A 40-year-old HIV-positive patient with CD4 count of 50 cells/µL is started on fluconazole for cryptococcal meningitis maintenance therapy. Which statement about fluconazole's mechanism is CORRECT?

• A Fluconazole inhibits squalene epoxidase, blocking ergosterol synthesis
• B Fluconazole binds directly to ergosterol and disrupts the membrane
• C Fluconazole inhibits fungal 14-alpha-demethylase, depleting ergosterol ✓
• D Fluconazole inhibits beta-1,3-glucan synthase, weakening the fungal cell wall

Explanation

Fluconazole, like all azole antifungals, inhibits the fungal cytochrome P450 enzyme 14-alpha-demethylase (CYP51), which catalyzes the conversion of lanosterol to ergosterol. Depletion of ergosterol and accumulation of toxic methylated sterols disrupt fungal membrane integrity and function. This mechanism is distinct from amphotericin B (which binds ergosterol directly) and echinocandins (which inhibit glucan synthase).

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.