Antifungal Drugs

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Types of Antifungal Drugs

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Polyenes, Allylamines, Azoles, Anti-metabolites, and echinocandins

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Polyenes

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Includes nystatin and amphotericin B. Bind ergosterol in fungal cell membrane leading to cell death. Is poorly absorbed and highly distributed. Toxicity includes nephrotoxicity, electrolyte wasting and infusion-related reactions.Broad antifungal spectrum which includes Candida spp, Cryptoccus neoformans, dimorphoc fungi and many molds.

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Three formulations of AmB

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Amphotericin B Colloidal Dispersion (ABCD), Amphotericin B Lipid Complex (ABLC), and Liposomal amphotericin B (LAmB). All have same efficacies. ABCD is best since lower infusion reactions

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Echinocandins

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Inhibits beta-1,3-glucan synthase which decreases beta 1,3-glucan production. Potent against Candida spp and Aspergillus spp but not Candida parapsilosis, cryptococcus, and many molds. Administrated IV with poor bioavailability, but well distributed. AE is heaptatoxicity and infusion related reactions including phlebitis. Is very expensive

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Azoles

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Includes fluconazole, itraconazole, voriconazole, posaconazole, and ketoconazole.Inhibits fungal P450 which decreases ergosterol formation. AE includes heptatotoxicity and rash.

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Fluconazole

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Good against all candidiasis, cryptococcus and treatment of some dimorphic fungi. Administrated IV, tablets and oral suspension. Has severe adverse effects and drug interactions

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Itraconazole

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Good against candida, cryptococcus, aspergillus, molds and dimorphic fungi. Has severe adverse effects and drug interactions

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Voriconazole

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Good against candida, cryptococcus, aspergillus, fusarium, and scedosporium. Administrated IV, capsules and oral solution where it is well absorbed and has non-linear elimination. AE include heptatoxicity as well as visual effects and hallucinations. Has drug interactions

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Posaconazole

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Good for prophylaxis against candida, cryptococcus, aspergillus and zygomycetes. Administrated orally and Has severe AE and drug interactions.

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Topical Azoles

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Ketoconazole which has poor oral absorption, sometimes used orally.

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5-Flucytosine (5-FC)

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An antimetabolite antifungal which replaces uracil, halting RNA production and DNA synthesis. Has high bioavailability and widely distributed including CNS. Good against candida, cryptococcus neoformans and aspergillus. AE includes bone marrow suppresion, GI intolerance, rash, heptatoxicity. Is a combination therapy for cryptococcal meningitis

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Terbinafine

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An allyamine antifungal that inhibits squalene epoxidase which prevents synthesis of ergosterol. Administrated orally and topically. Active against dermatophytes, candida, and asperfillus. Concentrates in nails, fat and skin and has a non-linear elimination (half life increases with repeated doses). AE is heptatoxicity, neutropenia and Stevens-Johnson syndrome. Clinical use for onychomycosis.