K+sparing diuretic

MOA:
  • These are either aldosterone antagonist or directly inhibit Na+ channels in DT and CD cells to indirectly conserve K+.

SPIRONOLACTONE & EPLERENONE:
  • Slow onsets and duration of action (24-72 hrs)
  • Steroid derivatives
  • The primary site of action of triameterene and spironolactone is the Distal tubule and collecting duct.
  • Spironolactone alters cardiac mortality
  • Pharmacologic antagonists of aldosterone in the collecting tubules
  • Combine and block intracellular aldosterone receptor → reduce expression of genes controlling synthesis of sodium ion channels and Na+/K+ ATPase.
  • Maximum dose of spironolactone in patients with cirrhosis and portal hypertension is spironolactone 400 mg
AMILORIDE & TRIAMPTERENE:
  • Block sodium channels in the same portion of the nephron.
  • Duration of action: 12—24 hours.
  • Increase sodium clearance and decrease K+ & H+ excretion.
  • May cause hyperkalemic metabolic acidosis.
  • Triamterene is only slightly soluble and may precipitate in the urine, causing kidney stones.
  • Amiloride blocks entry of Li+ through Na+ channels in the CD cells and mitigates diabetes insipidus induced by lithium.
  • Given as an aerosol it affords symptomatic improvement in cystic fibrosis by increasing fluidity of respiratory secretions
THERAPEUTIC USES:-
  • Treatment of potassium wasting caused by chronic therapy with loop and thiazide diuretics (combination in a single pill).
  • Nephrogenic Diabetes Insipidus is Thiazide / Amiloride diuretics and salt restriction
  • Treatment of aldosteronism in cirrhosis and heart failure.
  • Spironolactone is the first drug to be given for Cirrhotic edema
  • In patients with decompensated cirrhosis on diuretic therapy with tender gynaecomastia the best diuretic to substitute is Amiloride (10-40 mg/day) for spironolactone
ADVERSE EFFECTS:
  • Hyperkalemia is the most important toxicity.
  • As an add-on drug, spironolcatone may be useful in hypertensive patients with significant hyperuricemia, hypokalemia, or glucose intolerance 
  • Can cause endocrine abnormalities (gynecomastia and antiandrogenic effects).
  • Antiandrogen is the most important adverse reaction of spironolactone therapy
INTERACTIONS:-
  • Given together with K+ supplements-dangerous hyperkalaemia can occur.
  • Aspirin blocks spironolactone action by inhibiting tubular secretion of canrenone.
  • More pronounced hyperkalaemia can occur in patients receiving ACE inhibitors/ angiotensin receptor blockers (ARBs).
  • Spironolactone increases plasma digoxin concentration.
Exam Question
  • 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 acts 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 triameterene and spironolactone is the Distal tubule and collecting duct.
  • Eplerenone & Sprionolactone 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
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