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Antifungal

Drugs

DrugInformation
Azoles Inhibits fungal cytochrome P-450 3-A dependent enzyme --> 14-alpha-demythylase which synthesizes ergosterol; not completely selective (drug interactions)
Ketoconazole Seldom used, PO, shampoo, poor absorption --> for mucosal infections only
Ketoconazole AE:N&V, hepatotoxicity, dose related inhibition of CYP450 responsible for testosterone synth and adrenal cortisol synth, severe drug interactions
Antacids, omeprazole, H2 blockers increase gastric pH will decrease blood levels of ketoconazole
Fluconazole against candidiasis, 90% Bioavailalibility, inhibitor of CYP 2C9, Asymptomatic increase in LFTs
MOA antifungal resistance Target enz modification, ergosterol biosynthetic pathway, efflux pumps, drug import
Itraconazole Take capsule with food, does not cross BBB, many drug interactions, for onychomycosis and 2nd line for blasto/histoplasmosi/aspergillosis, for febrile neutropic pts; AE: taste disturbances
Voriconazole vs. fusarium, scedosporium and aspergillus, AE: visual disturbances, many drug interactions, CPY2C19
Allylamines Inhibit squalene oxidase
Terbinafine PO and Topical, vs. dermatophytes --> onchyomycosis and OTC for athlete's foot, AE: GI, hepatic injury
Amphotericin B MOA: Binds to ergosterol resulting in a change in membrane permeability --> leakage; classic one the most serious toxic side effects (fungizone); IV only, drug accumulate then slowly released (kidney most retained, eye least), renal toxicity + hypotension
Echinocandins (Caspofungin and Micafungin) Cyclic lipopeptides that non-competitively inhibits 1,3-beta-D-Glycan syhnthase (essential in cell wall integrity) --> no osmotic support, No P450 interaction, IV only, vs. candida and aspergillus, no AE (b/c humans have no cellwall, asym elev ser transam
Flucytosine (Ancotil) synthetic fluorinated pyrimidine, IV or PO, anti-metabolite, rapid conversion of 5-FC to 5-FU, AE: bone marrow toxicity, narrow therapeutic window if with Amphotericin B
Created by: gladho
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