Pharmacotherapy Newsletter

Volume 1, Issue 6, 02/23/2009

Question

How does the opioid medication, meperidine (Demerol®), cause seizures and who is at risk?

Answer

Meperidine (pethidine, Demerol®) is a well known opioid analgesic that has been used in practice since the early 1940's.  Unfortunately, meperidine is also known to induce seizures from the accumulation of meperidine's metabolite, normeperidine (also called norpethidine).^1-3  When meperidine is administered, it undergoes extensive hepatic metabolism via N-demethylation to produce normeperidine.²  Normeperidine has a half-life of 15-20 hours which is 5-10 times greater than the half-life of the parent compound, meperidine.^2,3  Therefore, when meperidine is administered on a scheduled basis, normeperidine can easily accumulate.  This is especially true in patients with renal impairment since normeperidine is primarily renally eliminated.⁴  In addition, meperidine rapidly appears in the cerebrospinal fluid (CSF) while normeperidine appears gradually and erratically in the CSF.⁵  The CSF penetration is important because normeperidine has half the analgesic potency as compared to meperidine but produces twice the potency as a proconvulsant compared with meperidine.⁶  See the figure below for the basic metabolism of meperidine.⁷