Abbreviations used: AR(s), adverse reaction(s); ADR(s), adverse drug reaction(s); NSAID(s), non-steroid anti­inflammatory drug(s)

absorption interactions, drug, 180-1 acemetacin, trade mark names and

manufacturers, 8 acetyl salicylic acid, see Aspirin action, drug, ~ pharmacoactivity activation (of drugs), 243-5, 246, 247

pathway, 244 Actol, generic name and manufacturer, 13 Actosal, generic name and manufacturer,

9 acyl-coenzyme A formation, 221-2 adjuvant induced arthritis, ~

arthritis Af1oxan, generic name and manufacturer,

14 age see also elderly

gastrointestinal susceptibility re­lated to, 164, 286-8

use of anti-arthritics correlated with, 152

aged, the, ~ elderly agranulocytosis

incidence, 7, 100-2 passim in Sweden, 66, 67

pyrazolone-induced, 7, 99-104 analytical epidemiological

studies, 101-3 assessment of previous case

reports, 100-1 registry data, 101

report rate, 33 Alrheumat, generic name and manufac­

turer, 12 Alrheumun, generic name and manufac­

turer, 12 albumin levels in the elderly, 7 alclofenac

ARs with, 8 • manufacturers, 8

aldosterone, 195, 196 allergic reactions, see hypersensitivity alminoprofen, trade mark names and

manufacturers, 8 Alnovin, generic name and manufacturer,

10 alpha-methine proton exchange, 222 amfenac sodium

hepatotoxicity, 17 manufacturers, 9

amorfazone, trade mark names and manufacturers, 9

Amuno, generic name and manufacturer, 12 anaemia

aplastic, 83 report rate, 33

haemolytic, 84-5 in rheumatoid patients, inappropriate

therapy, 250 anaphylaxis/anaphylactoid reactions, 17,

81 Anaprox, generic name and manufacturer,

13 angioedema, 6 angiotensin-converting enzyme, 195, 196

inhibitors function, 195 NSAID interactions with, 195-200

animal(s) experimentation, ethics of, 267 inter species differences in

propionate chiral inversion, 222-3, 223

Ansaid, generic name and manufacturer, 11

antacids, 292 effect on drug absorption, 180, 181 NSAID interactions with, 185, 193

anthranilic acid, relative safety, 18 anti-arthritic drugs, ~ antirheumatic

drugs anticoagulants, NSAID interactions with,

183, 184 antidiuretics, NSAID interactions with,

88 antihypertensives, NSAID interactions

with, 185, 192, 196-7, 198-9, 204-10, see also beta blockers; diuretics

antimalarials, conditional activity, 262 antipyretics, conditional activity, 261 antirheumatic (antiarthritic) drugs, 22-

3 patient drug preferences, 139, 140,

142, 143 slow acting, 22

anti-ulcer drugs, 307-8 antrafenine, trade mark names and

manufacturers, 9 Anturan, generic name and manufacturer,

14

315

SIDE-EFFECTS OF ANTI-INFLAMMATORY DRUGS

aplastic anaemia, ~ anaemia arachidonic acid cyclo-oxygenase, 233 Archless, generic name and manufacturer,

11 Arlef, generic name and manufacturer, 11 Arquel, generic name and manufacturer,

13 Arret, generic name and manufacturer, 9 arthritis and rheumatism

adjuvant-induced, rats with, 256-7 cytochrome levels in, 249, 250 NSAID gastrotoxicity in, 265, 266-

7 collagen induced, 272-3 historical aspects of treatment, 5 osteo-, 292-3

patient drug preferences, 139, 140 perforated ulcers in patients with,

291 psoriatic, patient drug preferences,

140, 142 rheumatoid, ~ rheumatoid arthritis seronegative, patient drug

preferences, 143 Arthrocine, generic name and manufac­

turer, 14 Arthropan, generic name and manufac­

turer, 9 Artiflam, generic name and manufacturer,

15 Artrinivo, generic name and manufac­

turer, 12 Artrivia, generic name and manufacturer,

12 aryl acetic acids, derivatives and

precursors of, 234 aryl propionic acids, 2-, ~

propionates aseptic meningitis, 87 aseptic necrosis, 80 aspirin (acetyl salicylic acid)

activity, conditional, 262-3 agranulocytosis, association with,

100 antiplatelet effect, 193 formulation, problems with, 7 interactions with other drugs, 184,

185, 186, 188 sensitivity, 80 side-effects (general features), 127

in children with rheumatoid arthritis, 125-32

gastrointestinal, 311-13 hepatic, 86 historical aspects, 6, 7 incidence, 50, 135

tolerance, 130 trade mark names and manufacturers, 8 transacetylation potential, 235

Aspirin, generic name and manufacturer, 8

assays, anti-inflammatory activity, 229 association/dissociation constants, con­

ditional, 259 asthma, 80

in the elderly, 156-7 Atilan, generic name and manufacturer,

11 Atophan, generic name and manufacturer,

9 Atrobione, generic name and manufac­

turer, 9

aurothiomalate, conditional activity, 261, 263

azapropazone ARs, 19

number of reports of, 64 interactions with other drugs, 182-3,

184 sales, 71 trade mark names and manufacturers, 9

Banamine, generic name and manufacturer, 11

Benalgin, generic name and manufacturer, 9

bendroflumethiazide, indomethacin inter­actions with, 205-6

benefit vs. risk, evaluating,S, 298 Benoral, generic name and manufacturer,

9 benorylate, trade mark names and

manufacturers, 9 benoxaprofen

ARs, 7, 21 detection, 75-6 failure in detection, 120 hepatic, 86

in the elderly, 7, 277-9 pharmacokinetic profile of, 277-9 prescription--event monitoring of,

112-23 passim trade mark names and manufacturers, 9

benzoic acid, structure--side-effects relationship, 18

benzydamine hydrochloride, trade mark names and manufacturers, 9

Benzyrin, generic name and manufacturer, 9

beta-blockers, NSAID interactions with, 204-10

Biarison, generic name and manufacturer, 14

Biarson, generic name and manufacturer, 14

biases affecting data interpretation from

ADR reports, 105-10 in patient drug prefernce studies,

148 bicarbonate, sodium, therapy, 6 binding sites

cyclo-oxygenase, drug interactions at, 193

protein, ~ protein binding sites bleeding, ~ gastrointestinal tract blood dyscrasias, 19, 83-5

in the elderly, 157, 166 incidence, 7, 65, 66 report rate, 33 reports from Sweden, 62, 65, 66

blood pressure, drug interactions and, 196, 197, 199, 200, 204-10 passim

bowel disease, drug histories of patients with, 304

BPPC, manufacturers, 9 Britai, generic name and manufacturer,

10 Britain, ~ United Kingdom bronchial constriction, 128 Brufen

generic name and manufacturer, 11

316

INDEX

Brufen (continued) overdosage, 174-5

Bufenid, generic name and manufacturer, 10

bufexamic acid, trade mark names and manufacturers, 9

Buss, Dr Carl, salicylate toxicity reports by, 5-6

Butacote, generic name and manufacturer, 13

Butazolidin, generic name and manufac­turer, 13

Butazolidine, generic name and manufac­turer, 13

butazones, ARs to, 7, 19 reported numbers of, 61, 64

butyl fenamate development, 20 trade mark names and manufacturers, 9

BW755c, effect on prostaglandin syn­thesis, 20

captopril, NSAID interactions with, 196, 197

carboxyl derivatives of NSAIDs, 233-4 carcinogen activation, 249 carcinogenicity of NSAIDs, 21 cardiovascular system, see also heart

ARs, 82-3 events with five NSAIDs, 116, 117,

118 protective effect of NSAIDs, 121

carprofen, trade mark names and manufac­turers, 9

Cebutid, generic name and manufacturer, 11

central nervous system ARs, 87, 144-5, 233

in the elderly, 157-8, 166 patients withdrawn from studies

due to, 128 events with five NSAIDs, 116, 117,

118 children with rheumatoid arthritis,

side-effects in, 125-35 chiral properties of the 'profens', ~

propionates chloroquine absorption, effect of ant­

acids on, 180, 181 choline salicylate, trade mark names and

manufacturers, 9 cimetidine, 292

effect on cytochromes, 254-5 cincophen

toxicity, 18 trade mark names and manufacturers, 9

Cindomet, generic name and manufacturer, 9

cinmetacin, trade mark names and manufacturers, 9

Cinopal, generic name and manufacturer, 10

clearance, enantioselective, 220-1, 223, 281-2

clidanac, trade mark names and manufac­turers, 10

Clinoril, generic name and manufacturer, 14

Clotam, generic name and manufacturer, 15

cloximate, manufacturers, 10

Clozic ARs, 8 generic name and manufacturer, 12

coenzyme A, esterification with, 221-2 cohort studies, 48 collagen-induced arthritis, 272-3 coma, 4 Combec, generic name and manufacturer, 9 Committee on Safety of Medicines, ADR

reports to/from, 300, 301 common side-effects, 76-8 concentration--effect relationships of

the propionates, 223-4 conditional drug activity, 259-73

factors determining, 269, 270 Conforted, generic name and manufac­

turer, 12 Coslan, generic name and manufacturer,

13 Coxigon, 21

generic name and manufacturer, 9 CS-600, manufacturers, 10 cutaneous reactions, ~ Skin cyclo-oxygenase

arachidonic acid-, inhibition, 233 binding sites, drug interactions at,

193 inhibitors, 237, 240, 309

cytochromes, 249-52, 254-6 differences between, 243, 256 induction, 245 P-448, 243, 244, 245

chemical activation by, 245, 246, 247, 248-9, 251

conditions increasing activities of, 251

roles, 248 P-450, 243, 244, 245

activity in rheumatoid patients, 249-52

destruction, 255 isoenzymes of, 248 roles, 242, 250-1

Daital, generic name and manufacturer: 10

Danfenona, generic name and manufac­turer, 11

data interpretation from ADR reports,

biases affecting, 105-10 patient, linking ADRs with other, 40

databases used in identifying ADRs, 48-9 in the elderly, 155-6

deaths, ~ fatalities debrisoquine metabolism, genetic

polymorphism, 248 Deflogix, generic name and manufacturer,

14 demographic data, importance, 41 denominators

chOice, incidence of ADR reports de­pendent on, 67-8

factors affecting, 106 issues/concerns, 45-6

post-marketing, 44-5 pre-marketing, 41-2

depression, salicylate induced, 5 dermatological ARs, ~ skin reactions detection/identification of side-

effects/ADRs, 75-6

317

SIDE-EFFECTS OF ANTI-INFLAMMATORY DRUGS

detection/identification (oontiDued) in the elderly, 156-66

detoxification of drugs, 243-5 conpromised, 267-8 pathways, 267-8

development of drugs, 8-21, 229-40 emerging, 237-8 historical, 229-33 rational, 231-3 recent, 21-2, 233-7

dextropropoxyphene, paracetamo1 combined with, 247

diarrhoea, 4, 78 diclofenac

ARs, number of reports of, 64 patient preferences for, 141 trade mark names and manufacturers,

10 Difenax, generic name and manufacturer,

10 difenpyramide, trade mark names and

manufacturers, 10 diflunisal

development, 235-6 trade mark names and manufacturers,

10 digoxin, NSAID interactions with, 185 dihydroxy-benzoate, 2,3-, anti-oxidant

activity, 273 dimensions, molecular, of cytochrome P-

448 activated chemicals, 245 diplosal, trade mark names and manufac­

turers, 10 dipyrone

alternatives to, 103 -attributed agranulocytosis, 100, 101

discriminant effects of drugs/toxins, ~ conditional drug

activity disease

bowel, drug histories of patients with, 304

drug interactions with, 259-73 infectious, ~ infections subsets, 41

dissociation/association constants, con­ditional, 259

Distalgesic, 247 diuretic

antihypertensive action of, 205-7 NSAID interactions with, 88, 204-12,

277-9 use in elderly, 160-1

documentation, 43-4, see also data Dolisal, generic name and manufacturer,

10 Dolobid, generic name and manufacturer,

10 Donorest, generic name and manufacturer,

11 Dorbanex, effect on benoxaprofen phar­

macokinetics, 277-9 Dorinamin, generic name and manufac­

turer, 9 dose/dosage, see also ingestion; over­

dosage considerations in patient preference

studies, 148 daily defined dose (DDD), 55

sales expressed in, 56, 57 average number of, per prescrip­

tion, 68

data, importance, 41 frequency, patient preferences, 149 historical aspects, 5 subsets, 41

drop-out rates, 39 Droxarol, generic name and manufacturer,

9 Droxary1, generic name and manufacturer,

9 Drug Surveillance Research Unit, 112,

123 duodenal ulcers, perforated, NSAID in­

gestion and, 289 Duraprox, generic name and manufacturer,

13 dyscrasias, blood, ~ blood dyscraias Dytransin, generic name and manufac­

turer, 11

ear, ARs of the, 117 Ecotrin, generic name and manufacturer,

8 efficacy versus risk, evaluating, 298 eicosanoid, 225

biosynthesis, 250, 252 -regulated phenomena, effect of

aspirin on, 262-3 eicosapentoic acid

aspirin interactions with, 262-3 and prostaglandin synthesis, 255

elderly, NSAIDs in, 151-67 ARs of, 21, 74

gastrointestinal, 77, 286-93 heightened risk, 154-5, 286-9

pharmacokinetic profile of, 275-9 enalapril, NSAID interactions with, 197,

198, 199 enantiomeric conposition of the

propionates, 223-4 endoscopy

gastroscopic, aspirin toxicity ob­served by, 6

records, retrospective studies of, 297

Endyne, generic name and manufacturer, 12

eno1ic acids development, 20 structure--side-effects relationship,

19 enterohepatic recirculation, con­

sequences, 78 environmental factors

ADRs influenced by, 106, 242, 243-7 passim, 249-52 passim

biases from, 106 enzyme

induction, 186-7 inhibition, 187

epidemiology • of ADRs in UK, 27-35 of drug-induced agranulocytosis, 101-

3 epidermal necrolysis, 107

incidence of NSAID associated, 65 epirizole, trade mark names and manufac­

turers, 10 Epiroten, generic name and manufacturer,

9 epithelial toxicity of the propionates,

16

318

INDEX

erythema multiforme, 78-9 erythrocytes, aplasia, 83 eterylate, trade mark names and manufac­

turers, 10 ethics of animal experimentation, 267 etodolac, trade mark names and manufac­

turers, 10 etofenamate, manufacturers, 10 eudysmic ratio of the propionates, 219,

220, 224 evaluation of NSAID-induced side­

effects, 48 in the elderly, 156-67

events definition, 112-13 distinction from ARB, 38-9 patterns of, for five NSAIDs, 114-19

excretion, enantioselective, 220-1, 223, 281-2

Experizole, generic name and manufac­turer, 10

eye functions, ARs, 62, 86, 117

fatalities establishing cause, 113

difficulties in, 119 gastrointestinal complication­

associated, 121, 122 in the elderly, 165

historical reports, 4 NSAID associated

in Sweden, 60 in US, 153

Feldene, 21 generic name and manufacturer, 14

females, elderly, gastrointestinal per­foration, 286-93

fenamates, development, 19, 20 fenamole, trade mark names and manufac­

turers, 10 Fenazole, generic name and manufacturer,

9 fenbufen

ARs in children with rheumatoid arthritis, 129

development, 20, 234 prescription--event monitoring of,

112-23 passim trade mark names and manufacturers,

10 fenclofenac

anti-inflammatory effect, 192 skin reactions to, 21 trade mark names and manufacturers,

10 fenclorac, manufacturers, 10 fenclozic acid, trade mark names and

manufacturers, 10 fendosal, trade mark names and manufac­

turers, 10 fenflumizole, manufacturers, 10 fenoprofen

ARB, 129 patient preferences for, 141 trade mark names and manufacturers,

10 fentiazac, trade mark names and manufac­

turers, 11 feprazone

toxicity, 19

trade mark names and manufacturers, 11

fever drug-induced, 81, 267 --metabolism--toxicity relationship,

268 Feximac, generic name and manufacturer,

9 Flanex, generic name and manufacturer,

13 Flenac, generic name and manufacturer,

10 Flogar, generic name and manufacturer,

13 Flogene, generic name and manufacturer,

11 Flogocid, generic name and manufacturer,

9 Flosint, generic name and manufacturer,

12 Flozin, generic name and manufacturer,

12 flufenamic acid, trade mark names and

manufacturers, 11 flufenisal

drugs developed from, 18 manufacturers, 11

flunixin, trade mark names and manufac­turers, 11

flunoxaprofen, trade mark names and manufacturers, 11

fluquazone, manufacturers, 11 flurbiprofen

patient preferences for, 141 trade mark names and manufacturers,

11 follow-up

questionnaires, 112-13 studies, 48

Forenol, generic name and manufacturer, 13

formulations, problems with, 7-8 fosfosal, manufacturers, 11 free radicals, ~ radicals Froben, generic name and manufacturer"

11 frusemide, NSAID interactions with, 185,

277-9 Fullsafe, generic name and manufacturer,

11 furobufen, manufacturers, 11 furofenac, manufacturers, 11 furosemide

indomethacin interactions With, 210-12

pirprofen interactions with, 210-11

gastritis, diffuse, 76 gastrointestinal tract, 285-314, ~

also rlecific regions ARB (general unspecified features),

8, 19, 21, 76-7, 143-4,163-6, 285-314

319

conditional, 266-7 death associated with, 122 differences between sexes, 144,

145, 149, 149-50 in the elderly, 162, 163-6 Osmosin asSOCiated, 121 patients withdrawn from studies

due to, 128

SIDE-EFFECTS OF ANTI-INFLAMMATORY DRUGS

gastrointestinal tract (continued) percent of patients with various,

230 piroxicam associated, ~

piroxicam in rats with inflammmatory dis­

ease, 265, 266-7 reducing, developments with objec-

tive of, 19-20 report rate, 30-1, 32 reports from SWeden, 62, 309-13 salicylate associated, 4-6, 6 under-reporting, 69

bleeding, 5, 6, 7, 296-7, 299-300, 304, 307, 309-13

in the elderly, 165 estimated number of reports of, 32 frequency of drug intake in

patients with, 309-13 events with five NSAIDs, 116, 117,

118 lower, ARs, 85, 144, 304-5 perforation, 165, 304

in the elderly, 165, 285-93 estimated number of reports, 32 histological features, 292

ulcers/ulceration, 7, 21, 76-7, 89, see also peptic ulcers

drugs treating, 307-8 in the elderly, 165 piroxicam associated, 69 reported incidence in Sweden, 65,

66 upper, ARs, 162, 285-93, 305, 310,

311 gastroscopy, aspirin toxicity observed

by, 6 Gaultheria poisoning, 4 generic (INN) names of NSAIDs, 8-15 genetic variations/po1ymorphisms

in drug actions, 263 in drug interactions, 215 in drug oxidation, 247-9

genito-urinary ARs, 86 gentisic acid formation, abolishing, 271 Gida1on, generic name and manufacturer,

10 glutametacin, trade mark names and

manufacturers, 11 glutathione oxidation/depletion, 246 Green Forms, 112, 114, 119 group health co-operative of Pudget

Sound, 49-50 gut, ~ gastrointestinal tract

haemato1ogical ARs, ~ blood dyscrasias haemorrhage, ~ gastrointestinal tract half life

of NSAIDs, 154, 155 NSAIDs with long, 7, 236

headaches, 78 hearing, ARs, 117 heart, failure, congestive (CHF), ~

~ cardiovascular system NSAID--diuretic interactions in

patients with, 211-12, 213 risks associated with, 161

heavy metals, conditional neph­rotoxicity, 264

hepatic recirculation, entero-, 78 hepatitis, 86

hepatotoxicity, 85-6 amfenac, 17 aspirin, 135 drugs (NSAID and non-NSAID) causing,

17, 159 in the elderly, 158-9, 166 reported incidence in Sweden, 63 report rate, 34 structure related to, 16, 17, 18

historical aspects of side-effects, 4-21 histories of patients, drug

with bowel disease, 304 obtaining, 299-300

HLA-DRJ, penicillamine toxicity as­sociated with, 251, 252, 254

hypersensitivity reactions, 6, 89-90 to zomepirac, 121

hypertensive patients, therapy, 196-7 hypog1ycaemics, NSAID interactions with,

184

Ibudros, generic name and manufacturer, 12

ibufenac structure, side-effects related to,

16 trade mark names and manufacturers,

11 ibuprofen

ARs (various), number of reports of, 64

development of, 231 ena1apri1 interaction with, 197, 199 gastrointestinal toxicity, report

rate, 31, 64 overdose, 173-5

estimating, practical problems in, 175

over-the-counter sales, 173-5 patient preferences for, 141 prototypes, 231 trade mark names and manufacturers,

11 ibuprofen guaico1ester, manufacturers,

12 ibuproxam, trade mark names and manufac­

turers, 12 leI 55,897 c1obuzarit, trade mark names

and manufacturers, 12 ideal NSAID, definition of, 238 identification of hazards/ADRs, ~

detection lmady1, generic name and manufacturer, 9 Imbera1, generic name and manufacturer,

14 Imotry1, generic name and manufacturer,

9 Inacid, generic name and manufacturer,

12 incidence

of perforated peptic ulcers, 286 of side-effects

in Sweden, 62, 63, 65, 66, 67 in US, 47-53, 152, 153

Indana1, generic name and manufacturer, 10

Indicin, generic name and manufacturer, 11

indigestion, NSAIDs and, 291 Indocid, generic name and manufacturer,

12

320

INDEX

Indocin, generic name and manufacturer, 12

Indoglucin, generic name and manufac­turer, 11

indole acetic acids, modifications, 20 Indolin, generic name and manufacturer,

9 Indomed, generic name and manufacturer,

12 indomethacin

and its analogues, development, 233 interactions with other drugs, 184,

185, 196, 197, 204-13 metabolism of, variations in, 214 peptic ulceration and, 292 -R isomers, 144 side-effects, 237, 204-13

CNS, 233 gastrointestinal, 62, 77, 144, 292 historical aspects, 7 psychological, 87 report rate, 30, 31, 64 short lasting, 209

slow-release (GITS) formulation, ~ Osmosin

sodium excretion and the effect of. 211, 212

tablet vs. capsule formulation, 7 tolerance, 130, 131 vasoconstrictory activity, 199-200,

215 indomethacin glycolate, 8

trade mark names and manufacturers, 12

Indomethacine, generic name and manufac­turer, 12

indoprofen ARs to, 21 trade mark names and manufacturers,

trade mark names and manufac­turers, 12

indoxamic acid, trade mark names and manufacturers, 13

infections activation, 158 effects on cytochrome pathways, 256 historical aspects of therapy,S masking, 158

inflammmation, pharmacology of, 261-3 information, ~ data Infrocin, generic name and manufacturer,

12 ingestion frequency of patients

with gastrointestinal bleeding, 309-13

with perforated ulcers, 289 INN name of NSAIDs, 8-15 intake, ~ ingestion Inteban SF, generic name and manufac­

turer, 12 interactions, drug, 88-9, 179-215

absorption, 180-1 beneficial, 192 conditional, 262 disease--, 259-73 during renal drug elimination, 187-8 metabolic, 186-7 NSAID--non NSAID, 88-9, 179-215

clinically relevant, 184-6 mechanisms, 180 responders vs. non-responders,

203-15

sites, 180 NSAID-NSAID, 186, 189 pharmacodynamic/pharmacokinetic, 186,

188, 189 protein binding site, 181-6

interleukin-1 properties, 267, 268 intestines, ~ gastrointestinal tract investigator, effect of, 42 ionazolac calcium, manufacturers, 12 iron

inappropriate administration to rheumatoid patients, 250

metabolism of rheumatoid subjects, 249-50

isofezo1ac, manufacturers, 12 isomers of the 'profens', ~

propionates isonixin, trade mark names and manufac­

turers, 12 Isoxal, generic name and manufacturer,

14 isoxepac, trade mark names and manufac­

turers, 12 isoxicam

development, 19 trade mark names and manufacturers,

12

jaundice, NSAID induced, 21 juvenile rheumatoid arthritis, ~

rheumatoid arthritis

kallikrein-kinin system, 196 ketoprofen

C-R (Oruvail), 142, 143 in the elderly, 275-6 patient preferences pharmacokinetic profile of, 275-6 tolerance, 130, 131 trade mark names and manufacturers,

12 kidney aging, see also entries under

Renal consequences of, 7, 160, 215 primary, 160 secondary, 160

Landruma, generic name and manufacturer, 13

laxatives, effect on benoxaprofen phar­macokinetiCS, 277-9

Lederfen, generic name and manufacturer, 10

liability concerns, 43 literature reports of ADRs, 43 lithium interaction with NSAIDs, 88-9,

184 liver metabolic functions in the

elderly, see also entries under hepati -; hepato-

locally active NSAIDs, 236-7 Lodine, generic name and manufacturer,

10 lofemizole, manufacturers, 12 log-linear trend analysis, 29-34

use, 31-2 Longmore, ADR reports by, 4 Loxonin, generic name and manufacturer,

12

321

SIDE-EFFECTS OF ANTI-INFLAMMATORY DRUGS

loxoprofen sodium, trade mark names and manufacturers, 12

lung, see entries under pulmonary lupus-like syndrome, drug-induced, 82 Lyzalgo, generic name and manufacturer,

13

Maclagan, Dr. TJ., reports of salicylate toxicity, 5

magnesium salicylate, trade mark names and manufacturers, 12

Maldocil, generic name and manufacturer, 14

males, peptic ulcers in, prevalence, 286, 287

manufacturers of NSAIDs, 8-15 marketing, pre- and post-, AR as­

sessmeent, 37-46 Mebron, generic name and manufacturer,

10 Meclofen, generic name and manufacturer,

13 meclofenamate sodium, trade mark names

and manufacturers, 13 mefenamic acid, trade mark names and

manufacturers, 13 meningitis, aseptic, 87 menopause and NSAID gastrotoxicity, 288-

9 mercaptopurine ,6-,

contra-inflammatory effect of, 266-7 meseclazone

development, 20 manufacturers, 13

metabolic drug interactions, 186-7 metabolism, drug, 7, 179-282 passim

compromised, 267-8 metals, heavy, conditional neph­

rotoxicity, 264 methine, alpha-, proton exchange, 222 Methrazone, generic name and manufac­

turer, 11 a-methylacetates, ~ propionates methyl salicylate

poisoning, 4 trade mark names and manufacturers,

13 Mezolin, generic name and manufacturer,

12 Midocil, generic name and manufacturer,

15 Minalfen, generic name and manufacturer,

S Minalfene, generic name and manufac­

turer, 8 miroprofen, manufacturers, 13 molecular dimensions of cytochrome P-448

activated chemicals, 245 mortalities, ~ fatalities Moxicam, generic name and manufacturer,

12 mucocutaneous side-effects, 145-6, ~

also skin Mundisal, generic name and manufacturer,

9 muscoskeletal reactions, 80 Myalex, generic name and manufacturer,

10

Nabanol, generic name and manufacturer, 10

nabumitone, manufacturers, 13 Nalfon, generic name and manufacturer,

10 names of NSAIDs

generic, 8-15 trade mark, 8-15

Naproxen (the trade-name), generic name and manufacturer, 13

naproxen sodium ARs to, 127

in children with rheumatoid arthritis, 125-8

number of reports of, 64 patient preferences for, 140, 142 thiazide interactions with, 207 tolerance, 130 trade mark names and manufacturers,

13 Naprozyn-S, generic name and manufac­

turer, 13 National Poisons Information Service,

NSAID overdose monitoring by, 173

natriuretic response to furosemide, NSAID effects on, 210-12

necrosis, aseptic, 80 nephritis, interstitial, NSAID-induced,

161 nephrotoxicity, conditional, 263-4 neutropenia, 84 newness of drugs, effects on reporting

reactions, 42-3 nictindole, manufacturers, 13 Niflan, generic name and manufacturer,

14 niflumic acid, trade mark names and

manufacturers, 13 Nifluril, generic name and manufacturer,

13 Nixyn, generic name and manufacturer, 12 non-carboxylic NSAI acids, structure-­

side-effects relationship, 19 nortriptyline metabolism, genetic

polymorphism, 248 Norvedan, generic name and manufacturer,

11 numerator issues

post-marketing, 42-4 pre-marketing, 38-42

Numide, generic name and manufacturer, 14

ocular ADRs, 62, 87, 117 oesophageal injury, 84-5 oestrogens, protective effect, 288-9 oleyl alcohol-induced inflammation, 265,

266-7 anchylosis, NSAID-induced, 21 Opren, 21

generic name and manufacturer, 9 Oraflex, generic name and manufacturer,

12 Oruvail (ketoprofen C-R), patient

preferences, 142, 143 Orgetein, generic name and manufacturer,

13 Orudis, generic name and manufacturer,

12 Osmosin (indomethacin slow-release)

development, 236

322

INDEX

Osmosin (continued) gastrointestinal ARs to, 7, 21, 121,

144 perceptual problem of, 304

generic name and manufacturer, 12 patient preferences for, 142 prescription event monitoring of,

112, 113-23 passim osteoarthritis, ~ arthritis overdosages, 88

ibuprofen, 173-5 oxametacin, trade mark names and

manufacturers, 13 oxazolopyridine, 240

topical, 237 oxaprozin, trade mark names and manufac­

turers, 13 oxepinac, manufacturers, 13 oxicams, structure--side-effects

relationship, 19 oxidases, mixed function, 248

role of, 243-7 oxidations, genetic polyrnorphisrns of,

247-9 oxprenolol, NSAID interactions with,

185, 207-10 oxygen radicals, 256-7 oxyphenylbutazone

toxicity, 7 relative, 71-2

trade mark names and manufacturers, 13

package insert, listing of reactions on, 43

Pacyl, generic name and manufacturer, 12 pancreatitis, 85 pancytopenia, reported incidence in

Sweden, 66, 67 paracetamol

activation, 246, 247 agranulocytosis, and, 100 therapy in children with rheumatoid

arthritis, 135 toxicity, 246-7

Paraflu, generic name and manufacturer, 11

Parfenac, generic name and manufacturer, 9

Parkemed, generic name and manufacturer, 13

Parlef, generic name and manufacturer, 11

Parsal, generic name and manufacturer, 13

parsa1mide, trade mark names and manufacturers, 13

pathological conditions, gastrotoxicity determined by, 265, 266

patients counting only once, importance of,

40, 45-6 data, linking ADRs with other, 40 drug preference studies, 137-43, 146-

50 problems with, 148, 149

environment, 242 number withdrawn during studies due

to ARs, 127, 128 status, 242

PEM, ~ prescription event monitoring

penicillamine toxicity, 251-2 peptic ulcers, 305, see also gastroin­

testinal tract in the elderly, 285-93 piroxicam associated, 69, 295-302

perception of ADRs, the problem of, 303-4 of gastrointestinal tolerance, 305-6

perfect NSAID, definition of, 238 perisoxal citrate, trade mark names and

manufacturers, 13 PGI2, ~ prostacyclin pharrnaco-activity of anti-arthritics

conditional, 261 duration of, 236

pharmacokinetic (pharmacodynamic) inter­actions involving NSAIDs, 180-8

pharrnacokinetic profiles (of drugs) alterations, age-related, 154-5 of benoxaprofen, 277-9 of ketoprofen, 275-6 selective effects dependent on, 20 Phenacetin, agranulocytosis and, 100

Phenoquin, generic name and manufac­turer, 9

phenylacetates activity, 21 moiety, 16 structure--side-effects relationship,

17 phenylbutazone

interactions with warfarin, 183, 187 toxicity/side-effects

historical aspects, 7 relative, 71-2

trade mark names and manufacturers, 13

phenylpropanolamine, NSAID interactions with, 185

phenyl propionic acid, 2-, ~ propionates

phenytoin interaction with NSAIDs, 182-3, 184

photosensitivity reactions, 21, 79 pindolol, NSAID interactions with, 204-5 piroxicam

advantages, 295 ARs, 7

case reports of, 296-7 number of reports of, 64 retrospective studies of, 297 in Sweden, reports of, 21, 59, 60,

62, 64, 296-7 development, 19 gastrointestinal reactions to, 62, 66

bleeding, 296-7, 299-300 ulceration, 69, 295-302

patient preferences for, 140, 143 prescribing habits, 299-300 prescription event monitoring of,

113-23 passim reports of ARs, 21, 59, 60, 62

case-, 296-7 number of, 64

trade mark names and manufacturers, 14

pirprofen

323

furosemide interaction, 210-11 oxprenolol interaction with, 207-8 trade mark names and manufacturers,

14

SIDE-EFFECTS OF ANTI-INFLAMMATORY DRUGS

pirproxen, trade mark names and manufac­turers, 14

plant extracts, salicylate from, 4 plasma protein binding sites, ~

protein binding sites platelet function inhibition, 83-4 polyarthritis, adjuvant-induced, ~

arthritis Ponase, generic name and manufacturer,

14 post-marketing

AR assessment, 42-4, see also prescription event monitoring

denominator considerations, 44 numerator considerations, 42

Ponstan, generic name and manufacturer, 13

Ponstel, generic name and manufacturer, 13

Poustyl, generic name and manufacturer, 13

Pontal, generic name and manufacturer, 13

Prafenid, generic name and manufacturer, 12

pranoprofen, trade mark names and manufacturers, 14

pre-marketing, AR assessment, 37-42 prescription(s)

ADR reports and, 28-9, 59, 63, 107 level/numbers

ADR reports using information on, 59

in Nottingham, UK, 305-6 and peptic ulcer perforation in­

cidence, 286, 288 risk calculations from, 306, 307 in US, 47-8

registers, ~ registries unfilled, 156

prescription event monitoring, 111-23 criticisms, 120

pro-drugs, 233-5 'profen' NSAIDs, ~ propionates proglumetacin maleate, trade mark names

and manufacturers, 14 proliferation of NSAIDs, ~ development propanolol, NSAID interactions with,

204-6 properties of NSAIDs, general, 152-4 propionates, 2-aryl/2-phenyl

('profens'), 217-28 active isomer preparations, 224 activity, 20-1, 218-20

enhancement, 223 stereoselective, 20-1, 219-20

chiral inversion, 217-28 consequences of, 223-4 metabolic, 220-3 species occurrence, 222-3

gastrointestinal toxicity, 16 generic names, 219, 220, 221, 222 prostaglandin synthesis inhibition

by, 20-1 sites of action, 219 stereoselective disposition, 220-1,

223, 281-2 structure

--side-effects relationship, 16 stereochemical, 218

proquazone development, 20

trade mark names and manufacturers, 14

prostacyclin (PGI2), 198 metabolites (6-keto-PGF1a), 196

excretion, 197, 198, 199 prostaglandin (PG), see also pros-

tacyclin counter-regulations, suppressed, 160 cytoprotective, 20 F2a excretion, effect of NSAIDs on,

206 role

in the inflammatory process, 20 in renal excretion, 188, 211, 212

synthesis, ~ prostaglandin syn­thesis

prostaglandin synthesis/ production, 74, 195

inhibitors, 20-1 effects, 74-5, 77-8, 188, 196,

218-19 Protaxil, generic name and manufacturer,

14 protein binding sites

plasma-drug interactions at, 181-6 enantiomeric competition at, 282

tissue-, drug interactions at, 181-6 protocol subsets, 45 Proxil, generic name and manufacturer,

14 psoriatic arthritis, patient drug

preferences with, 140, 142 psychological ADRs, 5, 87 Puget Sound studies, 49-50 pUlmonary ADRs, 80-2 pUlmonary infiltrates, 80-1 pulmonary oedema, 80 pyrazolone

-induced granulocytosis, ~ granulocytosis

withdrawal/restriction, 101

questionnaires, follow-up, 112-13' questioning patients, intensive, 299-

300, 304 Quinophen, generic name and manufac­

turer, 9

radicals, free cytochrome damage by, 255 in inflammatory disease, 239-40 scavengers, 239, 240

ranking order of prefered drugs by patients, 139,

140, 141, 142, 143, 147 clinical significance, 147 comparisons between two hospitals,

147 of prescriptions and ADRs, 107-8

Rantudil, generic name and manufacturer, 8

rare ARs to NSAIDs, 73-98 red cell aplasia, 83 Regilon, generic name and manufacturer,

11 registries, drug, 98

324

evaluation of risk/benefit ratio from, 58

limitations, 75-6

INDEX

registries (continued) value, 97

regulatory bodies, responsibilities, 108 Reyes' syndrome, 271 renal drug clearance, drug interactions

during, 187-8 renal failure and NSAIDs in the elderly,

161-2 renal function

compromised, ARs in patients with, 77-8, 97-8, 212

consequences of aging, 160, 215 renal toxicity, 21, 77-8, 97-8

conditional, 263-4 in the elderly, 154, 159-62, 167 structure related to, 16, 18

Rengasil, generic name and manufacturer, 14

report(s) (of ADRs) data interpretation, biases affect-

ing, 105-10 literature-, 43 number in Sweden, 59-60, 63, 64, 66 prescriptions and, 28-9, 107

reporting of ADRs, 28-35

to Committee on Safety of Medicines, 300-1

constancy of, 28 factors affecting, 28, 42-3 systems for monitoring, 58 under-, 69, 75, 107 validity of intercountry com­

parisons based on, 105-6 events, lack of uniformity, 39 selective, 68

Restid, generic name and manufacturer, 13

respiratory distress, 4 respiratory infections, differential

dignosis, 201 'responders' and 'non-responders' to

NSAID drug interactions, 203-15 division into, criticisms concerning,

214-15 responses to coadministration of NSAIDs

and non-NSAIDs, variation be­tween patients, 203-15

Restogen, generic name and manufacturer, 11

restricted NSAIDs, 8-15 passim rheumatism, ~ arthritis rheumatoid arthritis (RA)

cytochrome P-450 activities in patients with, 249-52

drugs for, ~ antirheumatic drugs side-effects in

in children, 125-35 causes of, 242

Rheumox, generic name and manufacturer, 9

Rimadyl, generic name and manufacturer, 9

Ririlim, generic name and manufacturer, 9

risks (of ADRs) in the elderly, 156, 159-60, 162,

166-7 evaluation, 166-7, 306, 307 vs. efficacy, evaluating, 298

Romadar, generic name and manufacturer, 10

Royal artillery, salicylate poisoning, 4

sa1e(s), see also Marketing ADRs in relation to, 62-6 data

evaluation of risk/benefit ratio requiring, 58

for NSAIDs in Sweden, 312-13 expression by the defined daily dose

(DDD), 56, 57 over-the-counter, of ibuprofen, 173-5 whole-, levels, 58

salicin, 4 side-effects, historical aspects, 4-6

salicyl alcohol, 4 salicylates

choline-, 9 dosage, 5 interactions, beneficial, 192-3 magnesium-, 12 methyl-, 4, 13 oxidized products of, formation of,

271-2 sales in Sweden, 56 Side-effects, historical aspects, 4-6 structure, modification, 19-20 toxic levels, 5

salicylic acid, 4 difluorophenyl addition to, 235 side-effects, historical aspects, 4-6

saligenin, 4 saluretic response to furosemide, NSAID

effects on, 210-12 Salsalate, generic name and manufac­

turer, 10 salt excretion, drugs affecting, NSAID

effects on, 210-12 Salyzoron, generic name and manufac­

turer, 9 sexes

ADR comparisons between, 144, 145, 149, 149-50, 286-8

studies of drug interactions specify­ing, 278, 279

sfericase, trade mark names and manufac­turers, 14

sialadenitis, 84 skin, see also epidermal necrolysis

ADRs, 7-8, 16, 78-80, 145-6 in the elderly, 158 incidence in Sweden, 65 patients withdrawn from studies

due to, 128 events, with five NSAIDs, 116, 117,

118 sodium, excretion of, drugs affecting,

NSAID effects on, 210-12 sodium bicarbonate therapy, 6 sodium salicylate, see salicylate Somalgen, generic name and manufacturer,

14 species (animal), differences between,

in propionate chiral inversion, 222-3, 223

Stakane, generic name and manufacturer, 9

stereochemical properties of the 'profens', ~ propionates

Stevens-Johnson syndrome, 8 incidence, 65

325

SIDE-EFFECTS OF ANTI-INFLAMMATORY DRUGS

Stimsen, generic name and manufacturer, 10

stomach, see also gastrointestinal tract aging of

consequences, 163 primary, 163 secondary, 163

erosion, drugs causing, 165 stomatitis, 84 stress, gastrointestinal complaints in­

duced by, 164 structure, side-effects related to, 15-

20, 21 sudoxicam

manufacturers, 14 toxicity, 19

Sulindac, generic name and manufacturer, 14

trade name and manufacturers, 14 sulindac

active reduced metabolite of, 235 ARs

renal, 78, 97-8 reported inCidence, 64, 65

development, 20, 234, 235 thiazide interaction with, 207 trade mark names and manufacturers,

14 sulphinpyrazone

conditional activity, 262 trade mark names and manufacturers,

14 sulphoxidation, impaired, 251-2 superoxide dismutase, trade mark names

and manufacturers, 14 suprofen, trade mark names and manufac­

turers, 14 Surgam, generic name and manufacturer,

15 Surika, generic name and manufacturer,

11 Sutoprofen, generic name and manufac­

turer, 14 Sweden

ADR reports from, 55-72 gastrointestinal bleeding studies in,

309-13 NSAIDs available in, 57

defined daily dose of, 57 year of first licence, 57

sales in of analgesics, 56 of NSAIDs, 56, 57

Synflex, generic name and manufacturer, 13

talniflumate, trade mark names and manufacturers, 14

Tamas, generic name and manufacturer, 9 Tanderil, generic name and manufacturer,

13 Tantum, generic name and manufacturer, 9 Tauston, generic name and manufacturer,

13 Tecramine, generic name and manufac­

turer, 11 tenoxicam

development, 19 manufacturers, 14

Teorema, generic name and manufacturer, 11

Teoremec, generic name and manufacturer, 11

terms and terminology consolidation of, 40 lack of uniformity in, 39-40

therapeutic benefit, ~ benefit thiazides, indomathacin interactions

with, 205-7 thiazolinobutazone, trade mark names and

manufacturers, 14 Thioxaprofene, generic name and manufac­

turer, 15 thrombocytes, ADRs, 83-4 thrombocytopenia, 84

reported incidence, 66, 67 tiabinac, manufacturers, 14 tiaprofenic acid

patient preferences for, 142 trade mark names and

manufacturers, 15 tif1amizole, manufacturers, 15 timegadine, manufacturers, 15 tioxaprofen, trade mark names and

manufacturers, 15 tissue protein binding sites, drug in­

teractions at, 181-6 Tolecgin, generic name and manufacturer,

15 Tolectin, generic name and manufacturer,

15 tolfenamic acid, trade mark names and

manufacturers, 15 tolmetin (sodium)

ARs, in children with rheumatoid arthritis, 129

trade mark names and manufacturers, 15

tolerance to NSAIDs in children with rheumatoid

arthritis, 129, 130, 131, 132-3 gastrointestinal, the perception of,

305-6 topically active NSAIDs, 236-7 trade mark names of NSAIDs, 8-15 transaminitis, 85 trends (in ADR reports)

analysis, ~ log linear trend analysis

constancy, 29-31 'I'rilisate, generic name and manufac-

turer, 12 trimethazone, manufacturers, 15 tuberculosis, reactivation, 81, 172 types of AR, 74-5

Udolac, generic name and manufacturer, 14

ulcer(s), ~ gastrointestinal ulcers and specific sites

ulcerogenic indices, 164 Unisal, generic name and manufacturer,

10 United Kingdom, ADRs in

epidemiology of, 27-35 historical aspects, 4-5

United States, incidence of side-effects in, 47-53, 152, 153

unusual ARs to NSAIDs, 73-98 urogenital ARs, 86 urticaria, 6, 79

326

INDEX

vasculitis, 82 vasoconstrictory activities of in­

domethacin, 199-200, 215 vasodilators, role in antihypertensive

mechanisms, 195, 198-200 vertigo, 4 Vialidon, generic name and manufacturer,

13 vision, effects of NSAIDs on, 62, 87,

117 Vol taren, generic name and manufacturer,

10 Voltarol, generic name and manufacturer,

10 vomiting, 4

warfarin, interaction with NSAIDs, 183, 184, 187

withdrawn NSAIDs, 8-15 passim, 233 in the 1980's, 21-2

xenobiotics, conditional capacity to me­tabolise, 266

yellow card scheme, 122 effectiveness, 301

Zepelan, generic name and manufacturer, 11

Zepelin, generic name and manufacturer, 11

zidometacin, manufacturers, 15 Zomax

generic name and manufacturer, 15 hypersensitivity reaction to, 21

zomepirac

327

allergic/hypersensitivity reactions, 21, 121

indications, 114, 115 prescription event monitoring, 113-23

passim trade mark names and manufacturers,

15