Mechanism of Action

Spironolactone (Aldactone) is structurally related to aldosterone and acts as a competitive inhibitor to prevent the binding of aldosterone to its specific cellular binding protein. Spironolactone thus blocks the hormone-induced stimulation of protein synthesis necessary for Na+ reabsorption and K+ secretion. Spironolactone, in the presence of circulating aldosterone, promotes a modest increase in Na+ excretion associated with a decrease in K+ elimination. The observations that spironolactone is ineffective in adrenalectomized patients and that the actions of spironolactone can be reversed by raising circulating al-

dosterone blood levels (surmountable antagonism) support the conclusion that spironolactone acts by competitive inhibition of the binding of aldosterone with receptor sites in the target tissue. Spironolactone acts only when mineralocorticoids are present.

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