Index. B Biotransformation, 112 Blood pressure, 72, 75 77

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1 Index A Acute gout, treatment, 41 Adenomatous polyposis coli (APC), 224 Adenomatous polyp prevention on Vioxx (APPROVe), 250 Ankylosing spondylitis (AS), Antiplatelet therapy, 138 Antithrombotic Trialists Collaboration (ATC), 134 Aspirin acute myocardial infarction, 154 acute occlusive stroke, 154 GI tract (see Gastrointestinal tract (GI) tract) NSAID AMPK/mTOR signaling, 189, 190 AP-1 inhibition, 190 clinical pharmacology, 184, 185 ERK signaling, 190 meta-analyses, 183 NF-kB signal transduction pathway, 190 non-cox proteins, 191 obesity, 183 pharmacodynamics and pharmacokinetics, 183, 184 randomized clinical trial, 182 Wnt/β-catenin pathway, 190 primary prevention, 154, 155 secondary prevention, 153, 154 Aspirin-triggered lipoxins (ATL), 28, 29, 111 Association pour la Prévention par l Aspirine du Cancer Colorectal (APACC), 224 Atrial fibrillation (AF), 75, 138 B Biotransformation, 112 Blood pressure, 72, C CaPP2 study, 225 Capsule endoscopy, 47 Cardiovascular disease (CVD) antiplatelet effect, 133 acute myocardial infarction, 154 acute occlusive stroke, 154 GI tract (see Gastrointestinal tract (GI) tract) primary prevention, 154, 155 secondary prevention, 153, 154 atherosclerotic plaque, 133 atrial fibrillation, 138 deep vein thrombosis, 139 economic implication, 138 LDA vs. placebo, 140 LDA vs. thienopyridines, 138 myocardial infarction, 133 NSAIDs (see Nonsteroidal anti-inflammatory drugs (NSAIDs)) oral antithrombotic agents, 139 primary prevention, 134, 137 pulmonary embolism, 139 secondary prevention, strategies, 139, 140 Clinical management inflammation, pain, and fever acetylsalicylic acid, fed and fasted state, 117 parameters, 114 pharmaceutical forms, 114 salicylic acid, self-medication, 114 soluble formulation, 116, 117 time to maximum plasma concentration (T max ), 115 pharmacodynamics (see Pharmacodynamics) pharmacokinetics (see Pharmacokinetics) Colonic diverticular bleeding, 147 Colorectal cancer (CRC) use, 220 case-control analysis, 220 chemoprevention, 204, 213 antineoplastic effects, 228 antitumor effect, 228 COX-1 inhibition, 228 cyclooxygenase, 227 dose and duration, 231, 232 location, 232 PGE 2, 227 platelets, 228, 230 risk-benefits, 232, 233 toxicity, 230, 231 # Springer International Publishing Switzerland 2016 A. Lanas (ed.), NSAIDs and Aspirin, DOI /

2 260 Index Colorectal cancer (CRC) (cont.) classes of medications, 204 COXIBs, COX-2 inhibition, 206 APPROVe, 250 cardiovascular events, 250, 251 celecoxib, 250 chemopreventive effects, 251 intestinal neoplasia, 250 polymorphisms, 251 PreSAP, 250 prevention, 251, 252 short-term use, 251 sporadic adenomas, 250 diagnosis, 226, 227 FAP, incidence, 220 NA-NSAIDs, , 212, 213 nitric oxide, randomized controlled trials adenomatous polyp, 223 APACC trial, 224 calcitriol and calcium, 224 cardiovascular trials, 221, 222 endoscopy and polypectomy, 223 long-term effects, 221 Physicians Health Study, 223 prevention, 223 risk reduction, 224 SALT, 221 prostanoid synthesis, 204 risk reduction, 220 sulindac, 249, 250 TEMPO, 215 USPSTF guidelines, 249 Congestive heart failure (CHF), 73, 74 Corticosteroids, 48 Cyclooxygenase (COX) inhibitors, 37 Cyclooxygenase (COX) pathway advantages, 17 arachidonate 5-LOX, 26 gastrointestinal tract, 23 pharmacological properties, 22 ATL, 28, 29 COXIBs, cypgs, dual COX-2/5-LO inhibitors, 27 eicosanoids autocrine/paracrine hormones, 20 biosynthesis, 19 cell membrane, 18 COX-2, glycerol, 18 inflammation, 20 lipoxins, 18 mammalian cells, 18 phospholipids, 18 PPARs, 20 prostacyclin, 20 structural products, 19 hydrogen sulfide, 27, 28 mpges-1 inhibitors, nitric oxide, 27, 28 prostanoid receptors, 25 Cyclopentenone PGs (cypgs), D Deep vein thrombosis (DVT), 139 Dyspepsia, 47 E Eicosanoids autocrine/paracrine hormones, 20 biosynthesis, 19 cell membrane, 18 COX-2, glycerol, 18 inflammation, 20 lipoxins, 18 mammalian cells, 18 phospholipids, 18 PPARs, 20 prostacyclin, 20 structural products, 19 Endothelial NO synthase activity (enos), 110 Epoxyeicosatrienoic acids (EETs), 18 European Society for Clinical and Economic Outcomes in Osteoarthritis (ESCEO), 38 Extracellular signal-regulated kinase (ERK) signaling, 190 F Familial cancer syndromes (FAP), G Gastrointestinal (GI) toxicity abdominal pain, 47 advanced age, 48 cardiovascular risk, concomitant use, 48 COX-2 inhibitors, 51 dyspepsia, 47 epidemiology, Helicobacter pylori infection, 49 histamine-2 receptor antagonist, 49 lower gastrointestinal tract, 47 misoprostol, 50 MUCOSA trial, 49 nausea, 47 osteoarthritis and dysmenorrhoea, 45 pathogenesis, 46 peptic ulcers, 45 PPIs, 50, 51 ulcer complications, 49 upper gastrointestinal tract, 46, 47 vomiting, 47

3 Index 261 Gastrointestinal (GI) tract adverse effects, 156 anticancer effect, 158 Antithrombotic Trialist s Collaboration, 164 complication, 164, 167 concomitant treatment, 161 co-therapy, 165 decision-making process, 159 diabetes, 165 dose dependent, 161 gastroprotective agents, 162, 163 H. pylori eradication, 161 incidence rate, 155 lower injury epidemiology, 146, 147 pathogenesis, 146 prevention, 148 risk factors, 147, 148 low- to moderate-risk prevention, 165 metabolic syndrome, 165 NSAIDs, 165 observational studies, 156 prevention, 146, 163, 164 primary prevention, 156 risk estimation, 159, 160 risk factors, 157, 158 SCORE system, 159 secondary prevention, 156 symptoms, 156 treatment, 156 upper injury epidemiology, 144 pathogenesis, 143, 144 prevention, 145, 146 risk factors, 144, 145 G-protein-coupled receptors (GPCRs), 177 H Helicobacter pylori infection, 49 Hemoxygenase-1 (HO-1), 110 Histamine H 2 -Receptor Antagonists (H 2 -RAs), 98 Histamine-2 receptor antagonist (H2RA), 49 I Inflammatory arthritides (IA), 70 L Low-dose (LDA). See Cardiovascular disease (CVD); Gastrointestinal (GI) tract Lynch syndrome, 225 M Misoprostol, 98, 99 Myocardial infarction, 63, 64 N Non NSAIDs (NA-NSAIDs), , 212, 213 Nonsteroidal anti-inflammatory drugs (NSAIDs) AMPK/mTOR signaling, 189, 190 AP-1 inhibition, 190 clinical pharmacology, 184, 185 ERK signaling, 190 meta-analyses, 183 NF-kB signal transduction pathway, 190 non-cox proteins, 191 obesity, 183 pharmacodynamics and pharmacokinetics, 183, 184 randomized clinical trial, 182 Wnt/β-catenin pathway, 190 ATB-346, 96 β-d-glucuronidase, 99 cancer prevention, 182 COX-1 EGFR, 185, 186 limitations, 188 local physiological mediator/modulator, PGDH downregulation, 187 platelet activation, 185 S1P release, 186, 187 COX-2 inhibitor, 94, 95, 189 CRC (see Colorectal cancer (CRC)) CVD aging, 62 American Geriatric Society, 81 AMI, 69, 70, 79, 80 atrial fibrillation, 75 blood pressure, 72, CHF, 73, 74 comorbid condition, 62 COX inhibition, 72 COX-2 inhibitors, 80, 81 diabetes mellitus, 71 genetic predisposition, 71, 72 glucocorticoids, 81 inflammatory arthritides, 70 meta-analysis, 65, 67 myocardial infarction, 63, 64 non-ischemic adverse effects, 73 osteoarthritis, 71 pain-activated spinal reflexes, 62 pain management, 63 peripheral edema, 78, 79 pharmacological and pharmacological interventions, 62 RCTs, 64, 65 renal function, sodium retention, 77, 78 stroke, 73 time dependence, 68 DA-9601, 99 efficacy, 175 GPIIb/IIIa receptor, 191 GPVI receptor, 192 H. pylori infection, 96 H 2 -RAs, 98

4 262 Index Nonsteroidal anti-inflammatory drugs (NSAIDs) (cont.) misoprostol, 98, 99 naproxen, 96 nitric oxide, 95 nonselective NSAIDs, 94 opioid analgesic, 93 P2Y12 receptor antagonists, 193 PAR, 192 patient education, 96, 97 pharmacological pain reliefs, 93 pharmacological prevention, 97 PPIs, 97, 98 prostanoid signaling biosynthesis, 177 early response gene, 177 EP receptors, 180, 181 GPCRs, 177 mpges1, 178, 180 PGE 2, 178 phospholipases, 177 physiological and pathophysiologic processes, 177 TXA 2, 181, 182 P-selectin, 192 randomized clinical trials, 96 rebamipide, 99 recommendations, 100 risk factors, 92, 93 self-medication, 96 toxic medication, 93 O Osteoarthritis acetaminophen, 39 cardiovascular thrombotic event, 39 COX-2-selective inhibitor, 39 ESCEO recommendations, 38 randomized controlled trials, 38, 39 Over-the-counter (OTC) adverse drug reactions, 130 adverse effects, 129 anxiety, 128 duration, 123 efficacy absorption, rapidity, 125 diclofenac, 124 ibuprofen, 124 naproxen, 124 safety (acetylsalicylic acid), diclofenac, 126 ibuprofen, 126 naproxen, 128 paracetamol (acetaminophen), 126 risk factors, 125 seminal case-control study, 129 P Peroxisome proliferator-activated receptors (PPARs), 20 Pharmacodynamics acetylation, 107 analgesic actions, 111 analgesic and antipyretic, 107 anti-inflammatory, 107, 111 antiplatelet, 109 antipyretic actions, 111 antithrombotic actions, 111 COX, 11 COX-1, 109 COX-2, 110 cytokines and tumor promoters, 5 enos, 110 hemeoxygenase-1, 110 leukocyte endothelial cell interaction, 11 nonselective vs. isoform-specific COX inhibitors allosteric monomer, classification, 6 ex vivo assays, 6 kinetic factors, 9 10 kinetics and allosterism, 8 paracetamol, 8 pharmacodynamic and toxicodynamic effects, 8 structural factors, 8 9 oxidative stress, 110 pharmacological actions, 107, 108 phospholipids, 3, 6 prostanoid synthesis, 3 prothrombotic and atherogenic stimuli, 6 salicylate, 107, 108 therapeutic effects, 3 Pharmacokinetics absorption, 12 biotransformation, 112 distribution, 12 14, 112 elimination, 14 15, 113 esterases, 113 intestine, 112 stomach, 112 Prevention of Sporadic Adenomatous Polyps (PreSAP) trial, 250 Prostanoid signaling biosynthesis, 177 early response gene, 177 EP receptors, 180, 181 GPCRs, 177 mpges1, 178, 180 PGE2, 178 phospholipases, 177 physiological and pathophysiologic processes, 177 TXA2, 181, 182 Proton pump inhibitors (PPIs), 50, 51, 97, 98 Pulmonary embolism (PE), 139 R Randomized controlled trial (RCT) adenomatous polyp, 223 APACC trial, 224 calcitriol and calcium, 224 cardiovascular trials, 221, 222

5 Index 263 endoscopy and polypectomy, 223 long-term effects, 221 osteoarthritis, 38, 39 Physicians Health Study, 223 prevention, 223 risk reduction, 224 SALT, 221 Rheumatoid arthritis (RA), S Second International Study of Infarct Survival (ISIS-2), 154 Self-medication, 96 Sphingosine-1-phosphate (S1P) release, 186, 187 Streptokinase (SK), 163 Swedish Aspirin Low-Dose Trial (SALT), 221 Systematic Coronary Risk Evaluation (SCORE), 159 T Tetramethyl-1-piperidinyloxy (TEMPO), 215 U V Veterans Administration (VA) Cooperative Study, 136 W