AMPHOTERICIN B

Structure/Class
  1. Amphoteric polyene macrolide
Pharmacodynamics
  1. Anti-fungal drug
    • Interferes with cell membrane function by binding to ergosterol (The predominant sterol of fungi is ergosterol, which is a major component of the fungal lipid cell membrane)
    • Therefore, it is the antifungal with the broadest spectrum of activity, including candida, Cryptococcus, aspergillus and histoplasma.
    • It is useful for life-threatening mycotic infections, and is often used as an initiation agent.
  2. Toxicity can be divided into immediate and long term.
    • Immediate
      1. Infusion related toxicity, i.e. fevers, chills, vomiting, headache, hypotension and muscle spasms.
      2. Treat by slowing down the infusion rate.
    • Long term
      1. Renal failure (most significant reaction) which may be irreversible.
      2. Anaemia (secondary to renal damage)
      3. Abnormal LFTs.
      4. Intrathecal amphotericin is very toxic.
Pharmacokinetics
  1. Parenteral administration. Poorly absorbed PO (PO use only for fungi in the GIT lumen)
  2. 90% bound to serum proteins.
  3. Does not penetrate CSF (use fluconazole for CSF fungal meningitis)
  4. No need for dose adjustments in hepatic/renal failure.