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Home , Acemetacin, Amfenac, Antrafenine, Benoxaprofen, Epirizole, Fenclofenac

Abbreviations used: AR(s), adverse , 17 reaction(s); ADR(s), adverse drug manufacturers, 9 reaction(s); NSAID(s), non-steroid anti• amorfazone, trade mark names and inflammatory drug(s) manufacturers, 9 Amuno, generic name and manufacturer, 12 anaemia absorption interactions, drug, 180-1 aplastic, 83 , trade mark names and report rate, 33 manufacturers, 8 haemolytic, 84-5 acetyl , see in rheumatoid patients, inappropriate action, drug, ~ pharmacoactivity therapy, 250 activation (of drugs), 243-5, 246, 247 anaphylaxis/anaphylactoid reactions, 17, pathway, 244 81 Actol, generic name and manufacturer, 13 Anaprox, generic name and manufacturer, Actosal, generic name and manufacturer, 13 9 angioedema, 6 acyl-coenzyme A formation, 221-2 angiotensin-converting , 195, 196 adjuvant induced arthritis, ~ inhibitors arthritis function, 195 Af1oxan, generic name and manufacturer, NSAID interactions with, 195-200 14 animal(s) age see also elderly experimentation, ethics of, 267 gastrointestinal susceptibility re• inter species differences in lated to, 164, 286-8 propionate chiral inversion, use of anti-arthritics correlated 222-3, 223 with, 152 Ansaid, generic name and manufacturer, aged, the, ~ elderly 11 agranulocytosis antacids, 292 incidence, 7, 100-2 passim effect on drug absorption, 180, 181 in Sweden, 66, 67 NSAID interactions with, 185, 193 -induced, 7, 99-104 anthranilic acid, relative safety, 18 analytical epidemiological anti-arthritic drugs, ~ antirheumatic studies, 101-3 drugs assessment of previous case , NSAID interactions with, reports, 100-1 183, 184 registry data, 101 antidiuretics, NSAID interactions with, report rate, 33 88 Alrheumat, generic name and manufac• antihypertensives, NSAID interactions turer, 12 with, 185, 192, 196-7, 198-9, Alrheumun, generic name and manufac• 204-10, see also beta blockers; turer, 12 albumin levels in the elderly, 7 antimalarials, conditional activity, 262 , conditional activity, 261 ARs with, 8 • antirheumatic (antiarthritic) drugs, 22- manufacturers, 8 3 aldosterone, 195, 196 patient drug preferences, 139, 140, allergic reactions, see hypersensitivity 142, 143 , trade mark names and slow acting, 22 manufacturers, 8 anti-ulcer drugs, 307-8 Alnovin, generic name and manufacturer, , trade mark names and 10 manufacturers, 9 alpha-methine proton exchange, 222 Anturan, generic name and manufacturer, sodium 14 315 SIDE-EFFECTS OF ANTI-INFLAMMATORY DRUGS aplastic anaemia, ~ anaemia aurothiomalate, conditional activity, cyclo-oxygenase, 233 261, 263 Archless, generic name and manufacturer, 11 ARs, 19 Arlef, generic name and manufacturer, 11 number of reports of, 64 Arquel, generic name and manufacturer, interactions with other drugs, 182-3, 13 184 Arret, generic name and manufacturer, 9 sales, 71 arthritis and rheumatism trade mark names and manufacturers, 9 adjuvant-induced, rats with, 256-7 cytochrome levels in, 249, 250 NSAID gastrotoxicity in, 265, 266- Banamine, generic name and manufacturer, 7 11 collagen induced, 272-3 Benalgin, generic name and manufacturer, historical aspects of treatment, 5 9 osteo-, 292-3 bendroflumethiazide, indomethacin inter• patient drug preferences, 139, 140 actions with, 205-6 perforated ulcers in patients with, benefit vs. risk, evaluating,S, 298 291 Benoral, generic name and manufacturer, psoriatic, patient drug preferences, 9 140, 142 benorylate, trade mark names and rheumatoid, ~ manufacturers, 9 seronegative, patient drug preferences, 143 ARs, 7, 21 Arthrocine, generic name and manufac• detection, 75-6 turer, 14 failure in detection, 120 Arthropan, generic name and manufac• hepatic, 86 turer, 9 in the elderly, 7, 277-9 Artiflam, generic name and manufacturer, pharmacokinetic profile of, 277-9 15 prescription--event monitoring of, Artrinivo, generic name and manufac• 112-23 passim turer, 12 trade mark names and manufacturers, 9 Artrivia, generic name and manufacturer, benzoic acid, structure--side-effects 12 relationship, 18 aryl acetic acids, derivatives and hydrochloride, trade mark precursors of, 234 names and manufacturers, 9 aryl propionic acids, 2-, ~ Benzyrin, generic name and manufacturer, propionates 9 aseptic meningitis, 87 beta-blockers, NSAID interactions with, aseptic necrosis, 80 204-10 aspirin (acetyl salicylic acid) Biarison, generic name and manufacturer, activity, conditional, 262-3 14 agranulocytosis, association with, Biarson, generic name and manufacturer, 100 14 antiplatelet effect, 193 biases formulation, problems with, 7 affecting data interpretation from interactions with other drugs, 184, ADR reports, 105-10 185, 186, 188 in patient drug prefernce studies, sensitivity, 80 148 side-effects (general features), 127 bicarbonate, sodium, therapy, 6 in children with rheumatoid binding sites arthritis, 125-32 cyclo-oxygenase, drug interactions gastrointestinal, 311-13 at, 193 hepatic, 86 protein, ~ protein binding sites historical aspects, 6, 7 bleeding, ~ incidence, 50, 135 blood dyscrasias, 19, 83-5 tolerance, 130 in the elderly, 157, 166 trade mark names and manufacturers, 8 incidence, 7, 65, 66 transacetylation potential, 235 report rate, 33 Aspirin, generic name and manufacturer, reports from Sweden, 62, 65, 66 8 blood pressure, drug interactions and, assays, anti-inflammatory activity, 229 196, 197, 199, 200, 204-10 association/dissociation constants, con• passim ditional, 259 bowel disease, drug histories of asthma, 80 patients with, 304 in the elderly, 156-7 BPPC, manufacturers, 9 Atilan, generic name and manufacturer, Britai, generic name and manufacturer, 11 10 Atophan, generic name and manufacturer, Britain, ~ United Kingdom 9 bronchial constriction, 128 Atrobione, generic name and manufac• Brufen turer, 9 generic name and manufacturer, 11 316 INDEX Brufen (continued) Clozic overdosage, 174-5 ARs, 8 Bufenid, generic name and manufacturer, generic name and manufacturer, 12 10 coenzyme A, esterification with, 221-2 bufexamic acid, trade mark names and cohort studies, 48 manufacturers, 9 collagen-induced arthritis, 272-3 Buss, Dr Carl, salicylate toxicity coma, 4 reports by, 5-6 Combec, generic name and manufacturer, 9 Butacote, generic name and manufacturer, Committee on Safety of Medicines, ADR 13 reports to/from, 300, 301 Butazolidin, generic name and manufac• common side-effects, 76-8 turer, 13 concentration--effect relationships of Butazolidine, generic name and manufac• the propionates, 223-4 turer, 13 conditional drug activity, 259-73 butazones, ARs to, 7, 19 factors determining, 269, 270 reported numbers of, 61, 64 Conforted, generic name and manufac• butyl fenamate turer, 12 development, 20 Coslan, generic name and manufacturer, trade mark names and manufacturers, 9 13 BW755c, effect on syn• Coxigon, 21 thesis, 20 generic name and manufacturer, 9 CS-600, manufacturers, 10 cutaneous reactions, ~ Skin captopril, NSAID interactions with, 196, cyclo-oxygenase 197 arachidonic acid-, inhibition, 233 carboxyl derivatives of NSAIDs, 233-4 binding sites, drug interactions at, carcinogen activation, 249 193 carcinogenicity of NSAIDs, 21 inhibitors, 237, 240, 309 cardiovascular system, see also heart cytochromes, 249-52, 254-6 ARs, 82-3 differences between, 243, 256 events with five NSAIDs, 116, 117, induction, 245 118 P-448, 243, 244, 245 protective effect of NSAIDs, 121 chemical activation by, 245, 246, , trade mark names and manufac• 247, 248-9, 251 turers, 9 conditions increasing activities Cebutid, generic name and manufacturer, of, 251 11 roles, 248 central nervous system P-450, 243, 244, 245 ARs, 87, 144-5, 233 activity in rheumatoid patients, in the elderly, 157-8, 166 249-52 patients withdrawn from studies destruction, 255 due to, 128 isoenzymes of, 248 events with five NSAIDs, 116, 117, roles, 242, 250-1 118 children with rheumatoid arthritis, side-effects in, 125-35 Daital, generic name and manufacturer: chiral properties of the 'profens', ~ 10 propionates Danfenona, generic name and manufac• chloroquine absorption, effect of ant• turer, 11 acids on, 180, 181 data choline salicylate, trade mark names and interpretation from ADR reports, manufacturers, 9 biases affecting, 105-10 cimetidine, 292 patient, linking ADRs with other, 40 effect on cytochromes, 254-5 databases used in identifying ADRs, 48-9 cincophen in the elderly, 155-6 toxicity, 18 deaths, ~ fatalities trade mark names and manufacturers, 9 debrisoquine metabolism, genetic Cindomet, generic name and manufacturer, polymorphism, 248 9 Deflogix, generic name and manufacturer, cinmetacin, trade mark names and 14 manufacturers, 9 demographic data, importance, 41 Cinopal, generic name and manufacturer, denominators 10 chOice, incidence of ADR reports de• clearance, enantioselective, 220-1, 223, pendent on, 67-8 281-2 factors affecting, 106 clidanac, trade mark names and manufac• issues/concerns, 45-6 turers, 10 post-marketing, 44-5 Clinoril, generic name and manufacturer, pre-marketing, 41-2 14 depression, salicylate induced, 5 Clotam, generic name and manufacturer, dermatological ARs, ~ skin reactions 15 detection/identification of side- cloximate, manufacturers, 10 effects/ADRs, 75-6 317 SIDE-EFFECTS OF ANTI-INFLAMMATORY DRUGS detection/identification (oontiDued) data, importance, 41 in the elderly, 156-66 frequency, patient preferences, 149 detoxification of drugs, 243-5 historical aspects, 5 conpromised, 267-8 subsets, 41 pathways, 267-8 drop-out rates, 39 development of drugs, 8-21, 229-40 Droxarol, generic name and manufacturer, emerging, 237-8 9 historical, 229-33 Droxary1, generic name and manufacturer, rational, 231-3 9 recent, 21-2, 233-7 Drug Surveillance Research Unit, 112, , paracetamo1 combined 123 with, 247 duodenal ulcers, perforated, NSAID in• diarrhoea, 4, 78 gestion and, 289 Duraprox, generic name and manufacturer, ARs, number of reports of, 64 13 patient preferences for, 141 dyscrasias, blood, ~ blood dyscraias trade mark names and manufacturers, Dytransin, generic name and manufac• 10 turer, 11 Difenax, generic name and manufacturer, 10 difenpyramide, trade mark names and ear, ARs of the, 117 manufacturers, 10 Ecotrin, generic name and manufacturer, 8 development, 235-6 efficacy versus risk, evaluating, 298 trade mark names and manufacturers, eicosanoid, 225 10 biosynthesis, 250, 252 , NSAID interactions with, 185 -regulated phenomena, effect of dihydroxy-benzoate, 2,3-, anti-oxidant aspirin on, 262-3 activity, 273 eicosapentoic acid dimensions, molecular, of cytochrome P- aspirin interactions with, 262-3 448 activated chemicals, 245 and prostaglandin synthesis, 255 diplosal, trade mark names and manufac• elderly, NSAIDs in, 151-67 turers, 10 ARs of, 21, 74 dipyrone gastrointestinal, 77, 286-93 alternatives to, 103 heightened risk, 154-5, 286-9 -attributed agranulocytosis, 100, 101 pharmacokinetic profile of, 275-9 discriminant effects of drugs/toxins, enalapril, NSAID interactions with, 197, ~ conditional drug 198, 199 activity enantiomeric conposition of the disease propionates, 223-4 bowel, drug histories of patients endoscopy with, 304 gastroscopic, aspirin toxicity ob• drug interactions with, 259-73 served by, 6 infectious, ~ infections records, retrospective studies of, subsets, 41 297 dissociation/association constants, con• Endyne, generic name and manufacturer, ditional, 259 12 Distalgesic, 247 eno1ic acids development, 20 antihypertensive action of, 205-7 structure--side-effects relationship, NSAID interactions with, 88, 204-12, 19 277-9 enterohepatic recirculation, con• use in elderly, 160-1 sequences, 78 documentation, 43-4, see also data environmental factors Dolisal, generic name and manufacturer, ADRs influenced by, 106, 242, 243-7 10 passim, 249-52 passim Dolobid, generic name and manufacturer, biases from, 106 10 enzyme Donorest, generic name and manufacturer, induction, 186-7 11 inhibition, 187 Dorbanex, effect on benoxaprofen phar• epidemiology • macokinetics, 277-9 of ADRs in UK, 27-35 Dorinamin, generic name and manufac• of drug-induced agranulocytosis, 101- turer, 9 3 dose/dosage, see also ingestion; over• epidermal necrolysis, 107 dosage incidence of NSAID associated, 65 considerations in patient preference , trade mark names and manufac• studies, 148 turers, 10 daily defined dose (DDD), 55 Epiroten, generic name and manufacturer, sales expressed in, 56, 57 9 average number of, per prescrip• epithelial toxicity of the propionates, tion, 68 16 318 INDEX erythema multiforme, 78-9 trade mark names and manufacturers, erythrocytes, aplasia, 83 11 eterylate, trade mark names and manufac• fever turers, 10 drug-induced, 81, 267 ethics of animal experimentation, 267 --metabolism--toxicity relationship, , trade mark names and manufac• 268 turers, 10 Feximac, generic name and manufacturer, , manufacturers, 10 9 eudysmic ratio of the propionates, 219, Flanex, generic name and manufacturer, 220, 224 13 evaluation of NSAID-induced side• Flenac, generic name and manufacturer, effects, 48 10 in the elderly, 156-67 Flogar, generic name and manufacturer, events 13 definition, 112-13 Flogene, generic name and manufacturer, distinction from ARB, 38-9 11 patterns of, for five NSAIDs, 114-19 Flogocid, generic name and manufacturer, , enantioselective, 220-1, 223, 9 281-2 Flosint, generic name and manufacturer, Experizole, generic name and manufac• 12 turer, 10 Flozin, generic name and manufacturer, eye functions, ARs, 62, 86, 117 12 , trade mark names and manufacturers, 11 fatalities flufenisal establishing cause, 113 drugs developed from, 18 difficulties in, 119 manufacturers, 11 gastrointestinal complication• , trade mark names and manufac• associated, 121, 122 turers, 11 in the elderly, 165 , trade mark names and historical reports, 4 manufacturers, 11 NSAID associated fluquazone, manufacturers, 11 in Sweden, 60 in US, 153 patient preferences for, 141 Feldene, 21 trade mark names and manufacturers, generic name and manufacturer, 14 11 females, elderly, gastrointestinal per• follow-up foration, 286-93 questionnaires, 112-13 fenamates, development, 19, 20 studies, 48 fenamole, trade mark names and manufac• Forenol, generic name and manufacturer, turers, 10 13 Fenazole, generic name and manufacturer, formulations, problems with, 7-8 9 fosfosal, manufacturers, 11 free radicals, ~ radicals ARs in children with rheumatoid Froben, generic name and manufacturer" arthritis, 129 11 development, 20, 234 frusemide, NSAID interactions with, 185, prescription--event monitoring of, 277-9 112-23 passim Fullsafe, generic name and manufacturer, trade mark names and manufacturers, 11 10 furobufen, manufacturers, 11 furofenac, manufacturers, 11 anti-inflammatory effect, 192 furosemide skin reactions to, 21 indomethacin interactions With, 210- trade mark names and manufacturers, 12 10 interactions with, 210-11 fenclorac, manufacturers, 10 , trade mark names and manufacturers, 10 gastritis, diffuse, 76 fendosal, trade mark names and manufac• gastrointestinal tract, 285-314, ~ turers, 10 also rlecific regions fenflumizole, manufacturers, 10 ARB (general unspecified features), 8, 19, 21, 76-7, 143-4,163-6, ARB, 129 285-314 patient preferences for, 141 conditional, 266-7 trade mark names and manufacturers, death associated with, 122 10 differences between sexes, 144, , trade mark names and manufac• 145, 149, 149-50 turers, 11 in the elderly, 162, 163-6 Osmosin asSOCiated, 121 toxicity, 19 patients withdrawn from studies due to, 128 319 SIDE-EFFECTS OF ANTI-INFLAMMATORY DRUGS gastrointestinal tract (continued) hepatotoxicity, 85-6 percent of patients with various, amfenac, 17 230 aspirin, 135 associated, ~ drugs (NSAID and non-NSAID) causing, piroxicam 17, 159 in rats with inflammmatory dis• in the elderly, 158-9, 166 ease, 265, 266-7 reported incidence in Sweden, 63 reducing, developments with objec- report rate, 34 tive of, 19-20 structure related to, 16, 17, 18 report rate, 30-1, 32 historical aspects of side-effects, 4-21 reports from SWeden, 62, 309-13 histories of patients, drug salicylate associated, 4-6, 6 with bowel disease, 304 under-reporting, 69 obtaining, 299-300 bleeding, 5, 6, 7, 296-7, 299-300, HLA-DRJ, penicillamine toxicity as• 304, 307, 309-13 sociated with, 251, 252, 254 in the elderly, 165 hypersensitivity reactions, 6, 89-90 estimated number of reports of, 32 to , 121 frequency of drug intake in hypertensive patients, therapy, 196-7 patients with, 309-13 hypog1ycaemics, NSAID interactions with, events with five NSAIDs, 116, 117, 184 118 lower, ARs, 85, 144, 304-5 perforation, 165, 304 Ibudros, generic name and manufacturer, in the elderly, 165, 285-93 12 estimated number of reports, 32 ibufenac histological features, 292 structure, side-effects related to, ulcers/ulceration, 7, 21, 76-7, 89, 16 see also peptic ulcers trade mark names and manufacturers, drugs treating, 307-8 11 in the elderly, 165 piroxicam associated, 69 ARs (various), number of reports of, reported incidence in Sweden, 65, 64 66 development of, 231 upper, ARs, 162, 285-93, 305, 310, ena1apri1 interaction with, 197, 199 311 gastrointestinal toxicity, report gastroscopy, aspirin toxicity observed rate, 31, 64 by, 6 overdose, 173-5 Gaultheria poisoning, 4 estimating, practical problems in, generic (INN) names of NSAIDs, 8-15 175 genetic variations/po1ymorphisms over-the-counter sales, 173-5 in drug actions, 263 patient preferences for, 141 in drug interactions, 215 prototypes, 231 in drug oxidation, 247-9 trade mark names and manufacturers, genito-urinary ARs, 86 11 gentisic acid formation, abolishing, 271 ibuprofen guaico1ester, manufacturers, Gida1on, generic name and manufacturer, 12 10 , trade mark names and manufac• glutametacin, trade mark names and turers, 12 manufacturers, 11 leI 55,897 c1obuzarit, trade mark names glutathione oxidation/depletion, 246 and manufacturers, 12 Green Forms, 112, 114, 119 ideal NSAID, definition of, 238 group health co-operative of Pudget identification of hazards/ADRs, ~ Sound, 49-50 detection gut, ~ gastrointestinal tract lmady1, generic name and manufacturer, 9 Imbera1, generic name and manufacturer, 14 haemato1ogical ARs, ~ blood dyscrasias Imotry1, generic name and manufacturer, haemorrhage, ~ gastrointestinal tract 9 half life Inacid, generic name and manufacturer, of NSAIDs, 154, 155 12 NSAIDs with long, 7, 236 incidence , 78 of perforated peptic ulcers, 286 hearing, ARs, 117 of side-effects heart, failure, congestive (CHF), ~ in Sweden, 62, 63, 65, 66, 67 ~ cardiovascular system in US, 47-53, 152, 153 NSAID--diuretic interactions in Indana1, generic name and manufacturer, patients with, 211-12, 213 10 risks associated with, 161 Indicin, generic name and manufacturer, heavy metals, conditional neph• 11 rotoxicity, 264 indigestion, NSAIDs and, 291 hepatic recirculation, entero-, 78 Indocid, generic name and manufacturer, hepatitis, 86 12 320 INDEX Indocin, generic name and manufacturer, sites, 180 12 NSAID-NSAID, 186, 189 Indoglucin, generic name and manufac• pharmacodynamic/pharmacokinetic, 186, turer, 11 188, 189 indole acetic acids, modifications, 20 protein binding site, 181-6 Indolin, generic name and manufacturer, interleukin-1 properties, 267, 268 9 intestines, ~ gastrointestinal tract Indomed, generic name and manufacturer, investigator, effect of, 42 12 ionazolac calcium, manufacturers, 12 indomethacin iron and its analogues, development, 233 inappropriate administration to interactions with other drugs, 184, rheumatoid patients, 250 185, 196, 197, 204-13 metabolism of rheumatoid subjects, metabolism of, variations in, 214 249-50 peptic ulceration and, 292 isofezo1ac, manufacturers, 12 -R isomers, 144 isomers of the 'profens', ~ side-effects, 237, 204-13 propionates CNS, 233 isonixin, trade mark names and manufac• gastrointestinal, 62, 77, 144, 292 turers, 12 historical aspects, 7 Isoxal, generic name and manufacturer, psychological, 87 14 report rate, 30, 31, 64 isoxepac, trade mark names and manufac• short lasting, 209 turers, 12 slow-release (GITS) formulation, ~ Osmosin development, 19 sodium excretion and the effect of. trade mark names and manufacturers, 211, 212 12 tablet vs. capsule formulation, 7 tolerance, 130, 131 vasoconstrictory activity, 199-200, jaundice, NSAID induced, 21 215 juvenile rheumatoid arthritis, ~ indomethacin glycolate, 8 rheumatoid arthritis trade mark names and manufacturers, 12 Indomethacine, generic name and manufac• kallikrein-kinin system, 196 turer, 12 C-R (Oruvail), 142, 143 ARs to, 21 in the elderly, 275-6 trade mark names and manufacturers, patient preferences trade mark names and manufac• pharmacokinetic profile of, 275-6 turers, 12 tolerance, 130, 131 indoxamic acid, trade mark names and trade mark names and manufacturers, manufacturers, 13 12 infections kidney aging, see also entries under activation, 158 Renal effects on cytochrome pathways, 256 consequences of, 7, 160, 215 historical aspects of therapy,S primary, 160 masking, 158 secondary, 160 inflammmation, pharmacology of, 261-3 information, ~ data Landruma, generic name and manufacturer, Infrocin, generic name and manufacturer, 13 12 laxatives, effect on benoxaprofen phar• ingestion frequency of patients macokinetiCS, 277-9 with gastrointestinal bleeding, 309- Lederfen, generic name and manufacturer, 13 10 with perforated ulcers, 289 liability concerns, 43 INN name of NSAIDs, 8-15 literature reports of ADRs, 43 intake, ~ ingestion interaction with NSAIDs, 88-9, Inteban SF, generic name and manufac• 184 turer, 12 liver metabolic functions in the interactions, drug, 88-9, 179-215 elderly, see also entries under absorption, 180-1 hepati-; hepato- beneficial, 192 locally active NSAIDs, 236-7 conditional, 262 Lodine, generic name and manufacturer, disease--, 259-73 10 during renal drug elimination, 187-8 lofemizole, manufacturers, 12 metabolic, 186-7 log-linear trend analysis, 29-34 NSAID--non NSAID, 88-9, 179-215 use, 31-2 clinically relevant, 184-6 Longmore, ADR reports by, 4 mechanisms, 180 Loxonin, generic name and manufacturer, responders vs. non-responders, 12 203-15 321 SIDE-EFFECTS OF ANTI-INFLAMMATORY DRUGS sodium, trade mark names and nabumitone, manufacturers, 13 manufacturers, 12 Nalfon, generic name and manufacturer, lung, see entries under pulmonary 10 lupus-like syndrome, drug-induced, 82 names of NSAIDs Lyzalgo, generic name and manufacturer, generic, 8-15 13 trade mark, 8-15 (the trade-name), generic name Maclagan, Dr. TJ., reports of salicylate and manufacturer, 13 toxicity, 5 naproxen sodium , trade mark names ARs to, 127 and manufacturers, 12 in children with rheumatoid Maldocil, generic name and manufacturer, arthritis, 125-8 14 number of reports of, 64 males, peptic ulcers in, prevalence, patient preferences for, 140, 142 286, 287 thiazide interactions with, 207 manufacturers of NSAIDs, 8-15 tolerance, 130 marketing, pre- and post-, AR as• trade mark names and manufacturers, sessmeent, 37-46 13 Mebron, generic name and manufacturer, Naprozyn-S, generic name and manufac• 10 turer, 13 Meclofen, generic name and manufacturer, National Poisons Information Service, 13 NSAID overdose monitoring by, meclofenamate sodium, trade mark names 173 and manufacturers, 13 natriuretic response to furosemide, , trade mark names and NSAID effects on, 210-12 manufacturers, 13 necrosis, aseptic, 80 meningitis, aseptic, 87 nephritis, interstitial, NSAID-induced, menopause and NSAID gastrotoxicity, 288- 161 9 nephrotoxicity, conditional, 263-4 mercaptopurine ,6-, neutropenia, 84 contra-inflammatory effect of, 266-7 newness of drugs, effects on reporting meseclazone reactions, 42-3 development, 20 nictindole, manufacturers, 13 manufacturers, 13 Niflan, generic name and manufacturer, metabolic drug interactions, 186-7 14 metabolism, drug, 7, 179-282 passim , trade mark names and compromised, 267-8 manufacturers, 13 metals, heavy, conditional neph• Nifluril, generic name and manufacturer, rotoxicity, 264 13 methine, alpha-, proton exchange, 222 Nixyn, generic name and manufacturer, 12 Methrazone, generic name and manufac• non-carboxylic NSAI acids, structure-• turer, 11 side-effects relationship, 19 a-methylacetates, ~ propionates nortriptyline metabolism, genetic polymorphism, 248 poisoning, 4 Norvedan, generic name and manufacturer, trade mark names and manufacturers, 11 13 numerator issues Mezolin, generic name and manufacturer, post-marketing, 42-4 12 pre-marketing, 38-42 Midocil, generic name and manufacturer, Numide, generic name and manufacturer, 15 14 Minalfen, generic name and manufacturer, S Minalfene, generic name and manufac• ocular ADRs, 62, 87, 117 turer, 8 oesophageal injury, 84-5 , manufacturers, 13 oestrogens, protective effect, 288-9 molecular dimensions of cytochrome P-448 oleyl -induced inflammation, 265, activated chemicals, 245 266-7 mortalities, ~ fatalities anchylosis, NSAID-induced, 21 Moxicam, generic name and manufacturer, Opren, 21 12 generic name and manufacturer, 9 mucocutaneous side-effects, 145-6, ~ Oraflex, generic name and manufacturer, also skin 12 Mundisal, generic name and manufacturer, Oruvail (ketoprofen C-R), patient 9 preferences, 142, 143 muscoskeletal reactions, 80 Orgetein, generic name and manufacturer, Myalex, generic name and manufacturer, 13 10 Orudis, generic name and manufacturer, 12 Osmosin (indomethacin slow-release) Nabanol, generic name and manufacturer, development, 236 10 322 INDEX Osmosin (continued) penicillamine toxicity, 251-2 gastrointestinal ARs to, 7, 21, 121, peptic ulcers, 305, see also gastroin• 144 testinal tract perceptual problem of, 304 in the elderly, 285-93 generic name and manufacturer, 12 piroxicam associated, 69, 295-302 patient preferences for, 142 perception prescription event monitoring of, of ADRs, the problem of, 303-4 112, 113-23 passim of gastrointestinal tolerance, 305-6 , ~ arthritis perfect NSAID, definition of, 238 overdosages, 88 perisoxal citrate, trade mark names and ibuprofen, 173-5 manufacturers, 13 , trade mark names and PGI2, ~ manufacturers, 13 pharrnaco-activity of anti-arthritics oxazolopyridine, 240 conditional, 261 topical, 237 duration of, 236 , trade mark names and manufac• pharmacokinetic (pharmacodynamic) inter• turers, 13 actions involving NSAIDs, 180-8 oxepinac, manufacturers, 13 pharrnacokinetic profiles (of drugs) , structure--side-effects alterations, age-related, 154-5 relationship, 19 of benoxaprofen, 277-9 oxidases, mixed function, 248 of ketoprofen, 275-6 role of, 243-7 selective effects dependent on, 20 oxidations, genetic polyrnorphisrns of, , agranulocytosis and, 100 247-9 Phenoquin, generic name and manufac• oxprenolol, NSAID interactions with, turer, 9 185, 207-10 phenylacetates oxygen radicals, 256-7 activity, 21 oxyphenylbutazone moiety, 16 toxicity, 7 structure--side-effects relationship, relative, 71-2 17 trade mark names and manufacturers, 13 interactions with , 183, 187 toxicity/side-effects historical aspects, 7 package insert, listing of reactions on, relative, 71-2 43 trade mark names and manufacturers, Pacyl, generic name and manufacturer, 12 13 pancreatitis, 85 phenylpropanolamine, NSAID interactions pancytopenia, reported incidence in with, 185 Sweden, 66, 67 phenyl , 2-, ~ propionates activation, 246, 247 phenytoin interaction with NSAIDs, 182- agranulocytosis, and, 100 3, 184 therapy in children with rheumatoid photosensitivity reactions, 21, 79 arthritis, 135 pindolol, NSAID interactions with, 204-5 toxicity, 246-7 piroxicam Paraflu, generic name and manufacturer, advantages, 295 11 ARs, 7 Parfenac, generic name and manufacturer, case reports of, 296-7 9 number of reports of, 64 Parkemed, generic name and manufacturer, retrospective studies of, 297 13 in Sweden, reports of, 21, 59, 60, Parlef, generic name and manufacturer, 62, 64, 296-7 11 development, 19 Parsal, generic name and manufacturer, gastrointestinal reactions to, 62, 66 13 bleeding, 296-7, 299-300 parsa1mide, trade mark names and ulceration, 69, 295-302 manufacturers, 13 patient preferences for, 140, 143 pathological conditions, gastrotoxicity prescribing habits, 299-300 determined by, 265, 266 prescription event monitoring of, patients 113-23 passim counting only once, importance of, reports of ARs, 21, 59, 60, 62 40, 45-6 case-, 296-7 data, linking ADRs with other, 40 number of, 64 drug preference studies, 137-43, 146- trade mark names and manufacturers, 50 14 problems with, 148, 149 pirprofen environment, 242 furosemide interaction, 210-11 number withdrawn during studies due oxprenolol interaction with, 207-8 to ARs, 127, 128 trade mark names and manufacturers, status, 242 14 PEM, ~ prescription event monitoring 323 SIDE-EFFECTS OF ANTI-INFLAMMATORY DRUGS pirproxen, trade mark names and manufac• trade mark names and manufacturers, turers, 14 14 plant extracts, salicylate from, 4 prostacyclin (PGI2), 198 sites, ~ metabolites (6-keto-PGF1a), 196 protein binding sites excretion, 197, 198, 199 platelet function inhibition, 83-4 prostaglandin (PG), see also pros- polyarthritis, adjuvant-induced, ~ tacyclin arthritis counter-regulations, suppressed, 160 Ponase, generic name and manufacturer, cytoprotective, 20 14 F2a excretion, effect of NSAIDs on, post-marketing 206 AR assessment, 42-4, see also role prescription event monitoring in the inflammatory process, 20 denominator considerations, 44 in renal excretion, 188, 211, 212 numerator considerations, 42 synthesis, ~ prostaglandin syn• Ponstan, generic name and manufacturer, thesis 13 prostaglandin synthesis/ Ponstel, generic name and manufacturer, production, 74, 195 13 inhibitors, 20-1 Poustyl, generic name and manufacturer, effects, 74-5, 77-8, 188, 196, 13 218-19 Pontal, generic name and manufacturer, Protaxil, generic name and manufacturer, 13 14 Prafenid, generic name and manufacturer, protein binding sites 12 plasma- , trade mark names and drug interactions at, 181-6 manufacturers, 14 enantiomeric competition at, 282 pre-marketing, AR assessment, 37-42 tissue-, drug interactions at, 181-6 prescription(s) protocol subsets, 45 ADR reports and, 28-9, 59, 63, 107 Proxil, generic name and manufacturer, level/numbers 14 ADR reports using information on, , patient drug 59 preferences with, 140, 142 in Nottingham, UK, 305-6 psychological ADRs, 5, 87 and peptic ulcer perforation in• Puget Sound studies, 49-50 cidence, 286, 288 pUlmonary ADRs, 80-2 risk calculations from, 306, 307 pUlmonary infiltrates, 80-1 in US, 47-8 pulmonary oedema, 80 registers, ~ registries pyrazolone unfilled, 156 -induced granulocytosis, ~ prescription event monitoring, 111-23 granulocytosis criticisms, 120 withdrawal/restriction, 101 pro-drugs, 233-5 'profen' NSAIDs, ~ propionates maleate, trade mark names questionnaires, follow-up, 112-13' and manufacturers, 14 questioning patients, intensive, 299- proliferation of NSAIDs, ~ development 300, 304 propanolol, NSAID interactions with, Quinophen, generic name and manufac• 204-6 turer, 9 properties of NSAIDs, general, 152-4 propionates, 2-aryl/2-phenyl ('profens'), 217-28 radicals, free active isomer preparations, 224 cytochrome damage by, 255 activity, 20-1, 218-20 in inflammatory disease, 239-40 enhancement, 223 scavengers, 239, 240 stereoselective, 20-1, 219-20 ranking order chiral inversion, 217-28 of prefered drugs by patients, 139, consequences of, 223-4 140, 141, 142, 143, 147 metabolic, 220-3 clinical significance, 147 species occurrence, 222-3 comparisons between two hospitals, gastrointestinal toxicity, 16 147 generic names, 219, 220, 221, 222 of prescriptions and ADRs, 107-8 prostaglandin synthesis inhibition Rantudil, generic name and manufacturer, by, 20-1 8 sites of action, 219 rare ARs to NSAIDs, 73-98 stereoselective disposition, 220-1, red cell aplasia, 83 223, 281-2 Regilon, generic name and manufacturer, structure 11 --side-effects relationship, 16 registries, drug, 98 stereochemical, 218 evaluation of risk/benefit ratio from, 58 development, 20 limitations, 75-6 324 INDEX registries (continued) Royal artillery, salicylate poisoning, 4 value, 97 regulatory bodies, responsibilities, 108 Reyes' syndrome, 271 sa1e(s), see also Marketing renal drug clearance, drug interactions ADRs in relation to, 62-6 during, 187-8 data renal failure and NSAIDs in the elderly, evaluation of risk/benefit ratio 161-2 requiring, 58 renal function for NSAIDs in Sweden, 312-13 compromised, ARs in patients with, expression by the defined daily dose 77-8, 97-8, 212 (DDD), 56, 57 consequences of aging, 160, 215 over-the-counter, of ibuprofen, 173-5 renal toxicity, 21, 77-8, 97-8 whole-, levels, 58 conditional, 263-4 , 4 in the elderly, 154, 159-62, 167 side-effects, historical aspects, 4-6 structure related to, 16, 18 salicyl alcohol, 4 Rengasil, generic name and manufacturer, salicylates 14 choline-, 9 report(s) (of ADRs) dosage, 5 data interpretation, biases affect- interactions, beneficial, 192-3 ing, 105-10 magnesium-, 12 literature-, 43 methyl-, 4, 13 number in Sweden, 59-60, 63, 64, 66 oxidized products of, formation of, prescriptions and, 28-9, 107 271-2 reporting sales in Sweden, 56 of ADRs, 28-35 Side-effects, historical aspects, 4-6 to Committee on Safety of structure, modification, 19-20 Medicines, 300-1 toxic levels, 5 constancy of, 28 salicylic acid, 4 factors affecting, 28, 42-3 difluorophenyl addition to, 235 systems for monitoring, 58 side-effects, historical aspects, 4-6 under-, 69, 75, 107 saligenin, 4 validity of intercountry com• saluretic response to furosemide, NSAID parisons based on, 105-6 effects on, 210-12 events, lack of uniformity, 39 , generic name and manufac• selective, 68 turer, 10 Restid, generic name and manufacturer, salt excretion, drugs affecting, NSAID 13 effects on, 210-12 respiratory distress, 4 Salyzoron, generic name and manufac• respiratory infections, differential turer, 9 dignosis, 201 sexes 'responders' and 'non-responders' to ADR comparisons between, 144, 145, NSAID drug interactions, 203-15 149, 149-50, 286-8 division into, criticisms concerning, studies of drug interactions specify• 214-15 ing, 278, 279 responses to coadministration of NSAIDs sfericase, trade mark names and manufac• and non-NSAIDs, variation be• turers, 14 tween patients, 203-15 sialadenitis, 84 Restogen, generic name and manufacturer, skin, see also epidermal necrolysis 11 ADRs, 7-8, 16, 78-80, 145-6 restricted NSAIDs, 8-15 passim in the elderly, 158 rheumatism, ~ arthritis incidence in Sweden, 65 rheumatoid arthritis (RA) patients withdrawn from studies cytochrome P-450 activities in due to, 128 patients with, 249-52 events, with five NSAIDs, 116, 117, drugs for, ~ antirheumatic drugs 118 side-effects in sodium, excretion of, drugs affecting, in children, 125-35 NSAID effects on, 210-12 causes of, 242 sodium bicarbonate therapy, 6 Rheumox, generic name and manufacturer, , see salicylate 9 Somalgen, generic name and manufacturer, Rimadyl, generic name and manufacturer, 14 9 species (animal), differences between, Ririlim, generic name and manufacturer, in propionate chiral inversion, 9 222-3, 223 risks (of ADRs) Stakane, generic name and manufacturer, in the elderly, 156, 159-60, 162, 9 166-7 stereochemical properties of the evaluation, 166-7, 306, 307 'profens', ~ propionates vs. efficacy, evaluating, 298 Stevens-Johnson syndrome, 8 Romadar, generic name and manufacturer, incidence, 65 10 325 SIDE-EFFECTS OF ANTI-INFLAMMATORY DRUGS Stimsen, generic name and manufacturer, Teoremec, generic name and manufacturer, 10 11 stomach, see also gastrointestinal tract terms and terminology aging of consolidation of, 40 consequences, 163 lack of uniformity in, 39-40 primary, 163 therapeutic benefit, ~ benefit secondary, 163 thiazides, indomathacin interactions erosion, drugs causing, 165 with, 205-7 stomatitis, 84 thiazolinobutazone, trade mark names and stress, gastrointestinal complaints in• manufacturers, 14 duced by, 164 Thioxaprofene, generic name and manufac• structure, side-effects related to, 15- turer, 15 20, 21 thrombocytes, ADRs, 83-4 sudoxicam thrombocytopenia, 84 manufacturers, 14 reported incidence, 66, 67 toxicity, 19 tiabinac, manufacturers, 14 , generic name and manufacturer, 14 patient preferences for, 142 trade name and manufacturers, 14 trade mark names and sulindac manufacturers, 15 active reduced metabolite of, 235 tif1amizole, manufacturers, 15 ARs timegadine, manufacturers, 15 renal, 78, 97-8 tioxaprofen, trade mark names and reported inCidence, 64, 65 manufacturers, 15 development, 20, 234, 235 tissue protein binding sites, drug in• thiazide interaction with, 207 teractions at, 181-6 trade mark names and manufacturers, Tolecgin, generic name and manufacturer, 14 15 sulphinpyrazone Tolectin, generic name and manufacturer, conditional activity, 262 15 trade mark names and manufacturers, , trade mark names and 14 manufacturers, 15 sulphoxidation, impaired, 251-2 (sodium) , trade mark names ARs, in children with rheumatoid and manufacturers, 14 arthritis, 129 , trade mark names and manufac• trade mark names and manufacturers, turers, 14 15 Surgam, generic name and manufacturer, tolerance to NSAIDs 15 in children with rheumatoid Surika, generic name and manufacturer, arthritis, 129, 130, 131, 132-3 11 gastrointestinal, the perception of, Sutoprofen, generic name and manufac• 305-6 turer, 14 topically active NSAIDs, 236-7 Sweden trade mark names of NSAIDs, 8-15 ADR reports from, 55-72 transaminitis, 85 gastrointestinal bleeding studies in, trends (in ADR reports) 309-13 analysis, ~ log linear trend NSAIDs available in, 57 analysis defined daily dose of, 57 constancy, 29-31 year of first licence, 57 'I'rilisate, generic name and manufac- sales in turer, 12 of , 56 trimethazone, manufacturers, 15 of NSAIDs, 56, 57 tuberculosis, reactivation, 81, 172 Synflex, generic name and manufacturer, types of AR, 74-5 13 Udolac, generic name and manufacturer, talniflumate, trade mark names and 14 manufacturers, 14 ulcer(s), ~ gastrointestinal ulcers Tamas, generic name and manufacturer, 9 and specific sites Tanderil, generic name and manufacturer, ulcerogenic indices, 164 13 Unisal, generic name and manufacturer, Tantum, generic name and manufacturer, 9 10 Tauston, generic name and manufacturer, United Kingdom, ADRs in 13 epidemiology of, 27-35 Tecramine, generic name and manufac• historical aspects, 4-5 turer, 11 United States, incidence of side-effects in, 47-53, 152, 153 development, 19 unusual ARs to NSAIDs, 73-98 manufacturers, 14 urogenital ARs, 86 Teorema, generic name and manufacturer, urticaria, 6, 79 11 326 INDEX vasculitis, 82 yellow card scheme, 122 vasoconstrictory activities of in• effectiveness, 301 domethacin, 199-200, 215 vasodilators, role in antihypertensive mechanisms, 195, 198-200 Zepelan, generic name and manufacturer, vertigo, 4 11 Vialidon, generic name and manufacturer, Zepelin, generic name and manufacturer, 13 11 vision, effects of NSAIDs on, 62, 87, zidometacin, manufacturers, 15 117 Zomax Vol taren, generic name and manufacturer, generic name and manufacturer, 15 10 hypersensitivity reaction to, 21 Voltarol, generic name and manufacturer, zomepirac 10 allergic/hypersensitivity reactions, vomiting, 4 21, 121 indications, 114, 115 prescription event monitoring, 113-23 warfarin, interaction with NSAIDs, 183, passim 184, 187 trade mark names and manufacturers, withdrawn NSAIDs, 8-15 passim, 233 15 in the 1980's, 21-2 xenobiotics, conditional capacity to me• tabolise, 266

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