Aldosterone antagonists indications

Antihypertensive drug name and dose is associated with compelling indications which are based on benefits from outcome studies or clinical guidelines. For example, the drug class aldosterone antagonists have eplerenone dosed at 25-50 mg per day which is indicated for heart failure patients after an Ml and supported by the EPHESUS trial. 

P-Blockers and ACE inhibitors are also indicated for post-myocardial infarction for the reduction of cardiovascular morbidity and mortality, as are aldosterone antagonists, in post-myocardial infarction patients with reduced left ventricular systolic function and diabetes or signs and symptoms of heart failure.2,48... 

ACE-I is recommended for all the patients in this stage unless contra-indicated. If contraindications for ACE-I exist an ARB can be given. However, the routine combination of ACE-I, ARB and aldosterone antagonists is not to be recommended. 

Intravenous application of sodium-free albumin and/or 10% mannitol can be successful, possibly with the additional administration of low-dose diuretics (such as xipamide, torasemide), whereby due attention should be paid to renal function. Diuretics or aldosterone antagonists may only be used if the indication is precise and all risks have been considered. 

Figure 10.1 Sites and mechanisms of action of diuretics. The location of each cell type along the nephron is indicated by the shading patterns. Spironoiactone (not shown) is a competitive aldosterone antagonist and acts primarily in the collecting duct. PT, proximal tubule LH, loop of Henie TAL, thick ascending limb DT, distal tubule DCT, distal convoluted tubule CD, collecting duct PC, principal cell CA, carbonic anhydrase CAI, carbonic anhydrase inhibitors , primary active transport. (Adapted with permission from Ellison D H 1991 The physiologic basis of diuretic synergism its role in treating diuretic resistance. Annals of Internal Medicine 114 886-894.)...

Indications Hyperaldosteronism, hirsutism, hypertension Category Aldosterone antagonist Diuretic Half-life 78-84 minutes... 

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. ... 

FIGURE 28-6 Effects of aldosterone on late distal tubule and collecting duct and diuretic mechanism of aldosterone antagonists. AIP, aldosterone-induced proteins ALDO, aldosterone MR, mineralocorticoid receptor CH, ion channel 1, activation of membrane-bound Na channels 2, redistribution of Na" channels from cytosol to membrane 3, de novo synthesis of Na+channels 4, activation of membrane-bound Na , K -ATPase 5, redistribution of Na , K -ATPase from cytosol to membrane 6, de novo synthesis of Na, K -ATPase 7, changes in permeability of tight junctions 8, increased mitochondrial production of ATP. BL and LM indicate basolateral and luminal membranes, respectively. 

Eplerenone is a selective aldosterone receptor antagonist that binds to the mineralocorticoid receptor (MR), blocking the binding of aldosterone. It is indicated in the treatment... 

Angiotensin II receptor antagonists are potassium-sparing, via their effects on aldosterone, and their potential to cause clinically important hyperkalaemia is well established. The incidence of hyperkalaemia varies depending on the clinical indication and other disease conditions, being lowest in essential hypertension, and highest in heart failure, diabetes, and renal impairment. For example, the incidence of hyperkalaemia in clinical studies in patients with hypertension was 0.9% with eprosartan - and 1.5% with losartan in type II diabetic patients with nephropathy, the incidence was 9.9% with losartan and 18.6% with irbesartan and in those with heart failure the incidence was 6.3% with candesartan. ... 

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