Pathophysiology
Clinical meaning
Antifungal drugs target structures unique to fungal cells—primarily ergosterol in the fungal cell membrane and beta-glucan in the fungal cell wall. Azoles (fluconazole, itraconazole, voriconazole, posaconazole) inhibit lanosterol 14-alpha-demethylase (CYP51), a cytochrome P450 enzyme essential for converting lanosterol to ergosterol. Without ergosterol, the fungal membrane becomes unstable and permeable, impairing cell growth (fungistatic for most Candida species). Polyenes (amphotericin B, nystatin) bind directly to ergosterol in the fungal membrane, creating pores that cause leakage of intracellular contents and cell death (fungicidal). Echinocandins (caspofungin, micafungin, anidulafungin) inhibit beta-1,3-D-glucan synthase, disrupting cell wall integrity—this target is absent in human cells, giving echinocandins an excellent safety profile. Flucytosine (5-FC) is converted intracellularly to 5-fluorouracil, which inhibits DNA and RNA synthesis; it is used only in combination (typically with amphotericin B for cryptococcal meningitis) due to rapid resistance when used alone. Terbinafine inhibits squalene epoxidase, another step in ergosterol synthesis, and is used primarily for dermatophyte infections. Drug selection depends on the fungal species, site of infection, host immune status, drug interactions (azoles are potent CYP450 inhibitors), and toxicity profile.