AMPHOTERICIN B

 Amphotericin B is an antifungal agent.

Toxicokinetics: Amphotericin B is highly bound to serum proteins and is eliminated in the urine and bile. Elimination is often prolonged after cessation of therapy.

Mechanism of Action: The antifungal actions of amphotericin relate to the drug’s ability to inhibit ergosterol synthesis. Ergosterols are components of the cell membrane that are unique to fungal organisms but similar to the sterols found in mammalian membranes.

 Amphotericin is a potent nephrotoxic agent that acts by causing renal vasoconstriction and a reduction in the glomerular filtration rate. There also may be direct actions of amphotericin on the cell membranes of the renal tubule cells.

Clinical Signs: The clinical syndrome is similar to acute renal failure with signs of depression, anorexia, and vomiting.

 Clinical Pathology:Elevated BUN and creatinine with decreased serum potassium and sodium are commonly found as a result of intoxication.

Lesions:

 Amphotericin B causes an acute renal tubular necrosis.

 Treatment: Initial therapy is to discontinue administration of the drug. Aggressive fluid therapy is indicated to prevent further damage to the kidneys. The addition of mannitol may increase the elimination of amphotericin B

 Prognosis: The prognosis depends on the severity of renal damage.