Drugs in Drugs in DermatologyDermatology
KCOM/Texas ConsortiumKCOM/Texas Consortium
Dermatology Residency ProgramDermatology Residency Program
PenicillinsPenicillins MOA: Inhibit bacterial wall synthesis by MOA: Inhibit bacterial wall synthesis by
binding to peptidoglycans.binding to peptidoglycans.
PenicillinsPenicillins
Dicloxacillin is unsurpassed as an Dicloxacillin is unsurpassed as an oral Beta-lactamase-resistant oral Beta-lactamase-resistant pencillin, effective against most pencillin, effective against most pyodermas.pyodermas.
Amoxicillin is hydrolyzed by Beta-Amoxicillin is hydrolyzed by Beta-lactamases and thus is not effective lactamases and thus is not effective against against Staphyloccocus aureusStaphyloccocus aureus and and many many EnterobacteriaceaeEnterobacteriaceae species species
PenicillinsPenicillins Adverse effects: Hypersensitivity, GI.Adverse effects: Hypersensitivity, GI. 5-10% of PCN allergic pts are also 5-10% of PCN allergic pts are also
allergic to Cephalosporins (?)allergic to Cephalosporins (?) Augmentin contains the Beta-Augmentin contains the Beta-
lactamase inhibitor Clavulanate, lactamase inhibitor Clavulanate, which synergistically increases which synergistically increases spectrum of activity against spectrum of activity against MRSA, MRSA, Haemophilus sp, Klebsiella sp, E. Haemophilus sp, Klebsiella sp, E. coli, Proteus sp, B. fragilis. coli, Proteus sp, B. fragilis.
CephalosporinsCephalosporins MOA: Inhibit PCN-binding proteins, MOA: Inhibit PCN-binding proteins,
preventing cell wall synthesis. Chemical preventing cell wall synthesis. Chemical structure is Beta-lactamase resistant.structure is Beta-lactamase resistant.
CephalosporinsCephalosporins
11stst Gen: Gen: Staph aureusStaph aureus, but not , but not MRSAMRSA
22ndnd Gen: Gen: H. influenzae, M. H. influenzae, M. catarrhalis, Neisseria sp, catarrhalis, Neisseria sp, some some EnterobacteriaceaeEnterobacteriaceae
33rdrd Gen: Gen: Pseudomonas aeruginosa Pseudomonas aeruginosa
CephalosporinsCephalosporins
Adverse Effects: GI, HypersensitivityAdverse Effects: GI, Hypersensitivity Ceclor – serum sicknessCeclor – serum sickness Hematologic – mild, Coombs Ab Hematologic – mild, Coombs Ab
positivity, hemolytic anemia is rare.positivity, hemolytic anemia is rare.
MacrolidesMacrolides MOA: binds to 50S subunit of ribosome, MOA: binds to 50S subunit of ribosome,
inhibiting RNA-dependent protein synthesisinhibiting RNA-dependent protein synthesis
MacrolidesMacrolides
Erythromycin is prototypeErythromycin is prototype Limited gram negative activityLimited gram negative activity Nausea, diarrheaNausea, diarrhea Erratic bioavaliabilityErratic bioavaliability Multiple daily dosesMultiple daily doses
MacrolidesMacrolides
Azithromycin and Clarithromycin offer Azithromycin and Clarithromycin offer enhanced potency and activity against enhanced potency and activity against gram positive and negative organismsgram positive and negative organisms
Azithromycin and Clarithromycin also Azithromycin and Clarithromycin also cover atypical mycobacteria, cover atypical mycobacteria, Toxoplasma gondii, Treponema Toxoplasma gondii, Treponema pallidum and Borrelia burgdorferipallidum and Borrelia burgdorferi
MacrolidesMacrolides
Azithromycin and Clarithromycin Azithromycin and Clarithromycin both have fewer GI side effects than both have fewer GI side effects than Erythromycin.Erythromycin.
Headaches, dizziness, liver enzyme Headaches, dizziness, liver enzyme elevations.elevations.
PregnancyPregnancy
Penicillins, Cephalosporins and Penicillins, Cephalosporins and Macrolides…..Macrolides…..
All generally accepted as safe during All generally accepted as safe during pregnancy.pregnancy.
Pregnancy category BPregnancy category B
FluoroquinolonesFluoroquinolones MOA: Inhibits MOA: Inhibits DNA gyraseDNA gyrase (topo-isomerase II) (topo-isomerase II)
which induces which induces negative supercoilingnegative supercoiling, , inhibiting replication of DNAinhibiting replication of DNA
FQsFQs
Low resistanceLow resistance High oral bioavaliabilityHigh oral bioavaliability Extensive tissue penetration.Extensive tissue penetration. Gram +/-, Gram +/-, PseudomonasPseudomonas, Mycobacteria, Mycobacteria
FluoroquinolonesFluoroquinolones
Interactions: decrease bioavaliability Interactions: decrease bioavaliability when administered with antacids that when administered with antacids that contain aluminum or magnesium, as well contain aluminum or magnesium, as well as iron or zinc containing products.as iron or zinc containing products.
FQs decrease metabolism of WARFARIN FQs decrease metabolism of WARFARIN theophylline and cyclosporine.theophylline and cyclosporine.
Decreased seizure thresholdDecreased seizure threshold
FQsFQs Adverse effects: GI, HA, dizziness, Adverse effects: GI, HA, dizziness,
agitation, insomnia.agitation, insomnia. Impair cartilage formation in animals so Impair cartilage formation in animals so
Pregnancy Category CPregnancy Category C Hypersensitivity, photosensitivity – qHSHypersensitivity, photosensitivity – qHS Blue-black leg hyperpigmentation on legs Blue-black leg hyperpigmentation on legs
revealing iron particles in the dermal revealing iron particles in the dermal macrophages reported.macrophages reported.
TetracyclinesTetracyclines MOA: Inhibits protein synthesis by MOA: Inhibits protein synthesis by
binding to the 30S ribosome subunit.binding to the 30S ribosome subunit.
TetracyclinesTetracyclines
Broad spectrum: G+ > G-, Broad spectrum: G+ > G-, Mycoplasmas, Mycoplasmas, Chlamydia, Rickettsia, SpirochetesChlamydia, Rickettsia, Spirochetes some some parasites.parasites.
Minocycline and Doxycycline more active Minocycline and Doxycycline more active against against StaphStaph and Group A and Group A Strep Strep than than TCNTCN
TetracyclinesTetracyclines
TCN must be taken 1 hour before or 2 TCN must be taken 1 hour before or 2 hours after meals and has short ½ life.hours after meals and has short ½ life.
Doxycycline and minocycline are well Doxycycline and minocycline are well absorbed with food and have longer ½ absorbed with food and have longer ½ life so require fewer daily doses.life so require fewer daily doses.
Excretion: TCN, MCN = renal, DCN = GI.Excretion: TCN, MCN = renal, DCN = GI. Potential for hepatotoxicity = relative Potential for hepatotoxicity = relative
contraindication in severe liver disease.contraindication in severe liver disease.
TetracyclinesTetracyclines
Acne, Rosacea, Perioral DerAcne, Rosacea, Perioral Der May be used in combination with May be used in combination with
Nicotinamide to tx bullous pemphigoid, Nicotinamide to tx bullous pemphigoid, DH, Linear IgA bullous derDH, Linear IgA bullous der
May be used to treat RMSF, May be used to treat RMSF, Rickettsia, Rickettsia, Lyme, Vibrio vulnificus, M. marinarumLyme, Vibrio vulnificus, M. marinarum, , Aquatic infectionsAquatic infections
TetracyclinesTetracyclines
Drug interactions: Potentiates effects of Drug interactions: Potentiates effects of oral anticoagulants, digoxin and lithium oral anticoagulants, digoxin and lithium by impairing use of prothrombin or by by impairing use of prothrombin or by decreasing vitamin D production by decreasing vitamin D production by bacteriabacteria
Anticonvulsants decrease DCN levels.Anticonvulsants decrease DCN levels.
TetracyclinesTetracyclines
Adverse effects: MC GI, esophagitis and Adverse effects: MC GI, esophagitis and pancreatitis rarepancreatitis rare
Brown teeth discoloration and delayed Brown teeth discoloration and delayed bone growth in children < 9 yrs. Oldbone growth in children < 9 yrs. Old
Blue-black pigmentation of nails, skin, Blue-black pigmentation of nails, skin, scars and sclera, black tonguescars and sclera, black tongue
Hypersensitivity, SJS, Drug-Lupus, Hypersensitivity, SJS, Drug-Lupus, Sweet’sSweet’s
Hematologic, Pseudotumor cerebriHematologic, Pseudotumor cerebri
Brown discoloration -TCNBrown discoloration -TCN
TCN in PregnancyTCN in Pregnancy
May be hepatotoxic in large doses in May be hepatotoxic in large doses in pregnant patients.pregnant patients.
Pregancy Category D – associated with Pregancy Category D – associated with retardation of skeletal growth and retardation of skeletal growth and permanent yellow-gray-brown permanent yellow-gray-brown discoloration if given in 2discoloration if given in 2ndnd half of half of pregnancy (during tooth development)pregnancy (during tooth development)
Rifampin – 4 R’sRifampin – 4 R’s
Revs up the CyP450 enzymesRevs up the CyP450 enzymes Red urineRed urine Resistance when used aloneResistance when used alone RNA polymerase inhibitedRNA polymerase inhibited
Indicated for TB, Rhinoscleroma, Indicated for TB, Rhinoscleroma, Leishmaniasis and difficult pyodermasLeishmaniasis and difficult pyodermas
RifampinRifampin
Drug interactions – decreased levels of Drug interactions – decreased levels of antiarrhythmics, anticonvulsants, azole antiarrhythmics, anticonvulsants, azole antifungals, theophylline, steroids, antifungals, theophylline, steroids, OCP’s, B-blockers, CCB’s, sulfonamides, OCP’s, B-blockers, CCB’s, sulfonamides, CORTICOSTEROIDS, WARFARINCORTICOSTEROIDS, WARFARIN
IT IS THE ONLY ANTIBIOTIC PROVEN IT IS THE ONLY ANTIBIOTIC PROVEN TO REDUCE EFFICACY OF OCP’sTO REDUCE EFFICACY OF OCP’s
RifampinRifampin Orange red discoloration of urine and Orange red discoloration of urine and
contact lensescontact lenses Hypersensitivity Syndrome: fever, chills, Hypersensitivity Syndrome: fever, chills,
bone pain, dizziness, HA as well as bone pain, dizziness, HA as well as pruritis, urticaria, acneiform, bullous pruritis, urticaria, acneiform, bullous pemphigoid, mucositis, exfoliative pemphigoid, mucositis, exfoliative dermatitis, exudative conjunctivitisdermatitis, exudative conjunctivitis
Hemolysis, thrombocytopenia, Hemolysis, thrombocytopenia, leukopenialeukopenia
ARF, ARF, ↑↑ LFT’s may accompany HS. LFT’s may accompany HS.
Rifampin in pregnancyRifampin in pregnancy
CONTRAINDICATED due to placental CONTRAINDICATED due to placental diffusion, fetal malformationsdiffusion, fetal malformations
Pregnancy category CPregnancy category C Post-natal hemorrhages in mother and Post-natal hemorrhages in mother and
infant – treated with Vitamin Kinfant – treated with Vitamin K Animal studies revealed cleft palate, Animal studies revealed cleft palate,
spina bifida, imperfect osteogenesisspina bifida, imperfect osteogenesis
TMP-SMXTMP-SMX
MOA: Disrupts enzymes in the MOA: Disrupts enzymes in the tetrahydrofolic acid pathway, thus tetrahydrofolic acid pathway, thus disrupting nucleic acid synthesisdisrupting nucleic acid synthesis
Broad spectrum: many G+, Broad spectrum: many G+, Enterobacteriaceae, H. influenzae, Enterobacteriaceae, H. influenzae, Brucella, Yersinia, Pseudomonas sp.Brucella, Yersinia, Pseudomonas sp. other than other than aeruginosa. aeruginosa. AlsoAlso Nocardia Nocardia asteroides, Atypical mycobacteriaasteroides, Atypical mycobacteria
TMP-SMXTMP-SMX Drug Interactions: increases prothrombin Drug Interactions: increases prothrombin
time in patients taking WARFARIN. time in patients taking WARFARIN. Avoid MTX due to THF effects.Avoid MTX due to THF effects. RARE FATAL Adverse reactions: SJS, RARE FATAL Adverse reactions: SJS,
TEN, fulminant hepatic necrosis, TEN, fulminant hepatic necrosis, agranulocytosis, aplastic anemia.agranulocytosis, aplastic anemia.
Also GI, Tremors, HA, nephritis.Also GI, Tremors, HA, nephritis. STOP DRUG AT 1STOP DRUG AT 1STST SIGN OF RASH SIGN OF RASH
TMP-SMX in pregnanyTMP-SMX in pregnany
Cleft palate in rats who received doses Cleft palate in rats who received doses 16 to 33 times the human dose.16 to 33 times the human dose.
Brumfitt & Pursell – retrospective study Brumfitt & Pursell – retrospective study found no difference in incidence of found no difference in incidence of congenital abnormalities between congenital abnormalities between mothers on TMP-SMX vs. placebo mothers on TMP-SMX vs. placebo (Quoted in PDR) (Quoted in PDR)
However, because TMP-SMX interferes However, because TMP-SMX interferes with nucleic acid synthesis, use only if with nucleic acid synthesis, use only if indicated. Category Cindicated. Category C
ClindamycinClindamycin MOA: binds 50S ribosomal subunit MOA: binds 50S ribosomal subunit
to block transpeptidation, thus to block transpeptidation, thus protein synthesis.protein synthesis.
Buy Buy ATAT 30, 30, CELCEL at 50 at 50 A A minoglycoside - 30minoglycoside - 30 T T etracycline – 30etracycline – 30 C C lindamycin - 50lindamycin - 50 E E rythromycin - 50rythromycin - 50 L L incomycin - 50incomycin - 50
ClindamycinClindamycin
Effective against most G+ and most Effective against most G+ and most anaerobic organisms, also anaerobic organisms, also Toxoplasma Toxoplasma gondii, Clostridium perfringensgondii, Clostridium perfringens
Poor G- activityPoor G- activity
ClindamycinClindamycin Drug interactions: enhances tubocurare, Drug interactions: enhances tubocurare,
pancuronium via neuromuscular blocking pancuronium via neuromuscular blocking propertiesproperties
Actual incidence of pseudomembranous Actual incidence of pseudomembranous colitis is actually much lower than originally colitis is actually much lower than originally perceived in the 1970’s and 1980’sperceived in the 1970’s and 1980’s
C. DifficileC. Difficile only in 0.1% to 10% of patients. only in 0.1% to 10% of patients. Adverse: GI, Maculopapular, Urticaria, DM, Adverse: GI, Maculopapular, Urticaria, DM,
SJS with polyarthritis, AnaphylaxisSJS with polyarthritis, Anaphylaxis
Clindamycin in pregnancyClindamycin in pregnancy
Animal studies revealed no Animal studies revealed no teratogenicity.teratogenicity.
No well controlled human studiesNo well controlled human studies Pregnancy Category BPregnancy Category B
TerbinafineTerbinafine MOA: Allylamine: inhibits squalene MOA: Allylamine: inhibits squalene
epoxidase which decreases ergosterol, epoxidase which decreases ergosterol, impairs fungal cell membrane formationimpairs fungal cell membrane formation
TerbinafineTerbinafine
Onychomycosis, T. Capitis, other Onychomycosis, T. Capitis, other tineastineasIneffective against Ineffective against Candida spCandida sp..Terbinafine increases toxicity of TCA’s, Terbinafine increases toxicity of TCA’s, Theophylline, Narcotics, Caffiene Theophylline, Narcotics, Caffiene Terfenadine, Cimetidine increase Terfenadine, Cimetidine increase toxicity of Terbinafine.toxicity of Terbinafine.
TerbinafineTerbinafine Common Adverse events: GI, HA, Common Adverse events: GI, HA,
morbilliform or maculopapular rash.morbilliform or maculopapular rash. Uncommon Adverse events: gastritis, Uncommon Adverse events: gastritis,
idiosyncratic hepatitis, SJS, TEN, idiosyncratic hepatitis, SJS, TEN, alopecia, visual disturbances, alopecia, visual disturbances, neutropenia, lymphopenia, tiredness, neutropenia, lymphopenia, tiredness, hypersensitivity syndrome, allergic hypersensitivity syndrome, allergic reaction. reaction.
Terbinafine in pregnancyTerbinafine in pregnancy
Category BCategory B Rabbits had no harm to fetus at doses 12 Rabbits had no harm to fetus at doses 12
to 23 times the human dose.to 23 times the human dose. Because treatment of onychomycosis Because treatment of onychomycosis
can wait until after pregnancy, it is not can wait until after pregnancy, it is not recommended in pregnancy.recommended in pregnancy.
ItraconazoleItraconazole MOA: Triazole, inhibits the CyP-450 enzyme MOA: Triazole, inhibits the CyP-450 enzyme
lanosterol 14-lanosterol 14-αα demethylase, so than lanosterol demethylase, so than lanosterol cannot become ergosterolcannot become ergosterol
ItraconazoleItraconazole
Broad spectrum antifungal.Broad spectrum antifungal. FDA Indications: Onychomycosis, Deep FDA Indications: Onychomycosis, Deep
fungal infections.fungal infections. Off label: Candida, Tineas, Pityrosporum Off label: Candida, Tineas, Pityrosporum
infections, Majocci’s granuloma, HIV infections, Majocci’s granuloma, HIV associated eosinophilic folliculitis, chronic associated eosinophilic folliculitis, chronic mucocutaneous Candidiasismucocutaneous Candidiasis
ItraconazoleItraconazole
Off label uses:Off label uses: Candida, TineasCandida, Tineas Pityrosporum infectionsPityrosporum infections Majocci’s granuloma,Majocci’s granuloma, HIV associated eosinophilic folliculitisHIV associated eosinophilic folliculitis Chronic mucocutaneous CandidiasisChronic mucocutaneous Candidiasis
ItraconazoleItraconazole
Common adverse events: GI, HA, Common adverse events: GI, HA, morbilliform or maculopapular rash.morbilliform or maculopapular rash.
FDA warnings for LFT’s and CHF. FDA warnings for LFT’s and CHF. Uncommon adverse events: gastritis, Uncommon adverse events: gastritis,
constipation, hepatitis (1:500,000), SJS, constipation, hepatitis (1:500,000), SJS, urticaria, vertigo, dizziness, tremor, urticaria, vertigo, dizziness, tremor, peripheral neuropathy, neutropenia, peripheral neuropathy, neutropenia, HTN, hypertriglyceridemia, fever, edema, HTN, hypertriglyceridemia, fever, edema, menstrual disorder, hypokalemia. menstrual disorder, hypokalemia.
Itraconazole – Itraconazole – increases toxicity increases toxicity of….of…. HMG CoA Reductase inhibitorsHMG CoA Reductase inhibitors BenzodiazepinesBenzodiazepines Oral HypoglycemicsOral Hypoglycemics DigoxinDigoxin SildenafilSildenafil Calcium channel blockersCalcium channel blockers WarfarinWarfarin AnticonvulsantsAnticonvulsants Immunosuppressants- cyclosporine, tacrolimusImmunosuppressants- cyclosporine, tacrolimus HIV-1 protease inhibitorsHIV-1 protease inhibitors Note: cisapride, astemizole and terfenadine were taken off the market, Note: cisapride, astemizole and terfenadine were taken off the market,
but may still exist in medicine cabinets across the country.but may still exist in medicine cabinets across the country.
ItraconazoleItraconazole
Serum Itraconazole levels decreased by:Serum Itraconazole levels decreased by: Anticonvulsants – phenytoin, Anticonvulsants – phenytoin,
carbamazepine, phenobarbitalcarbamazepine, phenobarbital Anti-TB meds – rifabutin, isoniazidAnti-TB meds – rifabutin, isoniazid H2 Antihistamines – Cimetidine, RanitidineH2 Antihistamines – Cimetidine, Ranitidine PPIs – Omeprazole, LansoprazolePPIs – Omeprazole, Lansoprazole Didanosine, RevirapineDidanosine, Revirapine
Itraconazole in Itraconazole in pregnancypregnancy
Category CCategory C Dose related maternal toxicity, fetal Dose related maternal toxicity, fetal
toxicity and teratogenicity in mice given toxicity and teratogenicity in mice given 10 times the human dose.10 times the human dose.
Skeletal defects, encephaloceles, Skeletal defects, encephaloceles, macroglossiamacroglossia
FluconazoleFluconazole MOA: inhibits lanosterol 14-MOA: inhibits lanosterol 14-αα demethylase demethylase
FluconazoleFluconazole
FDA: Vaginal, Oropharyngeal, Esophageal FDA: Vaginal, Oropharyngeal, Esophageal Candidiasis, Cryptococcal meningitis, Candidiasis, Cryptococcal meningitis, Candida prophylaxis in BM transplant ptsCandida prophylaxis in BM transplant pts
Exception: Exception: Candida kruseiCandida krusei Off label: Tineas, TV, Lymphocutaneous or Off label: Tineas, TV, Lymphocutaneous or
visceral Sporotrichosis, Chronic muco-visceral Sporotrichosis, Chronic muco-cutaneous Candidiasis, Onychomycosiscutaneous Candidiasis, Onychomycosis
Fluconazole Fluconazole increases toxicity increases toxicity of….of….
TCA antidepressantsTCA antidepressants PhenytoinPhenytoin TheophyllineTheophylline WarfarinWarfarin Oral HypoglycemicsOral Hypoglycemics ZidovudineZidovudine Cyclosporine, TacrolimusCyclosporine, Tacrolimus Note: cisapride, astemizole and terfenadine were taken off the Note: cisapride, astemizole and terfenadine were taken off the
market, but may still exist in medicine cabinets across the market, but may still exist in medicine cabinets across the country.country.
Fluconazole in pregnancyFluconazole in pregnancy
Category CCategory C No well controlled studies in pregnant No well controlled studies in pregnant
women.women. Use only if potential benefit outweighs Use only if potential benefit outweighs
risk.risk. Reports of pregnant women with Reports of pregnant women with
coccidiomycosis treated with 400-800mg coccidiomycosis treated with 400-800mg daily resulting in multiple congenital daily resulting in multiple congenital anomaliesanomalies
GriseofulvinGriseofulvin
MOA: destruction of mitotic spindle MOA: destruction of mitotic spindle formation, arresting mitosis in metaphaseformation, arresting mitosis in metaphase
T. Capitis 6-8w, OnychomycosisT. Capitis 6-8w, Onychomycosis Adverse: GI, N/V, HA, Visual & PsychAdverse: GI, N/V, HA, Visual & Psych Porphyrin metab. impaired, photo, LE, PCT.Porphyrin metab. impaired, photo, LE, PCT. Decreases Warfarin, Cyclosporine, OCPDecreases Warfarin, Cyclosporine, OCP Alcohol (potentiated by Griseofulvin)Alcohol (potentiated by Griseofulvin) Phenobarbital (decreased levels of Grise) Phenobarbital (decreased levels of Grise)
KetoconazoleKetoconazole
MOA: ergosterol synthesis impairedMOA: ergosterol synthesis impaired Indications: Indications: Histoplasmosis, Candidiasis, Histoplasmosis, Candidiasis,
Blastomycosis, Coccidiomycosis, Para-Blastomycosis, Coccidiomycosis, Para-coccidiomycosis, Peudoallescheriasiscoccidiomycosis, Peudoallescheriasis
Adverse: GI, N/V, anorexia20% elevated Adverse: GI, N/V, anorexia20% elevated LFTs, 5% overt hepatitis, Fatal rarely. LFTs, 5% overt hepatitis, Fatal rarely.
Decreased testosterone, decreased Decreased testosterone, decreased libido, impotence, irreg. menses libido, impotence, irreg. menses
KetoconazoleKetoconazole Increases toxicity of…..Increases toxicity of….. Cyclosporine, Warfarin, Phenytoin, Cyclosporine, Warfarin, Phenytoin,
Digoxin, Oral HypoglycemicsDigoxin, Oral Hypoglycemics Cisapride, Astemizole, Terfenadine*.Cisapride, Astemizole, Terfenadine*.
Pregnancy category CPregnancy category C Teratogenic in animals, no human Teratogenic in animals, no human
studies.studies.
AcyclovirAcyclovir MOA: Herpes infected cells create viral MOA: Herpes infected cells create viral
Thymidine kinase (TK) 100 times faster than Thymidine kinase (TK) 100 times faster than non-infected cells.non-infected cells.
Acyclovir is an acyclic guanine nucleoside Acyclovir is an acyclic guanine nucleoside analog that is phosphorylated by viral TK 3 analog that is phosphorylated by viral TK 3 times (triphosphate form)times (triphosphate form)
Interferes with viral DNA polymerase, Interferes with viral DNA polymerase, preventing viral replicationpreventing viral replication
Tzanck SmearTzanck Smear
AcyclovirAcyclovir
Greater activity against HSV-1 than HSV-2.Greater activity against HSV-1 than HSV-2. HSV encephalitis -mortality decreased 50%HSV encephalitis -mortality decreased 50% H. Zoster (Varicella) if given early.H. Zoster (Varicella) if given early. Low toxicity, mild nausea, HA.Low toxicity, mild nausea, HA. Rarely reversible nephrotoxicity, CNS.Rarely reversible nephrotoxicity, CNS. Pregnancy Category C*Pregnancy Category C* * Note: VCV & FCV are Category B* Note: VCV & FCV are Category B
ValcyclovirValcyclovir
MOA: same as acyclovir except this is MOA: same as acyclovir except this is the L-valyl ester or “prodrug” of acyclovirthe L-valyl ester or “prodrug” of acyclovir
Increased bioavaliablity, absorption.Increased bioavaliablity, absorption. Once absorbed is rapidly converted to Once absorbed is rapidly converted to
acyclovir.acyclovir. Rare risk of thrombocytopenic purpuraRare risk of thrombocytopenic purpura
FamcyclovirFamcyclovir MOA: another prodrug of AcyclovirMOA: another prodrug of Acyclovir 77% bioavaliability for Famciclovir77% bioavaliability for Famciclovir 55% bioavaliability for Valcyclovir55% bioavaliability for Valcyclovir 15-30% bioavaliability for Acyclovir15-30% bioavaliability for Acyclovir All “Cyclovirs” indicated for Herpes All “Cyclovirs” indicated for Herpes
infections and H. Zoster by FDAinfections and H. Zoster by FDA Off label: recurrent EM, primary VaricellaOff label: recurrent EM, primary Varicella
AcyclovirAcyclovir ValcyclovirValcyclovir FamcycloviFamcyclovi
Simplex Simplex 1st1st
200mg 200mg 5x/d x 10d5x/d x 10d
1000mg 1000mg BID x 10dBID x 10d
250mg 250mg TID x 10dTID x 10d
Simplex Simplex
recurrentrecurrent
400mg 400mg TID x 5dTID x 5d
500mg 500mg BID x 5dBID x 5d
125mg 125mg BID x 5 dBID x 5 d
Simplex Simplex suppresssuppress
400mg BID400mg BID 500mg QD500mg QD 250mg BID250mg BID
Zoster Zoster acuteacute
800mg 800mg 5x/d x 10d5x/d x 10d
1000mg 1000mg TID x 10dTID x 10d
500mg 500mg TID x 10dTID x 10d
Varicella, Varicella, 1st1st
20mg/kg 20mg/kg QID x 7dQID x 7d
Not well Not well evaluatedevaluated
Not well Not well evaluatedevaluated
CorticosteroidsCorticosteroids
MOA: Binds to GCR (Glucocorticoid MOA: Binds to GCR (Glucocorticoid Receptor) on cell, GCR is activated and Receptor) on cell, GCR is activated and translocates to the nucleus, binding to translocates to the nucleus, binding to GCRE’s (Glucocorticoid Response GCRE’s (Glucocorticoid Response Elements) of multiple genes. CS can act Elements) of multiple genes. CS can act as an agonist or antagonist for these as an agonist or antagonist for these genes, thus having multiple effects on genes, thus having multiple effects on various organ systems.various organ systems.
Corticosteroid MOACorticosteroid MOA
TRANSCRIPTION of NFkB & AP-1 TRANSCRIPTION of NFkB & AP-1 decreased = thus less cytokine decreased = thus less cytokine productionproduction
APOPTOSIS of T lymphocytes and APOPTOSIS of T lymphocytes and eosinophilseosinophils
SIGNAL TRANSDUCTION of SIGNAL TRANSDUCTION of Phospholipase A2, eicosinoids and COX-Phospholipase A2, eicosinoids and COX-2 inhibited = decreased prostaglandins, 2 inhibited = decreased prostaglandins, LKTs, 12-HETE, 15-HETE LKTs, 12-HETE, 15-HETE
B cells – Ab productionB cells – Ab production T cells – IL-2T cells – IL-2 Lymphocytes – NK cells & cytotoxicLymphocytes – NK cells & cytotoxic PMNs – margination, chemotaxisPMNs – margination, chemotaxis Mast – degranulation, histamine releaseMast – degranulation, histamine release Monos/Macs – IL-1, INFMonos/Macs – IL-1, INFγγ Langerhans – antigen processingLangerhans – antigen processing Eos, Basos – recruitment, # and functionEos, Basos – recruitment, # and function Fibroblasts – collagen, ground substance Fibroblasts – collagen, ground substance Membrane – stabilizationMembrane – stabilization Angiogenesis, Vasoconstriction, PermeabilityAngiogenesis, Vasoconstriction, Permeability
Systemic Adverse eventsSystemic Adverse events Adrenal crisisAdrenal crisis HyperglycemiaHyperglycemia HypertensionHypertension CHF, edema, fluid CHF, edema, fluid
overloadoverload HyperlipidemiaHyperlipidemia Cushingoid changesCushingoid changes Bone growthBone growth OsteoporosisOsteoporosis
OsteonecrosisOsteonecrosis Bowel PerforationBowel Perforation Peptic Ulcer DiseasePeptic Ulcer Disease CataractsCataracts Agitation/PsychosisAgitation/Psychosis Opportunistic Opportunistic
InfectionsInfections Opportunistic CancerOpportunistic Cancer MyopathyMyopathy
Cutaneous Adverse Cutaneous Adverse eventsevents
Impaired wound healingImpaired wound healing Striae, atrophy, telangiectasias, purpuraStriae, atrophy, telangiectasias, purpura Steroid acne/rosaceaSteroid acne/rosacea Acanthosis nigricansAcanthosis nigricans Staph, Herpesvirus infectionsStaph, Herpesvirus infections Telogen effluvium, hirsuitismTelogen effluvium, hirsuitism Fat atrophy, injection site cystallization Fat atrophy, injection site cystallization Flare of pustular psoriasis, rhus derm.Flare of pustular psoriasis, rhus derm.
TaperingTapering
If starting dosage is…If starting dosage is… Taper in increments ofTaper in increments of
100mg100mg 20mg20mg
60mg60mg 10mg10mg
20mg20mg 5mg5mg
10mg 10mg 2.5mg2.5mg
CS Indications….CS Indications….
Bullous: Pemphigus, pemphigoid, EBA, Bullous: Pemphigus, pemphigoid, EBA, SJS, TEN, EM Minor, Linear IgA BD, SJS, TEN, EM Minor, Linear IgA BD,
Autoimmune: SLE, DM, Alopecia AreataAutoimmune: SLE, DM, Alopecia Areata Vasculitis: Systemic, PG, Behcet’s, Vasculitis: Systemic, PG, Behcet’s,
Sweet’sSweet’s Dermatitis: Contact, Atopic, Dermatitis: Contact, Atopic,
Erythroderma, LPErythroderma, LP Other: Sarcoidosis, Sunburn, Urticaria, Other: Sarcoidosis, Sunburn, Urticaria,
Acne/hirsuitism, PHN preventionAcne/hirsuitism, PHN prevention
CS Absolute CS Absolute ContraindicationsContraindications
Systemic Fungal InfectionsSystemic Fungal Infections Herpes Simplex KeratitisHerpes Simplex Keratitis HypersensitivityHypersensitivity
Steroid Withdrawal Steroid Withdrawal Syndrome v. Adrenal CrisisSyndrome v. Adrenal Crisis
SWSSWS Fatigue, lethargyFatigue, lethargy DepressionDepression Mood swingsMood swings HeadacheHeadache Myalgias/ArthralgiasMyalgias/Arthralgias Anorexia, N/VAnorexia, N/V Weight lossWeight loss
Adrenal CrisisAdrenal Crisis All SWS symptoms All SWS symptoms
plus…..plus….. HypoglycemiaHypoglycemia HypotensionHypotension ShockShock HypokalemiaHypokalemia HyponatremiaHyponatremia
CS Drug interactions….CS Drug interactions….
Azoles, Macrolide, OCPs, hormones Azoles, Macrolide, OCPs, hormones increase serum levels of CS.increase serum levels of CS.
CS may increase levels of potassium CS may increase levels of potassium depleting diuretics, digitalis and depleting diuretics, digitalis and cyclosporinecyclosporine
Anticonvulsants may decrease levels of Anticonvulsants may decrease levels of CS.CS.
Steroids in pediatricsSteroids in pediatrics
1mg/kg/day for 2-3 weeks1mg/kg/day for 2-3 weeks Dose halved every 4 to 7 daysDose halved every 4 to 7 days
Steroids in pregnancySteroids in pregnancy
Original animal studies showed Original animal studies showed teratogenicity, cleft lip, cleft palateteratogenicity, cleft lip, cleft palate
Multiples human studies of pregnant Multiples human studies of pregnant patients who needed steroids such as patients who needed steroids such as SLE, Severe asthma and organ SLE, Severe asthma and organ transplant showed NO INCREASED transplant showed NO INCREASED RISK of teratogenicity.RISK of teratogenicity.
If absolutely medically indicated, use the If absolutely medically indicated, use the steroids.steroids.
MethotrexateMethotrexate
MOA: inhibits enzyme dihydrofolate MOA: inhibits enzyme dihydrofolate reductase, prevents conversion of reductase, prevents conversion of dihydrofolate (DHF) to tetrahydrofolate dihydrofolate (DHF) to tetrahydrofolate (THF). THF is essential for synthesis of (THF). THF is essential for synthesis of thymidine and purine nucleotides that thymidine and purine nucleotides that form DNA and RNA. form DNA and RNA.
FDA approved for psoriasis as it inhibits FDA approved for psoriasis as it inhibits rapid proliferation of keratinocytes.rapid proliferation of keratinocytes.
MethotrexateMethotrexate 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 – Adverse eventsMTX – Adverse events
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- Adverse eventsMTX- Adverse events
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 Adverse eventsMTX Adverse events 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.
Drugs that ↑ MTX toxicityDrugs that ↑ MTX toxicity
NSAIDSNSAIDS SulfonamidesSulfonamides DipyridamoleDipyridamole ProbenecidProbenecid ChloramphenicolChloramphenicol PhenothiazinesPhenothiazines PhenytoinPhenytoin TetracyclinesTetracyclines
MTX indicationsMTX indications FDA:FDA: Psoriasis, Pustular, Erythrodermic Psoriasis, Pustular, Erythrodermic OFF LABELOFF LABEL: : Proliferative: PRP, PLEVA, REITER’SProliferative: PRP, PLEVA, REITER’S Bullous: PEMPHIGUS, PEMPHIGOIDBullous: PEMPHIGUS, PEMPHIGOID Autoimmune: DM, SLE, SCLAutoimmune: DM, SLE, SCL Vascultits: LCV, PAN, BEHCET’S, PGVascultits: LCV, PAN, BEHCET’S, PG Dermatitis: ADDermatitis: AD Other: SARCOID, KELOIDS, LP, KA, MFOther: SARCOID, KELOIDS, LP, KA, MF
Monitoring MTXMonitoring MTX
Baseline: H&P, Review meds, PMHx.Baseline: H&P, Review meds, PMHx. CBC, COMP, Hepatitis profile.CBC, COMP, Hepatitis profile. HIV screen if risk factors present.HIV screen if risk factors present. Liver bx: @1.5g and @ each gram Liver bx: @1.5g and @ each gram CBC, LFT every weekly x 2-4 weeksCBC, LFT every weekly x 2-4 weeks CBC, LFT 1 week after each dose CBC, LFT 1 week after each dose ↑↑ Renal Profile 2x/yearRenal Profile 2x/year
Grade I – mild fatty Grade I – mild fatty infiltration- WNL.infiltration- WNL.
Grade II – Moderate Grade II – Moderate fatty infiltration. fatty infiltration.
Grade IIIA - Mild Grade IIIA - Mild fibrosis – re-biopsy fibrosis – re-biopsy @ 6 mos, but stay @ 6 mos, but stay on the MTX.on the MTX.
Grade IIIB – Grade IIIB – Fibrosis moderate Fibrosis moderate to severe.to severe.
Grade IV – Grade IV – Cirrhosis.Cirrhosis.
Azathioprine: MOAAzathioprine: MOA
6-thioguanine6-thioguanine is is a purine analog a purine analog which is which is incorporated into incorporated into DNA & RNA, thus DNA & RNA, thus inhibiting purine inhibiting purine synthesis and cell synthesis and cell divisiondivision
Azathioprine MetabolismAzathioprine Metabolism
HGPRTHGPRT – converts AZTP to active form - – converts AZTP to active form - Lesch NyanLesch Nyan pts lack it = non-responders pts lack it = non-responders
Thiopurine methyltransferaseThiopurine methyltransferase - - (TPMT)(TPMT) - 88% pts are homozygous for high - 88% pts are homozygous for high activity, need higher dosingactivity, need higher dosing
Xanthine OxidaseXanthine Oxidase (XO) breaks down (XO) breaks down AZTP, and is inhibited by AZTP, and is inhibited by AllopurinolAllopurinol
AzathioprineAzathioprine