Question
Amphotericin B.
Answer
Amphotericin B is a polyene antifungal, the broadest-spectrum systemic antifungal available.
MOA: amphotericin B → binds ergosterol directly in the fungal cell membrane → forms pores that disrupt membrane integrity → leakage of intracellular contents → fungicidal. Its selectivity depends on ergosterol-versus-cholesterol binding preference, which is real but imperfect — residual affinity for cholesterol in human cell membranes, particularly renal tubular cells, is the direct mechanistic basis for its nephrotoxicity.
Uses: severe systemic/invasive fungal infections (invasive candidiasis, aspergillosis, cryptococcal meningitis), visceral leishmaniasis (particularly the liposomal formulation).
Adverse effects: nephrotoxicity (dose-limiting), infusion-related reactions (fever, chills, rigors — “shake and bake”), hypokalemia, hypomagnesemia, anemia. Liposomal formulations were developed specifically to reduce the off-target renal binding while preserving antifungal efficacy.