antifúngics

Antifúngics, or antifungals, are drugs used to treat fungal infections in humans and animals. They encompass a range of chemical classes with distinct mechanisms, spectra of activity, and safety profiles. Antifungal therapy is guided by the suspected or confirmed pathogen, site of infection, patient immune status, and local resistance patterns, with choices balancing efficacy and toxicity.

Major antifungal classes include polyenes (for example amphotericin B and nystatin), azoles (fluconazole, itraconazole, voriconazole, posaconazole, isavuconazole), allylamines (terbinafine), echinocandins (caspofungin, micafungin, anidulafungin), and the pyrimidine analogue flucytosine. Polyenes bind ergosterol in the fungal membrane to form pores; azoles inhibit lanosterol 14α-demethylase, reducing ergosterol synthesis; allylamines inhibit squalene epoxidase; echinocandins block β-1,3-glucan synthesis in the cell wall; flucytosine is converted to 5-fluorouracil and disrupts DNA and RNA synthesis.

Pharmacology varies by agent. Many antifungals are active systemically and given orally or intravenously; some have limited distribution to the central nervous system. Amphotericin B is effective but nephrotoxic, though liposomal formulations reduce toxicity. Azoles can cause hepatotoxicity and have substantial drug interactions via cytochrome P450 enzymes. Echinocandins are IV and generally well tolerated but have limited CNS penetration.

Clinical use covers life-threatening invasive infections caused by Candida, Cryptococcus, and Aspergillus, as well as mucorales, certain endemic fungi, and common dermatophyte infections. Resistance may arise through target mutations, efflux, or altered drug uptake, necessitating susceptibility testing and combination or sequence-based strategies.