Diuretics aldosterone receptor antagonists

Potassium-sparing diuretics are useful both to avoid excessive potassium depletion and to enhance the natriuretic effects of other diuretics. Aldosterone receptor antagonists in particular also have a favorable effect on cardiac function in people with heart failure. 

Potassium-Sparing Diuretics. Potassium-sparing diuretics act on the aldosterone-sensitive portion of cortical collecting tubules, and partially in the distal convoluted tubules of the nephron. The commonly used potassium-sparing diuretics are triamterene, amiloride, and spironolactone (Table 3). Spironolactone is a competitive aldosterone receptor antagonist, whereas triamterene and amiloride are not (44,45). 

Ascites. Patients with cirrhosis, especially fiver cirrhosis, very often develop ascites, ie, accumulation of fluid in the peritoneal cavity. This is the final event resulting from the hemodynamic disturbances in the systemic and splanchnic circulations that lead to sodium and water retention. When therapy with a low sodium diet fails, the dmg of choice for the treatment of ascites is furosemide, a high ceiling (loop) diuretic, or spironolactone, an aldosterone receptor antagonist/potassium-sparing diuretic. 

When ascites and edema become severe, diuretic therapy can be very useful. However, cirrhotic patients are often resistant to loop diuretics because of decreased secretion of the drug into the tubular fluid and because of high aldosterone levels. In contrast, cirrhotic edema is unusually responsive to spironolactone and eplerenone. The combination of loop diuretics and an aldosterone receptor antagonist may be useful in some patients. 

Several mechanisms have been postulated to underlie the benefits of aldosterone receptor antagonists in heart failure (30). Aldosterone-induced cardiac fibrosis may reduce systolic function, impair diastolic function, and promote intracardiac conduction defects, with the potential for serious dysrhythmias. Aldosterone may also increase vulnerability to serious dysrhythmias by other mechanisms. The diuretic and hemodynamic effects of spironolactone in RALES and EPHESUS were subtle, and there were no significant changes in body weight, sodium retention, or systemic blood pressure. 

Aldosterone receptor antagonist K -sparing diuretic action in the collecting tubules used in aldosteronism, HTN, and female hirsutism. Tox h3 per-kalemia, gynecomastia. 

Aldosterone antagonists potassium-sparing diuretics (mineralocorticoid receptor antagonists)... 

Paradoxically, these agents—not positive inotropic drugs—are the first-line therapies for chronic heart failure. The drugs most commonly used are diuretics, ACE inhibitors, angiotensin receptor antagonists, aldosterone antagonists, and blockers (Table 13-1). In acute failure,... 

ACE INHIBITORS, ANGIOTENSIN II RECEPTOR ANTAGONISTS POTASSIUM-SPARING DIURETICS, ALDOSTERONE ANTAGONISTS t risk of hyperkalaemia Additive retention of potassium Monitor serum potassium every week until stable, then every 3-6 months... 

Concurrent administration of potassium supplements, potassium-sparing diuretics, or salt substitutes can precipitate hyperkalemia in ACE inhibitor-treated patients, in whom aldosterone is suppressed (SED-14, 674). Regular monitoring of serum potassium is essential in these patients, because of the risk of hyperkalemia in patients given potassium (or potassium-sparing diuretics) and ACE inhibitors or angiotensin receptor antagonists. 

Spironolactone is a competitive antagonist at aldosterone receptors. It acts through its active metabohte, canrenone. Canrenone itself has also been used as a potassium-sparing diuretic for intravenous use and its potassium salt has been used orally, in the hope of avoiding the hormonal adverse effects of spironolactone. 

Hyperkalemia Despite some reduction in the concentration of aldosterone, significant K+ retention is rarely encountered in patients with normal renal function who are not taking other drugs that cause retention. However, ACE inhibitors may cause hyperkalemia in patients with renal insufficiency or in patients taking K+-sparing diuretics, K+ supplements, adrenergic receptor antagonists, or NSAIDs. 

A. Receptor Antagonists Spironolactone, an antagonist of aldosterone at its receptor, has been discussed in connection with the diuretics (see Chapter 15). Mifepristone (RU 486) is an inhibitor at glucocorticoid receptors as well as progesterone receptors (see Chapter 40) and has been used in the treatment of Cushing s syndrome. 

There is an increased risk of hyperkalaemia if angiotensin II receptor antagonists are given with potassium-sparing diuretics (such as amiloride and the aldosterone antagonists, epierenone and spironolactone), particularly if other risk factors are also present... 

ACE inhibitors do not completely block aldosterone synthesis. Since this steroid hormone is a potent inducer of fibrosis in the heart, specific antagonists, such as spironolactone and eplerenone, have recently been very successfully used in clinical trials in addition to ACE inhibitors to treat congestive heart failure [5]. Formerly, these drugs have only been applied as potassium-saving diuretics in oedematous diseases, hypertension, and hypokalemia as well as in primary hyperaldosteronism. Possible side effects of aldosterone antagonists include hyperkalemia and, in case of spironolactone, which is less specific for the mineralocorticoid receptor than eplerenone, also antiandrogenic and progestational actions. 

The answer is c. (Hardmanr pp 706-708.) Spironolactone is an aldosterone antagonist that acts on the mineralocorticoid receptor It is a Kksparing diuretic. It can also function as an androgen antagonist, which could explain the gynecomastia and erectile dysfunction. Women with hirsutism are sometimes treated with spironolactone. 

Spironolactone and eplerenone block the mineralocorticoid receptor, the target site for aldosterone. In the kidney, aldosterone antagonists inhibit sodium reabsorption and potassium excretion. However, diuretic effects are minimal, suggesting that their therapeutic benefits result from other... 

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