A 45-year-old man on phenelzine (MAOI) for treatment-resistant depression eats a tyramine-rich meal (aged cheese, chianti wine). Within 30 minutes he develops severe occipital headache, flushing, diaphoresis, and BP 210/130 mmHg. What is the pathophysiological mechanism of this hypertensive crisis?
- A Direct agonism of alpha-1 adrenergic receptors by tyramine metabolites
- B Tyramine inhibits aldehyde dehydrogenase, causing acetaldehyde accumulation
- C Tyramine displaces norepinephrine from nerve terminals; normally MAO-A in gut and liver metabolises tyramine — with MAO inhibited, tyramine reaches systemic circulation intact and triggers massive NE release ✓
- D Tyramine potentiates serotonin synthesis, causing serotonin syndrome
Explanation
Tyramine is normally broken down by intestinal and hepatic MAO-A before reaching systemic circulation. When MAO is irreversibly inhibited by phenelzine, dietary tyramine enters circulation intact and enters noradrenergic nerve terminals via the norepinephrine transporter, where it displaces large amounts of NE into the synapse — a 'false transmitter' pressor response. The resultant massive catecholamine surge produces the 'cheese reaction': hypertensive crisis with headache, diaphoresis, and risk of hypertensive encephalopathy or haemorrhagic stroke. Management: IV phentolamine (alpha blocker) or sublingual nifedipine/captopril. Serotonin syndrome results from combined serotonergic drugs, not dietary tyramine.
Reference: Kaplan & Sadock's Synopsis of Psychiatry, 11th ed.
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Written and medically reviewed by the StethoPrep medical team.