Aldosterone antagonists clinical effects

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. 

Aldosterone (183) is one of the key steroid hormones involved in regulation of the body s mineral and fluid balance. Excess levels of this steroid quickly lead to marked retention of sodium chloride, water and, often as a consequence, hypertension. The aldosterone antagonist spironolactone (184) has proven of great clinical value in blocking the effects... 

UTHIUM LOOP DIURETICS, POTASSIUM-SPARING DIURETICS, ALDOSTERONE ANTAGONISTS, THIAZIDES t plasma concentrations of lithium, with risk of toxic effects L renal excretion of lithium Monitor clinically and by measuring blood lithium levels for lithium toxicity. Loop diuretics are safer than thiazides... 

Spironolactone is poorly absorbed after oral administration and has a delayed onset of action it may take several days until a peak effect is produced. It has a somewhat slower onset of action than triamterene and amiloride (discussed later), but its natriuretic effect is modestly more pronounced, especially during long-term therapy. Spironolactone is rapidly and extensively metabolized, largely to the active metabohte canrenone. Canrenone and potassium canrenoate, its K+ salt, are available for clinical use in some countries outside the United States. Canrenone has a half-life of approximately 10 to 35 hours. The metabolites of spironolactone are excreted in both the urine and feces. New selective aldosterone receptor antagonists (SARA), such as eplerenone, have been developed but have not yet been introduced into clinical practice. Eplerenone and canrenone exhibit fewer steroidlike side effects (gynecomastia, hirsutism). 

Angiotensin II receptor antagonists are potassium-sparing, via their effects on aldosterone, and their potential to cause clinically important hyperkalaemia is well established. The incidence of hyperkalaemia varies depending on the clinical indication and other disease conditions, being lowest in essential hypertension, and highest in heart failure, diabetes, and renal impairment. For example, the incidence of hyperkalaemia in clinical studies in patients with hypertension was 0.9% with eprosartan - and 1.5% with losartan in type II diabetic patients with nephropathy, the incidence was 9.9% with losartan and 18.6% with irbesartan and in those with heart failure the incidence was 6.3% with candesartan. ... 

Not fully understood. It eould be that, as with the ACE inhibitors, angiotensin n reeeptor antagonists inhibit aldosterone secretion, resulting in increased sodium loss by the kidney tubules. This causes lithium retention and thus an increase in lithium levels. However, angiotensin II receptor antagonists have less effect on aldosterone than the ACE inhibitors, making a clinically significant interaction less likely. Animal studies show that ramipril, but not losartan, decreases the excretion of lithium by the kidney, which would support this idea. 

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