A patient on phenelzine (MAOI) for refractory depression is inadvertently given pethidine for post-operative pain. The life-threatening interaction is mediated by:
- A Accumulation of tyramine causing norepinephrine release and hypertensive crisis
- B Pethidine's weak serotonin reuptake inhibitory effect combined with MAOI causing serotonin syndrome ✓
- C MAOI inhibiting codeine O-demethylation increasing morphine levels
- D Naloxone-resistant respiratory depression due to receptor desensitisation
Correct answer: B. Pethidine's weak serotonin reuptake inhibitory effect combined with MAOI causing serotonin syndrome
Explanation
Pethidine (meperidine) is unique among opioids in having a significant serotonin reuptake inhibitory (SNRI-like) property. When combined with an MAOI (which prevents serotonin degradation by MAO-A), serotonin accumulates to toxic levels causing serotonin syndrome: hyperthermia, myoclonus, agitation, and autonomic instability. This is NOT a tyramine reaction (option A). Morphine and codeine can also cause problems with MAOIs but via less clear mechanisms. This interaction is a classic contraindication.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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Written and medically reviewed by the StethoPrep medical team.