WBR1106

Author	[[PageAuthor::William J Gibson (Reviewed by Yazan Daaboul, M.D.)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pharmacology
Sub Category	SubCategory::General Principles
Prompt	[[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	[[AnswerA::Blocks Gi activation]]
Answer A Explanation	[[AnswerAExp::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	[[AnswerB::Blocks Gq activation]]
Answer B Explanation	[[AnswerBExp::Diphenhydramine is a Histamine H1 receptor blocker. The H1 receptor is linked to an intracellular G-protein of the Gq class.]]
Answer C	[[AnswerC::Blocks Gs activation]]
Answer C Explanation	[[AnswerCExp::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	[[AnswerD::Increases Gi activity]]
Answer D Explanation	[[AnswerDExp::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	[[AnswerE::Increases Gq activity]]
Answer E Explanation	[[AnswerEExp::Diphenhydramine blocks the transduction of activating signals from the H1 receptor and thereby blocks rather than increases Gq activity.]]
Right Answer	RightAnswer::B
Explanation	[[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	Approved::Yes
Keyword	WBRKeyword::Adrenergic, WBRKeyword::Histamine, WBRKeyword::Sleep, WBRKeyword::GPCR, WBRKeyword::Gq, WBRKeyword::Signaling
Linked Question	Linked::
Order in Linked Questions	LinkedOrder::