Aldactone (Spironolactone)

Spironolactone
Brand Names: Aldactone® | Spirono™

Classification:
Cardiovascular Agents
»Antihypertensive Agents
»Diuretics

Electrolytic and Renal Agents
»Diuretics
»Potassium-sparing diuretics

Description: Spironolactone is a potassium-sparing diuretic. In patients with severe heart failure (NYHA Class IV), spironolactone has been shown to improve overall survival and NYHA functional class, and to reduce hospitalizations when added to conventional therapy (e.g., ACE inhibitor, loop diuretic, digoxin). It is frequently used to treat ascites associated with cirrhosis and also has been used as a diagnostic aid for primary hyperaldosteronism. It is also used to treat hypokalemia. Compared to thiazide or loop diuretics, it is a relatively weak agent for treating hypertension or generalized edema, although its effects can be additive with thiazide diuretics. While not FDA-approved indications, polycystic ovary syndrome and female hirsutism have been treated with spironolactone. Spironolactone was approved by the FDA in 1960.

Mechanism of Action: Spironolactone inhibits the effects of aldosterone on the distal renal tubules. Unlike amiloride and triamterene, spironolactone exhibits its diuretic effect only in the presence of aldosterone, and these effects are enhanced in patients with hyperaldosteronism. Aldosterone antagonism enhances sodium, chloride, and water excretion, and reduces the excretion of potassium, ammonium, and phosphate. Spironolactone does not inhibit renal transport mechanisms or carbonic anhydrase activity.

Spironolactone is a poor antihypertensive, but it does have modest hypotensive effects. The hypotensive mechanism of spironolactone is unknown. It is possibly due to the ability of the drug to inhibit aldosterone’s effect on arteriole smooth muscle. Spironolactone also can alter the extracellular-intracellular sodium gradient across the membrane. In general, diuretics lower blood pressure by initially decreasing cardiac output and reducing plasma and extracellular fluid volume. Cardiac output and extracellular fluid volume eventually return to normal, but peripheral resistance is reduced, resulting in lower blood pressure. In general, diuretics worsen LVH and glucose tolerance, and exert detrimental effects on the lipid profile.

ALDACTIONE Tablets Aldactone Tablets (Tab 25 mg)

Pharmacokinetics: Approximately 70 - 90% of a dose of spironolactone is absorbed from the GI tract following oral administration. Food will enhance absorption when given concurrently. There is considerable first-pass elimination and significant enterohepatic recirculation. The onset of diuresis is gradual, with peak effects occurring on the third day after administration. The duration of action after multiple doses of spironolactone is 2 - 3 days. Spironolactone is extensively metabolized, via hepatic pathways, to active metabolites. The clinical effects of spironolactone are partially due to canrenone, a metabolite. Spironolactone and its metabolites may cross the placenta, and canrenone distributes into breast milk. The parent drug and canrenone are greater than 90% plasma protein-bound. Both unchanged drug (less than 10%) and its metabolites are excreted primarily in the urine. The remainder of a dose is excreted in the feces via biliary elimination. The half-life of spironolactone after a single dose is 1.3 - 2 hours. The half-life of canrenone ranges from 10 - 35 hours.

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References
_{. Pitt B, Zannad F, Remme WJ. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med 1999;341:709 - 17.}

Aldactone (Spironolactone)

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