Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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Drugs in Dermatology Drugs in Dermatology KCOM/Texas Consortium KCOM/Texas Consortium Dermatology Residency Dermatology Residency Program Program
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Transcript of Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

Page 1: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

Drugs in Drugs in DermatologyDermatology

KCOM/Texas ConsortiumKCOM/Texas Consortium

Dermatology Residency ProgramDermatology Residency Program

Page 2: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

PenicillinsPenicillins MOA: Inhibit bacterial wall synthesis by MOA: Inhibit bacterial wall synthesis by

binding to peptidoglycans.binding to peptidoglycans.

Page 3: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 4: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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.

Page 5: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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.

Page 6: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 7: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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.

Page 8: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

MacrolidesMacrolides MOA: binds to 50S subunit of ribosome, MOA: binds to 50S subunit of ribosome,

inhibiting RNA-dependent protein synthesisinhibiting RNA-dependent protein synthesis

Page 9: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

MacrolidesMacrolides

Erythromycin is prototypeErythromycin is prototype Limited gram negative activityLimited gram negative activity Nausea, diarrheaNausea, diarrhea Erratic bioavaliabilityErratic bioavaliability Multiple daily dosesMultiple daily doses

Page 10: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 11: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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.

Page 12: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 13: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 14: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

FQsFQs

Low resistanceLow resistance High oral bioavaliabilityHigh oral bioavaliability Extensive tissue penetration.Extensive tissue penetration. Gram +/-, Gram +/-, PseudomonasPseudomonas, Mycobacteria, Mycobacteria

Page 15: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 16: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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.

Page 17: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

TetracyclinesTetracyclines MOA: Inhibits protein synthesis by MOA: Inhibits protein synthesis by

binding to the 30S ribosome subunit.binding to the 30S ribosome subunit.

Page 18: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 19: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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.

Page 20: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 21: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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.

Page 22: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 23: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

Brown discoloration -TCNBrown discoloration -TCN

Page 24: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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)

Page 25: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 26: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 27: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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.

Page 28: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 29: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 30: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 31: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.
Page 32: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 33: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

ClindamycinClindamycin MOA: binds 50S ribosomal subunit MOA: binds 50S ribosomal subunit

to block transpeptidation, thus to block transpeptidation, thus protein synthesis.protein synthesis.

Page 34: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 35: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 36: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 37: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 38: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 39: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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.

Page 40: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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.

Page 41: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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.

Page 42: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 43: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 44: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 45: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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.

Page 46: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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.

Page 47: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 48: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 49: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

FluconazoleFluconazole MOA: inhibits lanosterol 14-MOA: inhibits lanosterol 14-αα demethylase demethylase

Page 50: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 51: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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.

Page 52: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 53: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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)

Page 54: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 55: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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.

Page 56: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 57: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

Tzanck SmearTzanck Smear

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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

Page 59: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 60: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 61: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 62: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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.

Page 63: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 64: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 65: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 66: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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.

Page 67: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 68: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 69: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

CS Absolute CS Absolute ContraindicationsContraindications

Systemic Fungal InfectionsSystemic Fungal Infections Herpes Simplex KeratitisHerpes Simplex Keratitis HypersensitivityHypersensitivity

Page 70: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 71: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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.

Page 72: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 73: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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.

Page 74: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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.

Page 75: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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.

Page 76: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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.

Page 77: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 78: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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.

Page 79: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

Drugs that ↑ MTX toxicityDrugs that ↑ MTX toxicity

NSAIDSNSAIDS SulfonamidesSulfonamides DipyridamoleDipyridamole ProbenecidProbenecid ChloramphenicolChloramphenicol PhenothiazinesPhenothiazines PhenytoinPhenytoin TetracyclinesTetracyclines

Page 80: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 81: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 82: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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.

Page 83: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 84: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

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

Page 85: Drugs in Dermatology KCOM/Texas Consortium Dermatology Residency Program.

AzathioprineAzathioprine