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Review Question - QID 101004

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QID 101004 (Type "101004" in App Search)
A 58-year-old man who had been complaining of increased shortness of breath with exertion and paroxysmal nocturnal dyspnea was started on a medical regimen to help stabilize his condition and relieve his fluid retention. Though his symptoms were improving, he noticed bilateral breast enlargement (Figure A) and returned to the clinic. The drug responsible for his breast enlargement also functions to do which of the following?
  • A

Increase the PR interval on EKG

4%

10/255

Inhibit angiotensin converting enzyme

3%

7/255

Bind mineralcorticoid receptors

80%

204/255

Inhibit the Na+/K+/2Cl- triple transporter in the thick ascending limb of the loop of Henle

10%

25/255

Increase tubular fluid osmolarity

3%

8/255

  • A

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The man described has congestive heart failure (CHF). Spironolactone is a mineralcorticoid antagonist that can cause gynecomastia as an adverse effect.

Drugs shown to reduce mortality in CHF include ACE inhibitors, beta-blockers, angiotensin II receptor blockers (ARBs), and spironolactone, which is known to have endocrine side effects including gynecomastia. Spironolactone prevents the binding of aldosterone to its receptor, and thus stops aldosterone-mediated sodium and water resorption in the cortical collecting tubule. By virtue of inhibiting aldosterone, spironolactone functions as a potassium-sparing diuretic. More selective mineralcorticoid antagonists like eplerenone are available and have lesser endocrine side effects.

Hoyt et al. describe the drug regimen recommended for reduced mortality and morbidity for patients with congestive heart failure. They recommend that patients with an ejection fraction less than 40 percent (decreased systolic function) should be treated with medication to improve symptoms and prevent progression of heart failure. ACE inhibitors, ARBs, beta-blockers and spironolactone are highlighted.

Salyer et al. detail pharmacologic causes of male gynecomastia, which they report accounts for 20% of all gynecomastia. Though commonly tested on exams, spironolactone is listed with verapamil, cimetidine, and first-generation antipsychotics as less common agents responsible for gynecomastia. Most common are anti-androgens, protease inhibitors, and nucleoside reverse transcriptase inhibitors. Discontinuation of the offending drug will sometimes lead to reversal of gynecomastia. If the drug cannot be changed, surgery or irradiation are included as other treatment options.

Figure A demonstrates an example of an elderly gentleman with gynecomastia.

Incorrect Answers:
Answer 1: An increased PR interval is the physiologic effect on a beta-blocker.
Answer 2: ACE inhibitors are a cornerstone of CHF therapy but are not known to cause gynecomastia.
Answer 4: Inhibition of the Na+/K+/2Cl- triple transporter is the mechanism of loop diuretics, more commonly used in edema therapy.
Answer 5: Increased tubular fluid osmolarity is the effect of osmotic diuretics like mannitol, which are contraindicated in CHF.

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