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The four classes of topical antifungal drugs are azole antifungals, polyene antifungals, allylamine antifungals, and other antifungals. Azole antifungals inhibit the enzyme that converts lanosterol into ergosterol. Common examples of azole antifungals include clotrimazole, econazole, ketoconazole, miconazole, and tioconazole.
The search for antifungal agents with acceptable toxicity profiles led first to the discovery of ketoconazole, the first azole-based oral treatment of systemic fungal infections, in the early 1980s. Later, triazoles fluconazole and itraconazole , with a broader spectrum of antifungal activity and improved safety profile were developed.
For example, the azole antifungals such as ketoconazole or itraconazole can be both substrates and inhibitors of the P-glycoprotein, which (among other functions) excretes toxins and drugs into the intestines. [34] Azole antifungals are also both substrates and inhibitors of the cytochrome P450 family CYP3A4, [34] causing increased ...
A second type of azole also failed to stop his infection, and he died less than a week later. ... Drug use contributes to resistance when antifungal drugs are prescribed too often, or if doctors ...
Antifungal resistance to drugs in the azole class tends to occur gradually over the course of prolonged drug therapy, resulting in clinical failure in immunocompromised patients (e.g., patients with advanced HIV receiving treatment for thrush or esophageal Candida infection).
Itraconazole (R51211), invented in 1984, is a triazole fungistatic antifungal agent prescribed to patients with fungal infections. The drug may be given orally or intravenously. Itraconazole has a broader spectrum of activity than fluconazole (but not as broad as voriconazole or posaconazole).
[23] [13] First made in 1977, [20] ketoconazole was the first orally-active azole antifungal medication. [23] However, ketoconazole has largely been replaced as a first-line systemic antifungal medication by other azole antifungal agents, such as fluconazole and/or itraconazole , because of ketoconazole's greater toxicity, poorer absorption ...
The mechanism of action of itraconazole is the same as the other azole antifungals: it inhibits the fungal-mediated synthesis of ergosterol, via inhibition of lanosterol 14α-demethylase. Because of its ability to inhibit cytochrome P450 3A4 CC-3, caution should be used when considering interactions with other medications. [25]
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