A 50-year-old man on a non-selective MAO inhibitor eats aged cheese and develops a hypertensive crisis with throbbing headache. The mechanism of this reaction is best explained by:
- A Displacement of accumulated norepinephrine from sympathetic vesicles by tyramine entering nerve terminals via NET ✓
- B Direct agonism of alpha-1 receptors by absorbed tyramine
- C Inhibition of hepatic metabolism of endogenous catecholamines leading to their accumulation
- D Potentiation of adrenal medullary epinephrine secretion through splanchnic nerve stimulation
Explanation
Tyramine is an indirectly acting sympathomimetic taken up into adrenergic nerve terminals by the norepinephrine transporter, then transported into vesicles where it displaces stored norepinephrine into the cytoplasm and thence into the circulation. Normally dietary tyramine is degraded by gut and hepatic MAO, but MAO inhibitors allow large amounts to reach the terminals, producing massive pressor responses. Tyramine itself is a weak direct agonist, so option B misses the essential indirect mechanism, and options C and D are not established mechanisms of the cheese reaction.
Reference: Katzung's Basic and Clinical Pharmacology, 15th ed.
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