WBR0942

Author	PageAuthor::William J Gibson (Reviewed by Serge Korjian)
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pharmacology
Sub Category	SubCategory::Neurology
Prompt	[[Prompt::A 33-year-old woman presents to the emergency department for a very painful headache for the past 5 hours. She recalls that prior to the onset of the headache, she experienced a bilateral loss of peripheral visual fields. She describes the pain as throbbing and localized to the frontotemporal areas. She also explains that she has to keep her eyes covered because the light worsens her pain. What is the mechanism of action of the most appropriate pharmacotherapy for this patient?]]
Answer A	[[AnswerA::5-HT1B/1D agonism]]
Answer A Explanation	[[AnswerAExp::Sumatriptan is a serotonin analogue that acts as a 5-HT1B/1D agonist to relieve migraine headaches.]]
Answer B	[[AnswerB::5-HT3 antagonism]]
Answer B Explanation	AnswerBExp::This is the mechanism of action of ondansetron, an anti-emetic used in conjunction with chemotherapy. Ondansetron is not effective in treating migraine headaches.
Answer C	AnswerC::Beta-adrenergic blockade
Answer C Explanation	AnswerCExp::This is the mechanism of action of propranolol, a non-selective beta-blocker. Although propranolol may be used for migraine prophylaxis, it is not an abortive therapy.
Answer D	AnswerD::Voltage-dependent sodium channel blockade and GABA potentiation
Answer D Explanation	AnswerDExp::This is the mechanism of action of valproic acid, an antiepileptic agent. Although valproate may be used for migraine prophylaxis, it is not an abortive therapy.
Answer E	AnswerE::Phosphodiesterase inhibition
Answer E Explanation	AnswerEExp::This is the mechanism of action of sildenafil. One side effect of sildenafil is headache.
Right Answer	RightAnswer::A
Explanation	[[Explanation::The patient in this vignette has the classical signs of a migraine headache. Migraines are often preceded by an aura, or a perceptual disturbance that may include an unpleasant smell, a visual disturbance, or unconventional thoughts. Migraines can have variable presentations but are classically described as moderate to severe headaches that are unilateral and localized most commonly to the frontotemporal areas. Several hypotheses have been suggested for the causes of migraines including irritation of CN V and release of substance P. Although non-opioid analgesics and NSAIDS are considered a first line therapy, sumatriptan is a more effective therapy for more severe migraine headaches. Sumatriptan is a serotonin 5-HT1B/1D agonist. Although the mechanism of action of sumatriptan is not clearly understood, the 5-HT1B receptors it activates are present in the cranial arteries and veins, suggesting a vascular mechanism (vasoconstriction). For patients with severe debilitating migraines that are not controlled by abortive therapies and lead to medication overuse (NSAIDS, triptans, analgesics), prophylaxis should be considered with either a non-selective beta-blocker, such as propranolol or timolol, or an antiepileptic agent, such as valproate or topiramate. Educational Objective: Sumatriptan is a serotonin analogue that acts as a 5-HT1B/1D agonist to relieve migraine headaches. References: Silberstein SD, Holland S, Freitag F, et al. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2012;78(17):1337-45. Diagnosis and management of headaches in young people and adults. NICE clinical guideline 150 (2012).]]
Approved	Approved::Yes
Keyword	WBRKeyword::Headache, WBRKeyword::Migraine, WBRKeyword::Migraine headache, WBRKeyword::Serotonin, WBRKeyword::5-HT, WBRKeyword::Mechanism
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