Azoles – Antifungals

Take a look at this particular diagram. We're going to start of with the azole antifungals. The right down at the bottom here. Now azole antifungals are often used in systemic infections. And they have a variable oral bioavailability. Some of them are actually intravenous only. Now inducers of cytochrome P450 such as rifampin may actually decrease the bioavailability of some these agents. So it is important to be aware that ketoconazole and other azole antifungals can be effected by inducers of cytochrome. In terms of toxicity, common toxic reactions include vomiting, diarrhea, rash and heptatotoxicity. Ketoconazole is a particularly bad drug for drug interaction and steroid blocking effects because it has lots of systemic effects as well as it's antifungal effect. In terms of how these agents work, they inhibit ergosterol formation. So ergosterol is going to be very important for the development of the cell wall within the fungal organisms. It reduces the membrane permeability and it allows leakage of cations and nutrients out of the fungal cell. Resistance is due to widespread use. And we're starting to see it more and more. It's usually because the susceptible enzymes that azoles act on, are either becoming reduced or changed. Ketoconazole is considered a narrow spectrum antifungal. More adverse events than other azoles. So it's falling out of favor. The patients that we use it on are usually patients who have chronic oral candidiasis. And sometimes patients who have dermatological fungal infections. I've mentioned to you before that it is a strong inhibitor of cytochrome P450. And may increase the level of other drugs. And inducers like rifampin may actually reduce ketoconazole levels. Now a newer agent is fluconazole. It's the drug of choice in most esophageal infections and oropharyngeal candidiasis. A single oral dose often eliminates completely vaginal...