Potassium-Sparing Diuretics

Potassium-Sparing Diuretics: Intro & MOA - The Potassium Keepers

• Definition: Diuretics that increase sodium excretion (natriuresis) without causing significant potassium loss (kaliuresis). Nicknamed "potassium keepers".
• Site of Action: Late Distal Tubule (DT) & Collecting Duct (CD) - specifically principal cells.
• Mechanism of Action (MOA): PSDs act via two main pathways:
  • Aldosterone Antagonists (Spironolactone, Eplerenone): Block aldosterone receptors → ↓Na+ reabsorption, ↓K+ secretion.
  • ENaC Blockers (Amiloride, Triamterene): Block epithelial sodium channels (ENaC) → ↓Na+ reabsorption, ↓K+ secretion.

⭐ Spironolactone is a prodrug; its structure is similar to aldosterone, contributing to its MOA and side effects (e.g., gynecomastia).

Classification & Drugs - The Salty Savers

• Aldosterone Antagonists: Block aldosterone receptors.
  • Spironolactone: Non-selective.
  • Eplerenone: Selective, fewer hormonal effects.
  • Finerenone: Non-steroidal, selective, renoprotective.
• Epithelial Sodium Channel (ENaC) Blockers: Directly inhibit ENaC.
  • Amiloride
  • Triamterene: Weak, often combined. 📌 Mnemonic: K STAys: Spironolactone, Triamterene, Amiloride, Eplerenone.

Pharmacokinetics - Journey of the Savers

• Oral absorption variable; Spironolactone ↑ with food.
• Metabolism: Spironolactone (active metabolites), Eplerenone (CYP3A4), Triamterene (active metabolite). Amiloride largely unchanged.

⭐ Spironolactone's active metabolite, canrenone, contributes to its prolonged effect.

Clinical Uses - When to Spare Potassium

• Primary Hyperaldosteronism (Conn's Syndrome): Spironolactone for diagnosis and therapy.
• Edema: In heart failure, cirrhosis, nephrotic syndrome; counteracts K+ loss from other diuretics.
• Hypertension: Adjunct, particularly in resistant hypertension.
• Heart Failure: NYHA Class II-IV with LVEF ≤35%; Spironolactone, Eplerenone reduce morbidity/mortality.

  ⭐ Aldosterone antagonists like Spironolactone and Eplerenone are proven to reduce mortality in patients with severe heart failure.

• Liddle's Syndrome: Amiloride or Triamterene are drugs of choice.
• Off-label (Spironolactone): Hirsutism, acne, PCOS due to antiandrogenic effects.

Adverse Effects & Contraindications - The Caution Zone

• Hyperkalemia: Most critical! Risk ↑ with renal impairment, diabetes, ACEi.
  • Metabolic Acidosis (hyperchloremic).
• Spironolactone: 📌 Antiandrogenic effects (gynecomastia, impotence, menstrual issues).
• Eplerenone: Less antiandrogenic; still hyperkalemia risk.
• Triamterene: Nephrolithiasis, megaloblastic anemia (rare), photosensitivity.
• Amiloride: GI upset, headache.
• ⚠️ Contraindications:
  • Hyperkalemia (K+ >5.0-5.5 mEq/L)
  • Severe renal insufficiency (CrCl <30 mL/min), anuria
  • Addison's disease (aldosterone antagonists)
  • Eplerenone + strong CYP3A4 inhibitors.

⭐ Most critical AE: Hyperkalemia, esp. with ACE inhibitors or renal failure.

Drug Interactions - The Risky Mixes

• ↑ Hyperkalemia Risk: ACEi, ARBs, NSAIDs, K+ supplements/salts, β-blockers, Trimethoprim, Cyclosporine, Tacrolimus, Heparin.
• Spironolactone: Salicylates ↓ effect; ↑ Digoxin.
• Eplerenone: CYP3A4 inhibitors ↑ levels (Strong C/I; Mod. dose ↓).
• Triamterene: Indomethacin (ARF); Cimetidine ↑ F.
• Amiloride: Lithium (↑ toxicity).

⭐ K+-sparing diuretics + ACEi/ARBs = notorious severe hyperkalemia.

High‑Yield Points - ⚡ Biggest Takeaways

• Act on late distal tubule & collecting duct, causing ↓K+ excretion.
• Classes: Aldosterone antagonists (Spironolactone, Eplerenone); ENaC blockers (Amiloride, Triamterene).
• Key uses: Hyperaldosteronism, heart failure (mortality benefit), prevent diuretic-induced hypokalemia.
• Hyperkalemia is the major dose-limiting toxicity; monitor serum K+.
• Spironolactone: Gynecomastia, anti-androgenic effects. Eplerenone is more selective.
• Amiloride/Triamterene: Direct ENaC blockade. Triamterene: kidney stones.
• Avoid with ACE inhibitors/ARBs due to ↑hyperkalemia risk_._