WBR0932

Author	PageAuthor::William J Gibson (Reviewed by Serge Korjian)
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pharmacology
Sub Category	SubCategory::Pulmonology
Prompt	[[Prompt::An investigational drug called Ro 47-0203 is being evaluated for the treatment of pulmonary hypertension. Scientists find that in an in-vitro assay measuring the isometric tension of pig aortic rings, Ro 47-0203 is able to induce a potent rightward shift of the concentration-response curve to endothelin-1. However, it has no additional effect when used concurrently with a selective endothelin A antagonist. Which of the following drugs does Ro 47-0203 most likely refer to?]]
Answer A	AnswerA::Bosentan
Answer A Explanation	AnswerAExp::Bosentan is a competitive antagonist of endothelin-1 receptors that is used to treat pulmonary hypertension.
Answer B	AnswerB::Diltiazem
Answer B Explanation	AnswerBExp::Diltiazem is a nondihydropyridine calcium channel blocker that prolongs survival in patients with pulmonary hypertension. Diltiazem does not bind endothelin receptors.
Answer C	AnswerC::Treprostinil
Answer C Explanation	AnswerCExp::Treprostinil is a synthetic analog of prostacyclin (PGI2). While treprostinil has been shown to improve symptoms for a subset of patients with pulmonary hypertension, it does not act through endothelin receptors.
Answer D	AnswerD::Sildenafil
Answer D Explanation	AnswerDExp::Sildenafil is a phosphodiesterase type 5 (PDE5) inhibitor that can increase vasodilation in response to nitric oxide, thereby improving pulmonary hypertension. Sildenafil is most commonly used to treat erectile dysfunction.
Answer E	AnswerE::Riociguat
Answer E Explanation	AnswerEExp::Riociguat is a soluble guanylate cyclase stimulator that increases vessel reactivity to nitric oxide and can thereby treat pulmonary hypertension.
Right Answer	RightAnswer::A
Explanation	[[Explanation::The drug described is able to cause a right-shift in the concentration-response curve to endothelin, meaning that higher doses of endothelin-1 are required to achieve the same response in the presence of Ro47-0203. Endothelins are the most potent vasoconstrictors known. Because Ro47-0203 acts antagonistically to endotelin-1, it is likely to be an enothelin receptor antagonist. The only endothelin receptor antagonist among the answer choices is Bosentan. Futhermore, the decrease in potency depicted by a right-shift in the concentration-response curve of endothelin demonstrates that Bosentan is a competitive (rather than a non-competitive) antagonist of endothelin-1 receptors. Educational Objective: Bosentan is a competitive antagonist of endothelin-1 receptors that is used to treat pulmonary hypertension. References: Véniant M, Clozel JP, Hess P, Clozel M. Endothelin plays a role in the maintenance of blood pressure in normotensive guinea pigs. Life Sci. 1994;55(6):445-54. First Aid 2013 page 564]]
Approved	Approved::Yes
Keyword	WBRKeyword::Pulmonary hypertension, WBRKeyword::Endothelin
Linked Question	Linked::
Order in Linked Questions	LinkedOrder::