Amphotericin vasoconstriction

Amphotericin B-induced ARF occurs in as many as 40% to 65% of patients treated with the conventional desoxycholate formulation.30 Nephrotoxicity is due to renal arterial vasoconstriction and distal renal tubule cell damage. Risk factors include high doses, treatment for at least 7 days, preexisting kidney dysfunction, and concomitant use of other nephrotoxic drugs.31 Three lipid-based formulations of amphotericin B have been developed in an attempt to decrease the incidence of ARF amphotericin B lipid complex, amphotericin colloidal dispersion, and liposomal amphotericin B. The range of... 

Acute tubular necrosis Ischemic Hypotension Vasoconstriction Exogenous toxins Contrast dye Heavy metals Drugs (amphotericin B, aminoglycosides, etc.) (continued)... 

Nephrotoxicity is the most common and the most serious long-term toxicity of amphotericin B administration. This drug reduces glomerular and renal tubular blood flow through a vasoconstrictive effect on afferent renal arterioles, which can lead to destruction of renal tubular cells and disruption of the tubular basement... 

The etiology of amphotericin-associated hypertension has not been elucidated, but it may be related to vasoconstriction. Of note, the traditional test dose appears not to identify individuals predisposed to hypertensive reactions four of six cases of amphotericin-associated hypertension received test doses without incident. 

Vasoconstriction Two of the most common drugs which induce AKI are calcineurin inhibitors and contrast agents, both involve significant renal vasoconstriction. In addition, amphotericin also share this mechanism. 

Heidemann HT, Gerkens JF, Jackson EK, Branch RA. Effect of aminophylline on renal vasoconstriction produced by amphotericin B in the rat. Naunyn Schmiedebergs Arch Pharmacol 1983 324 148-52. 

Sawaya BP, Weihprecht H, Campbell WR, et al. Direct vasoconstriction as a possible cause for amphotericin B-induced nephrotoxicity in rats. J Clin Invest 1991 87 2097-107. 

Hardie W, Ebert J, Takahashi K, Badr KF. Thromboxane A2 receptor antagonism reverses amphotericin B-induced renal vasoconstriction in the rat. Prostaglandins 1993 45 47-56. 

Reiner NE, Thompson WL. Dopamine and saralasin antagonism of renal vasoconstriction and oliguria caused by amphotericin B in dogs. J Infect Dis 1979 140 564-575. 

The mechanisms of kidney injury include direct tubular epithelial cell toxicity with increased tubular permeability and necrosis, as well as arterial vasoconstriction and ischemic injury (Fanos and Cataldi 2000). Overall, the combined effects of increased cell energy and oxygen requirements due to greater cell membrane permeability, and reduced cellular oxygen delivery due to renal vasoconstriction, results in renal medullary tubular epithelial cell necrosis and kidney injury. Risk factors include CKD, higher average daily doses, volume depletion, and concomitant administration of diuretics and other nephrotoxins (e.g., cyclosporine) (Deray 2002 Costa and Nucci 2001). Rapid infusions of amphotericin B have the potential... 

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