Hyperaldosteronism treatment

The use of CA inhibitors as diuretics is limited by their propensity to cause metabolic acidosis and hypokalemia. Their use can be indicated in patients with metabolic alkalosis and secondary hyperaldosteronism resulting for example from aggressive use of loop diuretics. Furthermore, CA inhibitors are effective dtugs to produce a relatively alkaline urine for the treatment of cysteine and uric acid stones as well as for the accelerated excretion of salicylates. Perhaps the most common use of CA inhibitors is in the treatment of glaucoma. 

Potassium-sparing diuretics are often coadministered with thiazide or loop diuretics in the treatment of edema and hypertension. In this way, edema fluid is lost to the urine while K+ ion balance is better maintained. The aldosterone antagonists are particularly useful in the treatment of primary hyperaldosteronism. 

Short-term preoperative treatment of patients with primary hyperaldosteronism. 

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. 

Salt and water retention mediated by secondary hyperaldosteronism can complicate hydralazine treatment, leading to weight gain and peripheral edema, loss of blood pressure control, and rarely cardiac failure (SED-8, 474). 

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. 

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. 

When there is severe hypokalemia, it should not be attributed immediately to diuretic treatment. It may well be due to primary hyperaldosteronism, occult chronic liver disease, or abuse of licorice or laxatives. 

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. 

The absolute diagnosis is relatively easy based on ctinical findings and pertinent laboratory findings. However, as in Cushing s disease, the discovery of the underlying etiology is mandatory to ensure proper treatment. Table 74—6 lists the various abnormalities that must be ruled out when suspicion of hyperaldosteronism is high. 

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. 

Triamterene is usually recommended in the treatment of oedema associated with nephrotic syndrome, cirrhosis of liver, and congestive heart failure. It has also been used for the control and management of idiopathic oedema, steroid-induced oedema, oedema caused by hyperaldosteronism and in such oedematus patients who fail to respond to other therapy. It is usually used in conjunction with other diuretics like thiazides. 

Spironolactone (Aldactone) Antagonist of aldosterone, inhibits Na+ retention. Treatment of hyperaldosteronism. Causes K+ retention. Diuretic actions are described in Table 4.3A. 

Consequently, diuretics have a variety of uses. Thiazide diuretics may be used either alone or in combination with other pharmacotherapy for the treatment of hypertension. Loop diuretics can provide immediate diuresis and are used for heart failure and in lieu of thiazides in patients with compromised renal function. In addition to more traditional uses, certain potassium-sparing diuretics provide added benefit to other pharmacotherapy in patients with primary hyperaldosteronism, heart failure, or post-acute myocardial infarction. Carbonic anhydrase inhibitors have limited use for diuresis however, they may be used to reduce intraocular pressure and treat acute mountain sickness. 

If hormone imbalance is present, treatment centers around restoring hormone status. For example, in hyperaldosteronism, the offending tumor or tissue is removed, and in Cushing syndrome (with corticosteroids that behave like aldosterone causing absorption of sodium), treatment centers on decreasing the excess aldosterone or corticosteroids. If the level of aldosterone or corticosteroids is severely limited in the body, a deficiency of either hormone could occur, resulting in hyponatremia. 6 In diabetes insipidus (i.e., decreased ADH secretion), supplemental ADH is provided. Care must be taken during treatment with supplement to avoid excess ADH intake, which will cause retention of water and potential for dilutional hyponatremia. 6... 

A new aspect of the abuse of diuretics has been reported by several authors (1 — 4 -). They noted the occurrence or aggravation of oedema during the first 10 days after discontinuance of prolonged diuretic treatment. The patients are mainly, but not exclusively (3 ) younger women taking diuretics for obesity and idiopathic oedema. The rapid retention of salt and water is due to secondary hyperaldosteronism induced by the diuretics. This kind of oedema will spontaneously disappear if the patient can be convinced of the necessity to avoid renewed diuretic treatment in spite of the initial troublesome fluid retention. 

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