Amphotericin B

1015

Summary

Amphotericin B is an antifungal drug that treats serious systemic fungal infections. Amphotericin works by binding to ergosterol in the fungal membrane, which leads to pore formation and fungal cell death. Acute side effects of amphotericin B include IV phlebitis, fever and chills, and hypotension. Prolonged use of amphotericin B can lead to kidney toxicity, low magnesium and potassium levels, and anemia.

Key Points

  • Amphotericin B
    • Mechanism
      • Binds ergosterol to form holes in fungal membranes
        • Ergosterol is unique to fungal membranes
        • Membrane holes, or pores, allow leakage of electrolytes, causing fungal cell lysis
    • Clinical Use
      • Serious systemic mycoses (fungal infections)
        • Cryptococcus
          • Given in combination with flucytosine
        • Blastomyces
        • Coccidioides
          • Used intrathecally for coccidioidal meningitis
        • Invasive aspergillus
        • Histoplasma
        • Candida
        • Mucor
    • Adverse Effects
      • Acute reactions (occur shortly after infusion)
        • Fever/chills
          • “shake and bake”
          • Include fever, chills, headaches, nausea, vomiting, and rigors
        • Hypotension
        • IV phlebitis
          • Primarily occurs in patients receiving infusions via a small peripheral vein
          • Local inflammation in blood vessels
        • Arrhythmias
      • Chronic reactions (occur with prolonged use)
        • Nephrotoxicity
          • May cause drug-induced tubular necrosis
          • Decrease in GFR and increase in creatinine
          • Hydration decreases nephrotoxicity
        • Hypokalemia & Hypomagnesemia
          • Thought to be related to renal toxicity above
          • Supplement K+ and Mg2+ because of altered renal tubule permeability
        • Anemia
          • Suppression of red cell production in bone marrow
      • Reduce toxicity with liposomal formulation of amphotericin
        • Reduced infusion reactions and nephrotoxicity