A 48-year-old man on tranylcypromine for resistant depression attends a party and eats aged cheese and red wine. Two hours later he has severe throbbing headache and blood pressure of 220/130 mmHg. The mechanism of this crisis is:

• A Direct alpha-1 agonism by tyramine acting on vascular smooth muscle
• B Displacement of stored norepinephrine from sympathetic nerve terminals by tyramine ✓
• C Inhibition of neuronal norepinephrine reuptake by tyramine
• D Central disinhibition of sympathetic outflow by tyramine

Explanation

Tyramine is an indirectly acting sympathomimetic taken up by NET into noradrenergic terminals where it displaces norepinephrine from storage vesicles. Normally MAO in the gut wall and liver degrades dietary tyramine, but MAO inhibitors allow it to reach the circulation intact, producing massive norepinephrine release and hypertensive crisis. Tyramine itself has negligible direct receptor activity, which rules out direct alpha-1 agonism.

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

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Written and medically reviewed by the StethoPrep medical team.