j371 Index Acetylsalicylic Acid. Karsten Schrör Copyright Ó 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN:
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1 j371 Index a Aberrant crypt foci (ACF) 343 ACE inhibitors 184, 246, 249, 252 Acetaminophen (Paracetamol) Alzheimers disease 361f. analgesic action 324ff. analgesic nephropathy 180, 182 asthma 197ff., 217ff. hepatotoxicity 188 osteoarthritis 334f. renal failure 181f. Acetylsalicylic acid (ASA), see Aspirin Acute coronary syndrome, see Coronary vascular disease Adenomatous Polyposis Coli (APC) 118f., 343f., 346, 349, 354 Allodynia 114 Alzheimers Disease Anti-inflammatory Prevention Trial (ADAPT) 363 Alzheimers disease 18, 359ff. actual situation 363 clinical trials 361ff. etiology 359 mode of aspirin action 360 pathophysiology 359 American Health Professionals study 233f. Angioedema 205 Anticoagulants cerebrovascular disease 269ff. coronary vascular disease 247ff. peripheral arterial disease 282 venous thrombosis 287f. Antiplatelet drugs 91f., 280, 289, 294 Antiplatelet/antithrombotic Trialists Collaboration 229 Antipyretic analgesics 322ff., 329, 340 Antithrombotics in the Prevention of Reocclusion in Coronary Thrombolysis (APRICOT) 248 Antitumorigenic effects, see Malignancies Apoptosis 69, 71, 118, 120ff., 354 Aprotinin 146f. Arthritis and rheumatism 332ff. actual situation 336 clinical trials 334f. mode of aspirin action 332ff. osteoarthritis 333ff. rheumatoid arthritis 332ff. Aspirin, see also Salicylate absorption 34ff., 40 actions on organs and tissues 86ff. alcohol 146, 168 analgesic/antipyretic actions 14, 86, 105, 111, 113f., 323 ff. antiinflammatory actions 106ff., 232 antiplatelet actions 15, 86, 88, 90, 262 antitumor effects 120ff. antiulcer drugs 170 bioavailability 38f. biotransformations 46ff. bleeding risk 15, 142ff., 152, 159f., 244f. chemical properties 25ff. clinical applications 225ff. coagulation 98 COX-independent actions 66ff., 122 ff. COX-inhibition 13f., 54ff., 120ff., 163f. desensitization 201 determination 30ff. dosing 41, 88, 92, 226ff., 251, 262f., 352f. Ductus arteriosus 151f. energy metabolism 79ff. esterases 46ff. excretion 49ff. fertility 150 fibrinolysis 98f., 242f. formulations 27ff., 40, 326 gene transcription 13f., 61ff., 69ff. hemostasis 89ff. hepatotoxicity 187f. Acetylsalicylic Acid. Karsten Schrör Copyright Ó 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN:
2 372j Index history 5ff., 19ff. hypersensitivity, see also Aspirin-induced asthma 197ff. inhibition of platelet function 90ff. inhibition of prostaglandin formation 12, 53ff. inhibition of kinases 67ff. interactions with NSAIDs 60f. 170, 249f. 308f. miscarriage 151 modes of action 53ff. pharmacokinetics 33ff., 46ff. pharmacological properties 225 pseudoallergic actions 197ff. renal failure 181ff. resistance 303ff. sphingosine-1-phosphate 58 thrombin generation 143f. toxicity 131ff. transcription factors 69ff., 123f. Aspirin Esomeprazole Chemoprevention Trial (ASPECT) 312f. Aspirin-induced asthma 197ff., 217f. clinical studies 201f. clinical symptoms 198f. leukotrienes 200f. mode of aspirin action 199f. pathophysiology 197ff. Aspirin-like drugs 18, 60 Aspirin-Myocardial Infarction Study (AMIS) 17 Aspirin-triggered lipoxin (ATL) 59, 108f., 163f. Atherosclerosis Risk in Communities Study (ARIC) 227 Audiovestibular system, see Ototoxicity b Baltimore Longitudinal Study of Ageing 361 Barbados Low-dose Aspirin Study in Pregnancy (BLASP) 294, 297 Bioavailability 38ff. Biotransformations 46ff. Birmingham Atrial Fibrillation Treatment of the Aged Study (BAFTA) 270 Bleeding disorders 142ff. bleeding time 142ff. bleeding risk in surgical interventions 144ff. GI tract 159ff., 169f. hemorrhagic stroke 264 pregnancy and labor 152 role of platelets 143 British medical doctors study (BMDS) 232f., 264 c Cancer, see Malignancies Cancer prevention study II (CPS-II) 227, 347f. Cardiovascular diseases, see also Coronary vascular diseases ACE-inhibitors 249 in patients with renal disease 182ff. statins 249 Celecoxib Long-term Arthritis Safety Study (CLASS) 171 Ceramide 121, 123 Cerebrovascular diseases 260ff. actual situation 270f. anticoagulants 269f. clopidogrel 269 dipyridamole 267ff. etiology 260 hemorrhagic stroke 264f. mode of aspirin action 261ff. primary prevention 263ff. secondary prevention 265ff. Chinese Acute Stroke Trial (CAST) 266f. Cilostazol 283 Clopidogrel cerebrovascular disease 269 coronary vascular disease 246f. peripheral arterial disease 282 resistance 303 Clopidogrel for High Atherothrombotic Risk, Ischemic Stabilization, Management and Avoidance (CHARISMA) 247f. Clopidogrel in Unstable Angina to Prevent Recurrent Ischemic Events (CURE) 246, 269 Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) 229, 240, 246, 269, 282 Collaborative low-dose aspirin study in pregnancy (CLASP) 227, 293ff. Colorectal cancer 343ff. actual situation 352ff. clinical trials 346ff. COX-2 expression and aspirin 61f., 120f., 344ff. etiology 344f. mode of aspirin action 345f. NSAIDs 352 pathophysiology 344ff. Combination Hemotherapy and Mortality Prevention Study (CHAMP) 248 Coronary vascular diseases 411ff. actual situation 250ff. acute coronary syndrome (ACS) 238ff. aspirin historical use 15f. anticoagulants 247ff. Clopidogrel 246f. coronary artery bypass grafting 244ff. coxibs 249f. coronary artery bypass graft surgery (CABG) 244ff. etiology 228f. mode of aspirin action 229ff. NSAIDs 249 percutaneous coronary interventions (PCI) 243f. primary prevention 231ff.
3 Index j373 secondary prevention 238ff. Cottbus Reinfarction Trial 240f. COX atherosclerosis 95f. gastric mucosa 160f. gene expression 14, 61, 359 historical aspects 13ff. inhibition by NSAIDs 54ff., 171, 335ff., 363 lipoxins 59 role in asthma 199f. transcription factors 69ff. COX-1 acetylation by aspirin 56ff. active site 55f. aspirin-induced asthma 199f. 12-HPETE 62 inhibition by aspirin 54ff. interaction with NSAIDs 308 platelet function 90ff. COX-2 acetylation by aspirin 59ff. gene expression 61, 120f., 359 inhibition by aspirin 56ff., 163 lipoxins 59 platelet function 90ff. tumor promotion 120ff., 345, 350 COX Coxibs cardiovascular risk 335f. interactions with aspirin 108, 170f. Critical Leg Ischemia Prevention Study (CLIPS) 279, 281 Cyclooxygenases, see COX d Deep vein thrombosis, see Venous thrombosis Desmopressin 146 Diabetes 183 Dicarboxylic acids 81, 209 Dipyridamole 267ff., 280, 282f. Dipyrone 308 Disease-modifying Antirheumatic Drugs (DMARDs) 332, 334 Ductus arteriosus 151f. Dutch TIA Trial 265f. e Endocannabinoids 111 Endothelium antiplatelet factors 96f. atherosclerosis 95ff. dysfunction 278 inflammation 108f. NO-synthase (enos) 74f. prostaglandin production 95ff. Energy metabolism 79ff. European and Australian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) 268 European Stroke Prevention Study-2 (ESPS-2) 267f. f Fatty acid metabolism 80ff. Ferritin 74 Fertility 150ff. Fetal development 150f. Fever 113ff., 323, 326 Fibrinolysis 98f., 242f., 278 g Gastrointestinal tract (GI) 157ff. aspirin and GI injury 161ff., 170 ff. clinical trials 166ff. coxibs 170f. gastric mucosa 358ff. gastrointestinal bleeding 159ff. Helicobacter pylori 164ff. mode of aspirin action 161ff. prostaglandins and GI injury 160f. Global Registry of Acute Coronary Events (GRACE) 227, 251, 276 h Habituation 139 Headache, see Pain Health Professionals Follow-up Study (HPFS) 347ff. Hearing disturbances, see Ototoxicity Heart failure 183f. Heart Outcomes Prevention Evaluation (HOPE) 310ff. Helicobacter pylori 164ff. Heme oxygenase 174f. Hemorrhage, see Bleeding disorders Hemorrhagic stroke, see Cerebrovascular diseases Hemostasis 89ff. Hepathoencephalopathy, see Reyes syndrome Hypertension 183, 235 Hypertension in pregnancy, see Preeclampsia Hypertension Optimal Treatment study (HOT) 234ff., 260, 264f. Hyperthermia 137f. Hyperventilation 79,134f. i Ibuprofen 56f., 60, 151, 171, 324 Indomethacin 56f., 143f., 151, 171 Inflammation 74, 105ff., 231 Inflammation marker 232 International Study on Infarct Survival (ISIS) 17, 99, 170, 227, 239, 242ff. International Stroke Trial (IST) 266
4 374j Index Ischemia, see individual organs Isoprostanes 94, 309 j Jamaica Low-Dose Aspirin Study Project (JLASP) 294, 297 k Kawasaki disease 339ff. clinical trials 340 mode of aspirin action 339 pathophysiology 339 Reyes syndrome 217, 340 Kidney 179ff. analgesic nephropathy 179f. clinical studies 181f. diabetes 183 mode of aspirin action 180 Kinases 66ff. Leukotrienes asthma 198ff. inflammation 106, 108 ototoxicity 193 Lipoxins, see also Aspirin-triggered Lipoxin 108 Liver 187ff. aspirin actions 80ff.,187 drugs and liver injury 84, 187 hepatotoxicity of salicylates 84f., 187, 210f. Reyes syndrome 84f. Lyell syndrome 206 m Malignancies 118ff., 343ff. Malondialdehyde 122 Management of Atherothrombosis with Clopidogrel in High-risk Patients with recent Transient Ischemic Attack or Ischemic Stroke (MATCH) 269 Maximal Individual Optimized Therapy for Acute Myocardial Infarction (MITRA) 251 Melbourne Colorectal Cancer Study 346 Metamizol, see Dipyrone Methylsalicylate 27 Migraine 326ff. Myocardial infarction, see Coronary vascular diseases Myocardial Infarction Registry (MIR) 251 n Neuroprotection 72f., 360 Nitric oxide (NO) 73, 96f., 164 endothelial NO-synthase (enos) 74, 143 inducible NO-synthase (inos) 73f., 106 Nonsteroidal antiinflammatory drugs (NSAIDs) Alzheimers disease 360ff. antiplatelet effects of aspirin 60, 249f., 308 asthma 199f. colorectal carcinoma 346ff. COX-1/COX-2-selectivity 55f. Ductus arteriosus 151, 292f. GI-effects 160f., 170f. interactions with aspirin 60f. miscarriage 151 mode of action 60, 108 osteoarthritis 333, 336 renal effects 181f. Nuclear factor kb (NFkB) 70ff., 123 Nuclear factor of activated T-cells (NFAT) 70f. Nurses Health Study (NHS) 181, 227, 348ff. o Orbital Atherectomy Study for Treatment of Peripheral Vascular Stenosis (OASIS) 248 Organ toxicity 157ff. Osteoarthritis 171, 333, 336 acetaminophen 335 clinical trials 334 Ototoxicity 191ff. clinical trials 193f. hearing disturbances 191f. mode of aspirin action 191f. pathophysiology 191 tinnitus 192 Oxidative phosphorylation 82ff. p Pain 110ff., 322ff. acetaminophen 324ff. cannabinoids 111 clinical studies 326ff. headache 326ff. mediators of pain 110ff. migraine 326ff. mode of aspirin action 111ff., 323ff. prostaglandins 110f. serotonin 112 Paracetamol, see Acetaminophen Perinatal Antiplatelet Review of International Studies (PARIS) 295, 297ff. Peripheral Arterial Disease (PAD) 276ff. actual situation 283 clinical trials 278ff. etiology 276 mode of aspirin action 276ff. other drug treatment 282f. peripheral transluminal angioplasty 281f. Phenacetin 180 Physicians Health Study, see US-Physicians Health Study Platelets 89ff.
5 Index j375 aspirin-insensitive inhibition 309, 315 bleeding time 143 cyclooxygenases 56ff., 308f. inhibition by aspirin 90ff. response variability, see also resistance 261f., 303ff. thrombotic risk 229f., 276f. thromboxane formation 91ff., 306f. time-dependent inhibition 91 Preeclampsia 290ff. actual situation 298 clinical trials 293ff. etiology 290 miscarriage 151, 298 mode of aspirin action 290f. Pregnancy 150ff. Pregnancy-induced hypertension, see Preeclampsia Prevention Regimen For Effectively avoiding Second Strokes (PROFESS) 268f. Primary Prevention Project (PPP) 170, 236f., 264 Prostacyclin, see also Prostaglandins 95ff., 291f. Prostaglandins biosynthesis 55ff. general aspects 12f. mode of aspirin action 11ff., 55 pain mediators 110f. receptors 122 Prostaglandin synthases, see COX r Resistance 303ff. clinical trials 262, 310ff. definition 304 measurement 304ff. mechanisms 303ff. role of thromboxane 306f. Reyes syndrome 208ff. actual situation 217f. asthma 217f. clinical studies 212ff. etiology 209 laboratory findings 209 morphological findings 209 pathophysiology 210 salicylates 84f., 211ff. Rheumatoid arthritis 332f. clinical studies 250, 334ff. mode of aspirin action 332f. myocardial infarction 332, 336 pathophysiology 332 Rotterdam Study 362 s Salicin 6, 26, 334f. Salicylate antiinflammatory actions 107f. antipyretic actions 115 biotransformations 47f. bleeding 98, 142f. chemical properties 25ff. determination 30f. energy metabolism 79ff. excretion 49f. fatty acid metabolism 80ff. gastric mucosal injury 162 history 19ff. inhibition of kinases 67ff. inhibition of prostaglandin synthesis 56f. natural sources 6, 42f. pharmacokinetics 38, 48ff. preeclampsia 291f. protonophoric properties 83ff. thrombotic events 277 toxicity 132ff. transcription factors 61f., 69ff. uncoupling of oxidative phosphorylation 82ff. Salicylic acid, see Salicylate Serotonin 112 Stroke, see Cerebrovascular diseases Study of Left Ventricular Dysfunction (SOLVD) 249 Swedish Angina Pectoris Aspirin Trial (SAPAT) 237f. Swedish Aspirin Low-Dose Trial (SALT) 266 Sydney Older Persons Study 361 t Thrombin 89, 144 Thrombosis 90 Thrombosis Primary Prevention Trial (TPT) 170, 236ff., 264 Thrombotic risk 229f., 244ff., 261f., 276f., 287, 290f. Thromboxane (A2) aspirin resistance 306f. biosynthesis 12f. inhibition 91, 97, 229, 261f., 292, 455 urinary excretion 277, 306f. Tinnitus, see also Ototoxicity 192 Toxicity, see also individual organs 131ff. clinical symptoms 131ff. dose-dependency 133ff. intoxication in children 135f. laboratory findings 135 treatment 136ff. Transcription factors colorectal carcinoma 123f. modulation by salicylates 69ff. u United Kingdom Transient Ischemic Attack Aspirin Trial (UK-TIA) 265
6 376j Index (First) United Kingdom Heart and Renal Protection Study (UK-HARP) 183 US-Physicians Health Study (US-PHS) 169, 231f., 278, 349f. US-Public Health Service Study (PHS) 213f. Urticaria 205 clinical trials 287f. etiology 287 mode of aspirin action 287 Veterans Administration Cooperative Trial 238f. VIOXX GI Clinical Outcomes Research (VIGOR) 335f. 250f., v Variability in antiplatelet responses, see Resistance Venous thrombosis 287ff. actual situation 288 air travelling 288 w Warfarin, see Anticoagulants Warfarin Antiplatelet Vascular Evaluation (WAVE) 270 Widals Triad, see Aspirin-induced asthma Womens Health Study (WHS) 227, 234f., 263f.
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