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Amphotericin B

  • Amphotericin B is one of the most potent antifungals and is the drug of choice for serious life-threatening systemic mycotic infections. Happily, fungal resistance to Amphotericin B is rare; however, the drug displays a wide variety of adverse effects.
Mechanism of Action
  • Amphotericin B binds to ergosterol in the cell wall of fungi and generates pores which permeabilize the cell wall. Deranges permeability of the fungal cell wall, especially to electrolytes, probably results in fungal cell death. At higher concentrations Amphotericin B begins binding cholesterol in the mammalian cell membrane and accounts for the drug's adverse effects.
  • Amphotericin B is administered intravenously or is injected in a number of different compounded forms
  • Free Drug: Amphotericin B is highly water insoluble and thus the free drug is typically solubilized with detergents and intravenously infused very slowly
  • Colloidal Dispersion: Amphotericin B can complexed with other compounds to form a colloidal suspension
  • Liposomal Complex: Amphotericin B can be incorporated into artificially-generated liposomes (small lipid sphericals) which reduces toxicity but increases the cost of the durg
Adverse Effects
  • Constitutional Reaction: Fevers and chills are common after intravenous infusion
  • Anemia: Occurs due to suppression of erythropoiesis and results in a normocytic anemia
  • Thrombophlebitis: Occurs at the site of intravenous administration
  • Nephrotoxicity: This is a predictable but reversible adverse effect and results in reduced GFR that manifests as elevated creatinine and occasionally intrinsic acute renal failure. The kidneys also lose potassium and magnesium and so patients should be supplemented with potassium to avoid hypokalemia.