Amphotericin B is selectively toxic to fungi compared with mammalian cells because it:

• A Is activated by a fungal-specific P450 enzyme (CYP51) to its membrane-active form
• B Is excluded from mammalian cells by the multi-drug resistance P-glycoprotein pump absent in fungi
• C Has higher binding affinity for ergosterol (the predominant fungal membrane sterol) than for cholesterol (the mammalian counterpart), forming pores that increase membrane permeability ✓
• D Inhibits fungal-specific 1,3-beta-D-glucan synthase, which is absent in mammalian cell membranes

Explanation

Amphotericin B is a macrolide polyene that intercalates into fungal membranes and binds ergosterol, forming transmembrane pores (aqueous channels) that cause K+, Mg2+, and organic molecule leakage. It also binds cholesterol in mammalian membranes (explaining nephrotoxicity and infusion reactions), but its binding affinity for ergosterol is considerably higher, conferring relative selectivity. Echinocandins (caspofungin, micafungin) target beta-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.