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Chapter 41 Diuretics 1
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Anatomy and Physiology
Basic functional unit of the kidney: nephron Four functionally distinct regions Glomerulus Proximal convoluted tubule Loop of Henle Distal convoluted tubule 2
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Anatomy and 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 3
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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 4
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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 5
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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 6
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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 7
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Diuretics Drugs that increase urinary output Two major applications
Treatment of hypertension Mobilization of edematous fluid to prevent renal failure 8
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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 10
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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 12
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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 13
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Furosemide (Lasix) Adverse effects
Hyponatremia, hypochloremia, and dehydration Hypotension Loss of volume Relaxation of venous smooth muscle Hypokalemia Ototoxicity 14
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Furosemide (Lasix) Adverse effects (cont’d) Ototoxicity Hyperglycemia
Hyperuricemia Use in pregnancy Impact on lipids, calcium, and magnesium 15
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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 16
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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 17
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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) 18
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Hydrochlorothiazide (HydroDIURIL)
Most widely used Action: early segment distal convoluted tubule Peaks in 4–6 hours Therapeutic uses Essential hypertension Edema Diabetes insipidus 19
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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 20
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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 21
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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 22
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Spironolactone (Aldactone)
Mechanism of action Blocks aldosterone in the distal nephron Retention of potassium Increased excretion of sodium 23
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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 24
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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 25
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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 26
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Triamterene (Dyrenium)
Adverse effects Hyperkalemia Leg cramps Nausea Vomiting Dizziness Blood dyscrasias (rare) 27
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Amiloride (Midamor) Mechanism of action Therapeutic uses
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. 28
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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 29
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Mannitol (Osmitrol) Adverse effects Edema Headache Nausea Vomiting
Fluid and electrolyte imbalance 30
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