Amphotericin B and azole antifungals both target ergosterol in the fungal cell membrane but differ fundamentally in their mechanism. Which statement accurately distinguishes them?
- A Amphotericin B directly binds ergosterol forming transmembrane ion channels that cause K+ leakage and cell death (fungicidal); azoles inhibit CYP51 (lanosterol 14-alpha-demethylase) blocking ergosterol synthesis, causing membrane dysfunction (primarily fungistatic) ✓
- B Azoles directly bind ergosterol; amphotericin B inhibits squalene epoxidase in ergosterol synthesis
- C Both are fungistatic at therapeutic concentrations; amphotericin B is reserved for its anti-inflammatory properties
- D Amphotericin B inhibits glucan synthase; azoles inhibit ergosterol synthesis at the same CYP51 step
Explanation
Amphotericin B binds ergosterol in the fungal plasma membrane with high affinity (low affinity for cholesterol in mammalian membranes, accounting for selectivity), forming aqueous pores or ion channels that result in K+, Mg2+, and other small molecule leakage, cell depolarization, and death. This direct membrane disruption makes it rapidly fungicidal. Azoles (fluconazole, voriconazole) inhibit fungal CYP51 (14-alpha-sterol demethylase), preventing conversion of lanosterol to ergosterol; depletion of ergosterol and accumulation of toxic sterol intermediates disrupts membrane integrity, but the effect is primarily fungistatic at usual concentrations.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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Written and medically reviewed by the StethoPrep medical team.