Pharmacology and Therapeutics of Asthma and COPD

374 Pages·2004·7.364 MB·English

by  L. B. Fernandes, P. J. Henry, R. G. Goldie (auth.), Professor Clive P. Page, Professor Peter J. Barnes (eds.)

Handbook of
Experimental Pharmacology
Volume
161
Editor-in-Chief
K. Starke, Freiburg i. Br.
Editorial Board
G.V.R. Born, London
M. Eichelbaum, Stuttgart
D. Ganten, Berlin
F. Hofmann, Munchen
B. Kobilka, Stanford, CA
W. Rosenthal, Berlin
G. Rubanyi, Richmond, CA
Springer-Verlag Berlin Heidelberg GmbH
Pharmacology and Therapeutics
of Asthma and COPD
Contributors
w.
P. J. Barnes, Busse, 1. Dziadzio, E. M. Erin,
1.B. Fernandes, R.G. Goldie, N.J. Gross, I.P. HaU,
T. T. Hansel, P.J. Henry, N.A. Jones, S. Kharitonov,
R. Lever, W. Neaville, C.P. Page, D. Spina , A.J. Tan,
R. C. Tennant, N. C. Thomson
Editors
Clive P. Page and Peter J. Barnes
, Springer
Professor
Clive P. Page
Sackler Institute of Pulmonary Pharmacology
GKT School of Biomedical Sciences
Sth Floor, Rodgkin Building
Guy's Campus
London SEI 1 UL, UK
e-mail: [email protected]
Professor
Peter J. Barnes
National Reart & Lung Institute
Department of Thoracic Medicine
Imperial College
Dovehouse Street
London SW3 6LY, UK
e-mail: [email protected]
With 39 Figures and 13 Tables
ISSN 0171-2004
ISBN 978-3-642-05590-4
Library of Congress Cataloging-in-Publication Data
Pharmacology and therapeutics of astbma and COPD / contributors, P.J. Bames .... [et al.]. ; editors,
Clive P. Page and Peter 1. Bames. p.; cm. - (Handbook of experimental pharmacology; v. 161) In
cludes bibliographical references and index.
ISBN 978-3-642-05590-4 ISBN 978-3-662-09264-4 (eBook)
DOI 10.1007/978-3-662-09264-4
1. Antiasthmatic agents. 2. Asthma-Chemotherapy. 3. Lungs-Diseases, Obstructive-Chemotherapy.
1. Page, C.P. II. Bames, Peter 1., 1946-III. Series. [DNLM: 1. Anti-Asthmatic Agents-pharmacology.
2. Astbma-drug therapy. 3. Pulmonary Disease, Chronic Obstructive-drug therapy. 4. Asthma-physio
pathology. 5. Pulmonary Disease, Chronic Obstructive-physiopathology. WF 553 P5358 2004]
QP905.H3 voI. 161 [RC591] 615'. s-dc21 [615'.72] 2003054274
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Preface
In 1991 we published volume 98 entitled Pharmacology of Asthma in this
prestigious series. Since that time an enormous amount of information has been
generated in the field of "pulmonary pharmacology", not least the recent recogni
tion that chronic obstructive pulmonary disease (COPD) is also an important lung
disease requiring considerable research effort and is a disease that has perhaps
been neglected with respect to the effort put into our understanding of asthma
and its treatment. This new information is brought together in the present volume
written by internationally recognised authorities.
The aim of the book is to provide an in-depth review of our current understand
ing of the pathogenesis of both asthma and COPD. This volume also discusses
the promising new options for pharmacological intervention of these diseases.
It is hoped this book will be invaluable for research scientists and clinicians in
volved in research and treatment of asthma and COPD. It is also envisaged that it
will be a major reference resource for respiratory physicians and those involved
in the development of novel drugs.
Each chapter is extensively referenced, generously illustrated with clear dia
grams and photographs, and represents a state-of-the-art review of this important
area of lung biology.
C. P. Page . P. J. Barnes, London
List of Contributors
(Their addresses can be found at the beginning of their respective chapters.)
Barnes, P.J. 79,219,303,349 Jones, N.A. 53,179
Busse, W. 273
Kharitonov, S. 303
Dziadzio,1. 273
Lever, R. 245
Erin, E. M. 303
Neaville, W. 273
Fernandes, 1. B. 3
Page,C.~ 53,179,245,349
Goldie, R. G. 3
Gross, N.J. 37 Spina, D. 153,179
Han, 1. P. 287 Tan, A. J. 303
Hansel, T. T. 303 Tennant, R. e. 303
Henry, P.J. 3 Thomson, N.e. 125
Contents
Part 1. Current Drugs
,B-Adrenoceptor Agonists ................ . . . . . . . . . . . . . . . . . . . . . . . . . 3
L. B. Fernandes, P. J. Henry, R. G. Goldie
Anticholinergic Bronchodilators. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 37
N.f. Gross
Theophylline in the Treatment of Respiratory Disease . . . . . . . . . . . . . . . . .. 53
N.A. Jones, c.P. Page
Corticosteroids. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 79
P.J. Barnes
Mediator Antagonists and Anti-Allergic Drugs ........................ 125
N. C. Thomson
Part 2. Future Drugs
New Bronchodilator Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 153
D. Spina
Selective Phosphodiesterase Inhibitors in the Treatment
of Respiratory Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 179
N.A. Jones, D. Spina, c.P. Page
Cytokine Modulators ............................................ , 219
P.J. Barnes
Inhibitors of Leucocyte-Endothelial Adhesion
as Potential Treatments for Respiratory Disease . . . . . . . . . . . . . . . . . . . . . .. 245
R. Leve~ C.P. Page
New Antiallergic Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 273
L. Dziadzio, W. Neaville, W. Busse
X Contents
Pharmacogenetics, Pharmacogenomics and Gene Therapy . . . . . . . . . . . . .. 287
I.P. Hali
Evaluation of New Drugs for Asthma and COPD:
Endpoints, Biomarkers and Clinical Trial Designs ...................... 303
P.l. Barnes, E.M. Erin, T. T. Hansel, S.Kharitonov,
A.~ Tan,R.C. Tennant
Novel Anti-inflammatory Therapies ................................. 349
P.l. Barnes, c.P. Page
Subject Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 373
Part 1
Current Drugs
p-Adrenoceptor Agonists
L. B. Fernandes . P. J. Henry . R. G. Goldie
Western Australian Institute for Medical Research, Pharmacology Unit,
School of Medicine and Pharmacology, The University of Western Australia,
35 Stirling Highway, 6009, Crawley, WA, Australia
e-mail: [email protected]
lntroduction . 4
1.1 Asthma. 5
1.2 COPD ..... 5
2 The Jl-Adrenoceptor and Its Associated Signal Transduction Processes. 6
2.1 f:l-Adrenoceptor Subtypes. . . . . . . . . . . . . . . . . . . . 6
2.2 Adenylyl Cyclase. . . . . . . . . . . . . . . . . . . . . . . . . 7
3 Distribution and Density of Jl-Adrenoceptors in the Lung . 8
4 Jl-Adrenoceptor Agonists. 9
4.1 Adrenaline......... 9
4.2 Isoprenaline........ 10
4.3 Selective f:lz-Adrenoceptor Agonists 10
4.4 Long-Acting f:lz-Adrenoceptor Agonists . 10
4.5 Delivery of f:lz-Adrenoceptor Agonists . 12
5 Major Sites of Therapeutic Action . 12
5.1 Airway Smooth Muscle ...... . 12
5.2 Tracheobronchial Microvessels. . . 12
6 Other Potential Therapeutic Tissue Targets. 14
6.1 Inflammatory Cells . . . . . . . . . . . . . . 14
6.2 Secretory Cells . . . . . . . . . . . . . . . . . 15
7 Adverse Reactions to JlrAdrenoceptor Agonists . 16
7.1 Primary Adverse Reactions ......... . 16
7.2 Other Significant Direct Adverse Reactions . 16
7.3 Stereoisomers of Salbutamol 16
8 Combination Therapy. . . . 17
8.1 Long-Acting f:lz-Adrenoceptor Agonists and Glucocorticoids 17
8.2 Dz-Receptor Agonists ..................... . 19
9 Pharmacogenetics of f:lrAdrenoceptor Agonists in Asthma. 19
10 Clinical Application . 21
10.1 Asthma . 21
10.2 COPD ........ . 23
11 Concluding Remarks 24
References . . . . . . . . . 25