Antifungals
Also known as: antifungal agents, antimycotics
Antifungals are drugs that kill or inhibit fungi, working mainly by disrupting ergosterol in the fungal cell membrane or by blocking synthesis of the fungal cell wall. The major classes are the polyenes, azoles, echinocandins, allylamines, and the nucleoside analog flucytosine.
Fungi are eukaryotes, so they share far more cellular machinery with human cells than bacteria do, and selective toxicity is correspondingly harder to achieve. Antifungal drugs exploit the few genuine differences. The dominant target is ergosterol, the sterol that stabilizes the fungal cell membrane where human membranes use cholesterol. The other target is the fungal cell wall, a structure human cells lack entirely.
The classes divide cleanly by mechanism. Polyenes — amphotericin B and nystatin — bind ergosterol directly and punch pores in the membrane, causing leakage of intracellular contents. Amphotericin B is potent but nephrotoxic, so it is reserved for severe systemic infection; nystatin is too toxic for systemic use and is applied topically or as an oral rinse. Azoles — fluconazole, itraconazole, voriconazole, posaconazole, and the topical agents clotrimazole and miconazole — inhibit the enzyme that converts lanosterol to ergosterol, blocking synthesis rather than attacking existing membrane. Echinocandins — caspofungin, micafungin, and anidulafungin — inhibit beta-1,3-glucan synthase and therefore target the cell wall; they are given intravenously and are used chiefly against Candida. Allylamines, principally terbinafine, block squalene epoxidase earlier in the ergosterol pathway and are common oral agents for nail and skin infections. Flucytosine is converted inside the fungal cell to a fluorouracil metabolite that disrupts nucleic acid synthesis, and griseofulvin binds microtubules to halt fungal mitosis.
Two practical themes recur across the class. Drug interactions are a defining feature of the azoles, which inhibit cytochrome P450 enzymes and can raise concentrations of many co-administered drugs. Toxicity monitoring also drives therapy selection: renal function with amphotericin B, liver enzymes with the oral azoles and terbinafine, and blood counts with flucytosine.
The PTCE tests antifungals within antimicrobials, focusing on recognizing brand and generic names, dosage forms and routes, common auxiliary labeling, and the interaction warnings that pharmacy technicians flag at the point of dispensing. USMLE Step 1 tests the same drugs from a mechanism angle within antimicrobial pharmacology, pairing each class with its molecular target, its characteristic adverse effects, and the organisms it covers.
Key takeaways
- Antifungals target ergosterol in the fungal cell membrane or the fungal cell wall, since fungi are eukaryotes and selective toxicity is difficult.
- Polyenes such as amphotericin B bind ergosterol and form membrane pores; azoles block ergosterol synthesis instead.
- Echinocandins inhibit beta-1,3-glucan synthase, attacking the cell wall rather than the membrane.
- Terbinafine inhibits squalene epoxidase and is widely used for nail and skin infections.
- Azoles inhibit cytochrome P450 enzymes, making drug interactions a defining concern of the class.
