Pharmacotherapy in Chronic Obstructive Pulmonary Disease

by Celli; Bartolome R.

• ISBN13: 9780824740290
• ISBN10: 0824740297
• Format: Hardcover
• Copyright: 2003-12-17
• Publisher: CRC Press

Summary

Presenting an integrated approach to pharmacotherapy, this volume considers the the application of clinical assessment to the drug development process. Important topics include the genetics of and sleep-related breathing disturbances in COPD.

Table of Contents

Introduction	p. iii
Preface	p. v
Contributors	p. ix
The Application of Clinical Assessment to the Drug Development Process
Providing Evidence of Therapeutic Benefit in Clinical Drug Development	p. 1
Introduction	p. 1
Regulation in the Development of Drugs	p. 2
Key Considerations in Clinical Program Designs	p. 3
Key Considerations in Endpoints: Application to COPD	p. 6
Summary	p. 14
References	p. 15
Measuring Outcomes
Physiology
Use of Expiratory Airflows and Lung Volumes to Assess Outcomes in COPD	p. 19
Introduction	p. 19
Expiratory Airflows	p. 19
Lung Volumes	p. 25
Other Measures	p. 31
Bronchodilator Reversibility and Airway Hyperreactivity	p. 32
Clinical Relevance	p. 32
Conclusion and Recommendations	p. 37
References	p. 38
Exercise Testing	p. 45
Introduction	p. 45
Exercise Limitation in COPD	p. 46
Exercise Testing: Field Tests	p. 54
Exercise Testing: Laboratory Tests	p. 56
Failure to Improve Exercise Performance After Bronchodilators	p. 57
Evaluating Mechanisms of Functional Improvement	p. 58
Utility of Constant-Load Exercise Testing: Examples	p. 61
Summary	p. 65
References	p. 66
Sleep-Related Breathing Disturbances in COPD	p. 73
Introduction	p. 73
Effects of Sleep on Respiration	p. 74
Sleep in Chronic Obstructive Pulmonary Disease	p. 76
Mechanisms of Nocturnal Oxygen Desaturation in COPD	p. 76
Consequences of Nocturnal Hypoxaemia in COPD	p. 77
Sleep Quality in COPD	p. 78
Contrasts with Exercise	p. 79
Investigation of Sleep-Related Breathing Disturbances in COPD	p. 79
Management of Respiratory Abnormalities During Sleep in COPD	p. 80
Pharmacological Therapy	p. 81
Conclusion	p. 84
References	p. 84
Airway and Alveolar Determinants of Airflow Limitation in COPD	p. 89
Introduction	p. 89
Large-Airways Airflow Limitation	p. 89
Small-Airways Airflow Limitation	p. 91
Alveolar Airflow Limitation	p. 93
References	p. 94
Gas Exchange	p. 95
Introduction	p. 95
Bronchodilators	p. 96
Glucocorticosteroids	p. 106
Vasodilators	p. 108
Other Drugs	p. 110
References	p. 110
Laboratory
Genetics of COPD	p. 119
Introduction	p. 119
Evidence of Genetic Risk	p. 120
Methods to Identify Susceptibility Genes	p. 120
Phenotypes	p. 122
Candidate Genes in COPD	p. 123
Therapeutic Implcations of COPD Genetics	p. 134
Pharmacogenetics of COPD	p. 134
Conclusion	p. 135
References	p. 136
Health Outcomes
Dyspnea	p. 145
Introduction	p. 145
The Measurement of Dyspnea	p. 146
Responsiveness	p. 151
Summary	p. 154
References	p. 154
Exacerbations of COPD	p. 159
Definition of a COPD Exacerbation	p. 159
Exacerbation Frequency	p. 160
Goals of Exacerbation Therapy	p. 161
Therapy of the Acute Exacerbation	p. 161
Prevention of COPD Exacerbation	p. 166
Conclusion	p. 170
References	p. 170
Health Status Measurement in COPD	p. 175
Introduction: The Multifactorial Nature of COPD	p. 175
Measuring the Overall Effect of Treatment	p. 177
Health Status Questionnaires	p. 177
Thresholds for Clinical Significance	p. 180
Health Status Changes Following Treatment	p. 180
Longitudianl Trends in Health Status	p. 182
Implications for Practice	p. 182
Assessment of Individual Patient Benefit	p. 183
Summary	p. 184
References	p. 184
Health Resource Utilization	p. 189
COPD--The Challenge	p. 189
Helath Care Utilization in COPD	p. 191
Economic Burden of COPD	p. 194
References	p. 199
Specific Therapy
Anticholinergics	p. 201
Introduction	p. 201
Rationale for Anticholinergic Therapy in COPD	p. 202
Muscarinic Receptor Subtypes in the Airways	p. 203
The Search for Selective Anticholinergics	p. 207
Tiotropuim Bromide	p. 207
Pharmacokinetics	p. 209
Side Effects	p. 210
Future Prospects	p. 211
References	p. 212
[beta]-Adrenergic Receptor Agonist Bronchodilators in the Treatment of COPD	p. 217
Introduction	p. 217
Mechanism of Action	p. 218
Clinical Response	p. 225
Adverse Effects of [beta]-Agonists	p. 228
Clinical Assessment of the COPD patient	p. 229
Effect of Dyspnea	p. 229
Effect on Exercise	p. 230
Quality of Life	p. 230
Exacerbations	p. 230
Use of [beta]-Agonist Bronchodilators in Clinical Practice	p. 231
Summary	p. 232
References	p. 233
Theophylline and Phospodiesterase Inhibitors in COPD	p. 239
Introduction	p. 239
Molecular Mechanisms of Action of Theophylline and Other PDE Inhibitors	p. 240
Pharmacological Effects of Theophylline	p. 242
Pharmacokinetics	p. 243
Dosing and Monitoring of Theophylline	p. 245
Toxicity	p. 248
The Effectiveness of Theophylline on Important Outcomes for COPD	p. 248
Selective Phosphodiesterase Inhibitors in the Treatment of COPD	p. 254
The Role of Theophylline in the Acute Exacerbation of COPD	p. 257
Theophylline and Phosphodiesterase Inhibitors Use in COPD: Where Does It Fit In?	p. 257
References	p. 259
Corticosteroids in COPD	p. 265
Introduction	p. 265
Impact of Corticosteroids on Inflammation in COPD	p. 268
Clinical Effects of Corticosteroids in COPD	p. 269
Adverse Effects	p. 281
Corticosteroids and Guidelines	p. 282
Combining an Inhaled Corticosteroid and a Long-Acting [beta subscript 2]-Agonist in COPD	p. 287
Conclusion	p. 290
References	p. 291
Antioxidants and Protease Inhibitors	p. 299
Introduction	p. 299
Oxidative Stress and COPD	p. 299
Proteases and COPD	p. 312
Conclusions	p. 318
References	p. 318
An Integrated Approach to the Pharmacological Therapy of COPD	p. 327
Introduction	p. 327
Change in Paradigm: A Constructive Analogy with Systemic Hypertension	p. 328
Proof of Concept	p. 330
COPD: A Pulmonary Disease with Systemic Consequences	p. 331
General Principles of Pharmacological Therapy in COPD	p. 333
Initiation of Drug Therapy	p. 334
Use of Corticosteroids	p. 337
Other Medications	p. 338
Management of Acute Exacerbations	p. 339
Summary and Conclusion	p. 341
References	p. 341
Index	p. 347
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