Hyperaldosteronism, spironolactone

Hyperaldosteronism is accompanied by elevation of blood pressure (115), and can be treated with an aldosterone antagonist, eg, spironolactone (117) which... 

Potassium-sparing by diuretic agents, particularly spironolactone, enhances the effectiveness of other diuretics because the secondary hyperaldosteronism is blocked. This class of diuretics decreases magnesium excretion, eg, amiloride can decrease renal excretion of potassium up to 80%. The most important and dangerous adverse effect of all potassium-sparing diuretics is hyperkalemia, which can be potentially fatal the incidence is about 0.5% (50). Therefore, blood potassium concentrations should be monitored carehiUy. 

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. 

Short test-400 mg/day for 4 days. If serum potassium increases but decreases when spironolactone is discontinued, consider a presumptive diagnosis of primary hyperaldosteronism. 

Aldosterone stimulates the rates of Na+ reabsorption and K+ secretion. This is relevant to the action of spironolactone, a diuretic that is a competitive inhibitor of aldosterone (discussed later). It is also pertinent because administration of diuretics can cause secondary hyperaldosteronism, which may exaggerate the potassium wasting that is a consequence of the increased delivery of Na+ and enhanced flow through distal convoluted tubules and collecting ducts. 

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. 

Mineralocorticoids help control the body s water volume and concentration of electrolytes, especially sodium and potassium. Aldosterone acts on kidney tubule cells, causing a reabsorption of sodium, bicarbonate, and water. Conversely, aldosterone decreases reabsorption of potassium, which is then lost in the urine. [Note Elevated aldosterone levels may cause alkalosis and hypokalemia, whereas retention of sodium and water leads to an increase in blood volume and blood pressure (see p. 180). Hyperaldosteronism is treated with spironolactone (see p. 232).]... 

Spironolactone competes for the mineralocorticoid receptor and thus inhibits sodium reabsorption in the kidney (see p. 232). It can also antagonize aldosterone and testosterone synthesis. It is effective against hyperaldosteronism. The drug is also useful in the treatment of hirsutism in women, probably due to interference at the androgen receptor of the hair follicle. 

Spironolactone, an aldosterone antagonist, is the drug of choice since secondary hyperaldosteronism often coexists in patients with hepatic ascites. Aldosterone is usually metabolised by the liver and is highly protein bound, therefore the free aldosterone levels are raised in cirrhosis. Spironolactone competes with aldosterone for receptor sites in the distal tubule, resulting in potassium retention and sodium and water loss. The initial dose of spironolactone is 100-200 mg and can be slowly increased according to response. There is a lag of 3-5 days between the beginning of spironolactone treatment and the onset of the natriuretic effect. 

Metoclopramide has been shown to significantly reduce spironolactone-induced diuresis in cirrhotic patients with ascites. When administered to patients with secondary hyperaldosteronism, metoclopramide significantly reduced urinary sodium excretion, with a corresponding increase in urinary potassium excretion and a significant increase in plasma aldosterone. This effect was not seen with domperidone. From this study it is recommended that metoclopramide is avoided during diuretic therapy in cirrhotic patients with ascites [15]. 

The use of spironolactone has received considerable support from the RALES trial, which implies that ACE inhibition even at high dose does not effectively suppress hyperaldosteronism in... 

Spironolactone (see p. 534) is a competitive aldosterone antagonist which also blocks the mineralocorticoid effect of other steroids it is used in the treatment of primary hyperaldosteronism and as a diuretic, principally when severe oedema is due to secondary hyperaldosteronism, e.g. cirrhosis, congestive cardiac failure. 

Spironolactone antagonises the sodium-retaining effect of aldosterone and other mineralocorticoids. It is used to treat primary and secondary hyperaldosteronism (p. 538). 

Spironolactone has been used as a potassium-sparing diuretic in cardiac failure and in the management of ascites and edema associated with hepatic cirrhosis with secondary hyperaldosteronism. It is also used to treat hyperaldosteronism due to adrenal tumors or adrenal hyperplasia. It has a weak positive inotropic effect and a modest antihypertensive effect, in keeping with its natriuretic action. 

In humans, spironolactone is absorbed readily and is metabolized in the liver to active compounds called canrenones. It is these metabolites that compete with aldosterone for its cytosolic receptor therefore, the maximal natriuretic effect is not observed until 24-48 h after treatment has been initiated. Spironolactone is indicated for the treatment of primary hyperaldosteronism but is also used in refractory edema and in secondary hyperaldosteronism consequent to use of loop or thiazide-type diuretics (Martinez-Maldonado Cordova 1990, Rose 1989, 1991, Wilcox 1991). In one study, the administration of spironolactone via nasogastric tube (1 and 2mg/kg) to ponies more than doubled the urinary excretion of sodium and reduced the urinary excretion of potassium for a period of 72 h, although there was no difference in the volume of urine produced (Alexander 1982). This suggests that spironolactone is a potassium-sparing agent in horses however, to date, no pharmacokinetic studies have been published. 

Secondary hyperaldosteronism plays a major role in the pathogenesis of edema in patients with cirrhosis. Therefore these patients should initially be treated with spironolactone in the absence of impaired GFR and hyperkalemia. Thiazides may then be added for patients with a creatinine clearance >50 mL/min. For those patients who remain diuretic resistant, a loop diuretic may replace the thiazide. Patients with impaired GFR (creatinine clearance of <30 mL/min) generally will require a loop diuretic, with addition of a thiazide in those who do not achieve adequate diuresis. Care should be taken to avoid hypokalemia, which may precipitate hepatic encephalopathy by increasing ammoniagenesis (Fig. 49-8). ... 

Spironolactone, a competitive inhibitor of aldosterone, is the drug of choice in bilateral adrenal hyperplasia (BAH)-dependent hyperaldosteronism. 

APA-Dependent Hyperaldosteronism. The treatment of choice for APA-dependent aldosteronism remains laparoscopic resection of the adenoma. If no primary lesion is found, resection of one and a half of the adrenal glands may be attempted, followed by supplemental spironolactone therapy. However, a recent retrospective analysis of patients with aldosterone-producing adenomas who chose medical management instead of surgical resection, revealed medical management to be efficacious in this population and should be considered as an alternative in patients in whom surgery is contraindicated. ... 

As with other K+-sparing diuretics, spironolactone often is coadministered with thiazide or loop diuretics in the treatment of edema and hypertension. Such combinations result in increased mobilization of edema fluid while causing lesser perturbations of K+ homeostasis. Spironolactone is particularly useful in the treatment of primary hyperaldosteronism (adrenal adenomas or bilateral adrenal hyperplasia) and of refractory edema associated with secondary aldosteronism (cardiac failure, hepatic cirrhosis, nephrotic syndrome, and severe ascites). Spironolactone is considered the diuretic of choice in patients with hepatic cirrhosis. Added to standard therapy, spironolactone substantially reduces morbidity and mortality and ventricular arrhythmias in patients with heart failure. 

THERAPEUTIC USES Spironolactone often is coadministered with thiazide or loop diuretics in the treatment of edema and hypertension. Such combinations result in increased mobilization of edema fluid with lesser perturbations of K+ homeostasis. Spironolactone is particularly useful in the treatment of primary hyperaldosteronism (due either to adrenal adenomas or bilateral adrenal... 

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)... 

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