WBR0371

Author	[[PageAuthor::Rim Halaby, M.D. [1]]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pharmacology
Sub Category	SubCategory::Renal
Prompt	[[Prompt::A 67 year old Caucasian male presents to his physician for his annual check-up. The patient has a significant history of hypertension controlled on medications. Appropriate work-up reveals the following parameters and their corresponding activity in the patient’s blood as shown in the figure below. Which medication is the patient most likely taking to control his blood pressure? ]]
Answer A	AnswerA::Valsartan
Answer A Explanation	AnswerAExp::Valsartan is an angiotensin II receptor blocker that blocks the AT1 receptor. With the use of ARB, concentrations of renin, AT I, and AT II are expected to be increased.
Answer B	AnswerB::Ramipril
Answer B Explanation	AnswerBExp::Ramipril is an ACEI that blocks the conversion of angiotensin I to angiotensin II. As such, the concentration of angiotensin I is expected to increase, while the concentration of angiotensin II will decrease with ACEI.
Answer C	AnswerC::Acebutolol
Answer C Explanation	AnswerCExp::Acebutolol is a beta-blocker that has a direct effect on sympathetic receptors. Although RAS is subsequently affected, beta-blockers do not have a direct activity on RAS.
Answer D	AnswerD::Nifedipine
Answer D Explanation	AnswerDExp::Nifedipine is a dihydropryridine calcium channel blocker that inhibits L-type calcium channel.
Answer E	AnswerE::Diltiazem
Answer E Explanation	AnswerEExp::Diltiazem is a non-dihydropyridine calcium channel blocker that also inhibits L-type calcium channel.
Right Answer	RightAnswer::A
Explanation	[[Explanation::The use of either valsartan, an angiotensin II receptor blocker (ARB) or ramipril, an angiotensin II converting enzyme inhibitor (ACEI) will stimulate renin secretion due to the interruption of angiotensin II feedback inhibition. As such, both medications significantly increase plasma renin concentration. However, ARB and ACEI act by different mechanisms to inhibit the renin-angiotensin system (RAS). Because ACEI block the enzyme activity, subsequent products of the enzyme, angiotensin II, are expected to decrease. In contrary, ARB inhibits the AT1 receptor, thus inhibiting the action of angiotensin II without actually affecting its concentration or production. As such, concentrations of renin, AT I, and AT II are expected to be increased with the use of ARB. Educational Objective Although ACEI and ARB inhibit the renin-angiotensin-system (RAS), they work by different mechanisms. ARB blocks AT I receptor thus causing an elevation of RAS compounds due to inhibition of feedback mechanism. ACEI inhibits the enzyme activity thus inhibiting conversion from AT I to AT II, leading to an increase in the former and a decrease in the latter. Reference: Chen L, Kim SM, Eisner C, et al. Stimulation of renin secretion by angiotensin II blockade is Gsα-dependent. J Am Soc Nephrol. 2010; 21(8):988-992. Educational Objective: References: ]]
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