Spironolactone

Spironolactone (Aldactone) is the only diuretic that has been shown in a double-blind multicenter prospective clinical trial to improve survival in CHF. The addition of spironolactone to digitalis and an angiotensin-converting enzyme (ACE) inhibitor significantly improved survival among patients with chronic severe heart failure. This study was conducted with patients who were not taking a p-adrenoceptor blocking agent. It is unclear at present whether the addition of spirono-lactone to a combination of digitalis, ACE inhibitor, and a p-blocker will also confer additional benefit.

Spironolactone competitively inhibits the binding of aldosterone to cytosolic mineralocorticoid receptors in the epithelial cells in the late distal tubule and collect ing duct of the kidney. Aldosterone enhances salt and water retention at the expense of enhanced renal K+ and H+ excretion. Spironolactone enhances diuresis by blocking sodium and water retention while retaining potassium. An obvious potential side effect is hyper-kalemia, which is aggravated by the potassium-retaining properties of the ACE inhibitors. The likely concomitant use of the loop diuretic furosemide, which depletes K+, dictates careful monitoring of serum potassium to avoid life-threatening rhythm disturbances.

There is also evidence for the existence of mineralo-corticoid receptors on cardiac myocytes. This raises the intriguing possibility that spironolactone could mediate important direct effects on the myocardium in CHF.

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