, and
socializing) without smoking and how to cope with the dysphoric mood
and the weight gain that can accompany smoking cessation.
The combined use of systemic nicotine administration and
behavioral counseling has resulted in sustained abstinence rates of
60 percent in well-controlled clinical trials.
Dependence on these ystemic nicotine products has been reported
in up to 20 percent of patients; therefore, careful supervision by the
physician of amount and duration of use is necessary.

1052
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Levothyroxine Sodium USP (generic, Synthroid, and other trade
names) - Sodium salt of natural isomer of thyroxine (T4) available as
tablets or powder for injection. Peak effect occurs after 9 days,
declines to one half maximum in 12 15 days. Absorption is variable.
In most cases, this is the drug of choice because of its stability,
content uniformity, low cost, lack of allergenic foreign protein, easy Suppression therapy with levothyroxin of benign nodules is no
lab interpretation, and long half life that allows for once daily longer recommended
administration.

332
 AD AE

333

334

335

336

337

338

339

340

341

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 AD AE

343

344

345

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350

351
352
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 AD AE

355

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359

360

361

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363

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 AD AE
365

366

367

368

369
370

371
 AD AE

372

373

374

375

376

377

378
379

380

381
 AD AE

382

383

384

385

386
 AD AE

387

388

389

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391

392

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 AD AE

394

395
396

397

398

399

400

401
 AD AE

402

403

404

405

406

407

408

409
 AD AE

410

411

412

413

414

415

416
 AD AE
417
418

419

420

421

422

423

424

425
 AD AE
426

427

428

429

430
431
432

433

434

435

436

437

438
 AD AE
439

440

441
442

443
444

445

446

447

448

449

450

451
 AD AE
452
453

454

455

456

457

458

459

460

461
 AD AE

462

463

464

465

466

467

468

469

470
 AD AE

471

472

473

474
475

476

477
 AD AE

478

479
 AD AE

480

481

482

483

485
 AD AE

486

487

488

489

490
 AD AE

491

492

493

494

495

496

497
 AD AE

498

499

500

501

502
 AD AE

503
 AD AE

504

505

506
 AD AE

507

508

509

510

511

512
 AD AE

513

514

515

516
 AD AE

517

518

520

521

522

523

524
 AD AE

525

526

527

528

529

530

531

532

533
 AD AE

534

535

536
 AD AE

537

538

539

540

541

542

543

544

545
 AD AE

546

547

548

549

550
 AD AE

551

552

553

554
 AD AE
555

556

557

558

559

560

561

562

563

564
565

566

567
568

569
 AD AE

570

571

572

573

574
 AD AE

575

576

577

578
579
580
581
582

583

584
 AD AE
585
586
587
588

589

590
591
592

593

594

595

596

597

598
599

600

601

602
 AD AE

603

Opiate receptors include delta (delta), kappa (kappa), and

(mu), which have been reclassified by an International Union of
Pharmacology subcommittee as OP1 (delta), OP2 (kappa), and
OP3 (), respectively.

604

605

606

607
 AD AE

608

609

610

611

612

613

614
 AD AE

615

616

617

618

619

620
 AD AE

621

622

623

624

625

626

627

628
 AD AE

629

630

631

632

633

634

635
 AD AE

636

637

638

639
 AD AE

640

641

642

643

644

645

646
 AD AE

647

648

649

650

651

652

653

654

655
 AD AE

656

657

658

659

660

661

662
 AD AE

663

664
 AD AE

665

666

667

668

669

670
 AD AE

671

672

673

674

675
676
677

678
 AD AE

679

680

681

682
683
684
 AD AE

685

686

687

688

689

690

691

692

693
694

695
 AD AE

696

697

698

699
 AD AE

700

701

702

703

704

705
 AD AE

706

707

708
 AD AE

709

710

711

712
 AD AE

713

714

715

716

717
 AD AE

718

719

720

721

722

723

724
 AD AE

725

726

727

728

729

730

731
 AD AE

732

733

734

735

736

737

738

739
 AD AE

740

741

742

743

744

745
 AD AE

746

747

748

749

750

751

752

753
 AD AE

754

755

756

757

758

759
 AD AE

760

761

762

763

764

765

766

767
 AD AE
768
769

770

771

772

773

774
775
776
777
778
779
780
781
782
783
784
785
786
787
788

789

790

791

792
793
794
 AD AE
795
796
797
798
799
800
801
802
803
804
805
806
807
808

809

810
811
812

813

814
815
816
817

818

819

820
 AD AE

821

822

823

824

825
826
827

828

829

830
831
832
833
834
 AD AE

835

836
837
838
839

840

841

842

843

844

845

846

847

848
849
 AD AE
850

851

852

853

854

855

856
857

858

859

860
861

862

863

864
 AD AE

865

866

867

868
869

870
 AD AE

871

872

873

874

875

876

877

878
 AD AE

879

880

881

882

883

884

885

886
 AD AE

887

888

889

890

891

892

893
 AD AE

894

895

896

897

898

899

900
 AD AE

901

902

903

904

905

906

907
908
909
910
911
912
913
914
 AD AE

Seizure Pearls:
915
Anti-Seizure Side Effects:
Sedation
Ataxia
Nystagmus
Diplopia

If you do not know the answer and Valproic acid is a choice, default
your answer to valproic acid!!!
When in doubt monitor the levelsmany of these drugs must be
monitored regularly.

916

917

918

919

920
 AD AE

921

922

923

924

925

926
 AD AE
927

928

929

930

931

932

933

934
 AD AE

935

936

937

938

939

940
 AD AE

941

942

943

944

945

946

947
 AD AE
948
949

950

951

952

953

954

955
 AD AE

956

957

958

959

960

961

962
 AD AE

963

964

965
966
967

968

969
970
971

972
 AD AE

973

974

975

976

977
 AD AE

978

979

980

981

982

If antipsychotic is used for pt in high aggitated psychotic

state, run dose up high until aggitated behavior reduces
(takes a few hours), but takes at least 1 wk to effect delusional
thought (straight jacket effect), peak improvement at 1-3 wks!!
Antipsychotic drugs - chemical straight jacket - high enough dose in Not known why effect takes so long to effect thought disorders.
anyone will calm their aggitation

983
 AD AE

984

985

986

987
 AD AE

988

989

990

991

992

993

994

995

996

997
 AD AE

998

999

1000

1001

1002
 AD AE
1003

1004

1005

1006

1007

1008

1009

1010
 AD AE

1011

1012

1013

1014

1015

1016
1017
1018

1019

1020

1021
 AD AE
1022

1023

1024

1025

1026

1027

1028

1029

1030
 AD AE

1031

1032

1033

1034

1035

1036

1037

1038
 AD AE

1039

1040

1041

1042

Alcoholism: Laboratory Findings - elevated or high normal

triglycerides CAGE questionaire.
mean corpuscular volume (MCV) # Have you ever felt you needed to Cut down on your drinking?
-glutamyl transferase (GGT) # Have people Annoyed you by criticizing your drinking?
serum uric acid # Have you ever felt Guilty about drinking?
carbohydrate-deficient transferrin (CDT) # Have you ever felt you needed a drink first thing in the morning
mild & fluctuating hypertension (Eye-opener) to steady your nerves or to get rid of a hangover?

1043

1044
 AD
1045
1046
1047
1048
Sensitization (Reverse tolerance): An increase in the response to
a drug after repeated administrations ; may take form of an increase
in potency, efficacy, or both. (ie graphically a leftward, upward shift,
in potency and in efficacy, respectfully)
Associated with psychostimulants such as cocaine and
methamphetamine. Increase is seen in motor stimulant effect of the
drug, but humans do not report increase in euphoric effect. The
sensitization phenomenon has instead been related to development
of psychotomimetic effects with repeated use of cocaine or
methamphetamine.
AE
Withdrawal and Physical Dependence
Physical dependence is a state that develops as a result of an
adaptation produced by resetting of homeostatic mechanisms in
presence of the drug. Tolerance to the drug may reflect the
adaptation that produces the state of physical dependence.
Appearance of a withdrawal syndrome upon cessation of the
drug is the only true evidence of physical dependence.
Withdrawal is characteristic for drug classes.
 AD
1049
1050
1051
Women who stop smoking before pregnancy or during the first
3 to 4 months of pregnancy reduce their risk for having low-
birth-weight infants to that of women who never smoked.
The health benefits of smoking cessation substantially exceed any
risks from the average 5-pound (2.3-kg) weight gain or any adverse
psychological effects after quitting.
1052
AE
People who successfully discontinue smoking are likely to have
been encouraged by someone close to them (such as a spouse or
children), to have been fearful of the ill effects of smoking, and to
have joined a support group of some type for ex-smokers.
Encouragement from a nonsmoking physician is also highly
correlated with abstinence.
 AD AE

1053

1054

1055

1056

1057
1058

1059
 AD AE

1060

1061

1062
 AF AG
1

9
 AF AG

10

11

12

13

14

15

16

17

18
 AF AG

19

20

21

22

23
24
 AF AG

25

26

27

28

29

30

31
 AF AG

32

33

34

35

36

37

38

39

40

41

42
43
 AF AG

44

45

46

47

48
49

50

51

52
53

54

55
 AF AG

56

57

58
59

60
 AF AG

61

62

63
64

65

66
 AF AG

67

68

69

70

71

72

73
 AF AG

74

75

76

77
 AF AG

78

79

80

81

82
 AF AG

83

84

85

86

87
 AF AG
88
89
90
91
92

93

94

95

96
 AF AG

97

98

99

100
101

102
 AF AG

103

104
105

106

107

108

109

110

111
 AF AG

112

113

114

115

116

117

118

119

120

121
 AF AG

122

123

124

125

126

127

128
 AF AG
129

130

131

132

133

134

135

136
 AF AG

137

138

139

140

141

142
 AF AG

143

144

145

146

147

148

149
 AF AG

150

151

152

153

154

155
 AF AG

156

157

158
 AF AG

159

160

161

162

163
164
165
 AF AG

166

167

168

169

170

171

172

173

174

175

176

177
 AF AG

178

179

180
181

182

183

184
 AF AG

185

186

187
188
189
190
191
192
193
194

195
196
197

198
 AF AG

199

200

201

202

203

204

205
 AF AG

206

207

208

209

210

211
 AF AG

212

213

214
 AF AG

215

216

217

218

219

220

221

222
 AF AG

223

224

225

226

227

228
 AF AG

229

230

231

232

233

234
 AF AG

235

236

237

238

239

240

241
 AF AG

242

243

244
245

246

247

248
 AF AG

249

250

251

252

253
 AF AG

254

255

256

257

258

259

260

261
 AF AG

262

263

264

265

266
 AF AG

267

268

269

270

271
272
273
 AF AG

274

275

276
 AF AG
277
278

279

280

281

282

283
 AF AG

284

285

286
 AF AG

287

288
 AF AG

289

290

291

292

293
 AF AG

294

295

296

297

298

299

300
301
302
 AF AG

303

304

305

306

307
 AF AG

308

309

310

311

312

313
 AF AG

314

315

316

317

318
319
 AF AG

320

321

322

323

324

325

326
 AF AG

327

328
329
330

331

332
 AF AG

333

334

335

336

337

338

339

340

341

342
 AF AG

343

344

345

346

347

348

349

350

351
352
353
354
 AF AG

355

356

357

358

359

360

361

362
363

364
 AF AG
365

366

367

368

369
370

371
 AF AG

372

373

374

375

376

377

378
379

380

381
 AF AG

382

383

384

385

386
 AF AG

387

388

389

390

391

392

393
 AF AG

394

395
396

397

398

399

400

401
 AF AG

402

403

404

405

406

407

408

409
 AF AG

410

411

412

413

414

415

416
 AF AG
417
418

419

420

421

422

423

424

425
 AF AG
426

427

428

429

430
431
432

433

434

435

436

437

438
 AF AG
439

440

441
442

443
444

445

446

447

448

449

450

451
 AF AG
452
453

454

455

456

457

458

459

460

461
 AF AG

462

463

464

465

466

467

468

469

470
 AF AG

471

472

473

474
475

476

477
 AF AG

478

479
 AF AG

480

481

482

483

485
 AF AG

486

487

488

489

490
 AF AG

491

492

493

494

495

496

497
 AF AG

498

499

500

501

502
 AF AG

503
 AF AG

504

505

506
 AF AG

507

508

509

510

511

512
 AF AG

513

514

515

516
 AF AG

517

518

520

521

522

523

524
 AF AG

525

526

527

528

529

530

531

532

533
 AF AG

534

535

536
 AF AG

537

538

539

540

541

542

543

544

545
 AF AG

546

547

548

549

550
 AF AG

551

552

553

554
 AF AG
555

556

557

558

559

560

561

562

563

564
565

566

567
568

569
 AF AG

570

571

572

573

574
 AF AG

575

576

577

578
579
580
581
582

583

584
 AF AG
585
586
587
588

589

590
591
592

593

594

595

596

597

598
599

600

601

602
 AF AG

603

604

605

606

607
 AF AG

608

609

610

611

612

613

614
 AF AG

615

616

617

618

619

620
 AF AG

621

622

623

624

625

626

627

628
 AF AG

629

630

631

632

633

634

635
 AF AG

636

637

638

639
 AF AG

640

641

642

643

644

645

646
 AF AG

647

648

649

650

651

652

653

654

655
 AF AG

656

657

658

659

660

661

662
 AF AG

663

664
 AF AG

665

666

667

668

669

670
 AF AG

671

672

673

674

675
676
677

678
 AF AG

679

680

681

682
683
684
 AF AG

685

686

687

688

689

690

691

692

693
694

695
 AF AG

696

697

698

699
 AF AG

700

701

702

703

704

705
 AF AG

706

707

708
 AF AG

709

710

711

712
 AF AG

713

714

715

716

717
 AF AG

718

719

720

721

722

723

724
 AF AG

725

726

727

728

729

730

731
 AF AG

732

733

734

735

736

737

738

739
 AF AG

740

741

742

743

744

745
 AF AG

746

747

748

749

750

751

752

753
 AF AG

754

755

756

757

758

759
 AF AG

760

761

762

763

764

765

766

767
 AF AG
768
769

770

771

772

773

774
775
776
777
778
779
780
781
782
783
784
785
786
787
788

789

790

791

792
793
794
 AF AG
795
796
797
798
799
800
801
802
803
804
805
806
807
808

809

810
811
812

813

814
815
816
817

818

819

820
 AF AG

821

822

823

824

825
826
827

828

829

830
831
832
833
834
 AF AG

835

836
837
838
839

840

841

842

843

844

845

846

847

848
849
 AF AG
850

851

852

853

854

855

856
857

858

859

860
861

862

863

864
 AF AG

865

866

867

868
869

870
 AF AG

871

872

873

874

875

876

877

878
 AF AG

879

880

881

882

883

884

885

886
 AF AG

887

888

889

890

891

892

893
 AF AG

894

895

896

897

898

899

900
 AF AG

901

902

903

904

905

906

907
908
909
910
911
912
913
914
 AF AG

915

916

917

918

919

920
 AF AG

921

922

923

924

925

926
 AF AG
927

928

929

930

931

932

933

934
 AF AG

935

936

937

938

939

940
 AF AG

941

942

943

944

945

946

947
 AF AG
948
949

950

951

952

953

954

955
 AF AG

956

957

958

959

960

961

962
 AF AG

963

964

965
966
967

968

969
970
971

972
 AF AG

973

974

975

976

977
 AF AG

978

979

980

981

982

Note that pharyngitis is often a baringer for

agranulocytosis!

983
 AF AG

984

985

986

987
 AF AG

988

989

990

991

992

993

994

995

996

997
 AF AG

998

999

1000

1001

1002
 AF AG
1003

1004

1005

1006

1007

1008

1009

1010
 AF AG

1011

1012

1013

1014

1015

1016
1017
1018

1019

1020

1021
 AF AG
1022

1023

1024

1025

1026

1027

1028

1029

1030
 AF AG

1031

1032

1033

1034

1035

1036

1037

1038
 AF AG

1039

1040

1041

1042

1043

1044
 AF
1045
1046
1047
Withdrawal and Physical Dependence: Signs and
symptoms of withdrawal tend to be opposite to the
original effects produced by the drug (e.g.,
1048 hyperactivity in the ANS during opioid withdrawal;
somnolence and lethargy during amphetamine
withdrawal). Signs and symptoms tend to be alleviated
by re-introduction of the drug or a drug from the same
class. (predicted by cross-tolerance pattern).
Avoidance of withdrawal can be a significant
determinant of drug-taking (e.g., opioids or
benzodiazepines). Withdrawal is less evident or less
severe for drugs with long vs short half-life (fall of
plasma concentration is less abrupt upon cessation of
drug)
AG
Fatality During Withdrawal Fatality Potential is
under the Withdrawal heading. It refers to the
possibility that a person will die as a consequence of
going through withdrawal. It does not refer to the
direct lethal potential of the drugs. For example,
opioids are directly lethal in overdose by depressing
respiration; although users complain that they feel
like they will die during withdrawal, in fact, opioid
withdrawal should be readily survivable for anyone in
relatively normal health.
 AF AG

1049

1050

1051

1052
 AF AG

1053

1054

1055

1056

1057
1058

1059
 AF AG

1060

1061

1062
 AH
1

9
 AH

10

11

12

13

14

15

16

17

18
 AH

19

20

21

22

23
24
 AH

25

26

27

28

29

30

31
 AH

32

33

34

35

36

37

38

39

40

41

42
43
 AH

44

45

46

47

48
49

50

51

52
53

54

55
 AH

56

57

58
59

60
 AH

61

62

63
64

65

66
 AH

67

68

69

70

71

72

73
 AH

74

75

76

77
 AH

78

79

80

81

82
 AH

83

84

85

86

87
 AH
88
89
90
91
92

93

94

95

96
 AH

97

98

99

100
101

102
 AH

103

104
105

106

107

108

109

110

111
 AH

112

113

114

115

116

117

118

119

120

121
 AH

122

123

124

125

126

127

128
 AH
129

130

131

132

133

134

135

136
 AH

137

138

139

140

141

142
 AH

143

144

145

146

147

148

149
 AH

150

151

152

153

154

155
 AH

156

157

158
 AH

159

160

161

162

163
164
165
 AH

166

167

168

169

170

171

172

173

174

175

176

177
 AH

178

179

180
181

182

183

184
 AH

185

186

187
188
189
190
191
192
193
194

195
196
197

198
 AH

199

200

201

202

203

204

205
 AH

206

207

208

209

210

211
 AH

212

213

214
 AH

215

216

217

218

219

220

221

222
 AH

223

224

225

226

227

228
 AH

229

230

231

232

233

234
 AH

235

236

237

238

239

240

241
 AH

242

243

244
245

246

247

248
 AH

249

250

251

252

253
 AH

254

255

256

257

258

259

260

261
 AH

262

263

264

265

266
 AH

267

268

269

270

271
272
273
 AH

274

275

276
 AH
277
278

279

280

281

282

283
 AH

284

285

286
 AH

287

288
 AH

289

290

291

292

293
 AH

294

295

296

297

298

299

300
301
302
 AH

303

304

305

306

307
 AH

308

309

310

311

312

313
 AH

314

315

316

317

318
319
 AH

320

321

322

323

324

325

326
 AH

327

328
329
330

331

332
 AH

333

334

335

336

337

338

339

340

341

342
 AH

343

344

345

346

347

348

349

350

351
352
353
354
 AH

355

356

357

358

359

360

361

362
363

364
 AH
365

366

367

368

369
370

371
 AH

372

373

374

375

376

377

378
379

380

381
 AH

382

383

384

385

386
 AH

387

388

389

390

391

392

393
 AH

394

395
396

397

398

399

400

401
 AH

402

403

404

405

406

407

408

409
 AH

410

411

412

413

414

415

416
 AH
417
418

419

420

421

422

423

424

425
 AH
426

427

428

429

430
431
432

433

434

435

436

437

438
 AH
439

440

441
442

443
444

445

446

447

448

449

450

451
 AH
452
453

454

455

456

457

458

459

460

461
 AH

462

463

464

465

466

467

468

469

470
 AH

471

472

473

474
475

476

477
 AH

478

479
 AH

480

481

482

483

485
 AH

486

487

488

489

490
 AH

491

492

493

494

495

496

497
 AH

498

499

500

501

502
 AH

503
 AH

504

505

506
 AH

507

508

509

510

511

512
 AH

513

514

515

516
 AH

517

518

520

521

522

523

524
 AH

525

526

527

528

529

530

531

532

533
 AH

534

535

536
 AH

537

538

539

540

541

542

543

544

545
 AH

546

547

548

549

550
 AH

551

552

553

554
 AH
555

556

557

558

559

560

561

562

563

564
565

566

567
568

569
 AH

570

571

572

573

574
 AH

575

576

577

578
579
580
581
582

583

584
 AH
585
586
587
588

589

590
591
592

593

594

595

596

597

598
599

600

601

602
 AH

603

604

605

606

607
 AH

608

609

610

611

612

613

614
 AH

615

616

617

618

619

620
 AH

621

622

623

624

625

626

627

628
 AH

629

630

631

632

633

634

635
 AH

636

637

638

639
 AH

640

641

642

643

644

645

646
 AH

647

648

649

650

651

652

653

654

655
 AH

656

657

658

659

660

661

662
 AH

663

664
 AH

665

666

667

668

669

670
 AH

671

672

673

674

675
676
677

678
 AH

679

680

681

682
683
684
 AH

685

686

687

688

689

690

691

692

693
694

695
 AH

696

697

698

699
 AH

700

701

702

703

704

705
 AH

706

707

708
 AH

709

710

711

712
 AH

713

714

715

716

717
 AH

718

719

720

721

722

723

724
 AH

725

726

727

728

729

730

731
 AH

732

733

734

735

736

737

738

739
 AH

740

741

742

743

744

745
 AH

746

747

748

749

750

751

752

753
 AH

754

755

756

757

758

759
 AH

760

761

762

763

764

765

766

767
 AH
768
769

770

771

772

773

774
775
776
777
778
779
780
781
782
783
784
785
786
787
788

789

790

791

792
793
794
 AH
795
796
797
798
799
800
801
802
803
804
805
806
807
808

809

810
811
812

813

814
815
816
817

818

819

820
 AH

821

822

823

824

825
826
827

828

829

830
831
832
833
834
 AH

835

836
837
838
839

840

841

842

843

844

845

846

847

848
849
 AH
850

851

852

853

854

855

856
857

858

859

860
861

862

863

864
 AH

865

866

867

868
869

870
 AH

871

872

873

874

875

876

877

878
 AH

879

880

881

882

883

884

885

886
 AH

887

888

889

890

891

892

893
 AH

894

895

896

897

898

899

900
 AH

901

902

903

904

905

906

907
908
909
910
911
912
913
914
 AH

915

916

917

918

919

920
 AH

921

922

923

924

925

926
 AH
927

928

929

930

931

932

933

934
 AH

935

936

937

938

939

940
 AH

941

942

943

944

945

946

947
 AH
948
949

950

951

952

953

954

955
 AH

956

957

958

959

960

961

962
 AH

963

964

965
966
967

968

969
970
971

972
 AH

973

974

975

976

977
 AH

978

979

980

981

982

983
 AH

984

985

986

987
 AH

988

989

990

991

992

993

994

995

996

997
 AH

998

999

1000

1001

1002
 AH
1003

1004

1005

1006

1007

1008

1009

1010
 AH

1011

1012

1013

1014

1015

1016
1017
1018

1019

1020

1021
 AH
1022

1023

1024

1025

1026

1027

1028

1029

1030
 AH

1031

1032

1033

1034

1035

1036

1037

1038
 AH

1039

1040

1041

1042

1043

1044
 AH

1045

1046

1047

1048

Tx for cocaine-associated MI or infarction -

phentolamine, also benzo, ASA, and nitroglycerine,
consider thrombolytics
 AH

1049

1050

1051

1052
 AH

1053

1054

1055

1056

1057
1058

1059
 AH

1060

1061

1062