Pharmacology of Potassium-Sparing Diuretics

Potassium-sparing diuretics are a class of diuretic medications that increase diuresis (urine production) while conserving potassium, contrasting with thiazide and loop diuretics that promote potassium loss. They are used primarily to counteract hypokalemia and as adjuncts in conditions involving excessive fluid retention or aldosterone excess.

Classification and Key Agents

Mechanisms of Action

1. Aldosterone Antagonists

• Spironolactone, Eplerenone:
  • Compete with aldosterone for intracellular receptors in principal cells of the late distal tubule and collecting duct.
  • Block transcription and synthesis of proteins that promote Na⁺ reabsorption and K⁺/H⁺ secretion.
  • Result: Modest natriuresis, reduced K⁺/H⁺ loss, decreased remodeling in heart failure.

2. ENaC Blockers

• Amiloride, Triamterene:
  • Directly block the ENaC on the luminal membrane of the same nephron segments.
  • Prevent Na⁺ entry, reducing potential for K⁺ secretion.
  • Effect not dependent on aldosterone level.

Pharmacokinetics

Clinical Uses

Adverse Effects

Drug Interactions & Precautions

• ACE Inhibitors, ARBs, NSAIDs: ↑ Hyperkalemia risk.
• CYP3A4 inhibitors (for eplerenone): May increase concentration/toxicity.
• Contraindications: Hyperkalemia, severe renal insufficiency, Addison disease.

Comparative Summary Table

References

1. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 14th ed. New York: McGraw-Hill; 2022.
2. Potassium-sparing diuretic. Wikipedia. 2023.
3. Amiloride—StatPearls [Internet]. 2024 Feb 27.
4. Potassium sparing diuretics—Osmosis. Jan 2025.

Key Pearls:

• Not potent diuretics alone; best used in combination to reduce K⁺ loss.
• Regularly monitor renal function and serum potassium.
• Spironolactone, eplerenone: mainstay in heart failure and hyperaldosteronism; be mindful of hormonal side effects with spironolactone, less with eplerenone.
• Amiloride/triamterene: primarily adjuncts; do not affect hormonal pathways.