Each week, Osmosis shares a USMLE® Step 1-style practice question to test your knowledge of medical topics. Today’s case involves a 25-year-old woman with a severe headache. Can you figure it out?
A 25-year-old woman comes to the emergency department because of a severe headache that began four hours ago. She describes the pain as pulsating and localized to the area above her left eye. She denies any nausea or vomiting. She tried an over-the-counter non-steroidal anti-inflammatory medication at home, which provided no relief. The patient receives another first-line medication for her condition and her symptoms soon resolve. This medication works by which of the following mechanisms of action?
A. Inhibition of H1 receptors
B. Inhibition of serotonin and norepinephrine reuptake from the synaptic cleft
C. Activation of somatostatin receptors
D. Activation of serotonin receptors
E. Inhibition of calcium channels in vascular smooth muscle cells
Scroll down to find the answer!
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The correct answer to today’s USMLE® Step 1 Question is…
D. Activation of serotonin receptors
Before we get to the Main Explanation, let’s look at the incorrect answer explanations. Skip to the bottom if you want to see the correct answer right away!
Incorrect answer explanations
The incorrect answers to today’s USMLE® Step 1 Question are…
A. Inhibition of H1 receptors
Incorrect: This is the mechanism of action of antihistamines such as diphenhydramine, commonly used to treat allergies and motion sickness. It can also be used in an acute migraine attack associated with nausea and vomiting, but this patient denies these symptoms.
B. Inhibition of serotonin and norepinephrine reuptake from the synaptic cleft
Incorrect: This is the proposed mechanism of action of amitriptyline, a tricyclic antidepressant which is often used in peripheral neuropathy, chronic pain, resistant depression and migraine prophylaxis. However, it is not used for migraines during the acute phase.
C. Activation of somatostatin receptors
Incorrect: This is the mechanism of action of octreotide, a somatostatin analogue that is used to treat acromegaly, gigantism, thyrotropinoma, carcinoid syndrome, and vasoactive intestinal peptide-secreting tumors (VIPomas). It has also shown to be effective at relieving acute cluster headaches, but not migraine headaches.
E. Inhibition of calcium channels in vascular smooth muscle cells
Incorrect: This is the mechanism of action of verapamil, which is commonly used as prophylactic treatment for cluster headaches. It is not used to treat acute migraine attacks.
Main Explanation
This patient’s presentation of pulsatile, unilateral headache is consistent with a migraine. Triptans, specifically sumatriptan, are used as first–lineabortive therapy for migraines after over-the-counter non-steroidal anti-inflammatories (NSAIDs) have failed. Sumatriptan is a serotonin (5-HT1B/1D) agonist. The drug binds to serotonin receptors in the brain, triggering vasoconstriction, inhibition of trigeminal nerve activation (thought to be the cause of migraine pain), and decreased vasoactive peptide release (reducing inflammation). It can be administered orally, subcutaneously, or intranasally, and reaches peak blood concentration in approximately 15 minutes (faster than any other migraine-specific medication). Triptans may cause adverse effects including coronary artery vasospasm, mild paresthesias, and serotonin syndrome (in combination with other 5-HT agonists). Therefore, they are contraindicated in patients with a history of ischemic, cardiac, cerebrovascular, or peripheral vascular disease, uncontrolled hypertension, and in women who are pregnant.
Major Takeaway
Triptans, specifically sumatriptan, are used as first-line abortive therapy for migraine headaches after over-the-counter non-steroidal anti-inflammatories have failed. It works by activating serotonin (5-HT1B/1D) receptors in the central nervous system.
References
Silberstein SD. Practice parameter: evidence-based guidelines for migraine headache (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology [published correction appears in Neurology 2000 Jan 9;56(1):142]. Neurology. 2000;55(6):754‐762. doi:10.1212/wnl.55.6.754
Colman I, Brown MD, Innes GD, Grafstein E, Roberts TE, Rowe BH. Parenteral metoclopramide for acute migraine: meta-analysis of randomised controlled trials. BMJ. 2004;329(7479):1369‐1373. doi:10.1136/bmj.38281.595718.7
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