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Chapter 41

Chapter 41. Diuretics. Anatomy and Physiology. Anatomy Basic functional unit of the kidney: nephron Four functionally distinct regions Glomerulus Proximal convoluted tubule Loop of Henle Distal convoluted tubule. Anatomy and Physiology. Physiology Three basic functions of diuretics

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Chapter 41

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  1. Chapter 41 Diuretics

  2. Anatomy and Physiology • Anatomy • Basic functional unit of the kidney: nephron • Four functionally distinct regions • Glomerulus • Proximal convoluted tubule • Loop of Henle • Distal convoluted tubule

  3. Anatomy and Physiology • Physiology • Three basic functions of diuretics • Cleansing of extracellular fluid (ECF) and maintenance of ECF volume and composition • Maintenance of acid-base balance • Excretion of metabolic wastes and foreign substances

  4. Anatomy and Physiology • Physiology (cont’d) • Three basic renal processes • Filtration:occurs at the glomerulus • Reabsorption • 99% of water, electrolytes, and nutrients undergo reabsorption • Active tubular secretion • Proximal convoluted tubule

  5. Anatomy and Physiology • Physiology (cont’d) • Processes of reabsorption that occur at specific sites along the nephron • Proximal convoluted tubule • Loop of Henle • Distal convoluted tubule (early segment) • Late distal convoluted tubule and collecting duct (distal nephron) • Sodium-potassium exchange • Regulation of urine concentration

  6. Introduction to Diuretics • How diuretics work • Most cause the blockade of sodium and chloride reabsorption • Adverse impact on extracellular fluid • May cause hypovolemia • Acid-base imbalance • Altered electrolyte levels

  7. Classification of Diuretics • High-ceiling (loop) diuretics • Thiazides and related diuretics • Potassium-sparing diuretics • Aldosterone antagonists • Nonaldosterone antagonists • Osmotic diuretics • Carbonic anhydrase inhibitors

  8. Diuretics • Drugs that increase urinary output • Two major applications • Treatment of hypertension • Mobilization of edematous fluid to prevent renal failure

  9. Fig. 41–1. Schematic representation of a nephron and collecting duct.

  10. Introduction to Diuretics • How diuretics work—mechanism of action • Blockade of sodium and chloride reabsorption • Site of action • Proximal tubule produces greatest diuresis • Adverse effects • Hypovolemia • Acid-base imbalance • Electrolyte imbalances

  11. Fig.41–2. Schematic diagram of a nephron showing sites of sodium absorption and diuretic action.

  12. Introduction to Diuretics • Classification of diuretics • Four major categories • High-ceiling (loop):furosemide • Thiazide:hydrochlorothiazide • Osmotic:mannitol • Potassium-sparing: two subdivisions • Aldosterone antagonists (spironolactone) • Nonaldosterone antagonists (triamterene) • Fifth group • Carbonic anhydrase inhibitors

  13. High-Ceiling (Loop) Diuretics • Furosemide (Lasix):most frequently prescribed loop diuretic • Mechanism of action • Acts on ascending loop of Henle to block reabsorption • Pharmacokinetics • Rapid onset (PO 60 min; IV 5 min) • Therapeutic uses • Pulmonary edema • Edematous states • Hypertension

  14. Furosemide (Lasix) • Adverse effects • Hyponatremia, hypochloremia, and dehydration • Hypotension • Loss of volume • Relaxation of venous smooth muscle • Hypokalemia • Ototoxicity

  15. Furosemide (Lasix) • Adverse effects (cont’d) • Ototoxicity • Hyperglycemia • Hyperuricemia • Use in pregnancy • Impact on lipids, calcium, and magnesium

  16. Furosemide (Lasix) • Drug interactions • Digoxin • Ototoxic drugs • Potassium-sparing diuretics • Lithium • Antihypertensive agents • Nonsteroidal anti-inflammatory drugs • Preparations, dosage, and administration • Oral • Parenteral

  17. Other High-Ceiling (Loop) Diuretics • Ethacrynic acid (Edecrin) • Bumetanide (Bumex) • Torsemide (Demadex) • All can cause: • Ototoxicity, hypovolemia, hypotension, hypokalemia, hyperuricemia, hyperglycemia, and disruption of lipid metabolism

  18. Thiazides and Related Diuretics • Also known as benzothiadiazides • Effects similar to those of loop diuretics • Increase renal excretion of sodium, chloride, potassium, and water • Elevate levels of uric acid and glucose • Maximum diuresis is considerably lower than that produced by loop diuretics • Not effective when urine flow is scant (unlike loop diuretics)

  19. Hydrochlorothiazide (HydroDIURIL) • Hydrochlorothiazide (HydroDIURIL) • Most widely used • Action:early segment distal convoluted tubule • Peaks in 4–6 hours • Therapeutic uses • Essential hypertension • Edema • Diabetes insipidus

  20. Hydrochlorothiazide (HydroDIURIL) • Adverse effects • Hyponatremia, hypochloremia, and dehydration • Hypokalemia • Use in pregnancy and lactation • Enters breast milk • Hyperglycemia • Hyperuricemia • Impact on lipids, calcium, and magnesium

  21. Hydrochlorothiazide (HydroDIURIL) • Drug interactions • Digoxin • Augments effects of hypertensive medications • Can reduce renal excretion of lithium (leading to accumulation) • NSAIDs may blunt diuretic effect • Can be combined with ototoxic agents without increased risk of hearing loss

  22. Potassium-Sparing Diuretics • Useful responses • Modest increase in urine production • Substantial decrease in potassium excretion • Rarely used alone for therapy • Aldosterone antagonist • Spironolactone • Nonaldosterone antagonists • Triamterene • Amiloride

  23. Spironolactone (Aldactone) • Mechanism of action • Blocks aldosterone in the distal nephron • Retention of potassium • Increased excretion of sodium

  24. Spironolactone (Aldactone) • Therapeutic uses • Hypertension • Edematous states • Heart failure (decreases mortality in severe failure) • Primary hyperaldosteronism • Premenstrual syndrome • Polycystic ovary syndrome • Acne in young women

  25. Spironolactone (Aldactone) • Adverse effects • Hyperkalemia • Benign and malignant tumors • Endocrine effects • Drug interactions • Thiazide and loop diuretics • Agents that raise potassium levels

  26. Triamterene (Dyrenium) • Mechanism of action • Disrupts sodium-potassium exchange in the distal nephron • Direct inhibitor of the exchange mechanism • Decreases sodium reuptake • Inhibits ion transport • Therapeutic uses • Hypertension • Edema

  27. Triamterene (Dyrenium) • Adverse effects • Hyperkalemia • Leg cramps • Nausea • Vomiting • Dizziness • Blood dyscrasias (rare)

  28. Amiloride (Midamor) • Mechanism of action • Blocks sodium-potassium exchange in the distal nephron • Therapeutic uses • To counteract potassium loss caused by more powerful diuretics • Adverse effects • Hyperkalemia • Drug interaction • ACE inhibitors; other drugs with hyperkalemia ACE = angiotensin-converting enzyme.

  29. Osmotic Diuretic • Mannitol (Osmitrol) • Promotes diuresis by creating osmotic force within lumen of the nephron • Pharmacokinetics • Drug must be given parenterally • Therapeutic uses • Prophylaxis of renal failure • Reduction of intracranial pressure • Reduction of intraocular pressure

  30. Mannitol (Osmitrol) • Adverse effects • Edema • Headache • Nausea • Vomiting • Fluid and electrolyte imbalance

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