A 45-year-old man on phenelzine for resistant depression undergoes an elective procedure and receives intramuscular pethidine for postoperative pain. Two hours later he is agitated, diaphoretic, hyperreflexic, and his temperature has risen to 40 degrees Celsius. Which property of pethidine explains this presentation?
- A Pethidine releases histamine from mast cells, producing vasodilation and pyrexia
- B Pethidine inhibits neuronal reuptake of serotonin, adding to serotonergic tone produced by monoamine oxidase inhibition ✓
- C Its active metabolite normeperidine accumulates and causes central serotonergic excitation
- D Pethidine is a mixed agonist-antagonist that displaces serotonin from platelet stores
Correct answer: B. Pethidine inhibits neuronal reuptake of serotonin, adding to serotonergic tone produced by monoamine oxidase inhibition
Explanation
Pethidine (meperidine) blocks serotonin and noradrenaline reuptake in addition to its mu agonism. Combined with an MAO inhibitor, this produces serotonin syndrome with hyperthermia, agitation, and hyperreflexia, and the combination is absolutely contraindicated. Normeperidine accumulation causes seizures, not serotonergic crisis, so option C describes a real toxicity of pethidine but the wrong one for this scenario.
Reference: Katzung Basic and Clinical Pharmacology, 15th ed.
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