K+ Sparing Diuretics

MOA:

• 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.

CLASSIFICATION:

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

ALDOSTERONE ANTAGONISTS:

• 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.

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.

Amiloride: 

• More potent.
• Decreases Ca2+ excretion.

Uses:

• 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.

THERAPEUTIC USES OF K+ DIURETICS:-

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.

ADVERSE EFFECTS:-

• Hyperkalemia – Most important toxicity.

INTERACTIONS:-

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.

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