Convulsions

Although most opiates produce convulsions when administered in very large doses, convulsions are most frequently observed when excessively large doses of MEPERIDINE (Demerol) or ¿-propoxyphene (Darvon) are administered. Emergent meperidine seizures are characterized by tremors and twitching, which may evolve into tonic-clonic (epileptic) convulsions. Focal and tonic-clonic seizures have been observed in patients overdosed with ¿-propoxyphene. The mechanisms whereby opioid drugs produce convulsive phenomena are not well understood and may involve several mechanisms, including (1) direct and indirect dysinhibition of glycine and GABA-mediated inhibition and (2) excitatory actions that are probably mediated by yet-to-be-classified receptors. The convulsant effects of ¿-propoxyphene can be readily antagonized by naloxone; however, meperidine's convulsant effects may be more resistant. Meperidine probably has a convulsant effect in its own right when administered in very large doses acutely, yet convulsant phenomena seen following the administration of multiple doses of meperidine are produced by the accumulation of a metabolite, normeperidine.

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