Pharmacology of Amphotericin B

Amphotericin B Pharmacology

• Amphotericin B elimination is unchanged in anephric patients.
• Hepatic or biliary disease has no known effect on the metabolism of the drug in humans.
• The primary route of excretion is through the bile.
• No dose adjustment is required in patients with compromised renal or hepatic function.
• The terminal phase of elimination has a half-life of approximately 15 days due to extensive binding to tissues.

Amphotericin B Untoward Effects

• All patients receiving amphotericin B therapy should be hospitalized, at least during the initiation of therapy.
• A test dose of 1 mg i.v. should be administered to gauge the severity of the reaction and guide the initial dosing regimen and premedication strategy.
• Infusion-related toxicity includes fever, chills, electrolyte imbalance, GI disturbances, and hypotension.
• Slower toxicity includes nephrotoxicity, liver test abnormalities, and anemia due to reduced production of erythropoietin by damaged renal tubular cells.
• Renal damage is the most significant of the slower toxicity, and renal impairment is seen in all patients treated with therapeutic doses of amphotericin B.

Mechanism of Action

• Amphotericin B is a polyene antibiotic that binds to ergosterol, reducing the level of ergosterol in the fungal cell membrane.
• It has the broadest spectrum of activity among all antifungal drugs.
• It is used as a "magic bullet" for systemic fungal infections, but is also the most toxic.

Administration and Precautions

• Intrathecal infusion is used for fungal meningitis.
• Low lipid solubility prevents it from crossing the blood-brain barrier.
• It is not recommended for oral administration due to its ineffectiveness.
• It should be administered IV, but not metabolized by the liver, to avoid toxicity.
• A low amount can cross the placenta, but it is still toxic and should be avoided during pregnancy.
• Hospitalization is necessary to monitor and reverse any toxic effects that may appear.
• Premedication with antihistamines and antipyretics can help alleviate adverse effects.

Interactions and Side Effects

• Rifampin and tetracyclin can enhance the activity of amphotericin B.
• Nephrotoxicity can be reduced by pre-hydration, monitoring plasma levels, and combination therapy with flotazin.
• Liposomal amphotericin B is associated with fewer toxic effects.
• The most common side effect is GI distress, and other possible side effects include allergic rash, eosinophilia, transient abnormalities of hepatic function, and thrombocytopenia.
• It can increase plasma concentrations of phenytoin, sulfonylureas, warfarin, and cyclosporine.

Test your knowledge on the pharmacology of Amphotericin B, including its elimination, metabolism, and effects on patients with renal or hepatic function. Learn about the dosage adjustments and untoward effects of this medication.