Spironolactone congestive heart failure

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. 

Triamterene can be used in the treatment of congestive heart failure, cirrhosis, and the edema caused by secondary hyperaldosteronism. It is frequently used in combination with other diuretics except spironolactone. Amiloride, but not triamterene, possesses antihypertensive effects that can add to those of the thiazides. 

Zannad F Alla F Dousset B, Perez A, Pitt B. Limitation of excessive extracellular matrix turnover may contribute to survival benefit of spironolactone therapy in patients with congestive heart failure insights from the randomized aldac-tone evaluation study (RALES). Rales Investigators. Circulation 2000 102 2700-2706. 

Agranulocytosis occurred in an 87-year-old man with congestive heart failure who took spironolactone 25 mg/ day for 3 weeks (6). The agranulocytosis rapidly... 

Tsutamoto T, Wada A, Maeda K, Mabuchi N, Hayashi M, Tsutsui T, et al. Effect of spironolactone on plasma brain natriuretic peptide and left ventricular remodeling in patients with congestive heart failure. J Am Coll Cardiol 2001 37 1228-33. 

Svensson M, Gustafsson F, Galatius S, et al. Hyperkalaemia and impaired renal function in patients taking spironolactone for congestive heart failure Retrospective smdy. Br Med J 2003 327 1141-1142. 

The sample of patients selected for a clinical trial may not be representative of the entire population of patients with that disease. Patients entered into a trial usually are selected according to the severity of their disease and other characteristics inclusion criteria) or are excluded because of coexisting disease, concurrent therapy, or specific features of the disease itself (exclusion criteria). It always is important to ascertain that the clinical characteristics of an individual patient correspond with those of patients in the trial. For example, the Randomized Aldactone Evaluation Study (RALES) showed that treatment with the mineralocorticoid-receptor antagonist spironolactone was associated with a 30% reduction in death in patients with severe congestive heart failure. Hyperkalemia, a potential adverse effect, was seen only rarely in this study, which excluded patients with serum creatinine levels >2.5 mg/dL. With the expanded use of spironolactone after RALES was published, numerous patients, many of whom did not meet the RALES inclusion criteria, developed severe hyperkalemia. Therefore, knowledge of the criteria for selecting the patients in a trial must inform the application of study results to a given patient. 

Studies also have shown direct effects of aldosterone on the heart and vascular lining aldosterone induces hypertension and interstitial cardiac fibrosis in animal models. The increased cardiac fibrosis is proposed to result from direct mineralocorticoid actions in the heart rather than from the effect of hypertension, because treatment with spironolactone, a MR antagonist, blocks the fibrosis without altering blood pressure. Similar effects of mineralocorticoids on cardiac fibrosis in human beings may explain, at least in part, the beneficial effects of spironolactone in patients with congestive heart failure (see Chapter 33). 

Spironolactone is an antagonist to aldosterone —the latter when elaborated in the body in excessive amounts gives rise to a syndrome called aldosteronism. Spironolactone, a synthetically produced steroid does not have a natural counterpart in the body, is diuretic when mercurial or thiazide diuretics are ineffective it prevents sodium retention and potassium excretion— effects opposite to aldosterone. Hence spironolactone is used in aldosteronism, against edema, in the treatment of congestive heart failure and in other conditions in which an accumulation of water, and water-retaining salt, is to be corrected. 

Drugs proved to reduce mortality in chronic congestive heart failure include all of the following EXCEPT (A) Captopril Carvedilol Digoxin Enalapril Spironolactone... 

Spironolactone (e.g., Aldactone) Antagonist of aldosterone (aldosterone causes Na+ retention). Also has actions similar to amiloride. Used with thiazides for edema (in congestive heart failure), cirrhosis, and nephrotic syndrome. Also to treat or diagnose hyperaldosteronism. As for amiloride. Also causes endocrine imbalances (acne, oily skin, hirsutism, gynecomastia)... 

A newer drug, epierenone, has a structure similar to that of spironolactone and a similar mechanism of action. It was initially approved for use in the treatment of hypertension but it can now be used in the treatment of patients with left ventricular systolic dysfunction and congestive heart failure after myocardial infarction. It has a half-life of approximately 5 hours and undergoes hepatic metabolism to inactive metabolites as its main route of elimination. Clinical experience with epierenone is currently limited. 

Spironolactone is prescribed for clients in stage C congestive heart failure in addition to loop diuretics for its diuretic effect without causing potassium loss. 

One of the factors that affects the incidence of hyperkalaemia appears to be the dose of spironolactone. In a preliminary investigation for the Randomised Aldactone Evaluation Study (RALES), 214 patients with congestive heart failure taking an ACE inhibitor and a loop diuretic with or without digitalis, were randomised to receive placebo or various doses of spironolactone for 12 weeks. The incidence of hyperkalaemia (defined as serum potassium level of 5.5 mmol/L or greater) was 5% for the placebo group, whereas it was 5%, 13%, 20%, and 24% when spironolactone was... 

A patient taking celecoxib with bumetanide developed a moderately raised serum creatinine. Another patient taking an ACE inhibitor, spironolactone and bumetanide developed severely raised serum creatinine, hyperkalaemia, and worsening of congestive heart failure shortly after starting celecoxib. A similar case occurred in another patient taking bumetanide about 8 days after starting rofecoxib. ... 

Diuretics (Figure 4.8) are an important class of drugs which act on the kidney to increase urine output and thereby reduce the fluid load in the body. They are valuable in the treatment of hypertension and congestive heart failure. There are several modes of action possible which result in different effects on the amount of sodium and potassium ions excreted. The thiazide diuretics are exemplified by furosemide (Hoechst, 1964) which is among the world s top 25 products by sales value, and cyclopenthiazide (Ciba, 1961) which is currently among the top 20 products by prescription number in the UK. Because agents of this type lead to loss of potassium they are commonly prescribed with potassium chloride. Triamterene (Smith Kline and French, 1962) and amiloride (MSD, 1971) are diuretics which do not produce potassium loss. Amiloride and triamterene are commonly used as combinations with hydrochlorthiazide (Ciba, 1959). Spironolactone (Searle, 1962)... 

Diuretics are used to increase the volume of urine excreted by the kidneys. They are effective in the treatment of edema associated with congestive heart failure. The thiazide diuretics (e.g., hydrochlorothiazide) have antihypertensive activity and are used to control blood pressure either alone or in combination with other antihypertensive agents. Spironolactone (an aldosterone antagonist) and amiloride are potassium-sparing diuretics. 

By increasing renal elimination of Na and fluid, thiazide and loop diuretics help relieve symptoms of heart failure. They are commonly used in chronic failure and for rapid reduction of congestion and edema in acute failure. Most diuretics do not slow the progression of heart failure. However, spironolactone reduces the mortality rate when used in conjunction with ACEIs. 

Acute severe congestive failure with pulmonary edema often requires a vasodilator that reduces intravascular pressures in the lungs. Furosemide has such vasodilating actions in the context of acute failure. Minoxidil would decrease arterial pressure and increase the heart rate excessively. Spironolactone is useful in chronic failure but not usually in acute pulmonary edema. The answer is (A). 

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