View source for WBR0932

 {{WBRQuestion
|QuestionAuthor=William J Gibson (Reviewed by Serge Korjian)
|ExamType=USMLE Step 1
|MainCategory=Pharmacology
|SubCategory=Pulmonology
|MainCategory=Pharmacology
|SubCategory=Pulmonology
|MainCategory=Pharmacology
|SubCategory=Pulmonology
|MainCategory=Pharmacology
|MainCategory=Pharmacology
|MainCategory=Pharmacology
|SubCategory=Pulmonology
|MainCategory=Pharmacology
|SubCategory=Pulmonology
|MainCategory=Pharmacology
|SubCategory=Pulmonology
|MainCategory=Pharmacology
|SubCategory=Pulmonology
|MainCategory=Pharmacology
|MainCategory=Pharmacology
|SubCategory=Pulmonology
|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?
|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.


|AnswerA=Bosentan
|AnswerAExp=Bosentan is a competitive antagonist of endothelin-1 receptors that is used to treat pulmonary hypertension.
|AnswerB=Diltiazem
|AnswerBExp=Diltiazem is a nondihydropyridine calcium channel blocker that prolongs survival in patients with pulmonary hypertension.  Diltiazem does not bind endothelin receptors.
|AnswerC=Treprostinil
|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.
|AnswerD=Sildenafil
|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.
|AnswerE=Riociguat
|AnswerEExp=Riociguat is a soluble guanylate cyclase stimulator that increases vessel reactivity to nitric oxide and can thereby treat pulmonary hypertension.
|EducationalObjectives=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
|RightAnswer=A
|WBRKeyword=Pulmonary hypertension, Endothelin,
|Approved=Yes
}}