68 Antifungal Therapy
The major groups of compounds include natural agents such as griseofulvin, amphotericin B and its lipid formulations, and synthetic agents including iodides, pyrimidine inhibitor (flucytosine), azoles (ketoconazole, itraconazole, fluconazole, voriconazole), allylamine derivative (terbinafine), mannoprotein complexing agents, ergosterol synthesis blockers, and chitin/glucan synthetase inhibitors (lufenuron and caspofungin) (Table 68-1).
Amphotericin B is a fungistatic agent. It works by binding to ergosterol in the fungal cell wall. This action results in an increased permeability of the cell wall. This drug also binds to cholesterol in mammalian cell membranes to a lesser degree and is responsible for some of the toxicities associated with amphotericin B.
Nephrotoxicity occurs in most dogs treated with this agent. The nephrotoxicity is characterized by vasoconstriction, reducing glomerular filtration rate (GFR), and by effects on the distal tubular area of the nephron. Distal tubular dysfunction results in metabolic acidosis because of a failure to excrete hydrogen ions. Dogs have metabolic acidosis and are unable to acidify the urine maximally. Polyuria and compensatory polydipsia develops. Serum urea nitrogen and creatinine concentrations may become elevated, and when greater than 50 mg/dl, therapy with the drug should be discontinued until these abnormalities resolve. In most instances, renal function returns to normal after therapy cessation unless high levels of amphotericin B are administered.