chapter 41
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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 - PowerPoint PPT PresentationTRANSCRIPT
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Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Chapter 41
Diuretics
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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
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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
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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
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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
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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
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Classification of Diuretics High-ceiling (loop) diuretics Thiazides and related diuretics Potassium-sparing diuretics
Aldosterone antagonists Nonaldosterone antagonists
Osmotic diuretics Carbonic anhydrase inhibitors
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Diuretics Drugs that increase urinary output Two major applications
Treatment of hypertension Mobilization of edematous fluid to prevent renal
failure
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Fig. 41–1. Schematic representation of a nephron and collecting duct.
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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
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Fig. 41–2. Schematic diagram of a nephron showing sites of sodium absorption and diuretic action.
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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
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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
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Furosemide (Lasix) Adverse effects
Hyponatremia, hypochloremia, and dehydration Hypotension
• Loss of volume• Relaxation of venous smooth muscle
Hypokalemia Ototoxicity
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Furosemide (Lasix) Adverse effects (cont’d)
Ototoxicity Hyperglycemia Hyperuricemia Use in pregnancy Impact on lipids, calcium, and magnesium
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Furosemide (Lasix) Drug interactions
Digoxin Ototoxic drugs Potassium-sparing diuretics Lithium Antihypertensive agents Nonsteroidal anti-inflammatory drugs
Preparations, dosage, and administration Oral Parenteral
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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
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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)
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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
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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
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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
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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
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Spironolactone (Aldactone) Mechanism of action
Blocks aldosterone in the distal nephron Retention of potassium Increased excretion of sodium
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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
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Spironolactone (Aldactone) Adverse effects
Hyperkalemia Benign and malignant tumors Endocrine effects
Drug interactions Thiazide and loop diuretics Agents that raise potassium levels
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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
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Triamterene (Dyrenium) Adverse effects
Hyperkalemia Leg cramps Nausea Vomiting Dizziness Blood dyscrasias (rare)
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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.
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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
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Mannitol (Osmitrol) Adverse effects
Edema Headache Nausea Vomiting Fluid and electrolyte imbalance