Pharm 101: Spironolactone

Class

Potassium-sparing diuretic

Pharmacodynamics

• Synthetic steroid
• Competitive antagonist to aldosterone at the mineralocorticoid receptor
  • Reduces K secretion –> reduces Na absorption in collecting duct
  • Also inhibits H secretion in parallel

Pharmacokinetics

• Slow onset and offset of effect
• Hepatic metabolism to active metabolites canrenone and 7-alpha-spirolactone (long half lives of 12-20 hours)
• Duration of action 24-48 hours

Clinical uses

• Primary hyperaldosteronism
• Secondary hyperaldosteronism:
  • CCF
  • Cirrhosis
  • Nephrotic syndrome

Adverse effects

• Hyperkalaemia
• Hyperchloraemic metabolic acidosis:
  • Due to inhibition of H secretion in parallel with K secretion
• Gynecomastia:
  • Potent inhibitor of androgen receptor

Precautions/contraindications

• Potassium supplements
• Dose adjustment in liver failure
• NSAIDs:
  • Action of aldosterone antagonists depend on renal prostaglandin production