antifungals

Antifungals are medicines used to treat infections caused by fungi. They can be given systemically or applied locally and are used for a range of conditions from superficial skin infections to life-threatening systemic diseases. Because fungi are eukaryotes like human cells, antifungal agents aim for selective toxicity by targeting fungal components such as ergosterol in the cell membrane or enzymes involved in fungal DNA synthesis and cell wall formation.

Major antifungal classes include polyenes (for example amphotericin B and nystatin), azoles (such as fluconazole, itraconazole, voriconazole, posaconazole, and isavuconazole), echinocandins (caspofungin, micafungin, anidulafungin), allylamines (terbinafine, naftifine), and the pyrimidine analogue 5-flucytosine. Polyenes bind ergosterol to form pores in the fungal membrane, while azoles inhibit lanosterol 14α-demethylase, reducing ergosterol synthesis. Echocandins block β-1,3-glucan synthesis in the cell wall. Allylamines inhibit squalene epoxidase, mainly affecting dermatophytes and other fungi in skin and nails. 5-flucytosine disrupts fungal nucleic acid synthesis but is often used with other agents due to rapid resistance when used alone.

Clinical use and spectrum vary by agent. Some drugs are broad-spectrum and used for systemic infections (e.g., cryptococcal meningitis, invasive candidiasis, aspergillosis), while others target dermatophyte or yeast infections. Resistance can arise through target enzyme mutations or efflux mechanisms, and cross-resistance is possible across related drugs. Safety concerns include nephrotoxicity with certain polyenes, hepatotoxicity and drug interactions with azoles, and marrow suppression with 5-flucytosine; monitoring and appropriate dosing are essential.