Aldosterone antagonists: Canrenone, Spironolactone
Canrenone is a specific antagonist of aldosterone. It is a competitive inhibitor of aldosterone receptors and inhibits the effects of aldosterone. It is inactive in absence of aldosterone. Spironolactone is a prodrug which is active after its conversion into canrenone.
By inhibiting the effects of aldosterone:
- it increases aqueous and sodium diuresis and is classified as a diuretic.
- it decreases urinary elimination of potassium, whose level in plasma tends to rise, it is a drug inducing hyperkalemia.
- it increases urinary excretion of calcium.
Canrenone is used for the treatment of primary or secondary hyperaldosteronism, edema and ascites of congestive heart failure and cirrhosis, and in the treatment of the arterial hypertension.
Canrenone is classified as an aldosterone antagonist and also as a potassium-sparing diuretic. Spironolactone, given at the dose of 25 mg/day as an adjunct to the other treatments, reduced the mortality of patients suffering from severe chronic congestive heart failure
Canrenone is not marketed now. Spironolactone, its precursor, is used: by oral route and converted into several metabolites, one of which is canrenone. Canrenoate is administered by parenteral route, generally intravenous infusion, and is converted into canrenone.
Combinations of diuretics spironolactone and either altizide or furosemide are used for the treatment of arterial hypertension and congestive heart failure.
Eplerenone is a spironolactone-like antagonist of aldosterone receptors. It is metabolized by the CYP3A4. Eplerenone is available in many countries under the name Inspra * for treatment of arterial hypertension and congestive heart failure.
Spironolactone and canrenoate can cause:
- hyperkalemia which is increased by high potassium intake and drugs retaining potassium.
- hyponatremia, especially in old subjects.
- endocrine disorders: erectile dysfunction, gynecomastia in men, menstruation troubles in women.
- sometimes drowsiness.