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Define Voriconazole
It is metabolized in the liver by CYP2C19, CYP2C9 and CYP3A4. CYP2C19 is genetically variant (about 3% to 5% of Caucasians and African-Americans and about 15% of Asians do not express it) and patients deficient in this enzyme may be exposed to higher concentrations of the drug. Voriconazole is contraindicated in patients taking rifampin, rifabutin, ergot alkaloids, long-acting barbitu- rates, carbamazepine, pimozide, quinidine, efavirenz (Sustiva), ritonavir (400 mg q12h) or sirolimus (Rapamune). Clinical monitoring or dose adjustment is required in patients taking warfarin (Coumadin, and others), sulfonylureas, statins, benzodiazepines, vinca alkaloids, nevirapine(Viramune) and HIV protease inhibitors other than indinavir. Omeprazole (Prilosec, and others), cyclosporine and tacrolimus require dose reductions when given with voriconazole. Patients taking phenytoin require enhanced doses of voriconazole and more frequent monitoring for phenytoin toxicity.
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1. Describe what effects epigenetic modifications such as methylation and acetylation can have in eukaryotic cells, and how these modifications are added or removed from chromatin.
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