THE AZOLES
Azole antifungal drugs are
synthetic compounds with broad-spectrum fungistatic activity. Azoles can be
di-vided into two groups: the older imidazole agents, in which the five-member
azole nucleus contains two ni-trogens, and the newer triazole compounds,
fluconazole and itraconazole, in which the azole nucleus contains three
nitrogens.
All azoles exert antifungal
activity by binding to cy-tochrome P450 enzymes responsible for the
demethyla-tion of lanosterol to ergosterol. Reduced fungal mem-brane ergosterol
concentrations result in damaged, leaky cell membranes. The toxicity of these
drugs de-pends on their relative affinities for mammalian and fungal cytochrome
P450 enzymes. The triazoles tend to have fewer side effects, better absorption,
better drug distribution in body tissues, and fewer drug interactions.
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