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

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



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



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



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


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


Classification of Diuretics

High-ceiling (loop) diuretics Thiazides and related diuretics Potassium-sparing diuretics

Aldosterone antagonists Nonaldosterone antagonists

Osmotic diuretics Carbonic anhydrase inhibitors


Diuretics

Drugs that increase urinary output Two major applications

Treatment of hypertension Mobilization of edematous fluid to prevent renal

failure


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



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


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



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


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


Furosemide (Lasix)

Adverse effects Hyponatremia, hypochloremia, and dehydration Hypotension

• Loss of volume• Relaxation of venous smooth muscle

Hypokalemia Ototoxicity


Furosemide (Lasix)

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


Furosemide (Lasix)

Drug interactions Digoxin Ototoxic drugs Potassium-sparing diuretics Lithium Antihypertensive agents Nonsteroidal anti-inflammatory drugs

Preparations, dosage, and administration Oral Parenteral


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


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)


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



Adverse effects Hyponatremia, hypochloremia, and dehydration Hypokalemia Use in pregnancy and lactation

• Enters breast milk Hyperglycemia Hyperuricemia Impact on lipids, calcium, and magnesium



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


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


Spironolactone (Aldactone)

Mechanism of action Blocks aldosterone in the distal nephron Retention of potassium Increased excretion of sodium



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



Adverse effects Hyperkalemia Benign and malignant tumors Endocrine effects

Drug interactions Thiazide and loop diuretics Agents that raise potassium levels


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


Triamterene (Dyrenium)

Adverse effects Hyperkalemia Leg cramps Nausea Vomiting Dizziness Blood dyscrasias (rare)


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.


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


Mannitol (Osmitrol)

Adverse effects Edema Headache Nausea Vomiting Fluid and electrolyte imbalance

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

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