Azole Antifungal Drug Toxicity—A Review

Abstract

The enormousness of Invasive fungal infections (IFIs) are coming much more into notice lately. The clinical manifestations vary and can range from colonization in allergic broncho-pulmonary disease to active infection in local aetiological agents. The increase of immunosuppressive agents in association with solid organ transplants, chemotherapy and improved life-saving medical techniques necessitating indwelling catheters led to a substantial increase in the occurrence of serious invasive fungal infections. Azole antifungals helped by adding to therapeutic options in treatment of IFIs works by inhibiting 14α-lanosterol demethylase, a key enzyme in ergosterol biosynthesis, resulting in depletion of ergosterol and accumulation of toxic 14α-methylated sterols in membranes of susceptible fungus. Azoles are classified into two: the triazoles (fluconazole, itraconazole, voriconazole, posaconazole, and isavuconazole) and the imidazoles (ketoconazole). Despite wide spectrum activity, these drugs show toxic effects like hepatitis and inhibition of steroid hormone synthesis, prolonged corrected for heart rate (QTc) intervals, Suppressive effects on spatial learning and memory in long-term treatments and treatment with higher concentrations. Many clinical cases have reported visual impairment, photopsia and photophobia along with many other symptoms. Drug interactions of azoles are numerous and show effects like seizures, neuropathy and serotonin toxicity. The review gives an overview of mechanism, spectrum of activity and toxic effects of azole drugs observed in clinical cases as well as animal studies.