A patient on phenelzine for depression is inadvertently given pethidine (meperidine) for postoperative pain. The patient develops hyperthermia, rigidity, and coma. The mechanism of this life-threatening interaction is:
- A Pethidine inhibits MAO-A, causing accumulation of norepinephrine
- B Pethidine inhibits serotonin reuptake and MAOIs prevent serotonin breakdown, causing serotonin syndrome ✓
- C Pethidine displaces phenelzine from plasma proteins, causing phenelzine toxicity
- D Pethidine is metabolized by CYP2D6 to normeperidine, which is neurotoxic when MAO is inhibited
Correct answer: B. Pethidine inhibits serotonin reuptake and MAOIs prevent serotonin breakdown, causing serotonin syndrome
Explanation
Pethidine inhibits serotonin reuptake. When combined with an MAOI, serotonin breakdown is blocked, leading to serotonin syndrome. This is a classic, potentially fatal drug interaction. Normeperidine accumulation causes neuroexcitability but is not the mechanism of the MAOI interaction. Pethidine does not inhibit MAO-A.
Reference: Katzung Basic and Clinical Pharmacology, 15th ed.
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Written and medically reviewed by the StethoPrep medical team.