Reviewing over a century of aspirin research and use, Aspirin and Related Drugs provides a comprehensive source of information on the history, chemistry, absorption in the body, therapeutic effects, toxicology, elimination, and future uses of aspirin.Highlighting the historical evolution of the salicylates and the commercial development of aspirin, the book reviews the pharmacokinetics of the salicylates, ibuprofen, and paracetamol as a basis for understanding the biodisposition of these analgesic drugs. Leading specialists discuss the therapeutic role of aspirin in the prevention and treatment of thrombo-embolic diseases, its place along with non-acetylated salicylates in the treatment of rheumatic diseases and plain, and the potential applications for aspirin and related drugs as prophylactics for colon cancer, Alzheimer's disease, and vascular dementia. They also present comparisons with other drugs used to treat pain and inflammation.With extensive data and literature covering a broad field, this is the definitive reference on the actions and applications of aspirin, salicylates, and related drugs. Physicians, pharmacists, pharmacologists, toxicologists, and chemists will find this resource useful in their daily work. It will also be valuable to pharmaceutical companies and researchers in the development of newer agents and novel applications.

Kim Rainsford is Professor of Biomedical Sciences and Director of the Biomedical Research Centre at Sheffield Hallam University, UK

Contributors

xiii

Preface

xv

Abbreviations and nomenclature

xix

History and Development of the Salicylates

1

(24)

K.D. Rainsford

Introduction

1

(1)

Early Use of Salicylate-containing Plants

1

(5)

Chemical Development of Salicylates

6

(1)

Clinical Observations on the Use of Salicylates in the Nineteenth Century

7

(6)

Early Clinical Studies with Salicylates in the Treatment of Rheumatoid Arthritis

13

(1)

Chemical Development and Early Clinical Studies with Aspirin

14

(3)

Aspects of the Commercial Development of Aspirin

17

(2)

Other Salicylates

19

(1)

References

19

(6)

The Industrial History of Analgesics: The Evolution of Analgesics and Antipyretics

25

(20)

J.R. McTavish

Recognition of Pain

25

(1)

Therapeutic Nihilism and Fevers

26

(1)

The Organic Chemical Industry

26

(2)

The Salicylates

28

(5)

The Value of a Good Name

33

(5)

Conclusion

38

(1)

References

39

(6)

Occurrence, Properties and Synthetic Developments of the Salicylates

45

(52)

K.D. Rainsford

Introduction

45

(1)

Naturally Occurring Salicylates

45

(6)

Chemical Properties

51

(6)

Commercial Synthesis and Properties of the Salicylates

57

(8)

Experimental Drugs

65

(13)

Various Chemical Applications

78

(1)

Conclusions

79

(1)

References

79

(18)

Pharmacokinetics and Metabolism of the Salicylates

97

(60)

G.G. Graham

M.S. Roberts

R.O. Day

K.D. Rainsford

Introduction

97

(1)

Absorption of Aspirin and Salicylate

97

(4)

Distribution of Aspirin and Salicylate

101

(5)

Elimination of Aspirin

106

(3)

Elimination of Salicylate

109

(3)

Metabolic Pathways of Salicylate

112

(5)

Factors Controlling the Elimination of Aspirin and Salicylate

117

(4)

Kinetics of Elimination of Salicylate

121

(2)

Pro-Drugs

123

(3)

Analytical Methods for the Salicylates

126

(4)

Salicylate Derivatives

130

(2)

Diflunisal

132

(2)

Salicylamide

134

(3)

References

137

(20)

Metabolism and Pharmacokinetics of Ibuprofen

157

(24)

G.G. Graham

K.M. Williams

Introduction

157

(1)

Absorption

157

(2)

Distribution

159

(3)

Elimination

162

(4)

Half-life and Clearance

166

(1)

Factors Affecting the Elimination of Ibuprofen

167

(3)

Pharmacokinetics, Plasma Concentrations and Clinical Response

170

(1)

Analytical Methods

171

(1)

References

172

(9)

Pharmacokinetics and Metabolism of Paracetamol (Acetaminophen)

181

(34)

G.G. Graham

M. Hicks

Introduction

181

(1)

Absorption

181

(2)

Distribution

183

(3)

Elimination

186

(5)

Half-life and Clearance

191

(1)

Factors Affecting the Elimination of Paracetamol

192

(7)

Metabolism of Pro-drugs

199

(1)

Analytical Methods

200

(1)

References

200

(15)

Pharmacology and Biochemistry of Salicylates and Related Drugs

215

(152)

K.D. Rainsford

Introduction

215

(5)

Anti-inflammatory Effects

220

(24)

Biochemical Effects of Salicylates in Relation to their Anti-inflammatory Actions

244

(47)

Analgesic Activity

291

(16)

Antipyresis

307

(2)

References

309

(46)

Appendix to Chapter 7

355

(12)

Side Effects and Toxicology of the Salicylates

367

(188)

K.D. Rainsford

Introduction

367

(2)

Occurrence of Adverse Events from NSAIDs, including Aspirin

369

(1)

Gastrointestinal Side Effects

370

(78)

Hepatotoxicity

448

(4)

Nephropathy

452

(13)

Hypersensitivity Reactions and Asthma

465

(7)

Teratogenesis and Pregnancy

472

(4)

Miscellaneous Side Effects

476

(2)

Acute Salicylate Poisoning

478

(7)

Conclusions

485

(1)

References

486

(69)

Reye's Syndrome and Aspirin

555

(32)

J.F.T. Glasgow

S.M. Hall

Introduction

555

(1)

Background

556

(1)

Definition

556

(1)

Clinical Features

557

(1)

Investigations

558

(2)

Differential Diagnosis

560

(1)

Aetiology and Pathogenesis

561

(14)

Management Principles

575

(2)

The Future

577

(2)

Conclusion

579

(1)

Acknowledgements

579

(1)

References

579

(8)

Salicylates in the Treatment of Acute Pain

587

(32)

K.D. Rainsford

Introduction

587

(1)

Concepts of the Mode of Action in Acute Pain

588

(1)

Early Observations in Various Pain States

588

(1)

Efficacy in Various Pain Conditions

589

(3)

Comparative Effects in Acute Pain States

592

(15)

References

607

(12)

Acetylsalicylic Acid for the Prevention and Treatment of Thromboembolic Diseases

619

(16)

K.E. Webert

J.G. Kelton

The Role of Platelets in Haemostasis and Thrombosis

619

(3)

The Role of Platelets in Acute and Chronic Vascular Injury

622

(1)

Effects of Acetylsalicylic Acid on Platelet Function

622

(2)

Pharmacokinetics of ASA

624

(1)

Dose Effect Relationships of ASA

625

(1)

The Effects of ASA on Coagulation Factors, other than Platelets

626

(1)

ASA for the Prevention of Vascular Thromboembolic Disease: Epidemiological Studies

626

(3)

ASA for the Treatment of Acute Vascular Thromboembolic Events

629

(2)

Novel Analogues of Salicylates and Further Developments

631

(1)

References

631

(4)

Use of Salicylates in Rheumatic and Related Conditions

635

(72)

W.W. Buchanan

W.F. Kean

K.D. Rainsford

Introduction

635

(1)

History

636

(1)

Rheumatoid Arthritis

637

(9)

Ostcoarthritis

646

(2)

Miscellaneous musculoskeletal disorders

648

(1)

Drug Kinetics and Monitoring

649

(2)

Adverse Events in Rheumatic Patients

651

(13)

Factors Affecting Side Effects and Therapeutic Effects

664

(2)

Toxicity

666

(1)

Conclusions

666

(1)

References

667

(40)

Aspirin and NSAIDs in the Prevention of Cancer, Alzheimer's Disease and Other Novel Therapeutic Actions

707

(52)

K.D. Rainsford

Introduction

707

(1)

Prevention of Colorectal and Other Cancers

707

(10)

Alzheimer's Disease and Related Dementias

717

(3)

Copper Salicylates in the Treatment of Inflammatory Diseases and Cancer

720

(3)

Therapeutic Uses of Aspirin in Pregnancy

723

(3)

Kawasaki Disease

726

(1)

Perturbed Metabolic States

727

(5)

Immunological Effects

732

(1)

Other Possible Uses

733

(2)

Miscellaneous

735

(1)

References

736

(23)

Index

759

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