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Diuretics power point presentation .pptx
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- 2. Contents • Introduction • Physiology •Loop diuretic- MOA, effects, clinical application, side-effects, toxicities/interaction • Thiazide diuretic – MOA, effects, clinical application, side-effects, toxicities/interaction • Osmotic diuretic- MOA, effects, clinical application, side-effects, toxicities/interaction
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- 4. H2O very high H2O high H2O low H2O low H2O vary 65 % Na+ ,K+ , Cl- , and Ca2+ , Mg2+ 85% NaHCO3, 100% glucose and amino acid 15-25% Na+ , K+ , Cl- , and Ca2+ , Mg2+ 4-8 % Na+ , Cl- , and Ca2+ (parathyroid hormone) 2-5% Na+ , K+ , H+
- 5. Diuretics Directly acting on differentsegments of the nephron A) Acting on the thick Ascending loop of henle (Loop Diuretics) Furosemide Bumetanide Torsemide Piretanide Ethacrynic Acid Indacrinone (uricsuric acid) B) Acting on Proximal (early) part of Distal tubule i) Thiazide Group Hydrochlorothiazide Chlorothiazide Benzthiazide Polythiazide Bendroflumethiazide Clopamide ii) Chemicallly related Variants Cholrthalidone Xipamide Indapamide Metolazone Quinethazone C) Acting on later part of Distal tubules and Collecting Ducts (aka K+ Sparing Diuretics) Inhibitors of Na+ Channels at Collecting Ducts Amiloride Triamterene Aldosterone receptor Antagonists at later part of distal tubules and collecting tubule Spironolactone Eplerenone Indirectly by modifying the contents of urinary filtrate Osmotic Diuretics Mannitol Glycerol Weak Diuretics which mainly have Non- diuretics use Carbonic Anhydrase Inhibitors Acetazolamide Dorzolamide Ethoxazolamide Dichlorphenamide Metha-zolamide
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- 15. Loop diuretics •MOA- inhibitingNa+ K+ /Cl- Cotransporter •Clinical Application- • Edematous conditions associated with congestive heart failure, cirrhosis of the liver, and renal disease including nephrotic syndrome. • Can be Hypertension (though thiazides preferred) esp. if it is complicated by renal impairment • Acute renal failure • Br-, I- or F- toxicity • Mild hyperkalemia • Non diuretic use – mild to mod hypercalcemia
- 16. Loop diuretics Side-effects – •Hyperuricemia - precipitates the attacks of Gout • Hypercalciuria and hypomagnesemia – chronic use • Hypokalemia (Hypokalemic metabolic alkalosis) – reverse by K+ replacement. • Ototoxicity (a) • Hyperglycemia • Hypersensitivity reactions • Others- GIT disturbances, Hepatotoxicity, pancreatitis with ethacrynic acid, Myalgia- bumetanide & piretanide Interaction- • May enhance digitalis toxicity cardiac irregularities • Serum lithium levels may rise • Indomethacin and NSAIDS
- 17. Diuretics Directly acting on differentsegments of the nephron A) Acting on the thick Ascending loop of henle (Loop Diuretics) Furosemide Bumetanide Torsemide Piretanide Ethacrynic Acid Indacrinone (uricsuric acid) B) Acting on Proximal (early) part of Distal tubule i) Thiazide Group Hydrochlorothiazide Chlorothiazide Benzthiazide Polythiazide Bendroflumethiazide Clopamide ii) Chemicallly related Variants Cholrthalidone Xipamide Indapamide Metolazone Quinethazone C) Acting on later part of Distal tubules and Collecting Ducts (aka K+ Sparing Diuretics) Inhibitors of Na+ Channels at Collecting Ducts Amiloride Triamterene Aldosterone receptor Antagonists at later part of distal tubules and collecting tubule Spironolactone Eplerenone Indirectly by modifying the contents of urinary filtrate Osmotic Diuretics Mannitol Glycerol Weak Diuretics which mainly have Non- diuretics use Carbonic Anhydrase Inhibitors Acetazolamide Dorzolamide Ethoxazolamide Dichlorphenamide Metha-zolamide
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- 25. Thiazide diuretics •MOA- inhibitingNa+ /Cl- symport (early DCT) •Clinical Application- • Edematous conditions associated with congestive heart failure, and renal diseases disease including nephrotic syndrome and pregnancy. • Avoided in edema due to cirrhosis of the liver • Essential Hypertension • Non diuretic use – • Paradoxical effect on diabetes insipidus • Helpful Idiopathic hypercalciuria • Renal stones – calcium oxalate
- 26. Thiazide diuretics Side-effects – •Hyperuricemia - precipitates the attacks of Gout • Hypercalcemia • Hypokalemia – given with K+ supplement / K+ Sparing • Hyperglycemia, Hyperlipidemia • Hypersensitivity reactions (patients allergic to sulfonamide- skin rashes, blood dyscrasias, and rarely pancreatitis) • Erectile Dysfunction in males- normalize after stopping. Interaction- • Digitalis • Lithium
- 27. Diuretics Directly acting on differentsegments of the nephron A) Acting on the thick Ascending loop of henle (Loop Diuretics) Furosemide Bumetanide Torsemide Piretanide Ethacrynic Acid Indacrinone (uricsuric acid) B) Acting on Proximal (early) part of Distal tubule i) Thiazide Group Hydrochlorothiazide Chlorothiazide Benzthiazide Polythiazide Bendroflumethiazide Clopamide ii) Chemicallly related Variants Cholrthalidone Xipamide Indapamide Metolazone Quinethazone C) Acting on later part of Distal tubules and Collecting Ducts (aka K+ Sparing Diuretics) Inhibitors of Na+ Channels at Collecting Ducts Amiloride Triamterene Aldosterone receptor Antagonists at later part of distal tubules and collecting tubule Spironolactone Eplerenone Indirectly by modifying the contents of urinary filtrate Osmotic Diuretics Mannitol Glycerol Weak Diuretics which mainly have Non- diuretics use Carbonic Anhydrase Inhibitors Acetazolamide Dorzolamide Ethoxazolamide Dichlorphenamide Metha-zolamide
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- 35. •MOA- passive reabsorptionH2O is reduced and excreted with small amount of sodium.(Aquaretic) •Clinical Application- • To treat oliguria state in shock or crush injury- to prevent renal failure • Non diuretic use- • Cerebral Edema and glaucoma. Osmotic diuretics
- 36. Side-effects – • Mayworsen the condition of cardiac failure or pulmonary edema. • Orally- may cause osmotic diarrhea - Osmotic diuretics
- 38. Diuretic combinations • Loop& thiazide diuretics • Potassium-sparing diuretics & Proximal tubule diuretics agents (loop or thiazides)
- 39. Recent drugs • Blockurea transport • Nesiritide (BNP) • Carperitide (ANP) • Ularitide (Urodilatin) • Sodium Glucose Cotransporter Inhibitors (SGLT 2) • Aldosterone antagonist- Finerenone and esaxerenone
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