Spironolactone, aldosterone antagonist

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... 

Aldosterone antagonists (spironolactone, eplerenone) are also potassium-sparing diuretics but are more potent antihypertensives with a slow onset of action (up to 6 weeks with spironolactone). 

The aldosterone antagonist, spironolactone> has been successfully used for the treatment of hypertension. Its natriuretic effect is associated with potassium retention. Specificity of spironolactone in certain types of hypertension had been suggested, but subsequently denied in well controlled studies(15,16). 

During the 1970s and 1980s, the synthetic aldosterone antagonist spironolactone (Fig. 17.3) [5] was used extensively (among others) as a diuretic agent for the treatment of edema, liver cirrhosis and certain cardiac diseases. 

Adrenalectomized rats treated with DOCA or aldosterone can be utilized to test aldosterone antagonists. Spironolactone has no effect in the absence of a min-eralocorticoid, but reverses in a dose-related manner the effect of DOCA on the Na+/K+ ratio in the urine (Kagawa et al. 1957 Bicking et al. 1965). 

The findings and observations described in the literature as well as the convincing efficacy of the aldosterone antagonist spironolactone confirm the importance of the RAAS in the genesis of renal sodium retention and hence also in the formation of ascites. 

General. Noteworthy reports- and reviews pertaining to the pharma-cologicalj endocrinological > and clinical aspects of diuretics have appeared in the recent literature. The use of diuretics in the treatment of hypertension has been reviewed with especial emphasis on the hypotensive action of the aldosterone antagonist, spironolactone.° Fundamental studies on the mechanism of transport of electrolyte across the tubular epithelium have indicated that phospholipids may play a critical role. Phospholipase C and pancreatic lipase markedly reduced the rate of reabsorption of saline droplets infused into rat proximal tubules. Likewise, phospholipase C reduced the ability of extractable lipids to bind sodium and potassium ions in rat kidney homogenates whereas, phospholipase D and ribonuclease appear to enhance cation binding. ... 

Posttraumatic secretion of aldosterone has also been measured. Increased quantities were found to be present during surgery, and in the urine subsequently (D3, HI 7, Zl). Also, the aldosterone antagonist spironolactone will abolish postoperative sodium retention without affecting potassium secretion, illustrating the dependence of sodium displacements after surgery on the hormone (J2, M8). 

The aldosterone antagonist spironolactone (Figure 7.4), which is used as a diuretic and antihypertensiveinactivates P450 enzymes in both the liver and steroidogenic tissues ", including the adrenal steroid ITof-hydroxylase " and... 

Hyperkalaemia with ACE inhibitors and potassium-sparing diuretics, and particularly the aldosterone antagonist spironolactone, is well documented and well established. If it occurs it can be serious and potentially life threatening. Its incidence depends on the presence of other risk factors, and clinically important hyperkalaemia usually only appears to develop if one or more of these are also present, particularly renal impairment. Other risk factors in patients with heart failure include advanced age and diabetes" (hyperkalaemia has been found to be relatively common in both non-insulin-dependent and insulin-dependent diabetics). In addition, doses of spironolactone greater than 25 mg daily increase the risk of hyperkalaemia. 

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