TITLE:
Cardiac Toxicity of Azole Antifungals
AUTHORS:
John D. Cleary, Kayla R. Stover, Jerry Farley, William Daley, Patrick B. Kyle, Jon Hosler
KEYWORDS:
Mycology; Azole Antifungals; Itraconazole; Animal Model
JOURNAL NAME:
Pharmacology & Pharmacy,
Vol.4 No.3,
June
20,
2013
ABSTRACT: Cardiac toxicity is an uncommon side effect of
anti-fungal therapy. Until the recent reports of itraconazole (ITZ) associated cardiac failure, amphotericin was the
antifungal most frequently reported with arrhythmias. We evaluated the cardiac
effect of azole antifungals, specifically ITZ, and possible mechanisms of
toxicity. Ex vivo live-heart studies
were performed utilizing Sprague Dawley rats. Short exposure (25 (2 - 2.5 ug/mL)
exposures, contractility decreased by 22.2% ± 15.7% and amplitude of left ventricular
pressure decreased by 11% ± 0.17%. Electron
micrograph and alterations in mitochondrial
respiration suggest mitochondrial toxicity as an underlying mechanism. In conclusion, ITZ was associated with reductions in
contractility, possibly secondary to mitochondrial dysfunction and dilated cardiomyopathy.