Spironolactone

Class

• Potassium-sparing diuretic

Indications

• • Diuretic effects

  • heart failure

    • ascites in patients with liver disease

    • low-renin hypertension

  • hypokalemia

    • secondary hyperaldosteronism

  • Conn's syndrome

  • Effects on the endocrine system

    • Hirsutism and acne

Administration/Absorption

• • Oral

    • Fairly rapidly absorbed from the gastrointestinal tract

    • Food increases the bioavailability of unmetabolized spironolactone by almost 100%.

Dosage

Distribution

• • Spironolactone and its metabolites are more than 90% bound to plasma proteins.

Mechanism

• • Spironolactone is a synthetic 17-lactone steroid

  • Renal competitive aldosterone antagonist

  • On its own, spironolactone is only a weak diuretic

    • It may be given alone or with other diuretic agents which act more proximally in the renal tubule

  • Due to its anti-androgen effect, it can also be used to treat hirsutism

    • Common component in hormone therapy for male-to-female transgendered people

  • Spironolactone inhibits the effect of aldosterone by competing for intracellular aldosterone receptor in the distal tubule cells

    • Antagonises a cytoplasmic mineralocorticoid receptor responsible for enhancing expression of Na+, K+-ATPase and the Na+ channel involved in a Na+ K+ transport in the distal tubule

    • This increases the secretion of water and sodium, while decreasing the excretion of potassium

  • Spironolactone has a fairly slow onset of action, taking several days to develop and similarly the effect diminishes slowly.

Excretion

• • Half-life 10 mins

  • Rapidly and extensively metabolized

    • Divided into two main routes

      • those in which the sulfur moiety is retained

      • those in which the sulfur moiety is removed by dethioacetylation.

    • Transformed to a reactive metabolite

      • Can inactivate adrenal and testicular cytochrome P450 enzymes

      • Has anti-androgenic activity.

  • Excreted primarily in the urine and secondarily in bile

Side effects

• • Oral LD₅₀ of spironolactone is greater than 1,000 mg/kg in mice, rats, and rabbits

  • Acute overdosage of spironolactone may be manifested by:

    • Drowsiness, mental confusion, maculopapular or erythematous rash, nausea, vomiting, dizziness, or diarrhea

  • Spironolactone has been shown to be a tumorigen in chronic toxicity studies in rats.

Interactions

Contraindications