USMLE PRACTICE QUESTION #116

TOPIC: Pharmacology MOA

Dec 28, 2024

USMLE practice question #116 will test your ability to recognize the mechanism of action of a commonly tested medication.

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A 35-year-old woman presents to the clinic with recurrent severe headaches that have significantly impacted her quality of life. She describes the headaches as unilateral, throbbing in nature, and often preceded by visual disturbances such as flashing lights and wavy lines. These episodes last between 4 to 72 hours and are associated with nausea, vomiting, photophobia, and phonophobia. She reports that the headaches have been occurring approximately twice per month for the past year. Over-the-counter medications, such as ibuprofen and acetaminophen, provide little relief, and she has had to miss work on several occasions due to the intensity of the symptoms. Neurological examination during the visit is unremarkable. The most appropriate medication for her situation works via which of the following mechanisms?

A) Agonist at serotonin 5-HT1B and 5-HT1D receptors
B) Antagonist at serotonin 5-HT2A receptors
C) Inhibition of cyclooxygenase-1 (COX-1) and COX-2 enzymes
D) Agonist at dopamine D2 receptors
E) Antagonist at substance P neurokinin-1 (NK1) receptors

Detailed Breakdown of Answers + Correct Answer Below ⏬

ANSWER + QUESTION BREAKDOWN

It’s important to adopt the correct MENTAL MODEL when answering USMLE questions; it saves time and increases accuracy. The mental model outlined below is a foundational component of our test-taking skills masterclass (check it out if you want to elevate your skills). Here’s how to think through this question:

Step 1. Read the last line to get to the heart of the question: “The most appropriate medication for her situation works via which of the following mechanisms?”

Step 2: Is this a first-, second-, or third-order question?
Answer: 3rd order. 1st: Diagnose the type of headache; 2nd: Identify the most appropriate medication; 3rd: Identify the medication’s MOA.

Step 3: Read the vignette carefully and ask yourself: “What’s the MOA of the most appropriate medication for this scenario?”

Step 4. Look at the answer choices and select the option most closely resembling your final thought from “Step 3” above.

GENERAL ANALYSIS

This vignette describes a 35-year-old woman with recurrent severe unilateral, throbbing headaches associated with visual disturbances (flashing lights, wavy lines), nausea, vomiting, photophobia, and phonophobia. These episodes last between 4 to 72 hours and are consistent with migraine with aura. The patient has tried over-the-counter medications without significant relief. Given the severity and impact on her quality of life, she is likely to be prescribed a triptan, a class of drugs commonly used to abort migraine attacks.

ANSWER CHOICES:

CHOICE A: Agonist at serotonin 5-HT1B and 5-HT1D receptors

Explanation: This mechanism is characteristic of the triptans. Stimulation of these receptors leads to vasoconstriction of dilated cranial blood vessels and inhibiting neuropeptide release (such as CGRP and substance P). These actions help to reduce migraine pain.

CHOICE B: Antagonist at serotonin 5-HT2A receptors

Explanation: Antagonism at serotonin 5-HT2A receptors is seen in medications used for other conditions, such as antipsychotics or certain antidepressants.

CHOICE C: Inhibition of cyclooxygenase-1 (COX-1) and COX-2 enzymes

Explanation: Inhibition of COX enzymes is the mechanism of action for nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen or aspirin. These drugs reduce inflammation by inhibiting prostaglandin synthesis.

CHOICE D: Agonist at dopamine D2 receptors

Explanation: Dopamine D2 receptor agonists are used in the treatment of Parkinson's disease and some other conditions but are not relevant to migraine treatment.

CHOICE E: Antagonist at substance P neurokinin-1 (NK1) receptors

Explanation: NK1 receptor antagonists block the action of substance P and are used primarily in treating chemotherapy-induced nausea and vomiting. Although substance P is involved in pain pathways, triptans do not act by antagonizing NK1 receptors.

FINAL VERDICT…

Triptans are selective serotonin receptor agonists that act at the 5-HT1B and 5-HT1D receptors, leading to vasoconstriction of dilated cranial blood vessels and inhibition of pro-inflammatory neuropeptide release (such as CGRP and substance P). This mechanism effectively reduces migraine pain by targeting both vascular changes and nociceptive transmission in the trigeminal pathway.

KEY CONCEPTS:

Triptans are selective serotonin receptor agonists that act specifically at 5-HT1B and 5-HT1D receptors.
By stimulating these receptors, triptans cause vasoconstriction of intracranial blood vessels, inhibit the release of pro-inflammatory neuropeptides (such as CGRP and substance P), and modulate nociceptive transmission in the trigeminal nerve pathway.
Triptans are highly effective in aborting acute migraine attacks but are not used for prevention.

CORRECT ANSWER: A) Agonist at serotonin 5-HT1B and 5-HT1D receptors