HIGH-YIELD PRINCIPLES IN

Pharmacology

“Take me, I am the drug; take me, I am hallucinogenic.” ``Pharmacokinetics and

—Salvador Dali Pharmacodynamics 228

“I was under medication when I made the decision not to burn the tapes.” ``Autonomic Drugs 233
—Richard Nixon
``Toxicities and
“I wondher why ye can always read a doctor’s bill an’ ye niver can read his Side Effects 243
purscription.”
—Finley Peter Dunne ``Miscellaneous 248
“Once you get locked into a serious drug collection, the tendency is to
push it as far as you can.”
—Hunter S. Thompson

Preparation for pharmacology questions is straightforward. Know all the

mechanisms, clinical use, and important adverse effects of key drugs and
their major variants. Obscure derivatives are low-yield. Learn their classic
and distinguishing toxicities as well as major drug-drug interactions.
Reviewing associated biochemistry, physiology, and microbiology
concepts can be useful while studying pharmacology. The exam has a
strong emphasis on ANS, CNS, antimicrobial, and cardiovascular agents
as well as on NSAIDs, which are covered throughout the text. Specific
drug dosages or trade names are generally not testable. The exam may
use graphs to test various pharmacology content, so make sure you are
comfortable interpreting them.

227

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 228 SEC TION II Pharmacology   
PHARMACOLOGY—PHARMACOKINETICS and Pharmacodynamics

PHARMACOLOGY—PHARMACOKINETICS AND PHARMACODYNAMICS

``

Enzyme kinetics
Noncompetitive inhibitor
Michaelis-Menten Km is inversely related to the affinity of the [S] = concentration of substrate;
Competitive V = velocity.
inhibitor (reversible)
1
kinetics enzyme for its substrate. V Uninhibited
Saturation
Vmax is directly proportional to the enzyme

Velocity (V)
1
Vmax
1
concentration. − Km
Vmax Km = [S] at 1⁄2 Vmax
1⁄2 Vmax
Most enzymatic reactions follow a hyperbolic 1
curve (ie, Michaelis-Menten kinetics); Km [S]
[S]
however, enzymatic reactions that exhibit a
sigmoid curve usually indicate cooperative Effects of enzyme inhibition
Saturation
Uninhibited
1 Saturation
kinetics (eg, hemoglobin).

Velocity (V)
Vmax V K
slope = m

Velocity (V)
Vmax Vmax
1 1 CompetitiveKminhibitor
= [S] at 1⁄2 Vmax
(reversible)
1⁄2 V
− Km 1⁄2 Vmax max Vmax
Noncompetitive inhibitor
Km 1 [S]
Km [S]
[S]

Lineweaver-Burk plot  y-intercept,  Vmax. Noncompetitive inhibitor

Uninhibited
1
1 V Competitive inhibitor
K
The further to the right the x-intercept (ie, V
slope = m
1 1
Uninhibited Vmax
closer to zero), the greater the Km and the − Km Vmax
lower the affinity.
1
1 [S]
[S]
Competitive inhibitors cross each other, Effects of enzyme inhibition
Noncompetitive inhibitor
whereas noncompetitive inhibitors do not. 1 Competitive inhibitor
Noncompetitive inhibitor
V Uninhibited
Competitive inhibitor (reversible)
1
Kompetitive inhibitors increase K m. V Uninhibited
1
− Km 1
1 Vmax
[S]
1
[S]

Competitive Competitive
inhibitors, inhibitors, Noncompetitive
Saturation
reversible irreversible inhibitors
Velocity (V)

Vmax
Competitive inhibitor (reversible)
Resemble substrate Yes Yes 1⁄2 Vmax No
Noncompetitive inhibitor
Overcome by  [S] Yes No No
Km [S]
Bind active site Yes Yes No
Effect on Vmax Unchanged  
Effect on Km  Unchanged Unchanged
Pharmacodynamics  potency  efficacy  efficacy

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PHARMACOLOGY—PHARMACOKINETICS and Pharmacodynamics SEC TION II 229

Pharmacokinetics
Bioavailability (F)
Volume of distribution
(Vd)
Clearance (CL)
Half-life (t1/2)
Fraction of administered drug reaching systemic circulation unchanged. For an IV dose, F = 100%.
Orally: F typically < 100% due to incomplete absorption and first-pass metabolism.
Theoretical volume occupied by the total amount of drug in the body relative to its plasma
concentration. Apparent Vd of plasma protein–bound drugs can be altered by liver and kidney
disease ( protein binding,  Vd). Drugs may distribute in more than one compartment.
amount of drug in the body
Vd =
plasma drug concentration
Vd COMPARTMENT DRUG TYPES
Low Intravascular Large/charged molecules; plasma protein bound
Medium ECF Small hydrophilic molecules
High All tissues including Small lipophilic molecules, especially if bound
fat to tissue protein
The volume of plasma cleared of drug per unit time. Clearance may be impaired with defects in
cardiac, hepatic, or renal function.
rate of elimination of drug
CL = = Vd × Ke (elimination constant)
plasma drug concentration
The time required to change the amount of drug in the body by 1⁄2 during elimination.
In first-order kinetics, a drug infused at a constant rate takes 4–5 half-lives to reach steady state. It
takes 3.3 half-lives to reach 90% of the steady-state level.
0.7 × Vd # of half-lives 1 2 3 4
t1/2 = in first-order elimination
CL
% remaining 50% 25% 12.5% 6.25%

Dosage calculations Cp × Vd In renal or liver disease, maintenance dose  and

Loading dose = loading dose is usually unchanged.
F
Cp × CL × τ Time to steady state depends primarily on
Maintenance dose = t1/2 and is independent of dose and dosing
F
frequency.
Cp = target plasma concentration at steady state
τ = dosage interval (time between doses), if not
administered continuously

Types of drug interactions

TERM DEFINITION EXAMPLE
Additive Effect of substance A and B together is equal to Aspirin and acetaminophen
the sum of their individual effects
Permissive Presence of substance A is required for the full Cortisol on catecholamine responsiveness
effects of substance B
Synergistic Effect of substance A and B together is greater Clopidogrel with aspirin
than the sum of their individual effects
Tachyphylactic Acute decrease in response to a drug after Nitrates, niacin, phenylephrine, LSD, MDMA
initial/repeated administration

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 230 SEC TION II Pharmacology   
PHARMACOLOGY—PHARMACOKINETICS and Pharmacodynamics

Receptor binding
100 100 100

Agonist Agonist plus Agonist Agonist Lower

alone competitive alone B antagonist alone
antagonist
A Partial agonist
50 50 50 alone
C
Agonist plus
competitive noncompetitive
antagonist antagonist

0 0 0
0.1 1.0 10 100 1000 0.1 1.0 10 100 1000 0.1 1.0 10 100 1000
Agonist dose Agonist dose Agonist dose

AGONIST WITH EFFECT EXAMPLE

AC
 ompetitive Shifts curve right ( potency), no change Diazepam (agonist) + flumazenil (competitive
antagonist in efficacy. Can be overcome by  the antagonist) on GABA receptor.
concentration of agonist substrate.
B Noncompetitive Shifts curve down ( efficacy). Cannot be Norepinephrine (agonist) + phenoxybenzamine
antagonist overcome by  agonist substrate concentration. (noncompetitive antagonist) on α-receptors.

C P
 artial agonist Acts at same site as full agonist, but with lower Morphine (full agonist) vs buprenorphine
(alone) maximal effect ( efficacy). Potency is an (partial agonist) at opioid μ-receptors.
independent variable.

Elimination of drugs
Zero-order Rate of elimination is constant regardless of Cp Capacity-limited elimination.
elimination (ie, constant amount of drug eliminated per PEA (a pea is round, shaped like the “0” in
unit time). Cp  linearly with time. Examples zero-order).
of drugs—Phenytoin, Ethanol, and Aspirin (at
high or toxic concentrations).
First-order elimination Rate of First-order elimination is directly Flow-dependent elimination.
proportional to the drug concentration (ie,
constant Fraction of drug eliminated per unit
time). Cp  exponentially with time. Applies to
most drugs.
Zero-order elimination First-order elimination
Elimination rate (=slope) Elimination rate (=slope)
4 U/h
Drug plasma concentration

Drug plasma concentration

2 U/h
Time of t1/2 is constant
↑
↑
Time of t1/2 as as concentration
↑
concentration
2 U/h 2 U/h
First t1/2 > First t1/2 =

2 U/h 1 U/h
Second t1/2 > Second t1/2 = 0.5 U/h
Third t1/2 Third t1/2

Time (h) Time (h)

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PHARMACOLOGY—PHARMACOKINETICS and Pharmacodynamics SEC TION II 231

Urine pH and drug Ionized species are trapped in urine and cleared quickly. Neutral forms can be reabsorbed.
elimination
Weak acids Examples: phenobarbital, methotrexate, aspirin (salicylates). Trapped in basic environments. Treat
overdose with sodium bicarbonate to alkalinize urine.
RCOOH RCOO – + H+
(lipid soluble) (trapped)
Weak bases Example: TCAs, amphetamines. Trapped in acidic environments. Treat overdose with ammonium
chloride to acidify urine.
RNH3+ RNH2 + H+
(trapped) (lipid soluble)

TCA toxicity is generally treated with sodium bicarbonate to overcome the sodium channel-
blocking activity of TCAs, but not for accelerating drug elimination.

Drug metabolism
Phase I Reduction, Oxidation, Hydrolysis with Geriatric patients lose phase I first.
cytochrome P-450 usually yield slightly polar, R- OH
water-soluble metabolites (often still active).
Phase II Conjugation (Methylation, Glucuronidation, Geriatric patients have More GAS (phase II).
Acetylation, Sulfation) usually yields very polar, Patients who are slow acetylators have  side
inactive metabolites (renally excreted). effects from certain drugs because of  rate of
metabolism.

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 232 SEC TION II Pharmacology   
PHARMACOLOGY—PHARMACOKINETICS and Pharmacodynamics

Efficacy vs potency
Efficacy Maximal effect a drug can produce. Represented by the y-value (Vmax).  y-value =  Vmax =
 efficacy. Unrelated to potency (ie, efficacious drugs can have high or low potency). Partial
agonists have less efficacy than full agonists.
RELATIVE EFFICACY
100 Vmax Drug A

Δ Efficacy

% Maximal effect
50 Vmax Drug B

0
Log (drug dose)

Potency Amount of drug needed for a given effect. Represented by the x-value (EC50). Left shifting =
 EC50 =  potency =  drug needed. Unrelated to efficacy (ie, potent drugs can have high or low
efficacy).
RELATIVE POTENCY

100

Drug A Drug B
% Maximal effect

Δ Potency
50
EC = Effective
concentration
EC50 EC50
0
Log (drug dose)

Therapeutic index Measurement of drug safety. TITE: Therapeutic Index = TD50 / ED50.
TD50 median toxic dose Safer drugs have higher TI values. Drugs with
= lower TI values frequently require monitoring
ED50   median effective dose
(eg, Warfarin, Theophylline, Digoxin,
Therapeutic window—dosage range that can Lithium; Warning! These Drugs are Lethal!).
safely and effectively treat disease. LD50 (lethal median dose) often replaces TD50
in animal studies.
Efficacy Toxicity
100
% of patients responding

Therapeutic index
50
ED = Effective dose
TD = Toxic dose
ED50 TD50

0
Log (drug concentration)

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 Pharmacology   
PHARMACOLOGY—Autonomic Drugs SEC TION II 233

PHARMACOLOGY—AUTONOMIC DRUGS
``

Central and peripheral nervous system

Medulla
Post Smooth muscle, gland
Parasympathetic ACh NN ACh M cells, nerve terminals,
Pre (long) (short) cardiac muscle

Spinal cord

ACh NN ACh M Sweat glands

Pre (short) Post (long)
α1 Smooth muscle, gland
ACh NN NE α2 cells, nerve terminals,
β1 cardiac muscle
Sympathetic
ACh NN D D1 Renal vasculature
smooth muscle
α1
Adrenal medulla NE α2
β1
ACh NN Blood α1 Cardiac muscle, vessels
Catecholamine α2
Epi β1
transmission
β2

ACh NM Skeletal muscle

SOMATIC Voluntary motor nerve
Neuromuscular
junction

Pelvic splanchnic nerves and CNs III, VII, IX and X are part of the parasympathetic nervous system.
Adrenal medulla is directly innervated by preganglionic sympathetic fibers.
Sweat glands are part of the sympathetic pathway but are innervated by cholinergic fibers.

Acetylcholine Nicotinic ACh receptors are ligand-gated Na+/K+ channels. Two subtypes: NN (found in autonomic
receptors ganglia, adrenal medulla) and NM (found in neuromuscular junction of skeletal muscle).
Muscarinic ACh receptors are G-protein–coupled receptors that usually act through 2nd
messengers. 5 subtypes: M1–5 found in heart, smooth muscle, brain, exocrine glands, and on sweat
glands (cholinergic sympathetic).

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 234 SEC TION II Pharmacology   
PHARMACOLOGY—Autonomic Drugs

G-protein–linked second messengers

RECEPTOR G-PROTEIN CLASS MAJOR FUNCTIONS
Sympathetic
  α1 q  vascular smooth muscle contraction,  pupillary dilator muscle
contraction (mydriasis),  intestinal and bladder sphincter muscle
contraction
  α2 i  sympathetic (adrenergic) outflow,  insulin release,  lipolysis,  platelet
aggregation,  aqueous humor production
  β1 s  heart rate,  contractility (one heart),  renin release,  lipolysis
  β2 s Vasodilation, bronchodilation (two lungs),  lipolysis,  insulin release,
 glycogenolysis,  uterine tone (tocolysis),  aqueous humor production,
 cellular K+ uptake
  β3 s  lipolysis,  thermogenesis in skeletal muscle,  bladder relaxation
Parasympathetic
  M1 q Mediates higher cognitive functions, stimulates enteric nervous system
  M2 i  heart rate and contractility of atria
  M3 q  exocrine gland secretions (eg, lacrimal, sweat, salivary, gastric acid),
 gut peristalsis,  bladder contraction, bronchoconstriction,  pupillary
sphincter muscle contraction (miosis), ciliary muscle contraction
(accommodation),  insulin release
Dopamine
  D1 s Relaxes renal vascular smooth muscle, activates direct pathway of striatum
  D2 i Modulates transmitter release, especially in brain, inhibits indirect
pathway of striatum
Histamine
  H1 q  nasal and bronchial mucus production,  vascular permeability,
bronchoconstriction, pruritus, pain
  H2 s  gastric acid secretion
Vasopressin
  V1 q  vascular smooth muscle contraction

  V2 s  H2O permeability and reabsorption via upregulating aquaporin-2 in

collecting twobules (tubules) of kidney
“After qisses (kisses), you get a qiq (kick) out of siq (sick) sqs (super qinky sex).”
H1, α1, V1, Gq DAG Protein HAVe 1 M&M.
Receptor Phospholipase C
M1, M3 kinase C
Lipids PIP2 +
IP3 [Ca2+]in Smooth muscle contraction

β1, β2, β3, D1, Gs ATP

Receptor
H2, V2
Adenylyl cyclase [Ca2+]in (heart)
Gi
– cAMP Protein kinase A
M2, α2, D2 Receptor –
Myosin light-chain
kinase (smooth
muscle)

MAD 2’s.

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 Pharmacology   
PHARMACOLOGY—Autonomic Drugs SEC TION II 235

Autonomic drugs Release of norepinephrine from a sympathetic nerve ending is modulated by NE itself, acting on
presyn­aptic α2-autoreceptors Ž negative feedback.
Amphetamines use the NE transporter (NET) to enter the presynaptic terminal, where they utilize
the vesicular monoamine transporter (VMAT) to enter neurosecretory vesicles. This displaces NE
from the vesicles. Once NE reaches a concentration threshold within the presynaptic terminal,
the action of NET is reversed, and NE is expelled into the synaptic cleft, contributing to the
characteristics and effects of  NE observed in patients taking amphetamines.
CHOLINERGIC NORADRENERGIC

AXON AXON
Tyrosine
Choline
Tyrosine

Choline+ DOPA
Acetyl-CoA
Dopamine
ChAT
ACh
Reserpine - Release-modulating
receptors
Ca2+ AT II
+ NE
ACh +
Ca2+ α2
-
+
Amphetamine,
+ Reuptake
Botulinum - ephedrine
ck
- ba
Cocaine, TCAs, e fe e d
Choline + amphetamine N e g at i v
acetate NE
Diffusion,
metabolism
ACh
receptor -
AChE inhibitors
AChE Adrenoreceptors α or β

POSTSYNAPTIC MEMBRANE POSTSYNAPTIC MEMBRANE

 represents transporters.

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 236 SEC TION II Pharmacology   
PHARMACOLOGY—Autonomic Drugs

Cholinomimetic Watch for exacerbation of COPD, asthma, and peptic ulcers in susceptible patients.
agents
DRUG ACTION APPLICATIONS
Direct agonists
Bethanechol Activates bowel and bladder smooth muscle; Postoperative ileus, neurogenic ileus, urinary
resistant to AChE. No nicotinic activity. retention
“Bethany, call (bethanechol) me to activate
your bowels and bladder.”
Carbachol Carbon copy of acetylcholine (but resistant to Constricts pupil and relieves intraocular
AChE). pressure in open-angle glaucoma
Methacholine Stimulates muscarinic receptors in airway when Challenge test for diagnosis of asthma
inhaled.
Pilocarpine Contracts ciliary muscle of eye (open-angle Potent stimulator of sweat, tears, and saliva
glaucoma), pupillary sphincter (closed-angle Open-angle and closed-angle glaucoma,
glaucoma); resistant to AChE, can cross blood- xerostomia (Sjögren syndrome)
brain barrier (tertiary amine). “You cry, drool,
and sweat on your ‘pilow.’ ”
Indirect agonists (anticholinesterases)
Donepezil,  ACh. Alzheimer disease (Dona Riva dances at the
rivastigmine, gala).
galantamine
Edrophonium  ACh. Historically used to diagnose myasthenia gravis;
replaced by anti-AChR Ab (anti-acetylcholine
receptor antibody) test.
Neostigmine  ACh. Postoperative and neurogenic ileus and
Neo CNS = No CNS penetration (quaternary urinary retention, myasthenia gravis,
amine). reversal of neuromuscular junction blockade
(postoperative).
Physostigmine  ACh. Phreely (freely) crosses blood-brain Antidote for anticholinergic toxicity;
barrier Ž CNS (tertiary amine). physostigmine “phyxes” atropine overdose.
Pyridostigmine  ACh;  muscle strength. Pyridostigmine gets Myasthenia gravis (long acting); does not
rid of myasthenia gravis. penetrate CNS (quaternary amine).

Cholinesterase Often due to organophosphates, such as DUMBBELSS.

inhibitor poisoning
parathion, that irreversibly inhibit AChE.
Causes Diarrhea, Urination, Miosis,
Bronchospasm, Bradycardia, Emesis,
Lacrimation, Sweating, and Salivation. May
lead to respiratory failure if untreated.
Organophosphates are often components of
insecticides; poisoning usually seen in farmers.
Antidote—atropine (competitive inhibitor) +
pralidoxime (regenerates AChE if given early).

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 Pharmacology   
PHARMACOLOGY—Autonomic Drugs SEC TION II 237

Muscarinic antagonists
DRUGS ORGAN SYSTEMS APPLICATIONS
Atropine, Eye Produce mydriasis and cycloplegia.
homatropine,
tropicamide
Benztropine, CNS Parkinson disease (“park my Benz”).
trihexyphenidyl Acute dystonia.
Glycopyrrolate GI, respiratory Parenteral: preoperative use to reduce airway
secretions.
Oral: drooling, peptic ulcer.
Hyoscyamine, GI Antispasmodics for irritable bowel syndrome.
dicyclomine
Ipratropium, Respiratory COPD, asthma (“I pray I can breathe soon!”).
tiotropium
Oxybutynin, Genitourinary Reduce bladder spasms and urge urinary
solifenacin, incontinence (overactive bladder).
tolterodine
Scopolamine CNS Motion sickness.

Atropine Muscarinic antagonist. Used to treat bradycardia and for ophthalmic applications.
ORGAN SYSTEM ACTION NOTES
Eye  pupil dilation, cycloplegia Blocks DUMBBeLSS in cholinesterase
Airway Bronchodilation,  secretions inhibitor poisoning. Does not block excitation
of skeletal muscle and CNS (mediated by
Stomach  acid secretion
nicotinic receptors).
Gut  motility
Bladder  urgency in cystitis
ADVERSE EFFECTS  body temperature (due to  sweating); Side effects:
rapid pulse; dry mouth; dry, flushed skin; Hot as a hare
cycloplegia; constipation; disorientation Dry as a bone
Can cause acute angle-closure glaucoma in Red as a beet
elderly (due to mydriasis), urinary retention Blind as a bat
in men with prostatic hyperplasia, and Mad as a hatter
hyperthermia in infants. Full as a flask
Jimson weed (Datura) Ž gardener’s pupil
(mydriasis due to plant alkaloids)

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 238 SEC TION II Pharmacology   
PHARMACOLOGY—Autonomic Drugs

Sympathomimetics
DRUG ACTION APPLICATIONS

Direct sympathomimetics
Albuterol, salmeterol, β2 > β1 Albuterol for acute asthma or COPD. Salmeterol
terbutaline for long-term asthma or COPD management.
Terbutaline for acute bronchospasm in asthma
and tocolysis.
Dobutamine β1 > β2, α Heart failure (HF), cardiogenic shock (inotropic
> chronotropic), cardiac stress testing.
Dopamine D1 = D2 > β > α Unstable bradycardia, HF, shock; inotropic and
chronotropic effects at lower doses due to β
effects; vasoconstriction at high doses due to α
effects.
Epinephrine β>α Anaphylaxis, asthma, open-angle glaucoma;
α effects predominate at high doses.
Significantly stronger effect at β2-receptor than
norepinephrine.
Fenoldopam D1 Postoperative hypertension, hypertensive crisis.
Vasodilator (coronary, peripheral, renal, and
splanchnic). Promotes natriuresis. Can cause
hypotension and tachycardia.
Isoproterenol β1 = β2 Electrophysiologic evaluation of
tachyarrhythmias. Can worsen ischemia.
Has negligible α effect.
Midodrine α1 Autonomic insufficiency and postural
hypotension. May exacerbate supine
hypertension.
Mirabegron β3 Urinary urge incontinence or overactive bladder.
Norepinephrine α1 > α2 > β1 Hypotension, septic shock.

Phenylephrine α1 > α2 Hypotension (vasoconstrictor), ocular procedures

(mydriatic), rhinitis (decongestant), ischemic
priapism.
Indirect sympathomimetics
Amphetamine Indirect general agonist, reuptake inhibitor, also Narcolepsy, obesity, ADHD.
releases stored catecholamines
Cocaine Indirect general agonist, reuptake inhibitor Causes vasoconstriction and local anesthesia.
Caution when giving β-blockers if cocaine
intoxication is suspected (can lead to
unopposed α1 activation, activation Ž extreme
hypertension, coronary vasospasm).
Ephedrine Indirect general agonist, releases stored Nasal decongestion (pseudoephedrine), urinary
catecholamines incontinence, hypotension.

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 Pharmacology   
PHARMACOLOGY—Autonomic Drugs SEC TION II 239

Norepinephrine vs NE  systolic and diastolic pressures as a result of α1-mediated vasoconstriction Ž  mean arterial
isoproterenol pressure Ž reflex bradycardia. However, isoproterenol (rarely used) has little α effect but causes
β2-mediated vasodilation, resulting in  mean arterial pressure and  heart rate through β1 and
reflex activity.

Norepinephrine (α > β) Epinephrine (α ≈ β) Isoproterenol (β > α)

Widened β1

Blood pressure
pulse
pressure

α1
Systolic
MAP β2 > α1
Diastolic β2

β1, reflex tachycardia

β1
Heart rate

Reflex bradycardia
Peripheral resistance

Unopposed α1

β2 > α1 Unopposed β2

CO CO ↑ CO ↑↑
↑ ↑

↑
HR HR ↑ HR ↑↑↑
MAP ↑↑ MAP ↑ MAP
PP ↑ PP ↑ PP ↑↑

Sympatholytics (α2-agonists)
DRUG APPLICATIONS ADVERSE EFFECTS
Clonidine, guanfacine Hypertensive urgency (limited situations), CNS depression, bradycardia, hypotension,
ADHD, Tourette syndrome, symptom control respiratory depression, miosis, rebound
in opioid withdrawal hypertension with abrupt cessation
α-methyldopa Hypertension in pregnancy Direct Coombs ⊕ hemolysis, drug-induced
lupus
Tizanidine Relief of spasticity Hypotension, weakness, xerostomia

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 240 SEC TION II Pharmacology   
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α-blockers
DRUG APPLICATIONS ADVERSE EFFECTS
Nonselective
Phenoxybenzamine Irreversible. Pheochromocytoma (used
preoperatively) to prevent catecholamine
(hypertensive) crisis
Orthostatic hypotension, reflex tachycardia
Phentolamine Reversible. Give to patients on MAO inhibitors
who eat tyramine-containing foods and for
severe cocaine-induced hypertension (2nd line)
α1 selective (-osin ending)
Prazosin, terazosin, Urinary symptoms of BPH; PTSD (prazosin); 1st-dose orthostatic hypotension, dizziness,
doxazosin, hypertension (except tamsulosin) headache
tamsulosin
α2 selective
Mirtazapine Depression Sedation,  serum cholesterol,  appetite

Effects of α-blocker (eg, phentolamine) on BP responses to epinephrine and phenylephrine

Epinephrine Phenylephrine
Before α-blockade After α-blockade Before α-blockade After α-blockade

Net pressor
Blood pressure
Blood pressure

Net pressor
Net depressor α1
effect

Suppression of
Systolic β2 > α1 Unopposed β2
MAP
Diastolic

β1
β1 Reflex tachycardia
Heart rate
Heart rate

Reflex bradycardia

Time Time

Epinephrine response exhibits reversal of mean arterial Phenylephrine response is suppressed but not reversed
pressure from a net increase (the α response) to a net because it is a “pure” α-agonist (lacks β-agonist
decrease (the β2 response). properties).

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 Pharmacology   
PHARMACOLOGY—Autonomic Drugs SEC TION II 241

β-blockers Acebutolol, atenolol, betaxolol, bisoprolol, carvedilol, esmolol, labetalol, metoprolol, nadolol,
nebivolol, pindolol, propranolol, timolol.
APPLICATION ACTIONS NOTES/EXAMPLES
Angina pectoris  heart rate and contractility, resulting in  O2
consumption
Glaucoma  production of aqueous humor Timolol
Heart failure  mortality Bisoprolol, carvedilol, metoprolol
Hypertension  cardiac output,  renin secretion (due to β1-
receptor blockade on JGA cells)
Hyperthyroidism Symptom control ( heart rate,  tremor), Propranolol
thyroid storm
Hypertrophic  heart rate Ž  filling time, relieving
cardiomyopathy obstruction
Myocardial infarction  mortality
Supraventricular  AV conduction velocity (class II Metoprolol, esmolol
tachycardia antiarrhythmic)
Variceal bleeding  hepatic venous pressure gradient and portal Nadolol, propranolol, carvedilol
hypertension (prophylactic use)
ADVERSE EFFECTS Erectile dysfunction, cardiovascular Use with caution in cocaine users due to risk
(bradycardia, AV block, HF), CNS (seizures, of unopposed α-adrenergic receptor agonist
sleep alterations), dyslipidemia (metoprolol), activity
and asthma/COPD exacerbations
SELECTIVITY β1-selective antagonists (β1 > β2)—acebutolol Selective antagonists mostly go from A to M (β1
(partial agonist), atenolol, betaxolol, bisoprolol, with 1st half of alphabet)
esmolol, metoprolol
Nonselective antagonists (β1 = β2)—nadolol, Nonselective antagonists mostly go from N to Z
pindolol (partial agonist), propranolol, timolol (β2 with 2nd half of alphabet)
Nonselective α- and β-antagonists—carvedilol, Nonselective α- and β-antagonists have modified
labetalol suffixes (instead of “-olol”)
Nebivolol combines cardiac-selective Nebivolol increases NO
β1‑adrenergic blockade with stimulation of
β3‑receptors (activate nitric oxide synthase in
the vasculature and  SVR)

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PHARMACOLOGY—Autonomic Drugs

Ingested seafood Toxin actions include Histamine release, Total block of Na+ channels, or opening of Na+ channels to
toxins Cause depolarization.
TOXIN SOURCE ACTION SYMPTOMS TREATMENT
Histamine Spoiled dark-meat fish Bacterial histidine Mimics anaphylaxis: Antihistamines.
(scombroid such as tuna, mahi- decarboxylase converts acute burning Albuterol and
poisoning) mahi, mackerel, and histidine to histamine. sensation of mouth, epinephrine if needed.
bonito. Frequently flushing of face,
misdiagnosed as fish erythema, urticaria,
allergy. itching. May progress
to bronchospasm,
angioedema,
hypotension.
Tetrodotoxin Pufferfish. Highly potent toxin; Nausea, diarrhea, Supportive.
binds fast voltage- paresthesias,
gated Na+ channels weakness, dizziness,
in cardiac/nerve loss of reflexes.
tissue, preventing
depolarization.
Ciguatoxin Reef fish such as Opens Na+ Nausea, vomiting, Supportive.
barracuda, snapper, channels, causing diarrhea; perioral
and moray eel. depolarization. numbness;
reversal of hot and
cold sensations;
bradycardia, heart
block, hypotension.

Beers criteria Widely used criteria developed to reduce potentially inappropriate prescribing and harmful
polypharmacy in the geriatric population. Includes > 50 medications that should be avoided in
elderly patients due to  efficacy and/or  risk of adverse events. Examples include:
ƒƒ α-blockers ( risk of hypotension)
ƒƒ Anticholinergics, antidepressants, antihistamines, opioids ( risk of delirium, sedation, falls,
constipation, urinary retention)
ƒƒ Benzodiazepines ( risk of delirium, sedation, falls)
ƒƒ NSAIDs ( risk of GI bleeding, especially with concomitant anticoagulation)
ƒƒ PPIs ( risk of C difficile infection)

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PHARMACOLOGY—TOXICITIES AND SIDE EFFECTS

``

Specific toxicity TOXIN TREATMENT

treatments Acetaminophen N-acetylcysteine (replenishes glutathione)
AChE inhibitors, organophosphates Atropine > pralidoxime
Antimuscarinic, anticholinergic agents Physostigmine, control hyperthermia
Arsenic Dimercaprol, succimer
Benzodiazepines Flumazenil
β-blockers Atropine, glucagon
Carbon monoxide 100% O2, hyperbaric O2
Copper Penicillamine, trientine (Copper penny)
Cyanide Nitrite + thiosulfate, hydroxocobalamin
Digitalis (digoxin) Anti-dig Fab fragments
Heparin Protamine sulfate
Iron Deferoxamine, deferasirox, deferiprone
Lead EDTA, dimercaprol, succimer, penicillamine
Mercury Dimercaprol, succimer
Methanol, ethylene glycol (antifreeze) Fomepizole > ethanol, dialysis
Methemoglobin Methylene blue, vitamin C (reducing agent)
OpiOids NalOxOne
Salicylates NaHCO3 (alkalinize urine), dialysis
TCAs NaHCO3 (stabilizes cardiac cell membrane)
Warfarin Vitamin K (delayed effect), fresh frozen plasma
(immediate)

Drug reactions—cardiovascular
DRUG REACTION
Coronary vasospasm
Cutaneous flushing
Dilated
cardiomyopathy
Torsades de pointes
CAUSAL AGENTS
Cocaine, Amphetamines, Sumatriptan, Ergot alkaloids (CASE)
Vancomycin, Adenosine, Niacin, Ca2+ channel blockers, Echinocandins, Nitrates (flushed from
VANCEN [dancing])
Red man syndrome—rate-dependent infusion reaction to vancomycin causing widespread pruritic
erythema. Manage with diphenhydramine, slower infusion rate.
Anthracyclines (eg, Doxorubicin, Daunorubicin); prevent with Dexrazoxane
Agents that prolong QT interval: antiArrhythmics (class IA, III), antiBiotics (eg, macrolides),
anti“C”ychotics (eg, haloperidol), antiDepressants (eg, TCAs), antiEmetics (eg, ondansetron)
(ABCDE)

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Drug reactions—endocrine/reproductive
DRUG REACTION CAUSAL AGENTS NOTES
Adrenocortical HPA suppression 2° to glucocorticoid
insufficiency withdrawal
Diabetes insipidus Lithium, demeclocycline
Hot flashes SERMs (eg, tamoxifen, clomiphene, raloxifene)
Hyperglycemia Tacrolimus, Protease inhibitors, Niacin, HCTZ, The People Need Hard Candies
Corticosteroids
Hyperprolactinemia Typical antipsychotics (eg, haloperidol), Presents with hypogonadism (eg, infertility,
atypical antipsychotics (eg, quetiapine), amenorrhea, erectile dysfunction) and
metoclopramide, methyldopa galactorrhea (more common in men)
Hyperthyroidism Lithium, amiodarone
Hypothyroidism AMiodarone, SUlfonamides, Lithium I AM SUddenly Lethargic
SIADH Carbamazepine, Cyclophosphamide, SSRIs Can’t Concentrate Serum Sodium

Drug reactions—gastrointestinal
DRUG REACTION CAUSAL AGENTS NOTES
Acute cholestatic Macrolides (eg, erythromycin)
hepatitis, jaundice
Diarrhea Acamprosate, antidiabetic agents (acarbose,
metformin, pramlintide), colchicine,
cholinesterase inhibitors, lipid-lowering
agents (eg, ezetimibe, orlistat), macrolides (eg,
erythromycin), quinidine, SSRIs
Focal to massive Halothane, Amanita phalloides (death cap Liver “HAVAc”
hepatic necrosis mushroom), Valproic acid, Acetaminophen
Hepatitis Rifampin, isoniazid, pyrazinamide, statins,
fibrates
Pancreatitis Didanosine, Corticosteroids, Alcohol, Valproic Drugs Causing A Violent Abdominal Distress
acid, Azathioprine, Diuretics (furosemide,
HCTZ)
Pill-induced Bisphosphonates, ferrous sulfate, NSAIDs, Caustic effect minimized with upright posture
esophagitis potassium chloride, tetracyclines and adequate water ingestion.
Pseudomembranous Ampicillin, cephalosporins, clindamycin, Antibiotics predispose to superinfection by
colitis fluoroquinolones resistant C difficile

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Drug reactions—hematologic
DRUG REACTION CAUSAL AGENTS NOTES
Agranulocytosis Clozapine, Carbamazepine, Propylthiouracil, Can Cause Pretty Major Collapse of
Methimazole, Colchicine, Ganciclovir Granulocytes
Aplastic anemia Carbamazepine, Methimazole, NSAIDs, Can’t Make New Blood Cells Properly
Benzene, Chloramphenicol, Propylthiouracil
Direct Coombs- Penicillin, methylDopa, Cephalosporins P Diddy Coombs
positive hemolytic
anemia
Drug reaction with Allopurinol, anticonvulsants, antibiotics, sulfa DRESS is a potentially fatal delayed hypersen-
eosinophilia and drugs sitivity reaction. Latency period (2–8 weeks)
systemic symptoms followed by fever, morbilliform skin rash, and
frequent multiorgan involvement. Treatment:
withdrawal of offending drug, corticosteroids.
Gray baby syndrome Chloramphenicol
Hemolysis in G6PD Isoniazid, Sulfonamides, Dapsone, Primaquine, Hemolysis IS D PAIN
deficiency Aspirin, Ibuprofen, Nitrofurantoin
Megaloblastic anemia Hydroxyurea, Phenytoin, Methotrexate, Sulfa drugs You’re having a mega blast with PMS
Thrombocytopenia Heparin, Vancomycin, Linezolid Help! Very Low platelets
Thrombotic Combined oral contraceptives, hormone Estrogen-mediated side effect
complications replacement therapy, SERMs (eg, tamoxifen,
raloxifene, clomiphene)

Drug reactions—musculoskeletal/skin/connective tissue

DRUG REACTION
Drug-induced lupus
Fat redistribution
Gingival hyperplasia
Hyperuricemia (gout)
Myopathy
Osteoporosis
Photosensitivity
Rash (Stevens-
Johnson syndrome)
Teeth discoloration
Tendon and cartilage
damage
CAUSAL AGENTS NOTES
Methyldopa, Sulfa drugs, Hydralazine, Having lupus is Mega “SHIPP-E”
Isoniazid, Procainamide, Phenytoin,
Etanercept
Protease inhibitors, Glucocorticoids Fat PiG
Cyclosporine, Ca2+ channel blockers, Can Cause Puffy gums
Phenytoin
Pyrazinamide, Thiazides, Furosemide, Niacin, Painful Tophi and Feet Need Care
Cyclosporine
Statins, fibrates, niacin, colchicine, daptomycin,
hydroxychloroquine, interferon-α,
penicillamine, glucocorticoids
Corticosteroids, depot medroxyprogesterone
acetate, GnRH agonists, aromatase inhibitors,
anticonvulsants, heparin, PPIs
Sulfonamides, Amiodarone, Tetracyclines, 5-FU SAT For Photo
Anti-epileptic drugs (especially lamotrigine), Steven Johnson has epileptic allergy to sulfa
allopurinol, sulfa drugs, penicillin drugs and penicillin
Tetracyclines Teethracyclines
Fluoroquinolones

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PHARMACOLOGY—Toxicities and Side Effects

Drug reactions—neurologic
DRUG REACTION CAUSAL AGENTS NOTES
Cinchonism Quinidine, quinine Can present with tinnitus, hearing/vision loss,
psychosis, and cognitive impairment
Parkinson-like Antipsychotics, Reserpine, Metoclopramide Cogwheel rigidity of ARM
syndrome
Peripheral neuropathy Phenytoin, vincristine
Pseudotumor cerebri Growth hormones, tetracyclines, vitamin A
Seizures Isoniazid (vitamin B6 deficiency), Bupropion, With seizures, I BITE my tongue
Imipenem/cilastatin, Tramadol, Enflurane
Tardive dyskinesia Antipsychotics, metoclopramide
Visual disturbance Topiramate (blurred vision/diplopia, haloes), These Drugs Irritate Very Precious Eyes
Digoxin (yellow-tinged vision), Isoniazid (optic
neuropathy/color vision changes), Vigabatrin
(bilateral visual field defects), PDE-5 inhibitors
(blue-tinged vision), Ethambutol (color vision
changes)

Drug reactions—renal/genitourinary
DRUG REACTION
Fanconi syndrome
Hemorrhagic cystitis
Interstitial nephritis
CAUSAL AGENTS NOTES
Cisplatin, ifosfamide, expired tetracyclines,
tenofovir
Cyclophosphamide, ifosfamide Prevent by coadministering with mesna
Penicillins, furosemide, NSAIDs, proton pump
inhibitors, sulfa drugs

Drug reactions—respiratory
DRUG REACTION CAUSAL AGENTS NOTES
Dry cough ACE inhibitors
Pulmonary fibrosis Methotrexate, Nitrofurantoin, Carmustine, My Nose Cannot Breathe Bad Air
Bleomycin, Busulfan, Amiodarone

Drug reactions—multiorgan
DRUG REACTION CAUSAL AGENTS NOTES
Antimuscarinic Atropine, TCAs, H1-blockers, antipsychotics
Disulfiram-like 1st-generation Sulfonylureas, Procarbazine, Sorry Pals, Can’t Go Mingle.
reaction certain Cephalosporins, Griseofulvin,
Metronidazole
Nephrotoxicity/ Loop diuretics, Aminoglycosides, cisPlatin, Listen And Pee Very TERriBly.
ototoxicity Vancomycin, amphoTERicin B Cisplatin toxicity may respond to amifostine.

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Drugs affecting pupil size

 pupil size
Anticholinergics (atropine, TCA, tropicamide,
scopolamine, antihistamines)
Drugs of abuse (amphetamines, cocaine, LSD)
Sympathomimetics
 pupil size
Antipsychotics (haloperidol, risperidone,
olanzapine)
Drugs of abuse (eg, heroin/opioids)
Parasympathomimetics (pilocarpine),
organophosphates

Cytochrome P-450 interactions (selected)

Inducers (+) Substrates Inhibitors (–)
Modafinil Anti-epileptics Sodium valproate
Chronic alcohol use Theophylline Isoniazid
St. John’s wort Warfarin Cimetidine
Phenytoin OCPs Ketoconazole
Phenobarbital Fluconazole
Nevirapine Acute alcohol abuse
Rifampin Chloramphenicol
Griseofulvin Erythromycin/clarithromycin
Carbamazepine Sulfonamides
Ciprofloxacin
Omeprazole
Metronidazole
Amiodarone
Grapefruit juice

Most chronic alcoholics Always Think When SICKFACES.COM (when

Steal Phen-Phen and Never Outdoors I Am drinking Grapefruit
Refuse Greasy Carbs juice)

Sulfa drugs Sulfonamide antibiotics, Sulfasalazine, Scary Sulfa Pharm FACTS

Probenecid, Furosemide, Acetazolamide,
Celecoxib, Thiazides, Sulfonylureas.
Patients with sulfa allergies may develop
fever, urinary tract infection, Stevens-
Johnson syndrome, hemolytic anemia,
thrombocytopenia, agranulocytosis, acute
interstitial nephritis, and urticaria (hives).
Symptoms range from mild to life threatening.

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pharmacology—Miscellaneous

PHARMACOLOGY—MISCELLANEOUS
``

Drug names
ENDING CATEGORY EXAMPLE
Antimicrobial
-azole Ergosterol synthesis inhibitor Ketoconazole
-bendazole Antiparasitic/antihelminthic Mebendazole
-cillin Transpeptidase (penicillin-binding protein) Ampicillin
-cycline Protein synthesis inhibitor Tetracycline
-ivir Neuraminidase inhibitor Oseltamivir
-navir Protease inhibitor Ritonavir
-ovir DNA polymerase inhibitor Acyclovir
-thromycin Macrolide antibiotic Azithromycin
CNS
-ane Inhalational general anesthetic Halothane
-azine Typical antipsychotic Thioridazine
-barbital Barbiturate Phenobarbital
-caine Local anesthetic Lidocaine
-ipramine, -triptyline TCA Imipramine, amitriptyline
-triptan 5-HT1B/1D agonist Sumatriptan
-zepam, -zolam Benzodiazepine Diazepam, alprazolam
Autonomic
-chol Cholinergic agonist Bethanechol, carbachol
-curium, -curonium Nondepolarizing paralytic Atracurium, vecuronium
-olol β-blocker Propranolol
-stigmine AChE inhibitor Neostigmine
-terol β2-agonist Albuterol
-zosin α1-antagonist Prazosin
Cardiovascular
-afil PDE-5 inhibitor Sildenafil
-dipine Dihydropyridine Ca2+ channel blocker Amlodipine
-pril ACE inhibitor Captopril
-sartan Angiotensin-II receptor blocker Losartan
-xaban Direct factor Xa inhibitor Apixaban, edoxaban, rivaroxaban
Other
-dronate Bisphosphonate Alendronate
-gliptin DPP-4 inhibitors Sitagliptin
-glitazone PPAR-γ activator Rosiglitazone
-limus Calcineurin inhibitor Everolimus, tacrolimus
-prazole Proton pump inhibitor Omeprazole
-prost Prostaglandin analog Latanoprost
-sentan Endothelin receptor antagonist Bosentan
-tidine H2-antagonist Cimetidine
-tropin Pituitary hormone Somatotropin

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Biologic agents
ENDING CATEGORY EXAMPLE
Monoclonal antibodies (-mab)—target overexpressed cell surface receptors
-ximab Chimeric human-mouse monoclonal Ab Rituximab
-zumab Humanized mouse monoclonal Ab Bevacizumab
-mumab Human monoclonal Ab Ipilimumab
Small molecule inhibitors (-ib)—target intracellular molecules
-tinib Tyrosine kinase inhibitor Imatinib
-zomib Proteasome inhibitor Bortezomib
-ciclib Cyclin-dependent kinase inhibitor Palbociclib
Receptor fusion proteins (-cept)
-cept TNF-α antagonist Etanercept
Interleukin receptor modulators (-kin)—agonists and antagonists of interleukin receptors
-leukin IL-2 agonist/analog Aldesleukin
-kinra Interleukin receptor antagonist Anakinra

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 250 SEC TION II Pharmacology 

NOTES
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