Antifungals are effective at killing fungi. Fungi that cause human diseases may exist in yeast form or in filamentous form. Fungi have cell wall as well as cell membrane which are useful as targets of many antifungals. They can be classified as follows.
Azoles: They inhibit the synthesis of ergosterol, which is a component of the fungal cell membrane, by inhibiting the cyt P450 enzyme. They are used to treat fungal infections of the skin, nails, and hair like athlete’s foot, ringworm, candida infections, and onychomycosis. Examples include clotrimazole (Gyne-Lotrimin), fluconazole (Diflucan), econazole (Ecoza, Spectazole), ketoconazole (Extina, Nizoral), miconazole (Monistat, Azolen, Zeasorb, Desenex), itraconazole (Sporanox), voriconazole (Vfend). Adverse effects include GI upset, diarrhea, hepatotoxicity, and rash. Ketoconazole may have anti-androgenic effects, including gynaecomastia, decreased libido, decreased sperm count, and motility. Voriconazole and fluconazole may cause hallucinations. Some antifungals like ketoconazole and itraconazole are absorbed better in the presence of an acidic pH.
Polyenes: They include amphotericin B, nystatin, and natamycin. Polyenes bind to ergosterol in the fungal cell membrane and disrupt it, leading to increased cellular permeability. Amphotericin B (AmBisome, Amphocin, Fungizone, Abelcet) is used to treat systemic fungal infections like Candida spp, Aspergillus spp, etc. Adverse effects include nephrotoxicity, hematologic toxicity, and infusion related reactions such as fever, headache, and thrombophlebitis. Premedication with acetaminophen and heparin is done to prevent infusion related adverse effects. Intravenous hydration with normal saline and correction of electrolyte imbalance helps to prevent nephrotoxicity. Nystatin (Bio-Statin, Mycostatin) is given orally or topically. Natamycin (Natacyn) is used as eye drops.
Echinocandins: They include caspofungin, micafungin and anidulafungin. They inhibit the enzyme beta 1,3 D-glucan synthase thereby blocking the synthesis of beta 1,3 D-glucan in the cell wall. This causes cell lysis. They are used in the treatment of Candidiasis, Aspergillosis etc. Anidulafungin can be safely used in the presence of hepatic or renal failure. C.neoformans is resistant to echinocandins as their cell wall lacks beta glucan. They are well tolerated.
Terbinafine: Terbinafine is an allylamine antifungal and inhibits the enzyme squalene monooxygenase that is involved in sterol synthesis. It is used to treat onychomycosis. It may cause hepatitis, elevated liver enzymes, and lymphopenia. Brand names include Lamisil, Terbinex.
Griseofulvin: Griseofulvin works by inhibiting mitotic spindle formation in fungal cells thus inhibiting DNA replication. It is used to treat fungal infection of nails, skin and hair. Adverse effects include rash, hives, nausea, diarrhea, dizziness, liver damage, immune skin reactions. Brands include Grifulvin V, Gris-PEG.
Ibrexafungerp: Ibrexafungerp inhibits an enzyme known as glucan synthase that is used to synthesize the fungal cell wall. It is used in the treatment of fluconazole resistant Candidal vulvovaginitis. Adverse effects include dizziness, abdominal pain, menstrual cramps, and flatulence. The brand name is Brexafemme.
Flucytosine: Flucytosine is converted to 5-fluorouracil by the enzyme cytosine deaminase inside fungal cells. 5FU interrupts fungal DNA and protein synthesis. Adverse effects include diarrhea, nausea, vomiting, bone marrow suppression, and hepatotoxicity. It is sold as Ancobon.