Amphotericin B (AMB.)

Amphotericin B is obtained from Streptomyces nodosus.

It is a polyene antifungal with a macrocyclic ring; one side has several conjugated double bonds and is highly lipophilic, while the other is hydrophilic with many OH groups.

A polar aminosugar and a carboxylic acid group are present at one end in some. They are all insoluble in water and are unstable.

Mechanism of action.

• Binds to ergosterol in the fungi cell membrane, causing damage and leakage of cell contents.
• It has a higher affinity for ergosterol in fungi cell membranes than cholesterol in humans.

Indication.

Active against a wide range of yeasts and fungi, including ;

• Candida albicansHistoplasma capsulatum
• Cryptococcus neoformans,
• Blastomyces dermatitidis,
• Coccidioides immitis,
• Torulopsis, Rhodotorula, Aspergillus, Sporothrix.

Clinical uses

• Applied topically for oral, vaginal and cutaneous candidiasis and otomycosis.
• Systemic mycoses and is the gold standard of antifungal therapy.
• However, it’s highly toxic.
• Effective drug for resistant cases of kala-azar and mucocutaneous leishmaniasis.

Adverse effects

• The acute reaction occurs with each infusion and includes chills, fever, aches, nausea, vomiting and dyspnoea lasting 2–5 hours.
• Nephrotoxicity is dose-related.
• Azotemia, reduced glomerular filtration rate, acidosis, hypokalaemia and inability to concentrate urine.
• Slow progressing anemia due to bone marrow depression.
• CNS toxicity: occurs only on intrathecal injection involving; headache, vomiting and nerve palsies.

Drug interaction.

• Aminoglycosides, vancomycin, cyclosporine and other nephrotoxic drugs enhance the renal impairment caused by amphotericin B.

Dosage.

• Orally (50–100 mg QID) for intestinal moniliasis;
• Topically for vaginitis, and otomycosis.
• FUNGIZONE OTIC 3% ear drops.