copyright © 2013, 2010 by saunders, an imprint of elsevier inc. chapter 41 diuretics
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Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Chapter 41
Diuretics
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• Proximal convoluted tubule• Loop of Henle• Distal convoluted tubule
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
• Maintenance of acid-base balance• Excretion of metabolic wastes and foreign substances
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• Reabsorption
99% of water, electrolytes, and nutrients undergo reabsorption
• Active tubular secretion Proximal convoluted tubule
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• Loop of Henle• Distal convoluted tubule (early segment)• Late distal convoluted tubule and collecting duct (distal
nephron) Sodium-potassium exchange Regulation of urine concentration
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
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
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
9Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Fig. 41–1. Schematic representation of a nephron and collecting duct.
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
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.
12Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
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 Pharmacokinetics
• Rapid onset (PO 60 min; IV 5 min) Therapeutic uses
• Pulmonary edema• Edematous states• Hypertension
14Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Furosemide (Lasix)
Adverse effects Hyponatremia, hypochloremia, and dehydration Hypotension
• Loss of volume• Relaxation of venous smooth muscle
Hypokalemia Ototoxicity
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
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
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
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)
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• Edema• Diabetes insipidus
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 Hyperglycemia Hyperuricemia Impact on lipids, calcium, and magnesium
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
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
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
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
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
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
27Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Triamterene (Dyrenium)
Adverse effects Hyperkalemia Leg cramps Nausea Vomiting Dizziness Blood dyscrasias (rare)
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.
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 Therapeutic uses
• Prophylaxis of renal failure• Reduction of intracranial pressure• Reduction of intraocular pressure
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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