A 42-year-old woman on phenelzine (irreversible MAO inhibitor) for refractory depression eats a meal of aged cheese and develops hypertensive crisis with severe headache. The mechanism of this interaction is best described as:

• A Tyramine displaces norepinephrine from synaptic vesicles; with MAO inhibited, excess norepinephrine floods the synapse ✓
• B Tyramine competitively inhibits dopamine-beta-hydroxylase, increasing dopamine-mediated vasoconstriction
• C Tyramine directly activates alpha-1 receptors in vascular smooth muscle
• D Phenelzine blocks hepatic first-pass metabolism of tyramine, increasing its oral bioavailability and direct vasopressor effect

Explanation

Tyramine (an indirect sympathomimetic found in aged cheese, fermented foods, and red wine) is normally inactivated by intestinal and hepatic MAO-A. When MAO is irreversibly inhibited by phenelzine, tyramine reaches the systemic circulation and enters sympathetic nerve terminals via the norepinephrine transporter (NET). Inside the terminal, tyramine displaces norepinephrine from storage vesicles, triggering a massive release of norepinephrine into the synapse and producing a hypertensive crisis. Tyramine itself has weak direct vasopressor activity but the indirect mechanism via norepinephrine release is dominant.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.