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Dose-related adverse effects of anticonvulsants
Authors:AS Troupin
Affiliation:Louisiana State University School of Medicine, New Orleans, USA.
Abstract:The serum concentration at which a given drug has full efficacy in delivering seizure control bears no predictable relationship to the concentration at which adverse effects will appear. In theory, the threshold for adverse effects should be considerably higher than that for efficacy. For each agent this obviously happens most of the time, or the anticonvulsant would not be on the market, but there are also patients in whom this relationship is reversed. The adverse effects of this class of drugs are discussed from three points of view: the adverse effect type, the kinetic factors that so frequently determine the presence of adverse effects, and the specific characteristics of each drug. Some less well recognized adverse effects syndromes that are not strictly dose related are considered. The importance of adverse effects in therapeutic monitoring is then addressed, and some strategies for maximising efficacy without the burden of long term functional impairment or distress are discussed. The usefulness of monotherapy is stressed with due attention to rational choice of second drugs, when necessary, based on mechanisms of antiepileptic action and adverse effects profiles. While most of these symptoms evolve gradually, there are times when acute, drastic, and even life threatening clinical overdose situations present themselves. Special attention is given to these scenarios, drawing on the drug profiles and clinical pharmacokinetics that define these events to propose methods of coping with the problems efficiently and effectively.
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