## Azole Mechanism of Action **Key Point:** Azoles (imidazoles and triazoles) inhibit **lanosterol 14α-demethylase (CYP51)**, a fungal cytochrome P450 enzyme critical for ergosterol biosynthesis. ### Mechanism of Action 1. **Enzyme inhibition:** Azoles bind to the heme iron of CYP51, blocking the demethylation of lanosterol 2. **Ergosterol depletion:** Ergosterol synthesis is halted, reducing the sterol content of the fungal cell membrane 3. **Membrane dysfunction:** Loss of ergosterol causes: - Increased membrane permeability - Leakage of cellular contents - Inhibition of membrane-bound enzymes - Fungistatic effect (growth inhibition) ### Azole Classification | Generation | Agents | Spectrum | CNS Penetration | Clinical Use | | --- | --- | --- | --- | --- | | **Imidazoles (older)** | Miconazole, ketoconazole | Broad but limited systemic use | Poor | Topical, vaginal candidiasis | | **Triazoles (modern)** | Fluconazole, itraconazole, voriconazole, posaconazole | Broad | Fluconazole: good; Voriconazole: moderate | Systemic infections, CNS involvement | **High-Yield:** **Fluconazole** is the drug of choice for cryptococcal meningitis and oral candidiasis because it achieves good CSF penetration. **Voriconazole** is preferred for invasive aspergillosis. **Warning:** Azoles are **fungistatic** (inhibit growth), not fungicidal — they require an intact immune system for clearance. In neutropenic patients, echinocandins or amphotericin B are preferred. **Clinical Pearl:** Azoles inhibit **human CYP450 enzymes** as well, leading to significant drug–drug interactions (e.g., with warfarin, cyclosporine, protease inhibitors).
Sign up free to access AI-powered MCQ practice with detailed explanations and adaptive learning.