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Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 41 Diuretics.

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Presentation on theme: "Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 41 Diuretics."— Presentation transcript:

1 Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 41 Diuretics

2 2Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Anatomy and Physiology  Anatomy  Basic functional unit of the kidney: nephron  Four functionally distinct regions Glomerulus Glomerulus Proximal convoluted tubule Proximal convoluted tubule Loop of Henle Loop of Henle Distal convoluted tubule Distal convoluted tubule

3 3Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Anatomy and Physiology  Physiology  Three basic functions of diuretics Cleansing of extracellular fluid (ECF) and maintenance of ECF volume and composition Cleansing of extracellular fluid (ECF) and maintenance of ECF volume and composition Maintenance of acid-base balance Maintenance of acid-base balance Excretion of metabolic wastes and foreign substances Excretion of metabolic wastes and foreign substances

4 4Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Anatomy and Physiology  Physiology (cont’d)  Three basic renal processes Filtration: occurs at the glomerulus Filtration: occurs at the glomerulus Reabsorption Reabsorption  99% of water, electrolytes, and nutrients undergo reabsorption Active tubular secretion Active tubular secretion  Proximal convoluted tubule

5 5Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Anatomy and Physiology  Physiology (cont’d)  Processes of reabsorption that occur at specific sites along the nephron Proximal convoluted tubule Proximal convoluted tubule Loop of Henle Loop of Henle Distal convoluted tubule (early segment) Distal convoluted tubule (early segment) Late distal convoluted tubule and collecting duct (distal nephron) Late distal convoluted tubule and collecting duct (distal nephron)  Sodium-potassium exchange  Regulation of urine concentration

6 6Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 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 7Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Classification of Diuretics  High-ceiling (loop) diuretics  Thiazides and related diuretics  Potassium-sparing diuretics  Aldosterone antagonists  Nonaldosterone antagonists  Osmotic diuretics  Carbonic anhydrase inhibitors

8 8Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Diuretics  Drugs that increase urinary output  Two major applications  Treatment of hypertension  Mobilization of edematous fluid to prevent renal failure

9 9Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Fig. 41–1. Schematic representation of a nephron and collecting duct.

10 10Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 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 11Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Fig. 41–2. Schematic diagram of a nephron showing sites of sodium absorption and diuretic action.

12 12Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Introduction to Diuretics  Classification of diuretics  Four major categories High-ceiling (loop): furosemide High-ceiling (loop): furosemide Thiazide: hydrochlorothiazide Thiazide: hydrochlorothiazide Osmotic: mannitol Osmotic: mannitol Potassium-sparing: two subdivisions Potassium-sparing: two subdivisions  Aldosterone antagonists (spironolactone)  Nonaldosterone antagonists (triamterene)  Fifth group  Carbonic anhydrase inhibitors

13 13Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. High-Ceiling (Loop) Diuretics  Furosemide (Lasix): most frequently prescribed loop diuretic  Mechanism of action Acts on ascending loop of Henle to block reabsorption Acts on ascending loop of Henle to block reabsorption  Pharmacokinetics Rapid onset (PO 60 min; IV 5 min) Rapid onset (PO 60 min; IV 5 min)  Therapeutic uses Pulmonary edema Pulmonary edema Edematous states Edematous states Hypertension Hypertension

14 14Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Furosemide (Lasix)  Adverse effects  Hyponatremia, hypochloremia, and dehydration  Hypotension Loss of volume Loss of volume Relaxation of venous smooth muscle Relaxation of venous smooth muscle  Hypokalemia  Ototoxicity

15 15Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Furosemide (Lasix)  Adverse effects (cont’d)  Ototoxicity  Hyperglycemia  Hyperuricemia  Use in pregnancy  Impact on lipids, calcium, and magnesium

16 16Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Furosemide (Lasix)  Drug interactions  Digoxin  Ototoxic drugs  Potassium-sparing diuretics  Lithium  Antihypertensive agents  Nonsteroidal anti-inflammatory drugs  Preparations, dosage, and administration  Oral  Parenteral

17 17Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 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 18Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 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 19Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Hydrochlorothiazide (HydroDIURIL)  Hydrochlorothiazide (HydroDIURIL)  Most widely used  Action: early segment distal convoluted tubule  Peaks in 4–6 hours  Therapeutic uses Essential hypertension Essential hypertension Edema Edema Diabetes insipidus Diabetes insipidus

20 20Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Hydrochlorothiazide (HydroDIURIL)  Adverse effects  Hyponatremia, hypochloremia, and dehydration  Hypokalemia  Use in pregnancy and lactation Enters breast milk Enters breast milk  Hyperglycemia  Hyperuricemia  Impact on lipids, calcium, and magnesium

21 21Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 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 22Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 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 23Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Spironolactone (Aldactone)  Mechanism of action  Blocks aldosterone in the distal nephron  Retention of potassium  Increased excretion of sodium

24 24Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 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 25Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Spironolactone (Aldactone)  Adverse effects  Hyperkalemia  Benign and malignant tumors  Endocrine effects  Drug interactions  Thiazide and loop diuretics  Agents that raise potassium levels

26 26Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 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 27Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Triamterene (Dyrenium)  Adverse effects  Hyperkalemia  Leg cramps  Nausea  Vomiting  Dizziness  Blood dyscrasias (rare)

28 28Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 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 29Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Osmotic Diuretic  Mannitol (Osmitrol)  Promotes diuresis by creating osmotic force within lumen of the nephron  Pharmacokinetics Drug must be given parenterally Drug must be given parenterally  Therapeutic uses Prophylaxis of renal failure Prophylaxis of renal failure Reduction of intracranial pressure Reduction of intracranial pressure Reduction of intraocular pressure Reduction of intraocular pressure

30 30Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Mannitol (Osmitrol)  Adverse effects  Edema  Headache  Nausea  Vomiting  Fluid and electrolyte imbalance


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