Anticonvulsant agents phenytoin

I with seizures and require anticonvulsant therapy. Phenytoin is the most frequently used agent, with a loading dose of 15 mg/kg followed by 300 mg by mouth daily (titrated to therapeutic levels between 10 and 20 mcg/mL). Diazepam 5 mg intravenously may be used for rapid control of persistent seizures. Prophylactic anticonvulsants have been used frequently, but a recent meta-analysis did not support their use.23 Thus, because adverse effects and drug interactions are common, the routine use of prophylactic anticonvulsants is not recommended. 

Topiramate, a sulfamate-substituted derivative of the monosaccharide cf-fructose, is an anticonvulsant agent (AHFS, 2000). The spectrum of topiramate s anticonvulsant activity resembles that of CBZ and phenytoin (Shank et ah, 2000). Topiramate has shown preliminary antimanic (McElroy et al., 2000) and possibly antidepressant efficacy in treatment-refractory, manic patients with BD type I (Calabrese et ah, 1998). 

Major events preceding this work are the fortuitous discovery of phenobarbital as an anticonvulsant agent, stmcture/hypnotic activity studies with barbiturates and hydantoins in the early 1920s by A.W. Dox in the Parke Davis laboratories, and the development of anticonvulsi-vant assay techniques in animals, by a number of laboratories. Phenytoin was the first item on the list of compounds sent to Putnam by Dox and W.G. Bywater in April 1936. It was found to have anticonvulsivants properties in animals late in 1936, but no public reports were issued until the following year. Clinical efficacy was established in 1937, but again no public reports were issued until 1938. Dilantin sodium capsules were prepared by Parke, Davis Co. and were ready for marketing the same year. ... 

True hypersensitivity reactions to phenytoin are related to the "aromatic" anticonvulsants. Thus, in patients in whom a reaction is suspected, other arene anticonvulsants such as carbamazepine, oxcarbazepine, phenobarbital, or primidone should be avoided, as there is a high rate of cross-reactivity (estimated as high as 80%). Valproic acid is an agent that can be safely used as an alternative anticonvulsant in such patients. 

ANTIARRHYTHMIC agents (Class I agents, e.g. disopyramide, flecainide. lignocaine. procainamide, quinidine) are sodium-channel blockers and are mainly used to treat atrial and ventricular tachycardias (see antiarrhythmic agents). ANTIEPILEPTICS have a number of mechanisms of action, but some appear to have a component involving modulation of sodium-channel function, e.g. carbamaxepine and phenytoin (see anticonvulsants). 

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