CNS Pharmacology USMLE Step 1 Practice Question
A 55-year-old man with major depressive disorder has been treated with fluoxetine 40 mg daily for 3 months with good symptom control. His psychiatrist plans to initiate phenelzine, an irreversible monoamine oxidase inhibitor (MAOI), due to inadequate response on higher doses. The patient is instructed to discontinue fluoxetine immediately and begin phenelzine the following day. Three days after starting phenelzine 15 mg three times daily, he presents to the emergency department with acute onset severe occipital headache, chest pain, diaphoresis, and tremor. Vital signs show temperature 40.1°C, heart rate 142/min, blood pressure 172/96 mmHg, and respiratory rate 24/min. Physical examination reveals hyperreflexia, bilateral ankle clonus, and generalized muscle rigidity. Laboratory studies show elevated serum creatinine phosphokinase. Which of the following best explains the physiologic mechanism underlying this patient's acute presentation?
Answer choices
- AInhibition of monoamine oxidase A in the GI tract leading to systemic tyramine accumulation from dietary sources
- BAbrupt serotonergic withdrawal syndrome resulting from discontinuation of fluoxetine 24 hours prior to MAOI initiation
- CExcessive serotonergic neurotransmission from concurrent MAOI activity and residual fluoxetine-induced serotonin reuptake inhibitionCorrect answer
- DPhenelzine-induced spontaneous norepinephrine and dopamine release with acute hypertensive response
- ECompetitive inhibition of fluoxetine metabolism via cytochrome P450 3A4, prolonging SSRI half-life and increasing toxicity
- FAcute serotonin syndrome precipitated by fluoxetine overdose due to impaired hepatic clearance in an elderly patient
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