ABSTRACT
I. INTRODUCTION Historically, as a therapeutic class, anticonvulsant agents have been associated with severe liver toxicity. Agents such as mephenytoin and phenacemide were removed from clinical use as a consequence of unacceptably high frequencies of liver toxicity and it is clear that a clinically significant risk of hepatotoxicity also accompanies the use of phenytoin (Dilantin, Parke-Davis, Morris Plains, New Jersey), carbamazepine (Tegretol, Novartis Pharmaceuticals, Basel, Switzerland), and valproic acid (Depakene, Abbott Laboratories, Abbott Park, Illinois), the three most commonly prescribed anticonvulsants at present. The complex pathogenesis of seizure disorders and their general refractoriness to anticonvulsant therapy often result in the use of two or more agents such that it becomes difficult to fully evaluate the hepatotoxic potential of individual agents. Nevertheless, the purpose of this
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chapter is to describe the clinical presentation, histopathology, mechanisms, and determinants of susceptibility of anticonvulsant-induced liver toxicity with a particular focus on the aromatic anticonvulsants phenobarbital, phenytoin, and carbamazepine, as well as lamotrigine, valproic acid, and felbamate.
