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Special Clinical Concerns |  |
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Side Effects and Toxicity: |
| Oral administration of nystatin can lead to anorexia and GI disturbances. The IV infusion of amphotericin B is potentially harmful, but the main concern is nephrotoxicity. Within 15 min of IV administration, renal arterial vasoconstriction occurs and lasts for 4-6 hr. This leads to diminished renal blood flow and glomerular filtration. Because amphotericin B binds to the cholesterol component in the membranes of the distal renal tubules, a change in permeability occurs in these
cells, leading to polyuria, polydipsia, concentration defects, and acidification abnormalities. The net result is a distal renal tubular acidosis syndrome. The metabolic acidosis leads to bone buffering, the excessive release of calcium into the circulation, and ultimately, nephrocalcinosis due to calcium precipitation in the acidic environment of the distal tubules. Almost every animal treated with amphotericin B suffers some degree of renal impairment, which may become
permanent depending on the total cumulative dose. The administration of amphotericin B can lead to a number of other adverse effects, including anorexia, nausea, vomiting, hypersensitivity reactions, drug fever, normocytic normochromic anemia, cardiac arrhythmias and even arrest, hepatic dysfunction, CNS signs, and thrombophlebitis at the injection site. |
| The incidence of serious adverse effects of amphotericin B therapy can be reduced. Pretreatment with antiemetic and antihistaminic agents prevents the nausea, vomiting, and hypersensitivity reactions. Giving corticosteroids IV also limits severe hypersensitivity reactions. Mannitol (1 g/kg, IV) with each dose of amphotericin B, and sodium bicarbonate (2 mEq/kg, IV or PO, daily) may help prevent acidification defects, metabolic acidosis, and azotemia; however, clinical evidence
of efficacy has not been proved. Saralasin (6-12 µg/kg/min, IV) and dopamine (7 µg/kg/min, IV) infusions have prevented oliguria and azotemia induced by amphotericin B in dogs. Administering IV fluids or furosemide before amphotericin B prevents pronounced decreases in renal blood flow and glomerular filtration rate. Newer preparations in which amphotericin B is mixed with lipid or liposomal vehicles are safer (particularly liposomes) and have maintained efficacy. |
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Interactions: |
| Amphotericin B may be combined with other antimicrobial agents with synergistic results. This often allows both the total dose of amphotericin B and the length of therapy to be decreased. Examples include combinations of 5-flucytosine and amphotericin B for the treatment of cryptococcal meningitis, minocycline and amphotericin B for coccidioidomycosis, and imidazole and amphotericin B for several systemic mycotic infections. Rifampin may also potentiate the antifungal activity
of amphotericin B. |
| Drugs that should be avoided during amphotericin B therapy include aminoglycosides (nephrotoxicity), digitalis drugs (increased toxicity), curarizing agents (neuromuscular blockade), mineralocorticoids (hypokalemia), thiazide diuretics (hypokalemia, hyponatremia), antineoplastic drugs (cytotoxicity), and cyclosporine (nephrotoxicity). |
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Effects on Laboratory Tests: |
| Plasma bilirubin, CK, AST, ALT, BUN, and eosinophil count increase. Plasma potassium and platelet count decrease. Urine protein increases. |
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