Amphotericin B is nephrotoxic. Its antifungal mechanism, which also explains its toxicity, is:

• A It inhibits fungal lanosterol 14-alpha-demethylase (CYP51), depleting ergosterol from the fungal membrane
• B It binds ergosterol in the fungal membrane and forms transmembrane pores, causing loss of intracellular ions and cell death; it also binds cholesterol in human cell membranes at higher concentrations, causing nephrotoxicity ✓
• C It inhibits beta-glucan synthase, disrupting fungal cell wall integrity and causing osmotic lysis
• D It intercalates into fungal DNA and inhibits RNA polymerase, causing fungal cell death

Explanation

Amphotericin B is a polyene antifungal that binds ergosterol — the principal sterol in fungal cell membranes — and inserts as oligomeric pore complexes, forming transmembrane channels that allow leak of K+, Mg2+, and H+ from fungal cells, causing cell death. At therapeutic concentrations, it preferentially binds ergosterol over cholesterol; however, at the doses required for systemic fungal infections, some binding to cholesterol in renal tubular cell membranes occurs, causing dose-dependent nephrotoxicity, hypokalaemia, and hypomagnesaemia. Liposomal formulations reduce renal toxicity by limiting free amphotericin exposure.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.