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Old 12-02-2011
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Drug Blunting of diuretic response by Ibuprofen

A 43-year-old male is diagnosed with hepatic cirrhosis due to prolonged heavy alcohol consumption. He develops massive ascites and lower extremity edema that responds well to furosemide therapy. However, a week later the patient receives high-dose ibuprofen for joint pains and soon develops worsening abdominal distention. Blunting of the diuretic response in this patient is due to interruption of which of the following substances?


A. Prostaglandins
B. Endothelin
C. Angiotensin II
D. Aldosterone
E. Natriuretic peptides
F. Bradykinin

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Old 12-02-2011
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Seems Prostaglandins to me
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Its A-PG...
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Old 12-03-2011
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Default please explain the reasons

Quote:
Originally Posted by usmle2011 View Post
Seems Prostaglandins to me
please explain the reasons for your answer , please gve the basis for ruling out other options
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Default Answer

Explanation:
Furosemide is a loop diuretic that works by inhibiting Na-K-2C1 symporters in the ascending limb of the loop of Henle. It binds to symporters and effectively blocks Na and Cl transport resulting in increased Na, Cl and fluid excretion. Additionally, loop diuretics also stimulate prostaglandin release. Prostaglandins have vasodilatory effects. Thus by stimulating renal prostaglandin release, loop diuretics also increase renal blood flow leading to increased GFR and enhanced drug delivery. Both factors ultimately enhance diuretic response.
Non-steroidal anti-inflammatory drugs like ibuprofen, naproxen, and indomethacin inhibit prostaglandin synthesis. Thus concurrent use of NSAIDs with loop diuretics can result in a decreased diuretic response.
(Choice B) Endothelin is a peptide found in smooth muscles that causes smooth muscle contraction. It is a very potent vasoconstrictor. Endothelin does not play a role in the effects of loop diuretics.
(Choice C) Angiotensin II is a peptide responsible for vasoconstriction and aldosterone release. Although loop diuretics do stimulate renin release leading to angiotensin II formation, angiotensin II does not play a role in the diuretic response of loop diuretics.
(Choice D) Aldosterone is a hormone secreted by the adrenal cortex. Aldosterone promotes Na reabsorption in the distal tubule and the collecting duct. Loop diuretics do not affect aldosterone. Rather, aldosterone antagonist diuretics like spironolactone work by inhibiting aldosterone.
(Choice E) Natriuretic peptides like ANP and BNP are natural proteins that help regulate Na and fluid balance in the body. They cause vasodilation, natriuresis, and diuresis in response to volume expansion. Nesiritide is a BNP analog that is used in the setting of acute decompensated heart failure for its vasodilatory and diuretic effects. Natriuretic peptides do not play a role in the effect of loop diuretics.
(Choice F) Bradykinin is a peptide that stimulates pain, vasodilation, and increased vascular permeability. It is an important mediator in the body’s inflammatory response. Bradykinin does not play a role in the effects of loop diuretics.
Educational Objective:
Furosemide is a loop diuretic that works by inhibiting Na-K-2C1 symporters in the loop of Henle effectively causing increased Na, Cl, and fluid excretion. Additionally, loop diuretics also stimulate prostaglandin release. By stimulating renal prostaglandin release, loop diuretics also increase renal blood flow leading to increased GFR and enhanced drug delivery. Thus concurrent use of NSAID5 with loop diuretics can result in a decreased diuretic response.
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