Transcript Chapter 16 Cholinesterase Inhibitors

Chapter 41
Diuretics
Copyright © 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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
2
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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
3
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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
4
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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
5
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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
6
Classification of Diuretics



High-ceiling (loop) diuretics
Thiazides and related diuretics
Potassium-sparing diuretics




Aldosterone antagonists
Nonaldosterone antagonists
Osmotic diuretics
Carbonic anhydrase inhibitors
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
7
Diuretics


Drugs that increase urinary output
Two major applications


Treatment of hypertension
Mobilization of edematous fluid to prevent renal
failure
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
8
Fig. 41–1. Schematic representation of a nephron and collecting duct.
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
9
Introduction to Diuretics

How diuretics work—mechanism of action


Site of action


Blockade of sodium and chloride reabsorption
Proximal tubule produces greatest diuresis
Adverse effects



Hypovolemia
Acid-base imbalance
Electrolyte imbalances
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
10
Fig. 41–2. Schematic diagram of a nephron showing sites of sodium
absorption and diuretic action.
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
11
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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
12
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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
13
Furosemide (Lasix)

Adverse effects


Hyponatremia, hypochloremia, and dehydration
Hypotension
• Loss of volume
• Relaxation of venous smooth muscle
 Hypokalemia
 Ototoxicity
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
14
Furosemide (Lasix)

Adverse effects (cont’d)





Ototoxicity
Hyperglycemia
Hyperuricemia
Use in pregnancy
Impact on lipids, calcium, and magnesium
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
15
Furosemide (Lasix)

Drug interactions







Digoxin
Ototoxic drugs
Potassium-sparing diuretics
Lithium
Antihypertensive agents
Nonsteroidal anti-inflammatory drugs
Preparations, dosage, and administration


Oral
Parenteral
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
16
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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
17
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)
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
18
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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
19
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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
20
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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
21
Potassium-Sparing Diuretics

Useful responses




Rarely used alone for therapy
Aldosterone antagonist


Modest increase in urine production
Substantial decrease in potassium excretion
Spironolactone
Nonaldosterone antagonists


Triamterene
Amiloride
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
22
Spironolactone (Aldactone)

Mechanism of action



Blocks aldosterone in the distal nephron
Retention of potassium
Increased excretion of sodium
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
23
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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
24
Spironolactone (Aldactone)

Adverse effects




Hyperkalemia
Benign and malignant tumors
Endocrine effects
Drug interactions


Thiazide and loop diuretics
Agents that raise potassium levels
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
25
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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
26
Triamterene (Dyrenium)

Adverse effects






Hyperkalemia
Leg cramps
Nausea
Vomiting
Dizziness
Blood dyscrasias (rare)
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
27
Amiloride (Midamor)

Mechanism of action


Therapeutic uses


To counteract potassium loss caused by more
powerful diuretics
Adverse effects


Blocks sodium-potassium exchange in the distal
nephron
Hyperkalemia
Drug interaction

ACE inhibitors; other drugs with hyperkalemia
ACE = angiotensin-converting enzyme.
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
28
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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
29
Mannitol (Osmitrol)

Adverse effects





Edema
Headache
Nausea
Vomiting
Fluid and electrolyte imbalance
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
30