Antifungal Pharmacotherapeutics
(Ans- Drug interactions: Multiple due to CYP 450 3A4 inhibition. -Sensitivity-Azoles (broad spectrum): Candida, Cryptococcus species, endemic mycoses, dermatophytes -itraconazole, posaco
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Antifungal Pharmacotherapeutics
(Ans- Drug interactions: Multiple due to CYP 450 3A4 inhibition. -Sensitivity-Azoles (broad spectrum): Candida, Cryptococcus species, endemic mycoses, dermatophytes -itraconazole, posaconazole, voriconazole: Aspergillus species -Itraconazole: histoplasmosis and blastomycosis -posaconazole: prophy of BMT pts and for infection refractory to other agents -Terbinafine: onychomycosis (fungus of nails) --off-label for tinea pedis (ring work of feet athlete's foot), tinea capitis, tinea corporis (ring of body), and tinea cruris (of groin/jock itch). -Precautions/Contraindications -Hepatic impairment --May cause hepatotoxicity -Ketoconazole --Prostate cancer -Vori: Preg D; other azoles Preg C; Terbinafine: Preg B (but no adequate human studies) -avoid antifungals while nursing
Antifungal Pharmacokinetics
(Ans- · Absorption of itraconazole is enhanced by food Absorption of griseofulvin is enhanced by fat Fluconazole is an inhibitor of CYP 450 3A4 and 2C9 Itraconazole is an inhibitor of CYP 450 3A4 Ketoconazole is an inhibitor of CYP 450 3A4
Antifungal Pharmacodynamics
(Ans- Polyene macrolides: amphotericin B and nystatin Azoles have broad spectrum activity: butoconazole, clotrimazole, ketoconazole, minonazole, terconazole, tioconazole, fluconazole, itraconazole Allylamines active against yeast and dermatophytes: naftifine, terbinafine Nuclear acid synthesis inhibitors: flucytosine Griseofulvin. -Azoles --Reduce fungal ergosterol synthesis in cell membranes by inhibition of fungal CYP450 enzymes --fungistatic at low concentrations; fungicidal at higher -Allylamines (terbinafine) --Interferes with synthesis of ergosterol in cell membranes of fungi earlier than that of azoles
Antifungal Spectrum of coverage
(Ans- 4 main classes -Polyene macrolides -Amphotericin B -Nystatin -Azoles -Imidazoles -Clotrimazole, ketoconazole, miconazole, terconazole-Triazoles -Fluconazole, itraconazole -Allylamines -Terbinafine -Nuclear acid synthesis inhibitors. -eukaryotic cells w/ a nucleus and rigid cell wall -Candida albicans=4th most common organism found in blood cultures in US -Four main classes of antifungals 1. macrocyclic polyenes: amphotericin B --IV only 2. azole group a. imidazoles b. triazoles: fluconazole, itraconazole, posaconazole, voriconazole 3. allylamines: terbinafine 4. nuclear acid synthesis inhibitors: flucytosine: only for cryptococcosis **Most commonly used in primary care: fluconazole, itraconazole, posaconazole, voriconazole, terbinafine
Anthelminthics Spectrum of Coverage
(Ans- The only common helminthic infections in the United States are caused by intestinal nematodes: Enterobius vermicularis (pinworm), Trichuris trichiura (whipworm), Ascaris lumbricoides (roundworm), Strongyloides stercoralis (threadworm), and the hookworms Ancylostoma duodenale and Necator americanus.
Anthelminthics Pharmacodynamics
(Ans- Helminthic parasites: 3 groups, nematodes (intestinal and tissue roundworms in US) -Mebendazole, pyrantel, thiabendazole: intestinal nematodes -mebendazole, thiabendazole, albendazole, ivermectin: tissue nematodes -cause paralysis, and even death in worm -Ivermectin: uses CYP450
Anthelminthics Pharmacokinetics
(Ans- Ivermectin is well absorbed with wide tissue distribution following oral administration. Albendazole, mebendazole, and pyrantel are very poorly absorbed with limited serum concentrations. The bioavailability of albendazole and ivermectin are significantly enhanced if co-administered with a fatty meal. Absorbed albendazole is widely distributed in nearly all organs and body compartments. The distribution of mebendazole and pyrantel is not known. Albendazole is rapidly converted by the liver to the primary metabolite, albendazole sulfoxide, which is further converted to other metabolites. These metabolites undergo almost exclusive biliary elimination. Absorbed mebendazole is extensively metabolized by the liver.
Anthelminthics Pharmacotherapeutics
(Ans- minimal -cautious concurrent use w/ other drugs metab'd in liver, and w/ hepatic impairment -renal impairment for those excreted via kidney -Preg C: benefits outweigh risks for albendazole, mebendazole, and pyrantel -mebendazole and pyrantel, not for <2yrs -albendazole not for <6yrs -ivermectin not for <15kg
Anthelminthics Clinical indications & dosing
(Ans- Pinworms: single dose of mebendazole, pyrantel pamoate,or albendazole Whipworms: pyrantel pamoate, albendazole, mebendazole Roundworms: mebendazole Hookworms: pyrantel pamoate, albendazole, mebendazole Threadworm: ivermectin or thiabendazole Scabies: off-label ivermectin in immunocompromised patients
· Rational drug selection Use CDC recommendations.
Anthelminthics ADRs
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