Dr ugs i n

Der mato lo g y

KCOM/Texas Consortium
Dermatology Residency Program
Pe nicil lin s
 MOA: Inhibit bacterial wall synthesis by
binding to peptidoglycans.
Pe nicil lin s

 Dicloxacillin is unsurpassed as an
oral Beta-lactamase-resistant
pencillin, effective against most
pyodermas.
 Amoxicillin is hydrolyzed by Beta-
lactamases and thus is not effective
against Staphyloccocus aureus and
many Enterobacteriaceae species
Pe nicil lin s
 Adverse effects: Hypersensitivity, GI.
 5-10% of PCN allergic pts are also
allergic to Cephalosporins (?)
 Augmentin contains the Beta-
lactamase inhibitor Clavulanate,
which synergistically increases
spectrum of activity against MRSA,
Haemophilus sp, Klebsiella sp, E.
coli, Proteus sp, B. fragilis.
 Ce phalo sp orin s
 MOA: Inhibit PCN-binding proteins,
preventing cell wall synthesis. Chemical
structure is Beta-lactamase resistant.
Ce phalosp orin s

 1st Gen: Staph aureus, but not

MRSA
 2nd Gen: H. influenzae, M.
catarrhalis, Neisseria sp, some
Enterobacteriaceae
 3rd Gen: Pseudomonas aeruginosa
Ce phalosp orin s

 Adverse Effects: GI, Hypersensitivity

 Ceclor – serum sickness
 Hematologic – mild, Coombs Ab
positivity, hemolytic anemia is rare.
 Ma cro lid es
 MOA: binds to 50S subunit of ribosome,
inhibiting RNA-dependent protein
synthesis
Ma cro lid es

 Erythromycin is prototype
 Limited gram negative activity
 Nausea, diarrhea
 Erratic bioavaliability
 Multiple daily doses
Ma cro lid es

 Azithromycin and Clarithromycin

offer enhanced potency and activity
against gram positive and negative
organisms
 Azithromycin and Clarithromycin
also cover atypical mycobacteria,
Toxoplasma gondii, Treponema
pallidum and Borrelia burgdorferi
Ma cro lid es

 Azithromycin and Clarithromycin

both have fewer GI side effects than
Erythromycin.
 Headaches, dizziness, liver enzyme
elevations.
Pr egnancy

 Penicillins, Cephalosporins and

Macrolides…..
 All generally accepted as safe during
pregnancy.
 Pregnancy category B
 Flu oroquin olones
 MOA: Inhibits DNA gyrase (topo-isomerase II)
which induces negative supercoiling,
inhibiting replication of DNA
FQs

 Low resistance
 High oral bioavaliability
 Extensive tissue penetration.
 Gram +/-, Pseudomonas, Mycobacteria
Flu oroquin olones

 Interactions: decrease bioavaliability

when administered with antacids that
contain aluminum or magnesium, as well
as iron or zinc containing products.
 FQs decrease metabolism of
WARFARIN theophylline and
cyclosporine.
 Decreased seizure threshold
FQs
 Adverse effects: GI, HA, dizziness,
agitation, insomnia.
 Impair cartilage formation in animals so
Pregnancy Category C
 Hypersensitivity, photosensitivity – qHS
 Blue-black leg hyperpigmentation on legs
revealing iron particles in the dermal
macrophages reported.
Te tracyc lin es
 MOA: Inhibits protein synthesis by
binding to the 30S ribosome subunit.
Te tracyc lin es

 Broad spectrum: G+ > G-, Mycoplasmas,

Chlamydia, Rickettsia, Spirochetes some
parasites.
 Minocycline and Doxycycline more active
against Staph and Group A Strep than
TCN
Te tracyc lin es
 TCN must be taken 1 hour before or 2
hours after meals and has short ½ life.
 Doxycycline and minocycline are well
absorbed with food and have longer ½
life so require fewer daily doses.
 Excretion: TCN, MCN = renal, DCN = GI.
 Potential for hepatotoxicity = relative
contraindication in severe liver disease.
Te tracyc lin es

 Acne, Rosacea, Perioral Der

 May be used in combination with
Nicotinamide to tx bullous pemphigoid,
DH, Linear IgA bullous der
 May be used to treat RMSF, Rickettsia,
Lyme, Vibrio vulnificus, M. marinarum,
Aquatic infections
Te tracyc lin es

 Drug interactions: Potentiates effects of

oral anticoagulants, digoxin and lithium
by impairing use of prothrombin or by
decreasing vitamin D production by
bacteria
 Anticonvulsants decrease DCN levels.
Te tracyc lin es
 Adverse effects: MC GI, esophagitis and
pancreatitis rare
 Brown teeth discoloration and delayed
bone growth in children < 9 yrs. Old
 Blue-black pigmentation of nails, skin,
scars and sclera, black tongue
 Hypersensitivity, SJS, Drug-Lupus,
Sweet’s
 Hematologic, Pseudotumor cerebri
Br own disc oloratio n
-TCN
TCN in Pr egnancy

 May be hepatotoxic in large doses in

pregnant patients.
 Pregancy Category D – associated with
retardation of skeletal growth and
permanent yellow-gray-brown
discoloration if given in 2nd half of
pregnancy (during tooth development)
Rifa mp in – 4 R’ s
 Revs up the CyP450 enzymes
 Red urine
 Resistance when used alone
 RNA polymerase inhibited

 Indicated for TB, Rhinoscleroma,

Leishmaniasis and difficult pyodermas
Rifa mp in

 Drug interactions – decreased levels of

antiarrhythmics, anticonvulsants, azole
antifungals, theophylline, steroids,
OCP’s, B-blockers, CCB’s, sulfonamides,
CORTICOSTEROIDS, WARFARIN
 IT IS THE ONLY ANTIBIOTIC PROVEN
TO REDUCE EFFICACY OF OCP’s
Rifa mp in
 Orange red discoloration of urine and
contact lenses
 Hypersensitivity Syndrome: fever, chills,
bone pain, dizziness, HA as well as
pruritis, urticaria, acneiform, bullous
pemphigoid, mucositis, exfoliative
dermatitis, exudative conjunctivitis
 Hemolysis, thrombocytopenia,
leukopenia
 ARF, ↑ LFT’s may accompany HS.
Rifa mp in i n pre gnancy

 CONTRAINDICATED due to placental

diffusion, fetal malformations
 Pregnancy category C
 Post-natal hemorrhages in mother and
infant – treated with Vitamin K
 Animal studies revealed cleft palate,
spina bifida, imperfect osteogenesis
TMP -SMX

 MOA: Disrupts enzymes in the

tetrahydrofolic acid pathway, thus
disrupting nucleic acid synthesis
 Broad spectrum: many G+,
Enterobacteriaceae, H. influenzae,
Brucella, Yersinia, Pseudomonas sp.
other than aeruginosa. Also Nocardia
asteroides, Atypical mycobacteria
TMP -SMX
 Drug Interactions: increases prothrombin
time in patients taking WARFARIN.
 Avoid MTX due to THF effects.
 RARE FATAL Adverse reactions: SJS,
TEN, fulminant hepatic necrosis,
agranulocytosis, aplastic anemia.
 Also GI, Tremors, HA, nephritis.
 STOP DRUG AT 1ST SIGN OF RASH
TMP -SMX i n p regnany
 Cleft palate in rats who received doses
16 to 33 times the human dose.
 Brumfitt & Pursell – retrospective study
found no difference in incidence of
congenital abnormalities between
mothers on TMP-SMX vs. placebo
(Quoted in PDR)
 However, because TMP-SMX interferes
with nucleic acid synthesis, use only if
indicated. Category C
Cli ndamy cin
 MOA: binds 50S ribosomal subunit
to block transpeptidation, thus
protein synthesis.
 Buy AT 30, CEL at 50
 A minoglycoside - 30
 T etracycline – 30
 C lindamycin - 50
 E rythromycin - 50
 L incomycin - 50
Cli ndamy cin

 Effective against most G+ and most

anaerobic organisms, also Toxoplasma
gondii, Clostridium perfringens
 Poor G- activity
 Cli ndamy cin
 Drug interactions: enhances tubocurare,
pancuronium via neuromuscular blocking
properties
 Actual incidence of pseudomembranous
colitis is actually much lower than originally
perceived in the 1970’s and 1980’s
 C. Difficile only in 0.1% to 10% of patients.
 Adverse: GI, Maculopapular, Urticaria, DM,
SJS with polyarthritis, Anaphylaxis
Cli ndamy cin in
pregnancy
 Animal studies revealed no
teratogenicity.
 No well controlled human studies
 Pregnancy Category B
Te rbin afin e
 MOA: Allylamine: inhibits squalene
epoxidase which decreases ergosterol,
impairs fungal cell membrane formation
Te rbin afin e
Onychomycosis, T. Capitis, other
tineas
Ineffective against Candida sp.
Terbinafine increases toxicity of TCA’s,
Theophylline, Narcotics, Caffiene
Terfenadine, Cimetidine increase
toxicity of Terbinafine.
Te rbin afin e
 Common Adverse events: GI, HA,
morbilliform or maculopapular rash.
 Uncommon Adverse events: gastritis,
idiosyncratic hepatitis, SJS, TEN,
alopecia, visual disturbances,
neutropenia, lymphopenia, tiredness,
hypersensitivity syndrome, allergic
reaction.
Te rbin afin e i n
pregnancy
 Category B
 Rabbits had no harm to fetus at doses 12
to 23 times the human dose.
 Because treatment of onychomycosis
can wait until after pregnancy, it is not
recommended in pregnancy.
Itra conazo le
 MOA: Triazole, inhibits the CyP-450 enzyme
lanosterol 14-α demethylase, so than lanosterol
cannot become ergosterol
Itra conazo le

 Broad spectrum antifungal.

 FDA Indications: Onychomycosis, Deep
fungal infections.
 Off label: Candida, Tineas, Pityrosporum
infections, Majocci’s granuloma, HIV
associated eosinophilic folliculitis, chronic
mucocutaneous Candidiasis
Itra conazo le

 Off label uses:

 Candida, Tineas
 Pityrosporum infections
 Majocci’s granuloma,
 HIV associated eosinophilic folliculitis
 Chronic mucocutaneous Candidiasis
Itra conazo le
 Common adverse events: GI, HA,
morbilliform or maculopapular rash.
 FDA warnings for LFT’s and CHF.
 Uncommon adverse events: gastritis,
constipation, hepatitis (1:500,000), SJS,
urticaria, vertigo, dizziness, tremor,
peripheral neuropathy, neutropenia,
HTN, hypertriglyceridemia, fever, edema,
menstrual disorder, hypokalemia.
Itra conazo le – increases toxicity
of….
 HMG CoA Reductase inhibitors
 Benzodiazepines
 Oral Hypoglycemics
 Digoxin
 Sildenafil
 Calcium channel blockers
 Warfarin
 Anticonvulsants
 Immunosuppressants- cyclosporine, tacrolimus
 HIV-1 protease inhibitors
 Note: cisapride, astemizole and terfenadine were taken off the market,
but may still exist in medicine cabinets across the country.
Itra conazo le

 Serum Itraconazole levels decreased by:

 Anticonvulsants – phenytoin,
carbamazepine, phenobarbital
 Anti-TB meds – rifabutin, isoniazid
 H2 Antihistamines – Cimetidine, Ranitidine
 PPIs – Omeprazole, Lansoprazole
 Didanosine, Revirapine
Itra conazo le in
pregnancy
 Category C
 Dose related maternal toxicity, fetal
toxicity and teratogenicity in mice given
10 times the human dose.
 Skeletal defects, encephaloceles,
macroglossia
Flu conazo le
 MOA: inhibits lanosterol 14-α demethylase
Flu conazo le

 FDA: Vaginal, Oropharyngeal, Esophageal

Candidiasis, Cryptococcal meningitis,
Candida prophylaxis in BM transplant pts
 Exception: Candida krusei
 Off label: Tineas, TV, Lymphocutaneous or
visceral Sporotrichosis, Chronic muco-
cutaneous Candidiasis, Onychomycosis
Flu conazo le increases toxicity of….

 TCA antidepressants
 Phenytoin
 Theophylline
 Warfarin
 Oral Hypoglycemics
 Zidovudine
 Cyclosporine, Tacrolimus
 Note: cisapride, astemizole and terfenadine were taken off the
market, but may still exist in medicine cabinets across the
country.
Flu conazo le in
pregnancy
 Category C
 No well controlled studies in pregnant
women.
 Use only if potential benefit outweighs
risk.
 Reports of pregnant women with
coccidiomycosis treated with 400-800mg
daily resulting in multiple congenital
anomalies
Gr ise ofulvi n

 MOA: destruction of mitotic spindle

formation, arresting mitosis in metaphase
 T. Capitis 6-8w, Onychomycosis
 Adverse: GI, N/V, HA, Visual & Psych
 Porphyrin metab. impaired, photo, LE, PCT.
 Decreases Warfarin, Cyclosporine, OCP
 Alcohol (potentiated by Griseofulvin)
 Phenobarbital (decreased levels of Grise)
Ke toconazo le

 MOA: ergosterol synthesis impaired

 Indications: Histoplasmosis, Candidiasis,
Blastomycosis, Coccidiomycosis, Para-
coccidiomycosis, Peudoallescheriasis
 Adverse: GI, N/V, anorexia20% elevated
LFTs, 5% overt hepatitis, Fatal rarely.
 Decreased testosterone, decreased
libido, impotence, irreg. menses
Ke toconazo le
 Increases toxicity of…..
 Cyclosporine, Warfarin, Phenytoin,
Digoxin, Oral Hypoglycemics
 Cisapride, Astemizole, Terfenadine*.

 Pregnancy category C
 Teratogenic in animals, no human
studies.
Ac yc lo vir
 MOA: Herpes infected cells create viral
Thymidine kinase (TK) 100 times faster than
non-infected cells.
 Acyclovir is an acyclic guanine nucleoside
analog that is phosphorylated by viral TK 3
times (triphosphate form)
 Interferes with viral DNA polymerase,
preventing viral replication
Tza nck Sme ar
Ac yc lo vir

 Greater activity against HSV-1 than HSV-2.

 HSV encephalitis -mortality decreased 50%
 H. Zoster (Varicella) if given early.
 Low toxicity, mild nausea, HA.
 Rarely reversible nephrotoxicity, CNS.
 Pregnancy Category C*
 * Note: VCV & FCV are Category B
Va lc yc lo vir

 MOA: same as acyclovir except this is

the L-valyl ester or “prodrug” of acyclovir
 Increased bioavaliablity, absorption.
 Once absorbed is rapidly converted to
acyclovir.
 Rare risk of thrombocytopenic purpura
Famcyc lo vir
 MOA: another prodrug of Acyclovir
 77% bioavaliability for Famciclovir
 55% bioavaliability for Valcyclovir
 15-30% bioavaliability for Acyclovir
 All “Cyclovirs” indicated for Herpes
infections and H. Zoster by FDA
 Off label: recurrent EM, primary Varicella
 Acyclovir Valcyclovir Famcyclovi

Simplex 200mg 1000mg 250mg

1st 5x/d x 10d BID x 10d TID x 10d
Simplex 400mg 500mg 125mg
recurrent TID x 5d BID x 5d BID x 5 d
Simplex 400mg BID 500mg QD 250mg BID
suppress
Zoster 800mg 1000mg 500mg
acute 5x/d x 10d TID x 10d TID x 10d
Varicella, 20mg/kg Not well Not well
1st QID x 7d evaluated evaluated
Co rticost eroid s

 MOA: Binds to GCR (Glucocorticoid

Receptor) on cell, GCR is activated and
translocates to the nucleus, binding to
GCRE’s (Glucocorticoid Response
Elements) of multiple genes. CS can act
as an agonist or antagonist for these
genes, thus having multiple effects on
various organ systems.
Co rticost eroid MOA
 TRANSCRIPTION of NFkB & AP-1
decreased = thus less cytokine
production
 APOPTOSIS of T lymphocytes and
eosinophils
 SIGNAL TRANSDUCTION of
Phospholipase A2, eicosinoids and COX-
2 inhibited = decreased prostaglandins,
LKTs, 12-HETE, 15-HETE
 B cells – Ab production
 T cells – IL-2
 Lymphocytes – NK cells & cytotoxic
 PMNs – margination, chemotaxis
 Mast – degranulation, histamine release
 Monos/Macs – IL-1, INFγ
 Langerhans – antigen processing
 Eos, Basos – recruitment, # and function
 Fibroblasts – collagen, ground substance
 Membrane – stabilization
 Angiogenesis, Vasoconstriction, Permeability
Syst emic Ad verse
eve nts  Osteonecrosis
 Adrenal crisis
 Hyperglycemia  Bowel Perforation
 Hypertension  Peptic Ulcer Disease
 CHF, edema, fluid  Cataracts
overload  Agitation/Psychosis
 Hyperlipidemia  Opportunistic
 Cushingoid changes Infections
 Bone growth  Opportunistic Cancer
 Osteoporosis  Myopathy
Cu taneous Ad ve rse
eve nts
 Impaired wound healing
 Striae, atrophy, telangiectasias, purpura
 Steroid acne/rosacea
 Acanthosis nigricans
 Staph, Herpesvirus infections
 Telogen effluvium, hirsuitism
 Fat atrophy, injection site cystallization
 Flare of pustular psoriasis, rhus derm.
Ta pering

If starting dosage is… Taper in increments of

100mg 20mg

60mg 10mg

20mg 5mg

10mg 2.5mg
CS I ndic ations… .
 Bullous: Pemphigus, pemphigoid, EBA,
SJS, TEN, EM Minor, Linear IgA BD,
 Autoimmune: SLE, DM, Alopecia Areata
 Vasculitis: Systemic, PG, Behcet’s,
Sweet’s
 Dermatitis: Contact, Atopic,
Erythroderma, LP
 Other: Sarcoidosis, Sunburn, Urticaria,
Acne/hirsuitism, PHN prevention
CS Ab so lute
Co ntr ain dic atio ns
 Systemic Fungal Infections
 Herpes Simplex Keratitis
 Hypersensitivity
Steroi d Wit hdraw al
Syndrome v. Adrenal
Cri si s
 SWS  Adrenal Crisis
 Fatigue, lethargy  All SWS symptoms
 Depression plus…..
 Mood swings  Hypoglycemia
 Headache  Hypotension
 Myalgias/Arthralgias  Shock
 Anorexia, N/V  Hypokalemia
 Weight loss  Hyponatremia
CS Dr ug in te ra ctions….

 Azoles, Macrolide, OCPs, hormones

increase serum levels of CS.
 CS may increase levels of potassium
depleting diuretics, digitalis and
cyclosporine
 Anticonvulsants may decrease levels of
CS.
St eroid s i n p ediatrics

 1mg/kg/day for 2-3 weeks

 Dose halved every 4 to 7 days
St eroid s i n p regnancy
 Original animal studies showed
teratogenicity, cleft lip, cleft palate
 Multiples human studies of pregnant
patients who needed steroids such as
SLE, Severe asthma and organ
transplant showed NO INCREASED
RISK of teratogenicity.
 If absolutely medically indicated, use the
steroids.
Me thotre xate
 MOA: inhibits enzyme dihydrofolate
reductase, prevents conversion of
dihydrofolate (DHF) to tetrahydrofolate
(THF). THF is essential for synthesis of
thymidine and purine nucleotides that
form DNA and RNA.
 FDA approved for psoriasis as it inhibits
rapid proliferation of keratinocytes.
Me thotre xate
 Liver - MC side effect on long term MTX.
 Avoid pts with alcoholism, cirrhosis,
hepatitis, liver disease or liver cancer.
 Risk of cirrhosis 0%-25%. Overall, the
risk is low for patients w/ cumulative dose
< 1500mg
 Liver biopsy recommended at 1500mg.
 Alcohol and Accutane synergistically
increase hepatotoxicity.
MTX – Ad ve rse eve nts

 Lung problems - Rarely, pneumonitis.

There is no way to predict who will have
this side effect and it can occur in
patients taking very low doses. There is
no benefit to taking a routine chest x-ray
prior to starting therapy with
methotrexate.
MTX - Ad ve rse e ve nts

 HEME: Pancytopenia is side effect with

the greatest risk of death. A supplement
of folic acid 1 to 5mg daily greatly
decreases the risk of blood problems.
 Dapsone, TMP/SMX, Sulfonamides all
increase hematologic toxicity
MTX Ad ve rse eve nts
 Lymphoma - rarely reported in psoriatics.
 GI: Nausea, lack of appetite are MC, but
diarrhea, vomitting & ulcerative stomatitis
are rare.
 Pregnancy Category X, Men on MTX
should avoid impregnating a woman.
 Nephrotoxicity only documented IV and
in doses much higher than those used in
treating psoriasis.
Dr ugs t hat ↑ M TX
toxic ity
 NSAIDS
 Sulfonamides
 Dipyridamole
 Probenecid
 Chloramphenicol
 Phenothiazines
 Phenytoin
 Tetracyclines
MTX in dic atio ns
 FDA: Psoriasis, Pustular, Erythrodermic
 OFF LABEL:
 Proliferative: PRP, PLEVA, REITER’S
 Bullous: PEMPHIGUS, PEMPHIGOID
 Autoimmune: DM, SLE, SCL
 Vascultits: LCV, PAN, BEHCET’S, PG
 Dermatitis: AD
 Other: SARCOID, KELOIDS, LP, KA, MF
Mo nitorin g MTX

 Baseline: H&P, Review meds, PMHx.

 CBC, COMP, Hepatitis profile.
 HIV screen if risk factors present.
 Liver bx: @1.5g and @ each gram
 CBC, LFT every weekly x 2-4 weeks
 CBC, LFT 1 week after each dose ↑
 Renal Profile 2x/year
 Grade I – mild fatty
infiltration- WNL.
 Grade II – Moderate
fatty infiltration.
 Grade IIIA - Mild
fibrosis – re-biopsy
@ 6 mos, but stay
on the MTX.
 Grade IIIB –
Fibrosis moderate
to severe.
 Grade IV –
Cirrhosis.
 Aza thio prin e: MOA
 6-thioguanine is
a purine analog
which is
incorporated into
DNA & RNA, thus
inhibiting purine
synthesis and cell
division
Aza thio prin e
Me taboli sm
 HGPRT – converts AZTP to active form -
Lesch Nyan pts lack it = non-responders
 Thiopurine methyltransferase - (TPMT)
- 88% pts are homozygous for high
activity, need higher dosing
 Xanthine Oxidase (XO) breaks down
AZTP, and is inhibited by Allopurinol
Aza thio prin e