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Acetylsalicylic Acid 2nd Ed.
Acetylsalicylic Acid 2nd Ed.
Edición/Edição:
Autores: Karsten Schror
Editorial:
ISBN: 9783527338054
Formato: Rústica/Paperback
Nº volumenes: 1 Páginas: 480
Año publicación/Ano de publicação: 2016
Disponibilidad/Disponibilidade: 15 días
Precio/Preço : 85,19 € 80,92 € (84,16€ iva incluído)
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Cómpralos juntos y ahorra
Acetylsalicylic Acid 2nd Ed. Oficina De Farmacia (G.M. Farmacia Y Parafarmacia)
· Acetylsalicylic Acid 2nd Ed. (Karsten Schror)
· Oficina De Farmacia (G.M. Farmacia Y Parafarmacia) (Ana Reyes Tejada Salas)
108,27 € 102,86 €
Descripción/Descrição
Written by a leading expert on Aspirin-related research, this is the first comprehensive treaty of the history, pharmacological effects and clinical applications of one of the most successful drugs ever.

The text is written with a wide audience in mind, and to be readily understandable for clinicians, pharmacists, biomedical researchers and pharmacologists alike.

This second, completely revised edition contains the latest results of clinical and pharmacological research on Acetylsalicylic acid, addressing the multiple pharmacological properties of this famous drug with a balanced view on their translation into clinical practice, including prevention from cardiovascular diseases and colorectal cancer.
Contents
Preface XIII
1 General Aspects 3
1.1 History 5
1.1.1 From Willow Bark to Salicylic Acid 5
1.1.1.1 Anti-Inflammatory and Analgesic Effects of Willow Bark and Leaves 5
1.1.1.2 Salicylates as the Active Ingredients of Willow Bark and Other Natural Sources 6
1.1.1.3 Chemical Synthesis of Salicylic Acid 6
Summary 8
References 8
1.1.2 Synthesis of Acetylated Salicylic Acid and First Medical Use 9
1.1.2.1 The Invention of Acetylated Salicylic Acid 9
1.1.2.2 Introduction of Acetylsalicylic Acid into the Clinics 15
Summary 16
References 16
1.1.3 Search for Pharmacological Modes of Action 18
1.1.3.1 Salicylates and Energy Metabolism of the Cell 18
1.1.3.2 Aspirin and Prostaglandin Formation 19
1.1.3.3 Aspirin and COX-2 21
Summary 23
References 23
1.1.4 Clinical Applications: A Piece of History 25
1.1.4.1 Anti-Inflammatory/Analgesic Actions 25
1.1.4.2 Antiplatelet/Antithrombotic Actions and the Bleeding Tendency 26
1.1.4.3 Aspirin and the History of Prevention of Myocardial Infarction and Stroke 27
Summary 30
References 30
1.1.5 Current Research Topics 32
1.1.5.1 Clinical Research 32
1.1.5.2 Basic Research 33
Summary 39
References 39
1.2 Chemistry 41
1.2.1 Structures and Chemical Properties of Salicylates 41
1.2.1.1 Salicin: The Natural Salicylate 41
1.2.1.2 Salicylates in Clinical Use 41
1.2.1.3 Aspirin Formulations 43
Summary 45
References 46
1.2.2 Determination of Salicylates 47
1.2.2.1 Gas–Liquid Chromatography 47
1.2.2.2 High-Performance Liquid Chromatography 47
1.2.2.3 Spectrophotometry 47
Summary 49
References 49
2 Pharmacology 51
2.1 Pharmacokinetics 54
2.1.1 Absorption and Distribution 54
2.1.1.1 Absorption and Bioavailability 54
2.1.1.2 Aspirin Formulations 57
2.1.1.3 Distribution and Plasma Levels 60
2.1.1.4 Modifying Factors 62
Summary 63
References 64
2.1.2 Biotransformation and Excretion 66
2.1.2.1 Aspirin Esterases 66
2.1.2.2 Biotransformations of Salicylic Acid 70
2.1.2.3 Excretion of Salicylates 71
Summary 72
References 72
2.2 Cellular Modes of Action 75
2.2.1 Inhibition of Cyclooxygenases 76
2.2.1.1 COX-Isoforms, Substrates, and Regulation 76
2.2.1.2 Inhibition/Modulation of Cyclooxygenases by Aspirin 78
2.2.1.3 The Different Pharmacology of Aspirin and NSAIDs 82
2.2.1.4 Modulation of COX-2 Gene Expression 84
2.2.1.5 Further Actions of Salicylates on Lipid Mediators 85
Summary 85
References 86
2.2.2 COX-Independent Actions of Aspirin on Cell Function 89
2.2.2.1 Salicylates in the Plant Kingdom 89
2.2.2.2 Transacetylation Actions by Aspirin 89
2.2.2.3 Aspirin and Nitric Oxide Formation 91
2.2.2.4 Salicylates and Kinases 92
2.2.2.5 Salicylates and Transcription Factors 96
Summary 98
References 99
2.2.3 Energy Metabolism 101
2.2.3.1 Different Pharmacodynamics of Aspirin and Salicylates 101
2.2.3.2 Fatty Acid β-Oxidation 102
2.2.3.3 Uncoupling of Oxidative Phosphorylation 106
2.2.3.4 Metabolic Actions of Salicylates and Reye’s Syndrome 108
Summary 109
References 110
2.3 Actions on Organs and Tissues 113
2.3.1 Hemostasis and Thrombosis 113
2.3.1.1 General Aspects 113
2.3.1.2 Platelets 115
2.3.1.3 Endothelial Cells 123
2.3.1.4 Plasmatic Coagulation 128
2.3.1.5 Fibrinolysis 128
Summary 129
References 130
2.3.2 Inflammation, Pain, and Fever 136
2.3.2.1 General Aspects 136
2.3.2.2 Inflammation 137
2.3.2.3 Pain 142
2.3.2.4 Fever 147
Summary 149
References 150
2.3.3 Aspirin and Malignancies 153
2.3.3.1 General Aspects 153
2.3.3.2 Pathophysiology 154
2.3.3.3 Modes of Aspirin Action 156
2.3.3.4 COX-Related Actions of Aspirin 157
2.3.3.5 Non-COX-Related Antitumor Actions of Aspirin 160
Summary 162
References 162
Contents VII
3 Toxicity and Drug Safety 167
3.1 Systemic Side Effects 170
3.1.1 Acute and Chronic Toxicity 170
3.1.1.1 General Aspects 170
3.1.1.2 Pathophysiology and Clinical Symptoms of Acute Overdosing 172
3.1.1.3 Treatment 175
3.1.1.4 Habituation 177
Summary 177
References 178
3.1.2 Bleeding Time and Bleeding Risk 180
3.1.2.1 Aspirin and Bleeding Time 180
3.1.2.2 Mode of Aspirin Action 181
3.1.2.3 Aspirin-Related Bleeding Risk in Long-Term Prevention and Acute Surgical Interventions 184
3.1.2.4 Prevention and Treatment of Bleedings 186
Summary 187
References 188
3.1.3 Safety Pharmacology in Particular Life Situations 191
3.1.3.1 Pregnancy and Fetal Development 191
3.1.3.2 The Elderly Patient 193
Summary 195
References 195
3.2 Organ Toxicity 198
3.2.1 Gastrointestinal (GI) Tract 198
3.2.1.1 General Aspects 198
3.2.1.2 Pathophysiology of Aspirin-Induced GI Injury 199
3.2.1.3 Mode of Aspirin Action 201
3.2.1.4 Clinical Studies 205
3.2.1.5 Aspirin and Other Drugs 209
Summary 211
References 211
3.2.2 Liver 216
3.2.2.1 General Aspects 216
3.2.2.2 Pathophysiology and Mode of Aspirin Action 216
3.2.2.3 Clinical Studies 217
Summary 217
References 218
3.2.3 Kidney 219
3.2.3.1 General Aspects 219
3.2.3.2 Analgesic Nephropathy and its Pathophysiology 219
3.2.3.3 Mode of Aspirin Action 220
3.2.3.4 Clinical Studies – Individuals without Kidney Diseases 221
3.2.3.5 Clinical Studies – Individuals with Preexisting Kidney Diseases 223
Summary 225
References 226
3.2.4 Audiovestibular System 228
3.2.4.1 General Aspects 228
3.2.4.2 Pathophysiology of Aspirin-Induced Hearing Loss and Tinnitus 228
3.2.4.3 Mode of Aspirin Action 228
3.2.4.4 Clinical Studies 230
Summary 231
References 231
3.3 Hypersensitivity to Aspirin and Reye’s Syndrome 233
3.3.1 Aspirin-Exacerbated Respiratory Disease (AERD, “Aspirin-Induced Asthma”) 233
3.3.1.1 History, Epidemiology, and Pathophysiology 233
3.3.1.2 Mode of Aspirin Action 237
3.3.1.3 Clinical Studies 239
3.3.1.4 Aspirin and Other Drugs 240
Summary 240
References 241
3.3.2 Urticaria/Angioedema and Stevens–Johnson and Lyell’s Syndrome 244
3.3.2.1 Urticaria/Angioedema 244
3.3.2.2 Stevens–Johnson Syndrome and Lyell’s Syndrome 245
Summary 245
References 245
3.3.3 Reye’s Syndrome 247
3.3.3.1 Clinics, Laboratory and Morphological Findings 248
3.3.3.2 Etiology and Pathogenesis 249
3.3.3.3 Clinical Studies 252
3.3.3.4 Actual Situation 256
Summary 258
References 259
4 Clinical Applications of Aspirin 263
4.1 Thromboembolic Diseases 268
4.1.1 Coronary Vascular Disease 269
4.1.1.1 General Aspects 269
4.1.1.2 Thrombotic Risk and Mode of Aspirin Action 271
4.1.1.3 Clinical Trials: Primary Prevention in Apparently Healthy Individuals 275
4.1.1.4 Clinical Trials: Primary Prevention in Individuals with Vascular Risk Factors 279
4.1.1.5 Clinical Trials: Cardiovascular Prevention in Patients with Stable Angina 284
4.1.1.6 Clinical Trials: Acute Coronary Syndromes (ACS) 285
4.1.1.7 Clinical Trials: Long-Term Secondary Prevention 288
4.1.1.8 Clinical Trials: Coronary Artery Bypass Graft Surgery (CABG) and Other Surgical Interventions 291
4.1.1.9 Aspirin and Other Drugs 292
4.1.1.10 Actual Situation 297
Summary 298
References 299
4.1.2 Cerebrovascular Diseases 307
4.1.2.1 General Aspects 307
4.1.2.2 Thrombotic Risk and Mode of Aspirin Action 308
4.1.2.3 Clinical Trials: Primary Prevention 312
4.1.2.4 Clinical Trials: Secondary Prevention 314
4.1.2.5 Aspirin and Other Drugs 318
4.1.2.6 Actual Situation 323
Summary 324
References 325
4.1.3 Peripheral Arterial Disease 330
4.1.3.1 General Aspects 330
4.1.3.2 Thrombotic Risk and Mode of Aspirin Action 330
4.1.3.3 Clinical Trials: Primary Prevention 332
4.1.3.4 Clinical Trials: Secondary Prevention 334
4.1.3.5 Clinical Trials: Peripheral Transluminal Angioplasty (PTA) and Surgical Interventions 336
4.1.3.6 Aspirin and Other Drugs 337
4.1.3.7 Actual Situation 339
Summary 339
References 339
4.1.4 Venous Thrombosis 343
4.1.4.1 General Aspects 343
4.1.4.2 Thrombotic Risk and Mode of Aspirin Action 343
4.1.4.3 Clinical Trials: Primary Prevention 344
4.1.4.4 Clinical Trials: Secondary Prevention 348
4.1.4.5 Aspirin and Other Drugs 350
4.1.4.6 Actual Status 350
Summary 351
References 351
4.1.5 Preeclampsia 354
4.1.5.1 General Aspects 354
4.1.5.2 Thrombotic Risk and Mode of Aspirin Action 354
4.1.5.3 Clinical Trials: Early Studies 358
4.1.5.4 Clinical Trials: Reasons for Data Variability 359
4.1.5.5 Actual Situation 363
Summary 364
References 365
4.1.6 Aspirin “Resistance” (High On-Aspirin Treatment Platelet Reactivity) 369
4.1.6.1 General Aspects 369
4.1.6.2 Definition and Types of Pharmacological Aspirin “Resistance” (HTPR) 370
4.1.6.3 Detection of Aspirin “Resistance” and Possible Pitfalls in Its Determination 371
4.1.6.4 Phenotypes of Aspirin “Resistance” (HTPR) 373
4.1.6.5 Clinical Trials 379
4.1.6.6 Actual Situation 383
Summary 383
References 384
4.2 Pain, Fever, and Inflammatory Diseases 389
4.2.1 Analgesia and Antipyresis 390
4.2.1.1 General Aspects 390
4.2.1.2 Pain, Fever, and Mode of Analgesic/Antipyretic Aspirin Action 390
4.2.1.3 Clinical Trials 394
4.2.1.4 Aspirin and Other Drugs 397
4.2.1.5 Actual Situation 397
Summary 397
References 398
4.2.2 Inflammatory Diseases 401
4.2.2.1 General Aspects 401
4.2.2.2 Rheumatoid Arthritis: Pathophysiology and Mode of Aspirin Action 402
4.2.2.3 Osteoarthritis: Pathophysiology and Mode of Aspirin Action 403
4.2.2.4 Systemic Inflammatory Response Syndrome (SIRS): Pathophysiology and Mode of Aspirin Action 403
4.2.2.5 HIV: Pathophysiology and Mode of Aspirin Action 404
4.2.2.6 Clinical Trials 405
4.2.2.7 Aspirin and Other Drugs 407
4.2.2.8 Actual Situation 410
Summary 410
References 411
4.2.3 Kawasaki’s Disease 414
4.2.3.1 General Aspects 414
4.2.3.2 Pathophysiology and Mode of Aspirin Action 414
4.2.3.3 Clinical Trials 415
4.2.3.4 Aspirin and Other Drugs 416
4.2.3.5 Actual Situation 416
Summary 416
References 417
4.3 Further Potential Clinical Indications 418
4.3.1 Colorectal Cancer 418
4.3.1.1 General Aspects 418
4.3.1.2 Pathophysiology of Intestinal Neoplasias 419
4.3.1.3 Mode of Aspirin Action 419
4.3.1.4 Clinical Trials: Primary Prevention 423
4.3.1.5 Clinical Trials: Secondary Prevention 428
4.3.1.6 Aspirin, Other Drugs, and Environmental Factors 431
4.3.1.7 Actual Situation 432
Summary 434
References 434
4.3.2 Alzheimer’s Disease 438
4.3.2.1 General Aspects 438
4.3.2.2 Pathophysiology and Mode of Aspirin Action 438
4.3.2.3 Clinical Trials 440
4.3.2.4 Aspirin and Other Drugs 444
4.3.2.5 Actual Situation 444
Summary 444
References 445
Appendix 1: Abbreviations 447
Appendix 2: Selected Clinical Trials and Their Acronyms – Only Published Trials 449
Index 453
Author Information
Karsten Schrör is Professor of Pharmacology and retired Chairman of the Department of Pharmacology and Clinical Pharmacology at the Heinrich-Heine-University in Düsseldorf, Germany. He obtained his M.D. at Martin-Luther-University Halle-Wittenberg (Germany) and carried out postdoctoral studies at the Universities of Halle, Mainz, Köln, the Wellcome Research Laboratories in Beckenham (UK) and the Jefferson Medical College, Philadelphia (USA). He held guest professorships at the Medical University of South Carolina at Charleston (USA) and the Department of Internal Medicine, Division of Hematology, University of Texas Medical Center, Houston (USA). Karsten Schrör is member of the German National Academy of Science (Leopoldina) and was President of the German Society for Pharmacology from 2005 to 2010. He has published extensively in the area of aspirin and prostaglandin research with focus on platelet functions and the clotting system and serves on several national and international review panels and advisory committees on thrombosis research, colorectal cancer and drug development.
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