Paper II
2023 July (Supplementary) (2010 Scheme)

Question

Azole antifungals

Q53 marksShort Notes

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: azoleinhibits 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.

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