A patient with chronic schizophrenia maintained on tranylcypromine is given intramuscular pethidine for postoperative pain. Two hours later he becomes agitated, hyperpyrexic, and rigid, and then develops generalised convulsions. Which feature specific to pethidine among the opioids explains this reaction?
- A Inhibition of neuronal reuptake of serotonin and noradrenaline ✓
- B Accumulation of the metabolite normeperidine
- C Potent histamine release from mast cells
- D Competitive blockade of dopamine D2 receptors
Correct answer: A. Inhibition of neuronal reuptake of serotonin and noradrenaline
Explanation
Pethidine uniquely inhibits the neuronal reuptake of serotonin and noradrenaline among commonly used opioids. When combined with a monoamine oxidase inhibitor, this produces serotonin excess with excitement, hyperpyrexia, rigidity, and convulsions, so the combination is absolutely contraindicated. Normeperidine accumulation causes seizures independently in renal impairment or with repeated dosing, but it is not the mechanism behind the MAOI interaction, which rules out option B.
Reference: KD Tripathi Essentials of Medical Pharmacology, 8th ed.
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