K+ Sparing Diuretics



  • Acts to indirectly conserve K+ by either of 2 ways,
    • As aldosterone antagonist.
    • Directly inhibit Na+ channels.
  • Site of action: In Distal Tubule (DT) & Collecting Duct (CD) cells in Kidney.


  • Epithelial Na2+ channel inhibitors.
    • Eg: Amiloride & Triamterene.
  • Aldosterone antagonists.
    • Eg: Spironolactone, Canrenone, Potassium canrenoate & Eplerenone


  • Pharmacologic antagonists of aldosterone in collecting tubules.
  • Primary site of action – Distal tubule & collecting duct.
    • Drugs act from interstitial side (other diuretics act from luminal side).
  • Used in combination with thiazides, loop diuretics to counteract K+ loss.

Drugs included:

  • Spironolactone, Canrenone, Potassium canrenoate & Eplerenone.
  • Slow onsets and duration of action (24-72 hrs).

Drug effect variation:

  • Maximum effect with high levels aldosterone levels –
    • During hepatic cirrhosis, nephrotic syndrome, CHF)
  • Minimum effect with aldosterone absence –
    • Addison’s disease.


  • Alters cardiac mortality.
  • Increases Ca2+ excretion.


  • Diuretic of choice in cirrhotic edema.
  • Treatment of hirsutism (Anti-androgenic action).
  • As competitive antagonist at of testosterone receptors.
  • As an add-on drug in hypertensive patients with significant hyperuricemia, hypokalemia, or glucose intolerance.
  • Maximum dose of spironolactone in patients with cirrhosis & portal hypertension – 400 mg.

Adverse effects:

  • Gynecomastia & impotence.
  • Hyperkalemia.

Drug interactions:

  • ACE inhibitors & potassium supplements increase hyperkalemia risk.


  • Hyperkalemia & GI disorders – Main adverse effects.

Drugs included:

  • Amiloride & Triamterne.
  • Block sodium channels in DT & CD.
  • Duration of action: 12—24 hours.
  • MOA: Increase sodium clearance & decrease K+ & H+ excretion.
  • May cause hyperkalemic metabolic acidosis.


  • More potent.
  • Decreases Ca2+ excretion.


  • Blocks entry of Li+ through Na+ channels in CD cells.
  • Mitigates diabetes insipidus induced by lithium.
  • As aerosol affords symptomatic improvement in cystic fibrosis by increasing fluidity of respiratory secretions.

Triamterene – 

  • Gets incompletely absorbed.

Adverse effects:

  • Only slightly soluble & may precipitate in urine, causing kidney stones.
  • Being weak folic acid antagonist leads to megaloblastic anemia especially in cirrhotic patients.
  • Photosensitivity impairs glucose tolerance & interstitial nephritis.


As combination drug:

  • Treatment of potassium wasting caused by chronic therapy with loop & thiazide diuretics.

Nephrogenic Diabetes Insipidus – 

  • Thiazide/Amiloride diuretics & salt restriction.
  • Treatment of aldosteronism in cirrhosis & heart failure.
  • In patients with decompensated cirrhosis on diuretic therapy with tender gynaecomastia.
  • Diuretic substitute – Amiloride  (10-40 mg/day) for spironolactone.


  • Hyperkalemia – Most important toxicity.


Hyperkalemia – 

  • With K+ supplements.
  • ACE inhibitors/ angiotensin receptor blockers (ARBs).
  • Aspirin blocks spironolactone action by inhibiting tubular secretion of canrenone.
  • Spironolactone increases plasma digoxin concentration.

Exam Important

  • In patients with decompensated cirrhosis on diuretic therapy with tender gynaecomastia, the best diuretic to substitute is Amiloride  (10-40 mg/day) for spironolactone
  • The usual maximum dose of furosemide and spironolactone in patients with cirrhosis and portal hypertension is Furosemide 160 mg and spironolactone 400 mg
  • Antiandrogen is the MOST important adverse reaction of spironolactone therapy
  • Spironolactone, Eplerenone & Triamterene drugs act as potassium-sparing diuretics
  • Triamterene is only slightly soluble and may precipitate in the urine, causing kidney stones.
  • Spironolactone should NOT be given with ACE inhibitors
  • Spironolactone alters cardiac mortality
  • The primary site of action of triamterene and spironolactone is the Distal tubule and collecting duct.
  • Eplerenone & Spironolactone are Aldosterone antagonist
  • Spironolactone is the first drug to be given for Cirrhotic edema
  • Mainstay of treatment of Nephrogenic Diabetes Insipidus is Thiazide / Amiloride diuretics and salt restriction
  • Spironolactone is least commonly used in  Hypertension


Don’t Forget to Solve all the previous Year Question asked on K+ SPARING DIURETICS

Module Below Start Quiz

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