Question
Azole antifungals
Answer
Azole antifungals inhibit the fungal ergosterol synthesis pathway.
Examples: Triazoles (Fluconazole, Itraconazole, Voriconazole, Posaconazole — systemic use), Imidazoles (Ketoconazole, Clotrimazole, Miconazole — mostly topical now).
MOA: azole → inhibits fungal cytochrome P450 14-alpha-demethylase → blocks conversion of lanosterol to ergosterol → ergosterol depletion and toxic sterol intermediate accumulation → fungistatic action.
Uses: fluconazole — candidiasis, cryptococcal meningitis (good CNS penetration); itraconazole — dermatophyte and dimorphic fungal infections; voriconazole — invasive aspergillosis.
Adverse effects: hepatotoxicity, CYP450 inhibition (numerous drug interactions), ketoconazole specifically — endocrine effects (gynecomastia, adrenal suppression) from its comparatively poor selectivity for fungal over human CYP450 enzymes, which has largely confined it to topical use today.

