A 52-year-old man is prescribed phenelzine (an MAOI) for atypical depression. He attends a birthday dinner and eats aged cheese and red wine. Within 30 minutes he develops a severe throbbing headache, flushing, diaphoresis, and his blood pressure is 210/120 mmHg. What is the mechanism of this hypertensive crisis?
- A Inhibition of MAO-A in gut and liver prevents first-pass metabolism of dietary tyramine, causing systemic sympathomimetic surge ✓
- B Phenelzine directly blocks alpha-adrenergic receptors, causing paradoxical hypertension with tyramine
- C Tyramine is converted to noradrenaline by MAO-A and causes vasoconstriction
- D Phenelzine inhibits CYP2D6, allowing tyramine to accumulate as an active MAOI
Explanation
Tyramine, an indirect sympathomimetic found in aged cheeses, cured meats, fermented products, and red wine, is normally inactivated by intestinal and hepatic MAO-A before reaching the systemic circulation. When MAO-A is inhibited by irreversible MAOIs like phenelzine, tyramine is absorbed intact, enters sympathetic nerve terminals, displaces stored noradrenaline, and causes a massive adrenergic surge producing hypertensive crisis. This 'cheese reaction' is the most dangerous MAOI drug-food interaction and can cause subarachnoid haemorrhage or stroke if untreated. Phentolamine (alpha-blocker) or sublingual nifedipine is used acutely.
Reference: Kaplan & Sadock's Synopsis of Psychiatry, 11th ed.
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