Antifungal agents

Antifungal agents

Antifungal drugs are a diverse group of medications used to treat fungal infections ranging from ringworm and athletes foot to esophageal candidiasis, coccidiomycosis, and cryptococcal meningitis. The antifungals are classified into several groups based on their structure and mechanisms of action. These classes include the polyenes, imidazoles, triazoles, allylamines, and echinocandins, as well as miscellaneous agents.

Polyene antifungals have an amphiphilic structure which binds to ergosterol, converting the fluid cell membrane of the fungal cell into a more crystalline state increasing permeability and precipitating cell lysis. Examples of polyenes (with date of approval and common brand names) include nystatin (1971: Mycostatin, Nystat) and amphotericin B (1971: Amphocin, Fungizone).

Imidazole and triazole antifungal drugs inhibit cytochrome P450 14a-demethylase which is responsible for converting lanosterol to ergosterol, which blocks cell membrane synthesis in fungi. Examples of imidazoles include ketoconazole (1981: Nizoral) and clotrimazole (1975: Mycelex). Examples of triazoles include fluconazole (1990: Diflucan), itraconazole (1992: Sporanox), posaconazole (2006: Noxafil) and voriconazole (2002: Vfend). Isavuconazonium (Cresemba: 2016) is a prodrug of isavuconazole and is available in both intravenous and oral forms, its indications restricted for serious, invasive fungal infections such as aspergilosis and mucormycosis. The triazoles are perhaps the most commonly used antifungal agents having excellent oral absorption, tolerance and tissue penetration.

The allylamines inhibit the enzyme squalene epoxidase, which is also required for ergosterol and thus fungal cytoplasmic membrane synthesis. An example of an allylamine is terbinafine (1998: Lamisil).

Echinocandins are the newest class of fungicidal agents. They inhibit the synthesis of ß-D-glucan in fungal cell walls via inhibition of the enzyme 1,3-ß glucan synthase. Examples of echinocandins include anidulafungin (2006: Eraxis), caspofungin (2001: Cancidas) and micafungin (2005: Mycamine). The echinocandins are administered intravenously and used largely for serious invasive fungal infections.

The miscellaneous fungicidal agents include the antimetabolite flucytosine (1971: Ancobon) and the microtubule inhibitor griseofulvin (2007: Grifulvin). Because pneumocystitis jiroveci (formerly carinii) is now considered a fungal agent, pentamine (1984: Pentam) may be considered a miscellaneous antifungal agent.

In general, the treatment of fungal infections is based upon inhibition of cell processes that are necessary in fungi, but do not harm critical cell pathways in human cells. Both fungi and humans are eukaryotic organisms and they share many cellular enzymes and pathways. These features account for the range of side effects seen with many antifungal agents. Most antifungal agents have been implicated in causing some degree of hepatotoxicity; clinically apparent liver injury with jaundice occurs most prominently with ketoconazole, fluconazole, voriconazole, and terbinafine.

• Dailymed label info on Antifungal agents
• FDA Antifungal agents

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