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Adverse Drug Reactions in the Gastrointestinal System Attributed to Ibuprofen

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Safety and Efficacy of Non-Prescription (OTC) Analgesics and NSAIDs

Abstract

Concern about the capacity of non-steroidal anti-inflammatory drugs (NSAIDs) to cause damage to the upper gastrointestinal tract goes back to the 1930s and 1940s when the first associations between ingestion of aspirin and gastrointestinal bleeding were reported [1, 2]. These were relatively small case series but the association was believed to be quite strong, and it was appreciated, even then, that widespread use of aspirin in the community might be responsible for large numbers of cases of gastrointestinal bleeding. The development of newer NSAIDs such as phenylbutazone and indomethacin followed. More recently introduced drugs, such as naproxen and ibuprofen, were thought to have lessened the risk of damage to the stomach and duodenum [3]. The belief in the lower risk of these newer drugs was quite strong; so much so that the entity of NSAID-induced gastrointestinal bleeding became controversial [4,5]. Surprisingly, in view of the widespread use of these drugs, there were very few properly controlled pharmacoepidemiological studies performed until the mid 1980s [6, 7]. Since then the effects of NSAIDs on the upper gastrointestinal tract have been the subject of quite intense investigation [6–21]. In fact, other than oral contraceptives and hormone replacement therapy, it is doubtful whether any single group of drugs has been so extensively investigated using epidemiological methods.

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References

  1. Douthwaite AH, Lintott GAM. Gastroscopic observation of the effect of aspirin and certain other substances on the stomach. Lancet. 1938;2:1222–5.

    Article  Google Scholar 

  2. Muir A, Cossar IA. Aspirin and ulcer. Br Med J. 1955;2;7–12.

    Article  PubMed  CAS  Google Scholar 

  3. Langman MJS. Epidemiological evidence for the association of aspirin and acute gastrointestinal bleeding. Gut. 1970;11:627–34.

    Article  PubMed  CAS  Google Scholar 

  4. Langman MJS, Spiro HM, Ingelfinger SJ. Aspirin and the stomach. In: Ingelfinger FJ, Ebert RV, Finland M, eds. Controversy and Internal Medicine 11, Philadelphia: WE Saunders. 1974:491–510.

    Google Scholar 

  5. Henry DA, Langman MJS. Drugs as gastric irritants. In: Dykes PW, Keighley MRV, eds. Drugs as Gastric Irritants. Bristol: John Wright & Sons Ltd. 1981:49–59.

    Google Scholar 

  6. Somerville K, Faulkner G, Langman M. Non-steroidal anti-inflammatory drugs in bleeding peptic ulcer. Lancet. 1986;1:462–4.

    Article  PubMed  CAS  Google Scholar 

  7. Carson JL, Strom BL, Morse ML et al. The relative gastrointestinal toxicity of the non-steroidal anti-inflammatory drugs. Arch Intern Med. 1987;147:1054–9.

    Article  PubMed  CAS  Google Scholar 

  8. Langman MJS, Weil J, Wainright P. Risks of bleeding peptic ulcer associated with individual non-steroidal anti-inflammatory drugs. Lancet. 1994;343:1075–8.

    Article  PubMed  CAS  Google Scholar 

  9. Henry D, Dobson A, Turner C. Variability in the risk of major gastrointestinal complications from non-aspirin nonsteroidal anti-inflammatory drugs. Gastroenterology. 1993;105(4):1078–8.

    PubMed  CAS  Google Scholar 

  10. Griffin MR, Piper JM, Daugherty JR, Snowden M, Ray WA. Nonsteroidal anti-inflammatory drug use and increased risk for peptic ulcer disease in elderly persons. Ann Intern Med. 1991;114(4):257–63.

    PubMed  CAS  Google Scholar 

  11. Laporte JR, Carne X, Vidal X, Moreno V, Juan J. Upper gastrointestinal bleeding in relation to previous use of analgesics and non-steroidal anti-inflammatory drugs. Catalan countries study on upper gastrointestinal bleeding, Lancet. 1991;337(8733):85–9.

    Article  PubMed  CAS  Google Scholar 

  12. Savage RL, Moller PW, Ballantyne CL, Wells J. Variation in the risk of peptic ulcer complications with nonsteroidal antiinflammatory drug therapy. Arthritis Rheum. 1993;36(1):84–90.

    Article  PubMed  CAS  Google Scholar 

  13. Nobili A, Mosconi P, Franzosi MG, Tognoni G. Non-steroidal anti-inflammatory drugs and upper gastrointestinal bleeding, a post-marketing surveillance case-control study. Pharmacoepidemiol Drug Safety. 1992;1:65–72.

    Article  Google Scholar 

  14. Kaufman W, Kelly JP, Sheehan JE. Nonsteroidal anti-inflammatory drug use in relation to major upper gastrointestinal bleeding. Clin Pharmacol Ther. 1993;53(4):485–94.

    Article  PubMed  CAS  Google Scholar 

  15. Perez-Gutthann S, Garcia-Rodriguez LA, Raiford DS. Individual non-steroidal anti-inflammatory drugs and the risk of hospitalisation for upper gastrointestinal bleeding and perforation in Saskatchewan: a nested case-control study. I. Pharmacoepidemiol Drug Safety. 1994;3(suppl.l):S63.

    Google Scholar 

  16. Garcia-Rodriguez LA, Walker AM, Perez-Gutthann S. Nonsteroidal antiinflammatory drugs and gastrointestinal hospitalizations in Saskatchewan: a cohort study. Epidemiology. 1992;3(4):337–42.

    Article  PubMed  CAS  Google Scholar 

  17. Abenhaim L, Moride Y. The effect of baseline susceptibility on the relative gastro-toxicity of individual NSAIDs in the elderly: a study with the Quebec database. Paper presented at the IXth International Conference on Pharmacoepidemiology, Washington DC, 1993.

    Google Scholar 

  18. Garcia-Rodriguez LA, Jick H. Risk of upper gastrointestinal bleeding and perforation associated with individual non-steroidal anti-inflammatory drugs. Lancet. 1994;343:769–72.

    Article  PubMed  CAS  Google Scholar 

  19. Gabriel SE, Jaakkimainen L, Bombardier C. Risk for serious gastrointestinal complications related to use of nonsteroidal anti-inflammatory drugs. A meta-analysis. Ann Intern Med. 1991;115(10):787–96.

    CAS  Google Scholar 

  20. Bollini P, Garcia-Rodriguez LA, Perez-Gutthann S, Walker AM. The impact of research quality and study design on epidemiologic estimates of the effect of nonsteroidal anti-inflammatory drugs on upper gastrointestinal tract disease. Arch Intern Med. 1992;152(6):1289–92.

    Article  PubMed  CAS  Google Scholar 

  21. Henry D, Lim L, Garcia Rodriguez LA et al. Variability in risk of major upper gastrointestinal complications with individual NSAIDs: results of a collaborative meta-analysis. Br Med J. 1996;312:1563–6.

    Article  CAS  Google Scholar 

  22. Vane JR, Botting RM. Mechanism of action of aspiring-like drugs. Semin Arthritis Rheum. 1997;26(6 Suppl. 1):2–10.

    Article  PubMed  CAS  Google Scholar 

  23. Clive DM, Stoff JS. Renal syndromes associated with nonsteroidal anti-inflammatory drugs. N Engl J Med. 1984;310:563–72.

    Article  PubMed  CAS  Google Scholar 

  24. Gyomber E, Vattay P, Szabo S, Rainsford KD. Role of early vascular damage in the pathogenesis of gastric haemorrhagic mucosal lesions induced by indomethacin in rats. Int J Exp Pathol. 1996;77(1):16.

    Google Scholar 

  25. Fenner H. Differentiating among nonsteroidal antinflammatory drugs by pharmacokinetic and pharmacodynamic profiles. Semin Arthritis Rheum. 1997;26(6 Suppl):28–33.

    Article  PubMed  CAS  Google Scholar 

  26. el-Assi MT, Genta RM, Karttunen TJ, Graham EY. Ulcer site and complications: relation to heliobacter pylori infection and NSAID use. Endoscopy. 1996;28(2):229–33.

    Article  Google Scholar 

  27. Lipscombe GR, Wallis M, Armstrong G, Goodman MJ, Rees WD. Influence of helicobacter pylori on gastric mucosal adaptations to naproxen in Man. Dig Dis Sci. 1996;41(8):1583–8.

    Article  Google Scholar 

  28. Santucci L, Fiorucci S, Patoia L, Di Matteo FM, Brunori PM, Morelli A. Severe gastric mucosal damage induced by NSAIDs in healthy subjects associated with helicobacter pylori infection and high levels of sedum pepsinogens. Dig Dis Sci. 1995;40(9):2074–80.

    Article  PubMed  CAS  Google Scholar 

  29. Laine L, Cominelli F, Sloane R, Casini-Riggi V, Marin-Sorensen M, Weinstein WM. Interaction of NSAIDs and Helicobacter pylori on gastrointestinal injury and prostoglandin production: a controlled double-blind trial. Elemen Pharmacol Ther. 1995;9(2):127–35.

    Article  CAS  Google Scholar 

  30. Taha AS, Sturrock RD, Russell RI. Mucosal erosions in long-term non-steroidal anti-inflammatory drug users: predisposition to ulceration and relation to helicobacter pylori, Gut. 1995;36(3):334–6.

    Article  PubMed  CAS  Google Scholar 

  31. Taha AS, Dahill S, Sturrock RD, Lee FD, Russell RI. Predicting NSAID-related ulcers - assessment of clinical and pathological factors and importance of differences in NSAID. Gut. 1994;35(7):891–5.

    Article  PubMed  CAS  Google Scholar 

  32. Graham DY. Non-steroidal anti-inflammatory drugs, helicobacter pylori, and ulcers: where we stand. Am J Gastroenterol. 1996;91(10):2080–6.

    PubMed  CAS  Google Scholar 

  33. Svanes C, Ovrebok K, Sereide O. Ulcer bleeding and perforation: non-steroidal anti-inflammatory drugs and helicobacter pylori. Scand J Gasterenterol. 1996;220(suppl):128–31.

    Article  CAS  Google Scholar 

  34. Janssen M, Dijkmans BA, Lamers CB, Zwinderman AH, van den Broucke JP. A gastroscopic study of the predictive value of risk factors for non-steroidal anti-inflammatory drugs and associated ulcer disease in rheumatoid arthritis. Br J Rheumatol. 1994;35(5):449–54.

    Article  Google Scholar 

  35. Meta S, Dasarathy S, Tandon RK, Mathur M, Malaviya AN. A prospective randomised study of the injurious effects of aspirin and naproxen on the gastroduodenal mucosa in patients with rheumatoid arthritis. Am J Gastroenterol. 1992;87(8):996–1000.

    Google Scholar 

  36. Svanes C, Ovrebo K, Soreide O, 1996. Ulcer bleeding and perforation: non-steroid anti-inflammatory drugs or helicobacter pylori. Scand J Gastroenterol. 1996;220(suppl):128–31.

    CAS  Google Scholar 

  37. Lanza F, Royer G, Nelson R. An endoscopic evaluation of the effects of non-steroidal anti-inflammatory drugs on the gastric mucosa. J Gastrointest Endose. 1975;21(3):103–5.

    Article  CAS  Google Scholar 

  38. Lanza FL, Royer GL Nelson RS, Chen TT; Seckman CE, Rack MF. The effects of ibuprofen indomethacin aspirin naproxen and placebo on the gastric mucosa of normal volunteers. Dig Dis Sci. 1979;24(11):823–8.

    Article  PubMed  CAS  Google Scholar 

  39. Caruso I, Bianchi Porro G. Gastroscopie evaluation of anti-inflammatory agents. Br Med J. 1980;280(6207):75–8.

    Article  PubMed  CAS  Google Scholar 

  40. Lanza FL, Royer GL, Nelson RS, Chen TT, Seckman CE, Rack MF. A comparative endoscopic evaluation of the damaging effects of non-steroidal anti-inflammatory agents on the gastric and duodenal mucosa. Am J Gastroenterol. 1981;75(1):17–21.

    PubMed  CAS  Google Scholar 

  41. Lanza F, Rack MF, Lynn M, Wolf J, Sanda M. An endoscopic comparison of the effects of otodolac, indomethacin, ibuprofen, naproxen, and placebo on the gastrointestinal mucosa. J Rheumatol. 1986;14:338–41.

    Google Scholar 

  42. Friedman H, Seckman CE, Lanza F, Royer G, Perry K, Francom S. Clinical pharmacology of pre-disintegrated ibuprofen 800mg tablets: an endoscopic and pharmacokinetic study. J Clin Pharmacol. 1990;30:57–63.

    PubMed  CAS  Google Scholar 

  43. Bergmann JS, Chassany O, Geneve J, Aviteboul M, Caulin C, Segrestaa JM. Endoscopic evaluation of the effects of ketoprofen, ibuprofen, and aspirin on the gastroduodenal mucosa. Eur J Clin Pharmacol. 1992;42:685–8.

    Article  PubMed  CAS  Google Scholar 

  44. Roth SH, Tindall EA, Jain AK. A controlled study comparing the effects of nabumetone, ibuprofen plus misoprostol on the upper gastrointestinal tract mucosa, Arch Intern Med. 1993;153:2565–71.

    Article  PubMed  CAS  Google Scholar 

  45. Aabakken L, Larsen S, Osnes M. Visual analogue skills for endoscopic evaluation of non-steroidal anti-inflammatory drug-induced mucosal damage in the stomach and duodenum. Scand J Gastroenterol. 1990;25:443–8.

    Article  PubMed  CAS  Google Scholar 

  46. Lanza FL, Graham DY, Davis RE, Rack MF, Endoscopic comparison of cimetidine and sucralfate for the prevention of naproxen-induced acute gastroduodenal injury. Dig Dis Sci. 1990;35(12):1494–9.

    Article  PubMed  CAS  Google Scholar 

  47. Laine L, Sloane R, Ferreti M, Cominelli F. A randomised double-blind comparison of placebo etodolac, and naproxen on gastrointestinal injury and prostaglandin production. Gastrointest Endosc. 1995;42:428–33.

    Article  PubMed  CAS  Google Scholar 

  48. Laine L. Non-steroidal anti-inflammatory drug gastropathy. Gastrointest Endosc Clin N Am. 1996;6(3):489–504.

    PubMed  CAS  Google Scholar 

  49. Lipscombe GR, Wallis N, Armstrong G, Goodman MJ, Reece WD. Gastric mucosal adaptation to etodolac and naproxen. Aliment Pharmacol Ther. 1995;9(4):379–85.

    Article  Google Scholar 

  50. Porrow GB, Montrone F, Petrillo M, Caruso I, Imbessi V. Gastroduodenal tolerability of nabumetone versus naproxen in the treatment of rheumatic patients. Am J Gastroenterol. 1995;90(9):1485–8.

    Google Scholar 

  51. Hawkey CJ. Non-steroidal anti-inflammatory drug gastropathy: causes and treatment. Scand J Gastroenterol. 1996;220(suppl):124–7.

    Article  CAS  Google Scholar 

  52. Coch N, Dezi A, Ferrario S, Capurso I. Prevention of non-steroidal anti-inflammatory drug -induced gastrointestinal mucosal injury. A meta-analysis of randomised control clinical trials. Arch Intern Med. 1996;56(20):2321–2.

    Google Scholar 

  53. Elliot SL, Yeomans ND, Buchanan RR, Smallwood RA. Efficacy of twelve months misoprostol as prophylaxis against NSAID-induced gastric ulcers. A placebo controlled trial. Scand J Rheumatol. 1994;23(4):171–6.

    Article  Google Scholar 

  54. Cales P, Zabotto B, Meskens C et al. Gastroesophageal endoscopical features in psoriasis, observer variability, interassociations in relationship to hepatic dysfunction. Gastroenterology. 1990;98:156–62.

    PubMed  CAS  Google Scholar 

  55. Sonnenberg A, Giger M, Kern L et al. How reliable is determination of ulcer size by endoscopy? Br Med J. 1979;2:1322–4.

    Article  PubMed  CAS  Google Scholar 

  56. Hudson M, Everitt S, Hawkey CJ. Interobserver variation in assessment of gastroduodenal lesions association with non-steroidal anti-inflammatory drugs. Gut. 1994;35:1030–2.

    Article  PubMed  CAS  Google Scholar 

  57. Graham DY, Agrawal NM, Roth SH. Prevention of NSAID-induced gastric ulcer with misoprostol: multicentre, double-blind, placebo-controlled trial. Lancet. 1988;2(8623):1277–80.

    Article  PubMed  CAS  Google Scholar 

  58. Graham DY, White RH, Moerland LW et al. Duodenal and gastric ulcer prevention with misoprostol in arthritis patients taking NSAIDs. Misoprostol study group. Ann Intern Med. 1993;119(4):157–262.

    Google Scholar 

  59. Raskin JB, White RH, Jackson JE et al. Misoprostol dosage in the prevention of nonsteroidal anti-inflammatory drug-induced gastric and duodenal ulcers: a comparison of three regimens. Ann Intern Med. 1995;123(5):344–50.

    PubMed  CAS  Google Scholar 

  60. Silverstein FE, Graham DY, Senior JR et al. Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving non-steroidal anti-inflammatory drugs. A randomised double-blind placebo controlled trial. Ann Intern Med. 1995;123(4):241–9.

    PubMed  CAS  Google Scholar 

  61. Lanza FL. Endoscopic studies of gastric and duodenal injury after the use of ibuprofen, aspirin and other non-steroidal anti-inflammatory agents. Am J Med. 1984;77(1A):19–24.

    Article  PubMed  CAS  Google Scholar 

  62. Rossi AC, Hsu JP, Faich GA. Ulcerogenicity of piroxicam: an analysis of spontaneously reported date. Br Med J. 1987;294(6565):147–50.

    Article  CAS  Google Scholar 

  63. Bateman DN. Re-evaluation of gut toxicity of NSAIDs. In: Vane J, Botting J, Botting R, eds. Improved non-steroidal anti-inflammatory drugs. COX-2 enzyme inhibitors. London. William Harvey Press/ Dordrecht: Kluwer Academic Publishers; 1996: 189–201.

    Chapter  Google Scholar 

  64. Der Simonian R, Laird N. Meta-analysis and clinical trials. Controlled Clin Trials. 1986;7:177–88.

    Article  Google Scholar 

  65. Fries J. Toward an understanding of NSAID-related adverse events: The contribution of longitudinal data. Scand J Rheumatol. 1996;25(Suppl. 102):3–8.

    Article  Google Scholar 

  66. Fries JF, Williams CA, Bloch DA, Michel BA. Non-steroidal anti-inflammatory drug associated gastropathy: Incidence and risk factor models. Am J Med. 1991;91:213–22.

    Article  PubMed  CAS  Google Scholar 

  67. Fries JF, Williams CA, Bloch DA. The relative toxicity of non-steroidal anti-inflammatory drugs. Arthritis Rheum. 1991;34(11):1353–60.

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. The Discipline of Clinical Pharmacology, Faculty of Medicine and Health Sciences, Australia

    D. Henry

  2. The Department of Clinical Toxicology, Newcastle Mater Hospital, Australia

    A. Drew

  3. The Department of General Medicine, Newcastle Mater Hospital, Newcastle, NSW, Australia

    S. Beuzeville

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  1. D. Henry
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  2. A. Drew
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  3. S. Beuzeville
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Editors and Affiliations

  1. Division of Biomedical Sciences, School of Science and Mathematics, Sheffield Hallam University, Sheffield, UK

    K. D. Rainsford

  2. M/P Biomedical Consultants, LLC, Mill Valley, CA, USA

    M. C. Powanda

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Henry, D., Drew, A., Beuzeville, S. (1998). Adverse Drug Reactions in the Gastrointestinal System Attributed to Ibuprofen. In: Rainsford, K.D., Powanda, M.C. (eds) Safety and Efficacy of Non-Prescription (OTC) Analgesics and NSAIDs. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-4878-8_3

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  • DOI: https://doi.org/10.1007/978-94-011-4878-8_3

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