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Potassium-Sparing Diuretics

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Potassium-Sparing Diuretics

Potassium sparing diuretics include Amiloride, Eplerenone, Spironolactone, and Triamterene.

Amiloride

Amiloride is a potassium-sparing diuretic used in the therapy of edema often in combination with thiazide diuretics. Amiloride has been linked to rare cases of clinically apparent drug induced liver disease. Amiloride (a mil' oh ride) is a pyrazinoylguanidine derivative that acts on the sodium channels of renal epithelial cells causing an increase in sodium excretion with little or no effect on potassium excretion, thus accounting for its potassium-sparing characteristics. Amiloride is similar in action to triamterene, but differs in chemical structure. Amiloride was approved for use in the United States in 1986, but is not widely used. Amiloride is available in 5 mg tablets in generic forms and under the brand name of Midamor. The typical dose of amiloride is 5 to 20 mg in one or two doses daily. Amiloride causes only a modest diuresis and it is often used in combination with a thiazide diuretic (such as hydrochlorothiazide: Moduretic), which takes advantage of it potassium-sparing characteristics to offset the potassium-wasting characteristics of the thiazides. The major side effects of amiloride include hyperkalemia, headache, dizziness, gastrointestinal upset and rash.

Eplerenone

Eplerenone is an aldosterone receptor antagonist and potassium-sparing diuretic used in the therapy of hypertension. Eplerenone therapy has been associated with transient elevations in serum aminotransferase levels, but has yet to be linked to cases of clinically apparent drug induced liver disease. Eplerenone (e pler' e none) is a competitive antagonist of aldosterone at the mineralocorticoid receptor. The aldosterone receptor in the late distal tubules and collecting ducts of the kidneys induces sodium reabsorption and potassium excretion in the distal tubule. Inhibition of this receptor promotes a sodium diuresis, but maintains body potassium levels. Eplerenone has a higher affinity for the aldosterone receptor than spironolactone and is claimed to have fewer anti-androgenic effects (gynecomastia, hair loss). However, the two molecules are structurally quite similar. Eplerenone was approved for use in the United States in 2002 for treatment of hypertension and later for improving survival of stable patients with heart failure after myocardial infarction. Eplerenone is available in 25 and 50 mg tablets generically and under the brand name of Inspra. The typical dose of eplerenone is 25 or 50 mg once daily initially, with modification of the dose based upon blood pressure response and tolerance, maintenance doses ranging from 25 to 100 mg daily in one or two divided doses. Eplerenone is well tolerated and the most common side effects are hyperkalemia and increases in serum creatinine.

Spironolactone

Spironolactone is an aldosterone receptor antagonist and potassium-sparing diuretic widely used in the therapy of edema, particularly in patients with cirrhosis in which hyperaldosteronism appears to play a major role. Spironolactone has been linked to rare cases of clinically apparent drug induced liver disease. Spironolactone (spir on oh lak' tone) is a competitive inhibitor of the mineralocorticoid receptor in the late distal tubule and collecting duct of the kidneys, which causes a decrease in sodium reabsorption and potassium excretion in the distal tubule. As a result, spironolactone promotes a sodium diuresis, but maintains body potassium levels. Spironolactone is particularly helpful in edematous states caused or exacerbated by hyperaldosteronism, which is typical of the edema and ascites caused by cirrhosis. Because of its potassium-sparing actions, spironolactone is also used in combination with thiazide or loop diuretics in an attempt to prevent hypokalemia. Chronic low dose therapy with spironolactone has also been reported to improve survival in patients with heart failure after myocardial infarction. Spironolactone was approved for use in the United States in 1960 and continues to be widely used. Spironolactone is available in 25, 50, 75 and 100 mg tablets generically and under the brand name of Aldactone. Fixed combinations of spironolactone and hydrochlorothiazide are also available under the brand name Aldactizide. The typical dose of spironolactone is 25 mg one to three times daily initially, with modification of the dose based upon clinical efficacy and tolerance to maintenance doses of 75 to 450 mg daily. The major side effects of spironolactone are due to its antiandrogen-like effects and include hair growth and gynecomastia.

Triamterene

Triamterene is a potassium-sparing diuretic widely used in the therapy of edema. Triamterene has been linked to rare cases of clinically apparent drug induced liver disease. Triamterene (trye am' ter een) is an inhibitor of renal epithelial sodium channels in the late distal tubule and collecting ducts of the kidney. As a result, triamterene promotes a mild sodium diuresis, but maintains body potassium levels. Triamterene is used largely in therapy of edema and can be safely used in patients with cirrhosis. Because of its potassium-sparing actions, triamterene is also used in combination with thiazide or loop diuretics in an attempt to prevent hypokalemia. Triamterene was approved for use in the United States in 1964 and continues to be widely used with more than 20 million prescriptions filled yearly. Triamterene is available in tablets and capsules of 50 and 100 mg in generic forms and under the brand name of Dyrenium. The typical dose of triamterene is 50 to 200 mg daily in one or two divided doses. Triamterene is also available in fixed dose combinations with hydrochlorothiazide (Maxide, Dyazide and generically). The major side effects of triamterene are dizziness, fatigue, headache, dry mouth, hyperkalemia and dehydration.

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