A patient with a recent history of ischemic heart disease is evaluated at an outpatient ps… — USMLE Step 2 CK

A patient with a recent history of ischemic heart disease is evaluated at an outpatient psychiatry practice. The $58$ -year-old male suffered a myocardial infarction $3$ months prior, for which he takes aspirin, ticagrelor, rosuvastatin, and metoprolol. He now describes a $6$ -week history of unremitting dysphoria, anhedonia, insomnia, and feelings of worthlessness, without any thoughts of self-harm. His physical examination and vital signs are unremarkable at this visit. A diagnosis of major depressive disorder is established, and pharmacotherapy is initiated. Eight days following this appointment, the patient arrives at the urgent care clinic complaining of severe dizziness and near-fainting episodes. Triage vital signs demonstrate a pulse of $40\text{/min}$ and a blood pressure of $88/54\text{ mm Hg}$ . A $12$ -lead electrocardiogram confirms pronounced sinus bradycardia. Which of the following psychiatric medications is most likely responsible for precipitating this patient's acute presentation?

ParoxetineAnswer
B
Sertraline
C
Escitalopram
D
Venlafaxine
E
Mirtazapine

Answer

Paroxetine

The correct answer is the medication that acts as a potent CYP2D6 inhibitor. The patient's presentation of new-onset severe bradycardia and hypotension shortly after starting psychiatric therapy strongly suggests metoprolol toxicity. Metoprolol is extensively metabolized in the liver by the cytochrome P450 2D6 (CYP2D6) enzyme. Paroxetine (along with fluoxetine) is a potent inhibitor of CYP2D6. Co-administration of paroxetine blocks the clearance of metoprolol, leading to elevated beta-blocker concentrations and resulting in symptomatic bradycardia and cardiogenic presyncope.

Step-by-Step Solution

Identify the primary acute clinical syndrome.

The patient presents with severe sinus bradycardia and hypotension 8 days after starting a new medication.

This establishes that the patient is suffering from an acute adverse drug effect.

Analyze the patient's existing medication regimen for potential interactions.

The patient is taking metoprolol, a beta-blocker known to cause bradycardia and hypotension when serum levels are excessively high.

This links the acute symptoms to a potential toxicity of an existing medication rather than a direct effect of a new one.

Determine the metabolic pathway of metoprolol and evaluate the new medication choices.

Metoprolol is metabolized by CYP2D6. Among the choices, paroxetine is a potent CYP2D6 inhibitor, which would lead to decreased metoprolol clearance and subsequent toxicity.

Identifying the pharmacokinetic interaction correctly isolates the most likely causative agent.

Key Concept

Pharmacokinetic drug-drug interactions: Strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine) can severely decrease the metabolism of beta-blockers like metoprolol, precipitating dangerous bradycardia and hypotension.

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