1 / 85

Drugs in Dermatology

Drugs in Dermatology. KCOM/Texas Consortium Dermatology Residency Program. Penicillins. MOA: Inhibit bacterial wall synthesis by binding to peptidoglycans. Penicillins. Dicloxacillin is unsurpassed as an oral Beta-lactamase-resistant pencillin, effective against most pyodermas.

liz
Télécharger la présentation

Drugs in Dermatology

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

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

  2. Penicillins • MOA: Inhibit bacterial wall synthesis by binding to peptidoglycans.

  3. Penicillins • 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

  4. Penicillins • 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.

  5. Cephalosporins • MOA: Inhibit PCN-binding proteins, preventing cell wall synthesis. Chemical structure is Beta-lactamase resistant.

  6. Cephalosporins • 1st Gen: Staph aureus, but not MRSA • 2nd Gen: H. influenzae, M. catarrhalis, Neisseria sp, some Enterobacteriaceae • 3rd Gen: Pseudomonas aeruginosa

  7. Cephalosporins • Adverse Effects: GI, Hypersensitivity • Ceclor – serum sickness • Hematologic – mild, Coombs Ab positivity, hemolytic anemia is rare.

  8. Macrolides • MOA: binds to 50S subunit of ribosome, inhibiting RNA-dependent protein synthesis

  9. Macrolides • Erythromycin is prototype • Limited gram negative activity • Nausea, diarrhea • Erratic bioavaliability • Multiple daily doses

  10. Macrolides • 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

  11. Macrolides • Azithromycin and Clarithromycin both have fewer GI side effects than Erythromycin. • Headaches, dizziness, liver enzyme elevations.

  12. Pregnancy • Penicillins, Cephalosporins and Macrolides….. • All generally accepted as safe during pregnancy. • Pregnancy category B

  13. Fluoroquinolones • MOA: Inhibits DNA gyrase (topo-isomerase II) which induces negative supercoiling, inhibiting replication of DNA

  14. FQs • Low resistance • High oral bioavaliability • Extensive tissue penetration. • Gram +/-, Pseudomonas, Mycobacteria

  15. Fluoroquinolones • 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

  16. 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.

  17. Tetracyclines • MOA: Inhibits protein synthesis by binding to the 30S ribosome subunit.

  18. Tetracyclines • Broad spectrum: G+ > G-, Mycoplasmas, Chlamydia, Rickettsia, Spirochetes some parasites. • Minocycline and Doxycycline more active against Staph and Group A Strep than TCN

  19. Tetracyclines • 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.

  20. Tetracyclines • 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

  21. Tetracyclines • 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.

  22. Tetracyclines • 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

  23. Brown discoloration -TCN

  24. TCN in Pregnancy • 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)

  25. Rifampin – 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

  26. Rifampin • 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

  27. Rifampin • 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.

  28. Rifampin in pregnancy • 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

  29. 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

  30. 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

  31. TMP-SMX in pregnany • 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

  32. Clindamycin • MOA: binds 50S ribosomal subunit to block transpeptidation, thus protein synthesis.

  33. Buy AT 30, CEL at 50 • A minoglycoside - 30 • T etracycline – 30 • C lindamycin - 50 • E rythromycin - 50 • L incomycin - 50

  34. Clindamycin • Effective against most G+ and most anaerobic organisms, also Toxoplasma gondii, Clostridium perfringens • Poor G- activity

  35. Clindamycin • 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

  36. Clindamycin in pregnancy • Animal studies revealed no teratogenicity. • No well controlled human studies • Pregnancy Category B

  37. Terbinafine • MOA: Allylamine: inhibits squalene epoxidase which decreases ergosterol, impairs fungal cell membrane formation

  38. Terbinafine Onychomycosis, T. Capitis, other tineas Ineffective against Candida sp. Terbinafine increases toxicity of TCA’s, Theophylline, Narcotics, Caffiene Terfenadine, Cimetidine increase toxicity of Terbinafine.

  39. Terbinafine • 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.

  40. Terbinafine in 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.

  41. Itraconazole • MOA: Triazole, inhibits the CyP-450 enzyme lanosterol 14-α demethylase, so than lanosterol cannot become ergosterol

  42. Itraconazole • 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

  43. Itraconazole • Off label uses: • Candida, Tineas • Pityrosporum infections • Majocci’s granuloma, • HIV associated eosinophilic folliculitis • Chronic mucocutaneous Candidiasis

  44. Itraconazole • 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.

  45. Itraconazole – 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.

  46. Itraconazole • Serum Itraconazole levels decreased by: • Anticonvulsants – phenytoin, carbamazepine, phenobarbital • Anti-TB meds – rifabutin, isoniazid • H2 Antihistamines – Cimetidine, Ranitidine • PPIs – Omeprazole, Lansoprazole • Didanosine, Revirapine

  47. Itraconazole in pregnancy • Category C • Dose related maternal toxicity, fetal toxicity and teratogenicity in mice given 10 times the human dose. • Skeletal defects, encephaloceles, macroglossia

  48. Fluconazole • MOA: inhibits lanosterol 14-α demethylase

  49. Fluconazole • 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

More Related