Spironolactone causes potassium retention similar to ACE inhibitors, therefore, hyperkalemia may occur. This combination should be avoided in patients with renal dysfunction.
With spironolactone the beneficial effect in the management of heart failure appears to the result of the following.
• Distal nephron blockade of aldosterone causes sodium and water excretion. This action is extremely important
in patients treated with furosemide; distal nephron blockade enhances the diuretic effect of loop diuretics and prevents recurrence of heart failure. Spironolactone appears to decrease cardiac fibrosis and endothelial dysfunction and increase nitric oxide bio-activity.
Spironolactone has a mild positive inotropic effect independent of and additive to that of digoxin; stroke volume is increased.
2. Eplerenone (Inspra)
The EPHESUS trial randomized 6000 patients and showed that this selective aldosterone blocker added to optimal medical therapy in patients with acute myocardial infarction and heart failure with ejection fractions less than 35% significantly reduced mortality and morbidity. The dose of 25 mg can be titrated up to 50 mg daily. It does not cause gynecomastia like spironolactone so it may replace spironolactone use in men. Both agents should not be used in patients with a serum creatinine greater than 1.3 mg/dl (115 mmol/L) or in type 2 diabetics with altered glomerular filtration rates because hyperkalemia may be precipitated. The serum creatinine does not reflect the creatinine clearance, particularly in the elderly who are most often treated for heart failure. In this randomized trial hyperkalemia occurred in 5.5 and 4% of patients in the treated and placebo groups, respectively.

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