Aspirin and Related Drugs

Aspirin and Related Drugs......Page 3
Contents......Page 6
Contributors......Page 11
Preface......Page 12
Abbreviations and Nomenclature......Page 16
Roman and Greek medicine......Page 27
Table of Contents......Page 0
European Middle Ages......Page 28
CHEMICAL DEVELOPMENT OF SALICYLATES......Page 32
CLINICAL OBSERVATIONS ON THE USE OF SALICYLATES IN THE NINETEENTH CENTURY......Page 33
Antipyretic activity......Page 34
Treatment of acute rheumatism ( rheumatic fever)......Page 35
EARLY CLINICAL STUDIES WITH SALICYLATES IN THE TREATMENT OF RHEUMATOID ARTHRITIS......Page 39
Synthesis and commercial development of aspirin......Page 40
ASPECTS OF THE COMMERCIAL DEVELOPMENT OF ASPIRIN......Page 43
REFERENCES......Page 45
RECOGNITION OF PAIN......Page 50
THE ORGANIC CHEMICAL INDUSTRY......Page 51
Acetanilid......Page 52
THE SALICYLATES......Page 53
Aspirin......Page 55
THE VALUE OF A GOOD NAME......Page 58
CONCLUSION......Page 63
REFERENCES......Page 64
NATURALLY OCCURRING SALICYLATES......Page 69
Structure and reactions of aspirin......Page 75
Non- enzymic hydrolysis of aspirin......Page 79
Solution chemistry of the salicylates......Page 80
Salicylic and acetylsalicylic acids, their salts and esters......Page 81
Salicylamide......Page 85
Salicylate derivatives......Page 86
Nitric oxide- releasing aspirins ( NO- aspirins)......Page 89
Meseclazone......Page 91
Aspirin anhydride......Page 92
Dihydroxy- and diacetoxybenzoic acids......Page 93
Ester pro- drugs......Page 94
Acetyl- 3,5- dibromosalicylic acid and dibromosalicyl- bis- fumarate (‘dispirit')......Page 100
Salicylate – selective electrodes......Page 102
REFERENCES......Page 103
ABSORPTION OF ASPIRIN AND SALICYLATE......Page 120
Presystemic metabolism......Page 121
Localisation in the stomach......Page 122
Percutaneous absorption......Page 123
Binding to plasma proteins......Page 124
Tissue uptake of aspirin and salicylate......Page 126
ELIMINATION OF ASPIRIN......Page 129
Hydrolysis of aspirin......Page 130
ELIMINATION OF SALICYLATE......Page 132
Urinary excretion of salicylate......Page 133
Salivary excretion of salicylate......Page 134
Salicylurate......Page 135
Hydroxylated salicylates: gentisate and 2,3- dihydroxybenzoate......Page 137
Comparative metabolic pathways of salicylate......Page 139
Genetics......Page 140
Sex......Page 141
Auto- induction of metabolism of salicylate......Page 142
Effects of salicylates on the disposition and pharmacological effects of other drugs......Page 143
KINETICS OF ELIMINATION OF SALICYLATE......Page 144
Comparative pharmacokinetics of salicylate......Page 145
Benorylate......Page 146
Salsalate ( salicylsalicylic acid)......Page 147
Methyl salicylate......Page 148
ANALYTICAL METHODS FOR THE SALICYLATES......Page 149
Colorimetric and spectrophotometric procedures......Page 150
Gas chromatography......Page 151
Nuclear magnetic resonance spectroscopy ( NMR)......Page 152
Oral absorption......Page 153
Elimination......Page 154
Distribution......Page 155
Elimination......Page 156
SALICYLAMIDE......Page 157
Elimination......Page 158
REFERENCES......Page 160
ABSORPTION......Page 179
Tissue distribution......Page 181
Synovial fluid and other peripheral sites......Page 182
Lipids......Page 183
Glucuronidation......Page 184
Metabolic oxidation......Page 185
Inversion of R- to S- ibuprofen and related metabolism......Page 186
HALF-LIFE AND CLEARANCE......Page 188
Age......Page 189
Rheumatoid arthritis......Page 190
Effects of ibuprofen on the clearance of other drugs......Page 191
PHARMACOKINETICS, PLASMA CONCENTRATIONS AND CLINICAL RESPONSE......Page 192
Stereoselective......Page 193
REFERENCES......Page 194
ABSORPTION......Page 203
Measures to limit the absorption of overdoses......Page 204
Central nervous system......Page 205
Muscle and adipose tissue......Page 206
Placenta......Page 207
Oxidative metabolism by cytochrome P450s......Page 208
Oxidative metabolism by peroxidases ( including prostaglandin H synthase)......Page 211
Transacetylation......Page 212
HALF-LIFE AND CLEARANCE......Page 213
Other drugs......Page 214
Steroids and cytokines......Page 218
Pregnancy......Page 219
Disease states......Page 220
METABOLISM OF PRO-DRUGS......Page 221
REFERENCES......Page 222
INTRODUCTION......Page 235
Studies in animal models......Page 240
Acute inflammatory models......Page 241
Chronic polyarthritis in rats......Page 257
Effects on the synthesis and metabolism of prostaglandins, thromboxanes and leukotrienes......Page 264
Effects of salicylates on free radical production and actions......Page 285
Peroxisomal metabolism......Page 286
Early phase amines and kinins......Page 287
Lysosomal and other hydrolases......Page 289
Endothelial damage, leucocyte migration and platelet accumulation......Page 291
Connective tissue metabolism......Page 298
Induction, modulation and perception of pain......Page 311
Analgesic activity of salicylates......Page 315
Comparative effects of salicylates in pain models in animals......Page 316
Mechanisms of analgesia......Page 321
Comparative efficacy of different salicylates......Page 327
Mode of actions of salicylates......Page 328
REFERENCES......Page 329
Appendix. Metabolic and Related Effects of Salicylates......Page 375
INTRODUCTION......Page 387
OCCURRENCE OF ADVERSE EVENTS FROM NSAIDs, INCLUDING ASPIRIN......Page 389
Historical......Page 390
Aspirin as a major cause of bleeding and ulceration......Page 393
Gastrointestinal side effects from salicylates in arthritic patients......Page 398
Assessment of gastrointestinal injury in humans......Page 399
Factors affecting gastrointestinal damage......Page 407
Site and pathology of lesions......Page 412
Studies in laboratory mammals......Page 413
Factors influencing gastric ulcerogenicity......Page 422
damage by aspirin in man with those in laboratory animals......Page 433
Intestinal damage......Page 435
Pathology of salicylate- induced gastrointestinal damage......Page 436
Biochemical effects......Page 444
Reduced production of mucus......Page 458
Mechanisms of gastric mucosal damage by salicylates......Page 461
Protection against aspirin- induced GI injury......Page 462
HEPATOTOXICITY......Page 468
NEPHROPATHY......Page 472
Analgesic abuse syndrome......Page 474
Studies in arthritic patients......Page 476
Pathology......Page 478
Biochemical effects of salicylates......Page 480
HYPERSENSITIVITY REACTIONS AND ASTHMA......Page 485
Aspirin- intolerant or aspirin sensitive asthma......Page 486
TERATOGENESIS AND PREGNANCY......Page 492
MISCELLANEOUS SIDE EFFECTS......Page 496
Toxic manifestations......Page 498
Management......Page 501
Available forms......Page 504
CONCLUSIONS......Page 505
REFERENCES......Page 506
INTRODUCTION......Page 575
DEFINITION......Page 576
Neurological signs......Page 577
Tissue pathology......Page 578
Laboratory diagnosis......Page 579
Inherited metabolic disorders ( IMD)......Page 580
Exogenous factors......Page 581
Reye's syndrome and aspirin......Page 584
Immune response......Page 590
Essential components of treatment are as follows......Page 595
Follow- up of survivors......Page 597
REFERENCES......Page 599
INTRODUCTION......Page 606
EARLY OBSERVATIONS IN VARIOUS PAIN STATES......Page 607
EFFICACY IN VARIOUS PAIN CONDITIONS......Page 608
Dental surgery......Page 611
General postoperative pain......Page 614
Postpartum and episiotomy......Page 615
Dysmenorrhoea......Page 616
Migraine and headache......Page 617
Minor aches and pains......Page 621
Cancer pain......Page 623
REFERENCES......Page 626
THE ROLE OF PLATELETS IN HAEMOSTASIS AND THROMBOSIS......Page 638
EFFECTS OF ACETYLSALICYLIC ACID ON PLATELET FUNCTION......Page 641
PHARMACOKINETICS OF ASA......Page 643
DOSE–EFFECT RELATIONSHIPS OF ASA......Page 644
Primary prevention of vascular disease......Page 645
Secondary prevention of vascular disease......Page 647
Treatment of acute myocardial infarction......Page 648
Treatment of acute ischaemic stroke......Page 649
REFERENCES......Page 650
INTRODUCTION......Page 652
HISTORY......Page 653
RHEUMATOID ARTHRITIS......Page 654
Aspirin versus non- acetylated salicylates......Page 656
Clinical use......Page 658
Juvenile rheumatoid arthritis......Page 659
Salicylazosulphapyridine ( sulphasalazine)......Page 660
OSTEOARTHRITIS......Page 663
Salicylates in osteoarthritis......Page 664
MISCELLANEOUS MUSCULOSKELETAL DISORDERS......Page 665
DRUG KINETICS AND MONITORING......Page 666
Interactions with anti- inflammatory drugs......Page 667
Gastrointestinal toxicity......Page 668
Renal adverse events......Page 673
Aspirin allergy......Page 675
Cardiovascular adverse effects......Page 677
Effects on joint destruction......Page 678
Thyroid function......Page 679
Reye's syndrome......Page 680
Age and sex......Page 681
CONCLUSIONS......Page 683
REFERENCES......Page 684
PREVENTION OF COLORECTAL AND OTHER CANCERS......Page 724
studies......Page 732
ALZHEIMER’S DISEASE AND RELATED DEMENTIAS......Page 734
Inflammatory components of the pathogenesis of AD......Page 735
of aspirin and related drugs......Page 736
Inflammatory diseases......Page 737
Cancer and other conditions......Page 739
THERAPEUTIC USES OF ASPIRIN IN PREGNANCY......Page 740
Pre- eclampsia......Page 741
KAWASAKI DISEASE......Page 743
Diabetes mellitus......Page 744
Thyroiditis and thyrotoxicosis......Page 747
Obesity......Page 748
Multiple sclerosis......Page 749
Sickle cell anaemia......Page 750
Thrombotic thrombocytopenic purpura......Page 751
MISCELLANEOUS......Page 752
REFERENCES......Page 753