WBR0932
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| Author | William J Gibson (Reviewed by Serge Korjian) |
|---|---|
| Exam Type | USMLE Step 1 |
| Main Category | Pharmacology |
| Sub Category | 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? |
| Answer A | Bosentan |
| Answer A Explanation | Bosentan is a competitive antagonist of endothelin-1 receptors that is used to treat pulmonary hypertension. |
| Answer B | Diltiazem |
| Answer B Explanation | Diltiazem is a nondihydropyridine calcium channel blocker that prolongs survival in patients with pulmonary hypertension. Diltiazem does not bind endothelin receptors. |
| Answer C | Treprostinil |
| Answer C Explanation | 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 | Sildenafil |
| Answer D Explanation | 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 | Riociguat |
| Answer E Explanation | Riociguat is a soluble guanylate cyclase stimulator that increases vessel reactivity to nitric oxide and can thereby treat pulmonary hypertension. |
| Right Answer | A |
| 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. |
| Approved | Yes |
| Keyword | Pulmonary hypertension, Endothelin |
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