Aldosterone receptor blocker

This chapter is divided into three sections. The first section covers renal tubule transport mechanisms. The nephron is divided structurally and functionally into several segments (Figure 15-1, Table 15-1). Many diuretics exert their effects on specific membrane transport proteins in renal tubular epithelial cells. Other diuretics exert osmotic effects that prevent water reabsorption (mannitol), inhibit enzymes (acetazolamide), or interfere with hormone receptors in renal epithelial cells (aldosterone receptor blockers). The physiology of each segment is closely linked to the basic pharmacology of the drugs acting there, which is discussed in the second section. Finally, the clinical applications of diuretics are discussed in the third section. 

Eplerenone is a selective aldosterone receptor blocker devoid of antiandrogenic effect. 

Cook, C.S. Zhang, L. Ames, G.B. Fischer, J. Zhang, J. Levin, S. Single-and repeated-dose pharmacokinetics of epierenone, a selective aldosterone receptor blocker, in rats, Xenobiotica, 2003, 33, 305-321. [LC-MS SPE]... 

ACE-I, angiotensin-converting enzyme inhibitor Aid Ant, aldosterone antagonist ARB, angiotensin receptor blocker BB, beta-blocker CCBA, calcium channel blocking agent DirVaso, direct vasodilator. 

Sites of action of drugs that interfere with the renin-angiotensin-aldosterone system. ACE, angiotensin-converting enzyme ARBs, angiotensin receptor blockers. 

At Cynthia s pharmacy, patients with heart disease are usually on several medications for their heart disease a diuretic, a beta blocker, and an angiotensin-converting enzyme (ACE) inhibitor. Patients with more severe disease may also be on an aldosterone inhibitor such as spironolactone, digoxin, hydralazine nitrate, and/or an angiotensin-receptor blocker (ARB). Some patients are... 

Pathophysiology In HF patients, the levels of aldosterone are elevated, even in the presence of ACE inhibitors or angiotensin-receptor blockers (34,35). Aldosterone has detrimental effects in HE such as causing potassium and magnesium loss, sodium retention, baroreceptor dysfunction, and myocardial fibrosis it also decreases the neuronal uptake... 

The nanopeptide losartan [LOW sar tan], a highly selective angiotensin II receptor blocker, has recently been approved for antihypertensive therapy. Its pharmacologic effects are similar to ACE inhibitors in that it produces vasodilation and blocks aldosterone secretion. Its adverse effects profile is improved over the ACE inhibitors, although it is fetotoxic. 

Treatment with angiotensin-converting enzyme inhibitors is also more likely to be associated with hyperkalemia in older individuals (69). Impaired angiotensin II formation limits this potent stimulus for aldosterone secretion, and this is superimposed on the already age-related decrease in activity of the renin-angiotensin-aldosterone axis. The same drug-induced hyporeninemic hypoaldosteronism is predicted for the angiotensin receptor blockers. However, to date this has not been documented clincally. 

Hypertension. The antihypertensive effect of ACE inhibitors and AT receptor blockers results primarily from vasodilatation (reduction of peripheral resistance) with little change in cardiac output or rate renal blood flow may increase (desirable). A fall in aldosterone production may also contribute to the blood pressure lowering action of ACE inhibitors. Both classes slow progression of glomerulopathy. Whether the long-term benefit of these drugs in hypertension exceeds that to be expected from blood pressure reduction alone remains controversial. 

However, in 85 patients enoxaparin therapy was associated with an increase in mean potassium concentration from 4.26 mmol/1 at baseline to 4.43 mmol/1 on the third day potassium concentrations exceeded 5.0 mmol/1 in 9% (15). There was no life-threatening or sjmptomatic hjrperkalemia. Neither plasma renin activity nor aldosterone concentrations changed significantly and there was no correlation between the increase in potassium concentrations and the presence of diabetes mellitus or treatment with angiotensin converting enzjmes inhibitors, angiotensin receptor blockers, beta-blockers, or potassium-wasting diuretics. 

Angiotensin receptor blockers are selective and competitive angiotensin II receptor antagonists (Table 12-1). They block vasoconstriction and aldosterone-secreting effects similar to... 

Spironolactone (aldosterone receptor antagonist) and amiloride and triamterene (Na+ channel blockers) prevent the above effects, leading to minor effects on Na+ reabsorption but major effects on the retention of K+ ions and protons. Thus, they cause small increases in urinary Na+ and marked decreases in urinary K+, resulting in hyperkalemia and acidosis. 

Angiotensin II Receptor Blockers 26 Aldosterone Antagonists 26 Statins 26 Nitrates 27... 

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