Potassium Sparing Diuretics

Types of Potassium Sparing Diuretics

• Sodium Channel Blockers
• Aldosterone Antagonists

Site of Action

• Act in late distal convoluted tubule and collecting duct
• Preserve potassium

Comparison with Other Diuretics

• Carbonic anhydrase inhibitors, loop diuretics, thiazide diuretics cause potassium loss (hypokalemia)
• Potassium sparing diuretics preserve potassium

Physiology

Principal Cells & Epithelial Sodium Channels

• Principal cells: found in collecting duct
• Contain epithelial sodium channels responsible for sodium reabsorption
• Reabsorption causes lumen negativity and trans-epithelial potential difference
• To neutralize: potassium and H+ are secreted
• Aldosterone promotes this secretion

Aldosterone Action

• Binds to aldosterone receptor on cell
• Activates nucleus to produce aldosterone-induced protein
• Protein activates sodium channels => sodium reabsorption
• Sodium reabsorption causes secretion of potassium & H+ to neutralize lumen negativity

Mechanism of Action: Potassium Sparing Diuretics

Epithelial Sodium Channel Inhibitors

• Basic in nature
• Enter proximal convoluted tubule by secretion (organic base secretory system)
• Example drugs: Amiloride and Triamterene
• Block sodium channels, hence sodium isn’t reabsorbed => excreted in urine
• Only 3% of sodium reabsorption occurs at collecting ducts => minimal diuresis (low ceiling diuretics)

Triamterene

• Less potent, shorter acting than Amiloride
• Adverse effects:
  • Incomplete absorption
  • Photosensitivity
  • Impairment of glucose tolerance
  • Interstitial nephritis, renal stone formation
  • Weak folic acid antagonist => megaloblastic anemia in cirrhosis

Amiloride

• More potent, longer acting than Triamterene
• Adverse effects:
  • Decreases Ca++ and Mg++ excretion
  • Increases urate excretion
• Uses:
  • Lithium-induced diabetes insipidus: inhibits lithium reabsorption via sodium channels
  • Cystic fibrosis: aerosol form decreases secretions