O. Topiramate

Topiramate has several actions that are believed to contribute to its broad spectrum of antiseizure activity. Topiramate blocks voltage-dependent sodium channels, and it has been shown to increase the frequency of chloride channel opening by binding to the GABAA receptor. High-voltage calcium currents (L type) are reduced by topiramate. It is a carbonic anhydrase inhibitor and may act at glutamate (NMDA) sites. Topiramate is effective and approved for use in partial and primary generalized epilepsy. It is also approved for treatment of migraine. Topiramate is eliminated renally, but it also has inactive metabolites. It inhibits CYP2C19 and is induced by phenytoin and carbamazepine. Lamotrigine is reported to cause an increase in topiramate concentration. Coadministration of topiramate reduces ethinyl estradiol. Therefore, women taking the drug should be counseled to use additional methods of birth control. Adverse effects include somnolence, weight loss, and paresthesias. Renal stones are reported to occur at a higher incidence than in a nontreated population. Glaucoma, oligohidrosis, and hyperthermia have also been reported. The latter are specifically related to the carbonic anhydrase activity.