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Additional resources for Antiepileptic drugs: combination therapy and interactions
These changes may contribute to efficacy and, perhaps more importantly, to side effects. VPA given in moderate dose is primarily metabolized to the 2-ene derivative in the mitochondria. When used at higher doses, and especially if co-administered with enzyme-inducing drugs such as PB or PHT, significant metabolism occurs in the hepatic CYP 450 system causing omega oxidation and producing putatively hepatotoxic and teratogenic products. Selection of AED combinations The principles that are used in selection of an added drug are different mechanisms and/or different adverse effects expectation, with the goal of an overall greater efficacy without a parallel increase in intolerable adverse effects.
M. D. B. Stephens, J. C. C. Talbot, P. A. Routledge, eds. , 1998b. Seymour RM, Routledge PA. Important drug–drug interactions in the elderly. Drug Ageing 1998; 6: 485–494. Shorr RI, Ray WA, Daugherty JR, et al. Concurrent use of nonsteroidal anti-inflammatory drugs and oral anticoagulants places elderly persons at high risk for hemorrhagic peptic ulcer disease. Arch Intern Med 1993; 153(14): 1665–1670. Stephens M. In Detection of New Adverse Reactions, 4th edn. M. D. B. Stephens, J. C. C. Talbot, P.
This is due perhaps to the varied distribution of these receptors in the brain. , 2000). , 2000). More selective ligands could thus result in benzodiazepine agonists that have less sedative effect and greater anticonvulsant potential. Importantly, single amino acid substitutions rendering certain subunits insensitive to benzodiazepines can thus radically alter the profile of these drugs. Importantly, a mutation in the ␥ subunit has been found to underlie a specific epilepsy syndrome in some families, and this mutation renders the GABAA receptors benzodiazepine insensitive.
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