Pharmacogenetics and enzyme induction/inhibition properties of antiepileptic drugs.
One of the major differences between the older antiepileptic drugs (AEDs) and the newer AEDs is the potential of the older AEDs for significant interactions with other medications. Many of the drug-drug interactions involving the older AEDs are reciprocal, i.e., both drugs affect each other. In contrast, the newer AEDs have either no or limited drug interaction potential. Despite our extensive understanding of and our ability to predict drug-drug interactions, serious drug interactions still occur. More than 30% of all new seizures occur in the elderly, and because this population may be taking a variety of other medications the addition of an AED can have profound impact on these other therapies. In women, the use of enzyme-inducing AEDs can cause significant alterations of sex hormones and can decrease the efficacy of oral contraceptives. In children and adults, the use of enzyme inducers may result in long-term endocrine effects, including bone loss and lipid, thyroid, and sex hormone abnormalities. Phenytoin and phenobarbital are metabolized by cytochrome P450 isozymes, with activity dependent on genetic polymorphism (CYP2C9, CYP2C19). The dosing of the newer AEDs is not affected by genetic polymorphism. The decreased induction and inhibition effects and the lack of significant genetic polymorphism of the newer AEDs allow increased ease of use and perhaps greater safety, especially for patients taking multiple medications.
Anderson
Gail D
GD
Department of Pharmacy, Box 357630,University of Washington, Seattle, WA 98195, USA. gaila@u.washington.edu
D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects / Q000494:pharmacology*; D001711:Biotransformation / Q000235:genetics*; D001851:Bone Diseases, Metabolic / Q000139:chemically induced; D001842:Bone and Bones / Q000378:metabolism; D002648:Child; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D004347:Drug Interactions / Q000235:genetics; D004703:Endocrine System / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics*; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D011110:Polymorphism, Genetic; D013963:Thyroid Hormones / Q000378:metabolism
D000927:Anticonvulsants; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D012739:Gonadal Steroid Hormones; D013963:Thyroid Hormones; D003577:Cytochrome P-450 Enzyme System; D014453:Glucuronosyltransferase