A patient on phenelzine for depression undergoes surgery and receives pethidine for postoperative analgesia. Two days later he develops agitation, hyperthermia, clonus and diarrhoea. The interaction between pethidine and phenelzine that explains this presentation is:

• A Phenelzine inhibits hepatic metabolism of pethidine, causing opioid overdose
• B Phenelzine displaces pethidine from plasma proteins, raising free opioid levels
• C Normeperidine accumulates and causes central cholinergic toxicity
• D Pethidine inhibits reuptake of serotonin, adding to the serotonergic effect of the MAO inhibitor ✓

Explanation

Pethidine is the classic opioid that must be avoided with MAO inhibitors because it blocks neuronal serotonin reuptake; combined with an MAO inhibitor this produces serotonin syndrome with hyperthermia, clonus and autonomic instability. The reaction is pharmacodynamic, not kinetic, so altered metabolism or protein binding does not explain it. Other opioids such as morphine or fentanyl are considered far safer in these patients.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

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Written and medically reviewed by the StethoPrep medical team.