A patient on tranylcypromine attends a party and eats aged cheese with red wine. He develops throbbing headache, marked hypertension and palpitations. Which mechanism explains this hypertensive crisis?

• A Tyramine directly stimulates vascular alpha-1 receptors at high concentration
• B MAO inhibition converts dietary tyramine into epinephrine within the adrenal medulla
• C Tyramine releases stored norepinephrine from adrenergic nerve endings as an indirect sympathomimetic ✓
• D Tranylcypromine sensitises baroreceptors, abolishing reflex bradycardia

Explanation

Tyramine is an indirectly acting sympathomimetic taken up by NET into noradrenergic terminals where it displaces stored norepinephrine into the synaptic cleft. Normally hepatic MAO-A degrades absorbed tyramine before it reaches circulation, but MAO inhibition allows large amounts to reach nerve endings, producing a surge of released norepinephrine and hypertensive crisis. Direct alpha-1 agonism is not the mechanism, since tyramine acts almost entirely through displacement of stored transmitter.

Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th ed.

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