ANTIFUNGAL DRUGS

Antifungal drugs are either fungicidal or fungistatic. These drugs typically belong to four major groups- polyenes, azoles, allylamines and miscellaneous antimetabolites.

Polyenes are produced by Streptomyces species. They bind to membrane sterols and disrupt their structure and function resulting in incresied membrane permeablility, leaking of cellular contents and ultimately cell death. Amphotericin B is used in treating several invasive and systemic mycoses. Nystatin is used as a topical agent in treating mucocutaneous Candidal infections.

Azoles are imidazoles, triazoles and thiazoles. These synthetic drugs primarily act on ergosterol biosynthesis by inhibiting the enzyme cytochrome P450 14a-demethylase resulting in ergosterol depletion and accumulation of methylated sterols in plasma membrane that severely affects its function. Azole drugs used as topical agents include ketoconazole, clotrimazole, miconazole and econazole. Azole drugs used for systemic therapy includes itraconazole, fluconazole and ketoconazole. The azole antifungals inhibit transformation of blastospores into invasive mycelial form in Candida albicans. Imidazole drugs are Miconazole, Ketoconazole, Clotrimazole, Econazole, Bifonazole, Butoconazole, Fenticonazole, Isoconazole, Oxiconazole, Sertaconazole, Sulconazole, and Tioconazole. Triazole drugs are Fluconazole, Itraconazole, Isavuconazole, Ravuconazole, Posaconazole, Voriconazole and Terconazole. Abafungin is a thiazole.

Allylamines-thiocarbamates inhibit ergosterol synthesis by interfering with enzymes (squalene epoxidase) involved in sterol synthesis. Examples include naftifine (topical) and terbinafine (oral). Amorolfine and Butenafine are other newer drugs. Tolnaftate is a topical thiocarbamate, which is effective topically against Trichophyton, Microsporum, and Epidermophyton spp.

Antimetabolites and other antimycotic drugs:
Morpholines inhibit two steps in ergosterol pathway, eg., amrolfine
Fluoropyrimidine 5-fluorocytosine is deaminated to 5-fluorouracil, converted to nucleoside triphosphate, and incorporated into RNA where it cause miscoding during transcription. Used in combination with other drugs in treatment of cryptococcal meningitis.
Polyoxins and nikkomycins: inhibits chitin synthase competitively; cell septation is inhibited and osmotic lysis of cells occurs.
Echinocandins (eg., Anidulafungin, Caspofungin & Micafungin) inhibit the synthesis of glucan in the cell wall, probably via the enzyme 1,3-beta glucan synthase.
Griseofulvin a compound derived from Penicillium griseofulvum that targets microtubule aggregation during nuclear division. It is a systemic antifungal used to treat Topical ringworm infections.
Ciclopirox olamine is most useful against Tinea versicolour.
Whitfield's ointment (a keratolytic agent) consists of 3% salicylic acid plus 6% benzoic acid. It has no significant antifungal activity, but helps remove keratinous layer to aid penetration of antifungals and are often used in treatment of topical fungal infections.

*Table source: www.vet.purdue.edu