Antifungals
Antifungals are drugs that kill fungi or stop them from growing. Disease-causing fungi may exist in a yeast form or a filamentous (mold) form. Fungi have both a cell wall and a cell membrane, and many antifungals work by targeting one of these structures.
They can be classified as follows.
Azoles: Azoles inhibit the synthesis of ergosterol (a key component of the fungal cell membrane) by inhibiting a cytochrome P450 enzyme. They’re used to treat fungal infections of the skin, nails, and hair, such as 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), and 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 decreased motility. Voriconazole and fluconazole may cause hallucinations. Some azoles (such as ketoconazole and itraconazole) are absorbed better in the presence of an acidic pH.
Polyenes: Polyenes include amphotericin B, nystatin, and natamycin. They bind to ergosterol in the fungal cell membrane and disrupt the membrane, which increases 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: Echinocandins include caspofungin, micafungin, and anidulafungin. They inhibit the enzyme beta 1,3 D-glucan synthase, which blocks synthesis of beta 1,3 D-glucan in the fungal cell wall. This weakens the cell wall and causes cell lysis. They’re 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 because its cell wall lacks beta glucan. Echinocandins are well tolerated.
Miscellaneous antifungals
Terbinafine: Terbinafine is an allylamine antifungal that inhibits the enzyme squalene monooxygenase, which is involved in sterol synthesis. It’s used to treat onychomycosis. It may cause hepatitis, elevated liver enzymes, and lymphopenia. Brand names include Lamisil and Terbinex.
Griseofulvin: Griseofulvin inhibits mitotic spindle formation in fungal cells, which inhibits DNA replication. It’s used to treat fungal infections of the nails, skin, and hair. Adverse effects include rash, hives, nausea, diarrhea, dizziness, liver damage, and immune skin reactions. Brands include Grifulvin V and Gris-PEG.
Ibrexafungerp: Ibrexafungerp inhibits an enzyme known as glucan synthase, which is used to synthesize the fungal cell wall. It’s 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 (5FU) 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.