Spironolactone aldosterone adverse effects

To reduce mortality, administration of an aldosterone antagonist, either eplerenone or spironolactone, should be considered within the first 2 weeks following MI in all patients who are already receiving an ACE inhibitor (or ARB) and have an EF of equal to or less than 40% and either heart failure symptoms or diagnosis of diabetes mellitus.3 Aldosterone plays an important role in heart failure and in MI because it promotes vascular and myocardial fibrosis, endothelial dysfunction, hypertension, left ventricular hypertrophy, sodium retention, potassium and magnesium loss, and arrhythmias. Aldosterone antagonists have been shown in experimental and human studies to attenuate these adverse effects.70 Spironolactone decreases all-cause mortality in patients with stable, severe heart failure.71... 

The diuretic effect of spironolactone develops fully only with continuous administration for several days. Two possible explanations are (1) the conversion of spironolactone into and accumulation of the more slowly eliminated metabolite canrenone (2) an inhibition of aldosterone-stimulated protein synthesis would become noticeable only if existing proteins had become nonfunctional and needed to be replaced by de novo synthesis. A particular adverse effect results from interference with gonadal hormones, as evidenced by the development of gynecomastia (enlargement of male breast). Clinical uses include conditions of increased aldosterone secretion, e.g., liver cirrhosis with ascites. 

Epierenone is a potassium-sparing diuretic. It is similar to spironolactone as an aldosterone antagonist, but has less affinity for androgen and progesterone receptors and may therefore have fewer adverse effects (1). 

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. 

Although spironolactone has been available for more than 30 years, its efficacy and safety in patients with heart failure have only recently been recognized in the Randomized Aldosterone Evaluation Study (RALES), in which it reduced mortahty (1). Based on this and numerous smaller trials, the use of spironolactone, in conjunction with ACE inhibitors, other diuretics, and possibly beta-blockers or digoxin, represents a promising strategy for patients with severe heart failure. Its main adverse effects are hyperkalemia and antiadrenergic complications (SED-14, 675). 

Urinary tract Acute renal insufficiency with hyperkalemia has been reported in a 76-year-old hypertensive woman taking both aliskiren and spironolactone [68 ]. Preexisting renal impairment and concomitant use of an aldosterone receptor antagonist were predisposing factors, and it is not surprising that the same pattern of adverse effects is seen in cases like this as have been seen with ACE inhibitors and angiotensin receptor blockers before. 

It has also been suggested that certain diuretics such as spironolactone (Aldactone) might be especially helpful in heart failure.14,42 Spironolactone blocks aldosterone receptors in the kidneys and other tissues, thereby producing a diuretic effect as well as preventing adverse cardiovascular changes associated with excess aldosterone production. Future studies will help clarify whether spironolactone should be used preferentially in heart failure because of its ability to reduce fluid volume and protect against aldosterone-induced damage.53... 

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