WBR1106

Author	[[PageAuthor::William J Gibson (Reviewed by Yazan Daaboul, M.D.)]]
Exam Type	USMLE Step 1
Main Category	Pharmacology
Sub Category	General Principles
Prompt	A nervous medical student is having a difficult time falling asleep on the night before an important exam. She decides to take an over-the-counter sleep aid that is also used to reduce allergies. Which of the following most accurately describes the molecular mechanism of this drug?
Answer A	Blocks Gi activation
Answer A Explanation	The α2, M2 and D2 receptors are coupled to Gi proteins. The H1 receptor is linked to an intracellular G-protein of the Gq class.
Answer B	Blocks Gq activation
Answer B Explanation	Diphenhydramine is a Histamine H1 receptor blocker. The H1 receptor is linked to an intracellular G-protein of the Gq class.
Answer C	Blocks Gs activation
Answer C Explanation	Beta-adrenergic, H2 and V2 receptor are linked to Gs proteins. However, the H1 receptor is linked to an intracellular G-protein of the Gq class.
Answer D	Increases Gi activity
Answer D Explanation	The α2, M2 and D2 receptors are coupled to Gi proteins. The H1 receptor is linked to an intracellular G-protein of the Gq class.
Answer E	Increases Gq activity
Answer E Explanation	Diphenhydramine blocks the transduction of activating signals from the H1 receptor and thereby blocks rather than increases Gq activity.
Right Answer	B
Explanation	The patient in this vignette is self-administering diphenhydramine (Benadryl) to help her fall asleep. Diphenyhdramine is a Histamine H1 blocker. The H1 receptor is linked to an intracellular G-protein (Gq) that activates phospholipase C and the phosphatidylinositol (PIP2) signaling pathway. Antihistamines, which act on this receptor, are used as anti-allergy drugs. By blocking histamine binding of the H1 receptor, diphenhydramine blocks Gq activation. Educational Objective: Antihistamines act on the H1 receptors and are used as anti-allergy drugs. By blocking histamine binding of the H1 receptor, diphenhydramine blocks Gq activation. References: Leurs R, Smit MJ, Timmerman H. Molecular pharmacological aspects of histamine receptors. Pharmacol Ther. 1995;66(3):413-463. First Aid 2015 page 248.
Approved	Yes
Keyword	Adrenergic, Histamine, Sleep, GPCR, Gq, Signaling
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