Voriconazole is a triazole antifungal used for invasive aspergillosis. Unlike fluconazole, it inhibits both lanosterol 14-alpha demethylase AND which other enzyme, accounting for its broader spectrum?
- A Squalene epoxidase (14-alpha-demethylase)
- B Sterol delta-22 desaturase, also involved in ergosterol biosynthesis in Aspergillus ✓
- C 1,3-beta-D-glucan synthase
- D Chitin synthase involved in Aspergillus cell wall assembly
Correct answer: B. Sterol delta-22 desaturase, also involved in ergosterol biosynthesis in Aspergillus
Explanation
Voriconazole inhibits fungal CYP51 (lanosterol 14-alpha-demethylase) — its primary triazole target. Unlike fluconazole, it also inhibits sterol delta-22 desaturase in Aspergillus spp., which is a unique enzyme in moulds not present in Candida; this second inhibition contributes to its activity against Aspergillus, Fusarium, and Scedosporium. Echinocandins (caspofungin) inhibit 1,3-beta-D-glucan synthase (option C); allylamine terbinafine inhibits squalene epoxidase.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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