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Diuretics

Diuretics. CHAPTER 25. Clinical Indication. Management of anuria, hypertension, and edema of any cause including chronic congestive heart failure or renal disease Management of glaucoma Management of primary hyperaldosteronism. Renal Function.

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Diuretics

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  1. Diuretics CHAPTER 25

  2. Clinical Indication • Management of anuria, hypertension, and edema of any cause including chronic congestive heart failure or renal disease • Management of glaucoma • Management of primary hyperaldosteronism

  3. Renal Function Kidneys remove waste from the blood and reabsorb water and sodium ions (Na+) before final excretion into the urine Along the renal tubules, sodium ions are reabsorbed into the cells and blood by exchange for hydrogen (H+) and potassium (K+) ions Water follows Na+ back into the blood (osmotic gradient)

  4. Renal Mechanisms • Renal tubules produce hydrogen ions (H+) and bicarbonate ions (HCO3-) through the enzyme carbonic anhydrase CO2 + H2O  H2CO3 HCO3 + H+ • H+ exchanged into the renal tubule filtrate acidifies the fluid • HCO3- absorbed into the blood neutralizes waste products from the cells

  5. Mechanism of Diuresis Diuretics promote water loss in the urine by • Blocking the production of H+ and bicarbonate (HCO3-) ions • Blocking the exchange of H+ for Na+ • Blocking the exchange of K+ for Na+ • Creating an osmotic gradient through a concentration of nonabsorbable molecules Effectiveness depends on the ability of the diuretic to block multiple ion exchange sites

  6. Classes of Diuretics • Osmotic diureticsMannitol • Organic acidsBumetanide, ethacrynic acid, furosemide, toresemide • Thiazide and thiazide-like diureticsHydrochlorothiazide, polythiazide, chlorthalidone, quinethazone • Potassium-sparing diureticsAmilirode, spironolactone, triamterene • Carbonic anhydrase inhibitors Acetazolamide

  7. Carbonic Anhydrase Inhibitors Reduce the production of hydrogen ions to exchange for sodium ions so water stays with sodium ions Loss of Na+Loss of K+ (hypokalemia) Reduction in H+ and HCO3- Metabolic acidosisRefractory – diuresis stops when acidosis develops

  8. Osmotic Diuretics Enter the tubules but cannot be reabsorbed so water stays with the concentration of diuretic molecules. Ion exchange mechanisms are not affected. • Mild diuresis • Diuresis continues as long as intravenous infusion is maintained

  9. Organic Acids (Loop diuretics) Inhibit sodium and chloride ion exchange in the tubule loop of Henle Potent Loss of large volumes of water in urine Loss of Na+ and Cl- in urine Loss of K+ (hypokalemia) Hypochloremic (low chloride) alkalosis Nonrefractory-diuresis continues when alkalosis develops Reduce plasma volume

  10. Thiazide and Thiazide-like Diuretics Inhibit sodium ion reabsorption by multiple mechanisms along the renal tubulesPotent Loss of large volumes of water in urine Loss of Na+ and Cl- in urine Loss of K+ (hypokalemia) Hypochloremic (low chloride) alkalosis Nonrefractory- diuresis continues when alkalosis develops Reduce plasma volume

  11. Potassium-Sparing Diuretics Inhibit K+ exchange for Na+ in the distal renal tubules • Spironolactone inhibits aldosterone receptors that control K+ exchange • Amilioride and triamterene inhibit other mechanisms to block K+ exchange • Mild diuresis • No significant effect on Na+, H+, Cl- or HCO3- • No effect on acid/base balance • Cause gynecomastia

  12. Adverse Effects Thiazide, Thiazide-like, and Loop Diuretics • Nausea • Diarrhea • Constipation • Headache • Anorexia • Hypotension (from water loss) • Dizzy, lightheaded, faint • Hypokalemia (from ion exchange) • Hyperuricemia • Hyperglycemia • Elevated serum creatinine or urine nitrogen (BUN) • Neurotoxicity, deafness (Loop diuretics)

  13. Special Considerations • Chronic diuretic use produces electrolyte and acid/base changes • Muscle cramping, weakness, and fatigue may occur from hypokalemia • Cardiac arrhythmias may occur from changes in serum Na+ and K+ • Potassium supplements (fruits) may balance the K+ loss • Electrolyte imbalance affects insulin secretion and glucose levels • Water loss produces weight loss and dehydration

  14. Drugs to Know • Acetazolamide (Diamox) • Uses • Glaucoma • Epilepsy • Acute mountain sickness • Mannitol (Osmitrol) – osmotic • Urea (Ureaphil) - osmotic • Furosemide (Lasix) – loop • Ethacrynic acid (Edicrin) - loop

  15. Drugs to Know • Spironolactone (Aldactone) – K+ sparing • Triamterine (Dyrenium) – K+ sparing

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