A 54-year-old man comes to the office due to new-onset muscle cramps. The patient has a history of hypertension and was started on hydrochlorothiazide 4 weeks ago. Blood pressure is 138/86 mm Hg and pulse is 78/min. Examination shows no abnormalities. Based on his most recent laboratory results, triamterene is added to the current therapy. Which of the following best describes the mechanism of action of this medication?

Question

A 54-year-old man comes to the office due to new-onset muscle cramps.  The patient has a history of hypertension and was started on hydrochlorothiazide 4 weeks ago.  Blood pressure is 138/86 mm Hg and pulse is 78/min.  Examination shows no abnormalities.  Based on his most recent laboratory results, triamterene is added to the current therapy.  Which of the following best describes the mechanism of action of this medication?

Quizplus · Accepted Answer

11ec160b_3b8f_9712_9249_7fd691545bb7_MD0001_00 Thiazide diuretics lower blood pressure by inhibiting Na⁺/Cl⁻ cotransporters in the distal convoluted tubules, thereby decreasing reabsorption of Na⁺ and Cl⁻. Both thiazides and loop diuretics induce volume loss with subsequent activation of the renin-angiotensin-aldosterone system. Aldosterone increases renal sodium resorption in exchange for potassium by upregulating the synthesis and activity of the following: Because of these effects, increased aldosterone levels commonly result in hypokalemia, which can lead to muscle cramps, weakness, and (when severe) cardiac arrhythmias. Potassium-sparing diuretics may be added to prevent hypokalemia. These weak diuretic medications act in the distal nephron, where they reduce potassium excretion via the following mechanisms: Triamterene and amiloride directly inhibit the epithelial sodium channel, preventing sodium from entering principal cells. This reduces the electrochemical gradient (ie, negative luminal charge) that helps drive potassium secretion. Aldosterone antagonists (ie, spironolactone, eplerenone) directly inhibit the mineralocorticoid receptor, resulting in decreased formation and activity of epithelial sodium channels and Na+/K+-ATPase pumps (Choice D). (Choice B) ACE inhibitors (eg, lisinopril) and angiotensin II blockers (eg, losartan) promote potassium retention by inhibiting the effects of angiotensin II, thereby reducing aldosterone production. (Choice C) Potassium supplements increase total potassium absorption by the gastrointestinal tract. They are another type of medication commonly prescribed to treat hypokalemia in patients on loop or thiazide diuretics. (Choice E) Digoxin, an antiarrhythmic medication, inhibits the Na+-K+-ATPase in cardiac and skeletal muscles and can also cause hyperkalemia. However, it is never prescribed to prevent hypokalemia. Educational objective: Potassium-sparing diuretics are often added to loop or thiazide diuretics to prevent hypokalemia. Amiloride and triamterene directly inhibit the epithelial sodium channel, preventing sodium from entering the principal cell, which reduces the electrochemical gradient (ie, negative luminal charge) that helps drive potassium secretion.

A 54-Year-Old Man Comes to the Office Due to New-Onset