MEPERIDINE, AN OPIOID analgesic that has been used clinically for over 60 years, is metabolized in the liver to meperidinic acid and normeperidine. Normeperidine has a long halflife (14 to 21 hours) that can increase to more than 30 hours in patients with renal failure or elderly patients with renal insufficiency, thereby increasing the risk for cerebral irritation. Central nervous system (CNS) excitation associated with normeperidine can range from agitation to tonic-clonic seizures. Five factors are thought to predispose patients to normeperidine-induced seizures: (1) renal failure, (2) alkaline urine, (3) coadministration of hepatic enzyme-inducing drugs, (4) coadministration of phenothiazines, and (5) doses greater than 100 mg every 2 hours for longer than 24 hours. The presence of any of the first 3 risk factors can result in higher plasma normeperidine levels, which could produce CNS excitation. The administration of phenothiazines lowers the seizure threshold, potentially increasing the risk for normeperidine-induced seizures. Finally, high doses of meperidine for greater than 24 hours result in high levels of both meperidine and normeperidine. An elevated ratio of normeperidine to meperidine concentration may result in a patient exhibiting CNS excitation, even if the patient does not have any of these 5 risk factors. With the exception of tramadol, no other opioid agonist has the potential to cause seizures.
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