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DIURETICS Part 1

DIURETICS Part 1. Prof. Hanan Hagar Pharmacology Department. Diuretics Are drugs that increase renal excretion of sodium and water resulting in increase in urine volume. Most diuretics act by interfering with the normal sodium reabsorption by the kidney.

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DIURETICS Part 1

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  1. DIURETICSPart 1 Prof. Hanan Hagar Pharmacology Department

  2. Diuretics • Are drugs that increase renal excretion of sodium and water resulting in increase in urine volume. • Most diuretics act by interfering with the normal sodium reabsorption by the kidney.

  3. Sites for water and electrolytes transport along the nephron

  4. Mechanism of action of diuretics • Most diuretics act by inhibiting carriers or transporters in luminal membrane of renal tubular cells required for tubular reabsorption of sodium from filtrate back into blood.

  5. Sodium Excretion Regulation

  6. Types of diuretics

  7. Site of action of diuretics

  8. Classification of diuretics • Carbonic anhydrase inhibitors • Loop diuretics • Thiazide diuretics • Potassium-sparing diuretics • Osmotic diuretics

  9. carbonic anhydrase Lumen Blood Luminal membrane Basolateral membrane

  10. Ascending loop of Henle

  11. Distal convoluted tubules (DCT)

  12. COLLECTING TUBULES (CT)

  13. COLLECTING TUBULES (CT)

  14. Diuretics

  15. Carbonic Anhydrase Inhibitors Acetazolamide – dorzolamide Mechanism of action: Inhibits carbonic anhydrase (CA) enzyme in PCT thus interferes with NaHCO3 re-absorption and causes diuresis.

  16. Carbonic Anhydrase Inhibitors CA is required for reversible reaction, in which CO2 +H2O H2CO3 H+ HCO3-

  17. Blood Lumen Basolateral membrane Luminal membrane Proximal tubules

  18. Carbonic Anhydrase Inhibitors

  19. Pharmacokinetics: • given orally once a day. • Onset of action is rapid (30 min). • Duration of action (12 h). • Excreted by active secretion in proximal convoluted tubules forming alkaline urine

  20. Pharmacological actions: • ↑ urine volume • ↑ urinary excretion of sodium, potassium , bicarbonate (alkaline urine). • Metabolic acidosis. • ↑ urinary phosphate excretion. • Weak diuretic properties. (decreases after several days ; self-limiting as the blood bicarbonate falls).

  21. Carbonic anhydrase inhibitors

  22. Therapeutic uses: • Open angle glaucoma (↓ IOP by reducing aqueous humor formation via blocking carbonic anhydrase in ciliary body of eye). • As prophylactic therapy, in acute mountain sickness (to decrease CSF and pH of brain). Note that IOP: intraocular pressure CSF: cerebrospinal fluid

  23. Therapeutic uses: • Epilepsy (decrease cerebrospinal fluid, CSF). • Urinary alkalinization to enhance renal excretion of acidic substances (cysteine in cystinuria). • Hyperphosphatemia • Metabolic alkalosis

  24. Adverse effects: • Hypokalemia (potassium loss). • Metabolic acidosis. • Renal stone formation (calcium phosphate stones). • Hypersensitivity reactions

  25. Dorzolamide • Is a carbonic anhydrase inhibitor • Used topically for treatment of increased intraocular pressure in open-angle glaucoma. • no diuretic or systemic side effects (Why?).

  26. LOOP DIURETICSHigh Ceiling diuretics • The most efficacious diuretics Efficacy: High 25-30% natriuresis Drugs as • Furosemide - Bumetanide Torsemide - Ethcrynic acid

  27. LOOP DIURETICS Mechanism: • inhibit Na+ / K+ / 2 Cl- co-transporter in the luminal membrane of the thick ascending loop of Henle (TAL). • inhibit Ca++ and Mg ++ re-absorption.

  28. Ascending loop of Henle

  29. Ascending loop of Henle

  30. Pharmacokinetics • Given orally or I. V. • Have fast onset of action (suitable for emergency) • Have short duration of action. • Bumetanide is the most potent • Excreted by active tubular secretion of weak acids into urine. • Interfere with uric acid secretion.

  31. Pharmacological effects: • ↑ urinary excretion of Na+ and K+ • ↑ urinary excretion Ca++ and Mg ++ • ↑ urine volume • ↑ renal blood flow.

  32. Uses: are drug of choice for emergency situations as: • Acute pulmonary edema due to heart failure • Edema due to nephrotic syndrome • Acute hyperkalaemia. • Acute hypercalcemia

  33. Adverse effects : • Acute hypovolemia (volume depletion). • Hyponatraemia. • Hypokalemia (dietary K supplementation or K-sparing diuretics). • Hypomagnesaemia • Metabolic alkalosis. • Postural hypotension

  34. Adverse effects : • Hyperuricemia (increase gouty attack). • Ototoxicity (risk increased if combined with aminoglycosides) • Hyperglycemia • Allergic reactions

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