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Diuretics

Diuretics . Nephron Structure. Diuretics . Drugs that increase the volume of urine flow. How do they works?. Diuretics affect ion transport in the nephron water is carried along with ions passively in order to maintain the osmotic pressure. Classes of diuretics .

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Diuretics

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  1. Diuretics

  2. Nephron Structure

  3. Diuretics • Drugs that increase the volume of urine flow

  4. How do they works? • Diuretics affect ion transport in the nephron water is carried along with ions passively in order to maintain the osmotic pressure

  5. Classes of diuretics • Carbonic anhydrase inhibitors • Works on proximal convoluted tubule • Loop diuretics • Works on thick ascending loop of henle • Thiazide diuretics • Works on distal convoluted tubule • Osmotic diuretics • Works on proximal convoluted tubule and collecting duct • Potassium sparing diuretics • Works on distal convoluted tubule

  6. Carbonic anhydrase inhibitor • Acetazolamide • CO2 + H2O H2CO3 H+ + H2C • Carbonic anhydrase inhibitors cause depletion of H+ decrease in Na abs. Increase water excretoin Carbonic anhydrase Exchange with Na+ and cause its reabsorption

  7. Clinical uses • Glaucoma • Metabolic alkalosis • Mountain sickness • Epilepsy • Not to use as diuretics because of its poor effect

  8. Side effects • Metabolic acidosis • Renal stones • Sulfa allergy

  9. Thiazide Diuretics Hydrochlorothiazide Metolazone

  10. Mechanism of Action • Thiazides freely filtered and secreted in proximal tubule • Bind to the electroneutralNaClcotransporter • Thiazides impair Na+ and Cl-reabsorption in the early distal tubule: “low ceiling” Thiazide

  11. THERAPEUTIC EFFECTS Increase Na Excretion Treatment for Nephrogenic Diabetes Insipidus Treatment for Mild Edema Treatment for Hypertension Treatment for Renal stones Decrease Ca Excretion

  12. ADVERSE EFFECTS Hypercalcemia Hypokalemia Hyperuricemia Hyponatremia Hyperglycemia Hypomagnesemia Hyperlipidemia Metabolic Alkalosis Impotence

  13. Ethacrynic Acid Furosemide Loop Diuretics • Also Called: • High Ceiling Diuretics

  14. Mechanism of action The ascending loop of henle • Inhibits Na-K-2Cl cotransporter of the ascending loop of henle

  15. THERAPEUTIC EFFECTS Treatment for Severe Edema Increase Na Excretion Treatment for Oliguric ARF Increase Urine Volume Treatment for Hypercalcemia Increase Ca Excretion Treatment for Pulmonary Edema Increase Venous Capacitance

  16. ADVERSE EFFECTS Hypocalcemia Ototoxicity Hypokalemia Metabolic Alkalosis Hypomagnesemia Hyperglycemia Hyperuricemia

  17. K-Sparing Diuretics Amiloride Na inhibitors 1- Triametrene Aldosterone antagonist 2- Spironolactone

  18. Mechanism of action of Na+ inhibitors • Inhibit Na abs and prevent K excretion • Have weak diuretic effects

  19. Mechanism of action of aldosterone antagonist • Prevent ther action of Na-K pump

  20. THERAPEUTIC EFFECTS Enhance Natriuresis Caused by Other Diuretics Used in Combination with Loop & Thiazide Diuretics Prevent Hypokalemia

  21. ADVERSE EFFECTS Triamterene Amiloride Hyperkalemia Hyperkalemia Renal Stones

  22. ADVERSE EFFECTS Spironolactone Hyperkalemia Gynecomestia Impotence Irregular menstrual cycle

  23. Osmotic diuretics Mannitol Urea

  24. Mechanism of action • They create osmotic pressure especially in proximal convoluted tubule and collecting duct • No effect on excreting Na+

  25. Clinical uses • In hospital via IV to manage the following situation • Increased intracranial pressure • Increased intraocular pressure • Acute renal failure

  26. ADVERSE EFFECTS Hypernatremia Hypovolemia Pulmonary edema

  27. Summary: Sites of Diuretic Action

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