Side Effects of Anti-Inflammatory Drugs IV: The Proceedings of the IVth International Meeting on Side Effects of Anti-inflammatory Drugs, held in Sheffield, UK, 7–9 August 1995

346 Pages·1997·19.46 MB·English

by  K. D. Rainsford (auth.)

SIDE EFFECTS OF
ANTI-INFLAMMATORY DRUGS IV
IVth International Meeting
SIDE EFFECTS OF
ANTI-INFLAMMATORY
DRUGSIV
The Proceedings ofthe IVth International Meeting on
Side Effects of Anti-in.flammatory Drugs,
held in Sheffield, UK, 7-9 August 1995
Edited by K.D. RAINSFORD
Division of Biomedical Sciences
School of Science and Medicine
Sheffield Hallam University
Sheffield, UK
SPRINGER SCIENCE+BUSINESS MEDIA, B.V.
Library of Congress Cataloging-in-Publication Data is available.
ISBN 978-94-010-6269-5 ISBN 978-94-011-5394-2 (eBook)
DOI 10.1007/978-94-011-5394-2
Printed on acid-free paper
AII Rights Reserved
© 1997 Springer Science+Business Media Dordrecht
Originally published by Kluwer Academic Publishers in 1997
Softcover reprint of the hardcover 1s t edition 1997
No part of this publication may be reproduced or utilized in any form or by any means, electronic,
mechanical, including photocopying, recording or by any information storage and retrieval system,
without written permission from the copyright owner.
CONTENTS
Preface xi
I. INTRODUCTION
Current status of side-effects from anti-inflammatory drugs
KD Rainsford 3
II. CLINICO-EPIDEMIOLOGICAL ASPECTS
The placebo response: clinical efficacy and toxicity
WW Buchanan and N Bellamy 11
Side-effects of non-steroidal anti-inflammatory drugs: studies from the Tayside
Medicines Monitoring Unit
TM MacDonald 25
Treatment decisions, side-effect liability and cost-effectiveness in osteoarthritis
GE Ehrlich 31
Measuring beneficial and adverse events in osteoarthritis clinical trials
N Bellamy 35
Do NSAIDs adversely affect joint pathology in osteoarthritis?
FS Walker, KD Rainsford 43
Safety of non-steroidal anti-inflammatory drugs during pregnancy and lactation
ME 0stensen 55
Side-effects from biologics in the therapy of rheumatic diseases
JD Isaacs 67
Oral tolerance from a general perspective, and the possible role of side-effects in
the gut
A Mitchison, U Gimsa, J Sieper 77
Summary of Debate: Management of side-effects from anti-inflammatory drugs
KD Rainsford 81
III. FUNDAMENTAL ASPECTS
The concept of conditional pharmacology and toxicology
MCPowanda 87
v
vi Contents
Inflammation, stress and environmental factors as determinants of NSAID
efficacy and toxicity
MW Whitehouse 97
Do you really know what your drug looks like or how it reacts?
CJL Lock (deceased) 103
IV. GASTROINTESTINAL TRACT - CLINICAL ASPECTS
Intestinal pathology from NSAIDs
F Halter, A Gut, C Ruchti 121
A clinician's view of strategies for preventing NSAID-induced gastrointestinal
ulcers
J Huang, RH Hunt 139
Protection from NSAID-induced gastrointestinal damage
RI Russell 153
An overview of the key role of misoprostol in the prophylaxis of NSAID-
associated ulcers and their complications
GC Fenn 161
Clinical update of the relative safety of nabumetone in long-term clinical trials
JA Lipani, M Poland 171
Global analysis of gastrointestinal safety of a new NSAID, meloxicam
M Distel, C Mueller, E Bluhmki 183
V. GASTROINTESTINAL TRACT - EXPERIMENTAL
Gastrointestinal adaptation, eicosanoids, and mucosal protection from NSAIDs
KD Rainsford 197
New insight into NSAID-induced gastropathy
RS Spangler 207
Cyclooxygenase selectivity and NSAIDs: cyclooxygenase-2 selectivity of
etodolac (Lodine)
KB Glaser 211
Differential inhibition of cyclooxygenase-l (COX-I) and -2 (COX-2) by
NSAIDs: Consequences on anti-inflammatory activity versus gastric and
renal safety
M Pairet, L Churchill, G Trummlitz, G Engelhardt 223
Polymer delivery of the mucosal protective prostaglandin misoprostol
WE Perkins, SJ Tremont, PW Collins, JC Stolzenbach, GW Gullikson 233
Contents vii
Nitric oxide-releasing NSAIDs, a novel class of safe and effective anti
inflammatory agents
P Del Soldato, I Cuzzolin, A Adami, A Conforti, F Crivellente, G Benoni 235
Mitochondrial function and modification of NSAID carboxyl moiety
T Mahmud, JM Wrigglesworth, DL Scott, I Bjarnason 243
Effects of a new class of NO-releasing NSAIDs on platelets and isolated arteries
P Minuz, C Lechi, S Bonapace, S Gaino, A Adami, L Cuzzolin, P Del Soldato,
G Benoni 249
Al and A2 adenosine receptors mediate opposite effects on NSAID-induced
gastric ulcers in the rat
C Salcedo, AG Fernandez, JM Palacios 257
Role of vagal nerve in defence mechanisms against NSAIDs-induced
gastrointestinal mucosal damage
G Mozsik, OME Abdel-Salam, B BOdis, 0 Karadi, L Nagy, J Szolcsanyi 265
Analysis of the inhibiting actIvity of presynaptic cxradrenoceptors against
NSAID-induced gastric mucosal lesions in the rat
K Gyires, C Blandizzi, M del Tacca 287
VI. DERMAT OXICITY
Mechanisms of adverse reactions in the skin from anti-rheumatic drugs
KD Rainsford 297
Can in-vitro assays predict chemically-induced skin damage?
MG Clare, HL Cormack 305
VII. NOVEL THERAPIES
The use of ketorolac tromethamine oral rinse for the treatment of periodontitis
in adults
PF Cavanaugh Jr 317
VIII. ABSTRACTS
Variability in risk of major upper gastro-intestinal complications with individual
NSAIDs. Importance of drug dose and half-life; results of meta analysis.
D Henry 327
Non-steroidal associated ulcer bleeding - defining the risk factors
MJS Langman
Variability in exposure to NSAIDs in relation to safety
J Urquhart, E de Klerk 328
viii Contents
Non-steroidal anti-inflammatory drugs and infertility
G Nuki, G Smith, C Hall, R Roberts 329
Perioperative use of NSAID and postoperative infectious complications
K-E Giercksky 330
Medico-legal issues of non-steroidal anti-inflammatory drugs (NSAIDs)
WF Kean, D Buxton 330
The use of DMARDs and combination therapies
RD Sturrock 333
Non-steroidal anti-inflammatory drugs and acute appendicitis: a case-control
study
KS Vaidya, A MacGregor, JMM Evans, AD McMahon, MM McGilchrist, G
White, DG McDevitt, FE Murray, TM MacDonald . 333
Non-steroidal anti-inflammatory drugs and colitis: a record-linkage case-control
study
JMM Evans, AD McMahon, MM McGilchrist, G White, FE Murray, DG
McDevitt, TM MacDonald 334
New exposure to NSAIDs and hospitalisation for upper gastrointestinal events
JMM Evans, AD McMahon, G White, FE Murray, MM McGilchrist, DG
McDevitt, TM MacDonald 335
Topical NSAIDs and upper gastrointestinal bleeding and perforation
JMM Evans, AD McMahon, MM McGilchrist, G White, FE Murray, DG
McDevitt, TM MacDonald 335
Non-steroidal anti-inflammatory drugs, aspirin and colo-rectal cancer
JMM Evans, AD McMahon, MM McGilchrist, G White, FE Murray, DG
McDevitt, TM MacDonald 336
The pattern of prescribing of community dispensed ulcer-healing drugs in
Tayside
AT Prach, MM McGilchrist, G White, DG McDevitt, TM MacDonald, FE
Murray 337
Clinical trials of the relative safety of nabumetone in long-term clinical trials:
proposed rationale for safety profile
MP Poland, JA Lipani 338
Cyclooxygenase-2: a novel target for safety anti-inflammatory drugs
P Isakson 339
Inhibitory action of hydrophilic polymers on gastric lesions induced by
indomethacin in rats
SE Harras, YI Kim, HW Jun 340
Contents ix
Copper-derivatives and gastroprotection
GP Velo, L Franco, E Rizzarelli 341
The P3-adrenoceptor agonist CL316243 prevents indomethacin-induced jejunal
ulceration in the rat
A Anthony, AK Bahl, AP Dhillon, IG Oakley, CF Spraggs, MA Trevethick,
RE Pounder, AJ Wakefield 343
IX. EPILOGUE
The dilemma of modern medicine
W. Watson Buchanan 347
Index 351
INFLAMMOPHARMACOLOGY
Basic and clinical studies on inflammation and
its pharmacological control
Alms and Scope
The journal Inffammopharmacology publishes papers on ail aspects of
inflammation and its pharmacological control, emphasizing comparisons of (a)
different inflammatory states, and (b) the actions, therapeutic efficacy and safety
of drugs employed in the treatment of inflammatory conditions. The comparative
aspects of the types of inflammatory conditions include gastrointestinal disease
(e.g. ulcerative colitis, Crohn's disease), parasitic diseases, toxicological
manifestations of the effects of drugs and environmental agents, and arthritic
conditions. Inflammopharmacology covers all the major aspects of the
experimentally-induced clinical pathology, its biochemistry and cell biology, as
well as the clinical and experimental pharmacology and toxicology of therapeutic
agents. The emphasis on comparative aspects of the actions of drugs is intended
to highlight their efficacy and toxicity profiles as well as the variability in their
clinical response and safety. ISSN 0925-4692
In summary the journal covers:
• Experimental development of in vitro systems and in vivo animal models
• Assay methodologies
• Biochemical, immunological and pharmacological studies
• Clinical pharmacology and therapeutics
• Drug-induced side-effects - their incidence and mechanisms
• Comparative drug studies and trials
• Novel approaches towards the therapy of inflammatory conditions, including
brief but carefully conducted reports on therapies with as yet undefined
materials (e.g. natural products, immunological agents) which may be
considered as giving leads or encouragement to others to further purify or
define the active ingredients and explore their actions.
The journal publishes peer-reviewed unsolicited papers, reviews, short commu
nications, letters to the editor, drug status reports, editorials and short summaries
of hypotheses, and supplements.
Editor-in-Chief: KD Rainsford
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