Amphotericin B Mechanism of Action

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What is the mechanism of action of Amphotericin B?

Forming pores in fungal cell membranes that disrupt membrane function

What is the primary route of excretion of Amphotericin B?

Urine

What is the purpose of premedication with a corticosteroid or antipyretic before administering Amphotericin B?

To reduce the risk of infusion-related reactions

What is the significance of the low therapeutic index of Amphotericin B?

It has a high risk of adverse effects

What is the primary mechanism of action of Amphotericin B against fungal cells?

Disrupting membrane function

What is the significance of adequate hydration in patients receiving Amphotericin B?

It decreases the risk of nephrotoxicity

What is the effect of Amphotericin B on fungal cells?

It has both fungicidal and fungistatic properties

What is the purpose of co-formulating Amphotericin B with sodium deoxycholate or artificial lipids?

To increase its solubility in water

What is the effect of other nephrotoxic drugs on the risk of nephrotoxicity associated with Amphotericin B?

They increase the risk of nephrotoxicity

What is the type of antifungal agent that Amphotericin B is classified as?

Polyene

Study Notes

Amphotericin B

  • Derived from Streptomyces nodosus, a naturally occurring polyene antifungal
  • Used to treat life-threatening mycoses

Mechanism of Action

  • Binds to ergosterol in fungal cell membranes
  • Forms pores that disrupt membrane function, causing leakage of electrolytes and small molecules
  • Ultimately leads to cell death
  • Exhibits both fungicidal and fungistatic properties

Spectrum of Activity

  • Effective against a broad range of fungi, including:
    • Candida albicans
    • Histoplasma capsulatum
    • Cryptococcus neoformans
    • Coccidioides immitis
    • Blastomyces dermatitidis
    • Various strains of Aspergillus
  • Also used to treat leishmaniasis

Pharmacokinetics

  • Administered through slow IV infusion
  • Insoluble in water, requires co-formulation with sodium deoxycholate or artificial lipids
  • Extensively bound to plasma proteins
  • Distributed throughout the body
  • Excreted primarily in the urine over an extended period
  • Limited penetration into certain body fluids

Adverse Effects

  • Low therapeutic index
  • Fever and chills:
    • Occur 1-3 hours after IV administration
    • Premedication with corticosteroid or antipyretic recommended
  • Renal impairment:
    • Azotemia exacerbated by other nephrotoxic drugs (aminoglycosides, cyclosporine, vancomycin)
    • Adequate hydration can decrease severity

Learn about the mechanism of action of Amphotericin B, a polyene antifungal drug derived from Streptomyces nodosus. Understand how it disrupts fungal cell membranes by binding to ergosterol, forming pores, and causing cell death. Explore its fungicidal and fungistatic properties and its effectiveness against a wide range of fungi.

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