Skip to main content
SpringerLink
Log in

Gastrointestinal damage and bleeding from non-steroidal anti-inflammatory drugs. I. Clinical and epidemiological aspects

  • Published:
InflammoPharmacology Aims and scope Submit manuscript

Abstract

The clinicoepidemiological data implicating NSAIDs in the development of gastrointestinal (GI) bleeding and ulceration, as well as the mortality therefrom is reviewed. Retrospective case-controlled cohort surveillance studies and meta-analyses as well as mortality statistics are considered. The conclusion is that NSAIDs are associated with an increased risk of upper GI ulceration and bleeding, especially in the elderly, and that this may contribute to appreciable mortality. Case reports implicating certain NSAIDs in the development of intestinal ulceration, perforation and diaphragm-like strictures raise the issue that while rare events these drugs may have potentially serious pathology in regions of the GI tract inaccessible to investigation. Rigorous and well-defined studies are required to establish conclusively the factors responsible for GI morbidity and mortality from NSAIDs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Gibson T. Nonsteroidal anti-inflammatory drugs - another look. Br J Rheumatol. 1989;27:87–90.

    Article  Google Scholar 

  2. Levy M, Miller DR, Kaufman DW et al. Major upper gastrointestinal tract bleeding. Relation to the use of aspirin and other non-narcotic analgesics. Arch Intern Med. 1988;148:281–5.

    Article  PubMed  CAS  Google Scholar 

  3. Price AH, Fletcher M. Mechanisms of NSAID-induced gastroenteropathy. Drugs. 1990;40(suppl.5):1–11.

    PubMed  CAS  Google Scholar 

  4. Soll AH, Weinstein WM, Kurata J, McCarthy D. Nonsteroidal anti-inflammatory drugs and peptic ulcer disease. Ann Intern Med. 1991;114:307–19.

    PubMed  CAS  Google Scholar 

  5. Kelly J. Salicylate ingestion: a frequent cause of gastric haemorrhage. Am J Med Sci. 1956;232:119–27.

    PubMed  CAS  Google Scholar 

  6. Allibone A, Flint FS. Bronchitis, aspirin, smoking and other factors of the aetiology of peptic ulcer. Lancet. 1958;2:179–82.

    Article  PubMed  CAS  Google Scholar 

  7. Alvarez AS, Summerskill WHJ. Gastrointestinal haemorrhage and salicylates. Lancet. 1958;2:920–5.

    Article  PubMed  CAS  Google Scholar 

  8. Muir A, Cossar IA. Aspirin and gastric haemorrhage. Lancet. 1959;1:539–41.

    Article  PubMed  CAS  Google Scholar 

  9. Grossman MI, Matsumoto KK, Lichter RJ. Fecal blood loss produced by oral and intravenous administrations of various salicylates. Gastroenterology. 1961;4:383–8.

    Google Scholar 

  10. Weiss A, Pitman ER, Graham EC. Aspirin and gastric bleeding. Gastroscopic observations, with review of literature. Am J Med. 1961;31:266–70.

    Article  PubMed  CAS  Google Scholar 

  11. Valman HB, Parry DJ, Coghill NF. Lesions associated with gastroduodenal haemorrhage, in relation to aspirin intake. Br Med J. 1968;4:661–3.

    PubMed  CAS  Google Scholar 

  12. Levy M. Aspirin use in patients with major upper gastrointestinal bleeding and peptic-ulcer disease. N Engl J Med. 1974;290:1158–62.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  14. Langman MJS. Epidemiologic evidence on the association between peptic ulceration and anti-inflammatory drug use. Gastroenterology. 1989;96:640–6.

    PubMed  CAS  Google Scholar 

  15. Henry DA, Johnston A, Dobson A et al. Fatal peptic ulcer complications and the use of NSAIDs, aspirin, and corticosteroids. Br Med J. 1987;295:1227–9.

    CAS  Google Scholar 

  16. McIntosh JH, Byth K, Piper KW. Environmental factors in aetiology of gastric ulcer: a case control study of exposure variables before the first symptoms. Gut. 1985;26:789–98.

    PubMed  CAS  Google Scholar 

  17. Gabriel C, Bombardier SE. NSAID induced ulcers, an emerging epidemic? J Rheumatol. 1989;17:1–4.

    Google Scholar 

  18. Armstrong CP, Blower AL. NSAIDs and life threatening complications of peptic ulceration. Gut. 1987;28:527–32.

    PubMed  CAS  Google Scholar 

  19. Faulkner G, Pritchard P, Somerville K, Langman MJS. Aspirin and bleeding peptic ulcers in the elderly. Br Med J. 1988;297:1311–13.

    CAS  Google Scholar 

  20. Agrawal N. Risk factors for gastrointestinal ulcers caused by nonsteroidal anti-inflammatory drugs (NSAIDs). J Fam Pract. 1991;32:619–24.

    PubMed  CAS  Google Scholar 

  21. Collier DSJ, Pain JA. NSAID and peptic ulcer perforation. Gut. 1985;26:359–63.

    PubMed  CAS  Google Scholar 

  22. Langman MJS, Well J, Lawson DH et al. Risk of bleeding peptic ulcer associated with individual non-steroidal anti-inflammatory drugs. Lancet. 1994;343:1075–52.

    Article  PubMed  CAS  Google Scholar 

  23. Bateman DN. NSAIDs: time to re-evaluate gut toxicity. Lancet. 1994;343:1051–2.

    Article  PubMed  CAS  Google Scholar 

  24. Anon. Relative safety of oral non-aspirin NSAIDs. Curr Prob Pharmacovigilance. 1994;20:9–11.

  25. Haslock I. Prevalence of NSAID-induced gastrointestinal morbidity and mortality. J Rheumatol. 1990;17(Suppl 20):2–6.

    Google Scholar 

  26. Henry DA. Gastrointestinal bleeding and non-steroidal anti-inflammatory drugs. In: Lawson DH, ed. Current Medicine 3. Edinburgh: Churchill-Livingstone; 1991:171–89.

    Google Scholar 

  27. Bjarnason I, Macpherson AJS. Intestinal toxicity of non-steroidal anti-inflammatory drugs. Pharm Ther. 1994;62:145–57.

    Article  CAS  Google Scholar 

  28. Bartle WR, Gupta A, Lazor J et al. Nonsteroidal anti-inflammatory drugs and gastrointestinal bleeding. A case control study. Arch Intern Med. 1986;146:2365–7.

    Article  PubMed  CAS  Google Scholar 

  29. Griffin MR, Ray WA, Schaffner W. NSAID use and death from peptic ulcer in elderly persons. Ann Intern Med. 1988;109:359–63.

    PubMed  CAS  Google Scholar 

  30. Smedley FH, Taube M, Leach R et al. NSAID indigestion: retrospective study of 272 bleeding or perforated peptic ulcers. Postgrad Med J. 1989;65:892–5.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  32. Laporte JR, Carne X, Vidal X, Moreno V, Jauan J. Upper gastrointestinal bleeding in relation to previous use of analgesics and non-steroidal anti-inflammatory drugs. Lancet. 1991;37:85–9.

    Article  Google Scholar 

  33. Henry D, Dobson A, Turner C. Variability in the risk of major gastrointestinal complications from nonaspirin non-steroidal anti-inflammatory drugs. Gastroenterology. 1993;105:1078–88.

    PubMed  CAS  Google Scholar 

  34. Garcia Rodriguez IA. 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 

  35. Daly LE, Bourke GJ, McGilvray J. Interpretation and uses of medical statistics, 4th edn. London: Blackwell Scientific Publications; 1992.

    Google Scholar 

  36. Beard K, Walker AM, Perera DR, Jick H. Nonsteroidal anti-inflammatory drugs and hospitalization for gastroesophageal bleeding in the elderly. Arch Intern Med. 1987;147:1621–3.

    Article  PubMed  CAS  Google Scholar 

  37. Carson JL, Strom BL, Soper KA, West SL, Morse ML. The association of nonsteroidal anti-inflammatory drugs with upper gastrointestinal tract bleeding. Arch Intern Med. 1987;147:85–8.

    Article  PubMed  CAS  Google Scholar 

  38. Guess HA, West R, Strand L et al. Fatal upper GI hemorrhage or perforation among users and non-users of nonsteroidal anti-inflammatory drugs in Saskatchewan, Canada 1983. J Clin Epidemiol. 1988;41:35–45.

    Article  PubMed  CAS  Google Scholar 

  39. Fries JF, Miller SR, Spitz PW, Williams CA, Hubert HB, Bloch DA. Toward an epidemiology of gastropathy associated with non-steroidal anti-inflammatory drug use. Gastroenterology. 1989;96:646–55.

    Google Scholar 

  40. Bloom B. Risk and cost of GI side effects associated with NSAIDs. Arch Intern Med. 1989;149:1019–22.

    Article  PubMed  CAS  Google Scholar 

  41. Stodolnik E, Maurer P, Hoigne R et al. Risk of acute upper gastrointestinal bleeding in patients with ulcerative disease and treatment with non-steroidal anti-inflammatory drugs (NSAIDs). Results from the Comprehensive Drug Monitoring Berne (CHDM). Eur J Clin Pharmacol. 1990;38:31–5.

    Article  PubMed  CAS  Google Scholar 

  42. Fries JF, Williams CA, Bloch DA. NSAID-associated gastropathy: incidence and risk factor models. Am J Med. 1991;91:213–22.

    Article  PubMed  CAS  Google Scholar 

  43. Kurata JH, Nogawa AN, Abbey DE, Petersen F. A prospective study of risk for peptic ulcer disease in seventh-day adventists. Gastroenterology. 1992;102:902–9.

    PubMed  CAS  Google Scholar 

  44. Katschinski BD, Zachewicz H, Goebell H. Nonsteroidal anti-inflammatory drugs and mortality from peptic ulceration in West Germany: 1952–1989. Dig Dis Sci. 1992;37:385–90.

    Article  PubMed  CAS  Google Scholar 

  45. Henry D, Robertson J. Nonsteroidal anti-inflammatory drugs and peptic ulcer hospitalization rates in New South Wales. Gastroenterology. 1993;104:1083–91.

    PubMed  CAS  Google Scholar 

  46. Zimmerman J, Arnon E, Ligumski M et al. Acute gastrointestinal bleeding in Jerusalem 1988–1991 — causes, characteristics and relation to non-steroidal anti-inflammatory drugs. Isr J Med Sci. 1993;29:292–7.

    PubMed  CAS  Google Scholar 

  47. Katschinski B, Logan R, Davies J et al. Prognostic factors in upper gastrointestinal bleeding. Dig Dis Sci. 1994;39:706–12.

    Article  PubMed  CAS  Google Scholar 

  48. Henry DA. The relationship between nonsteroidal anti-inflammatory drugs, the treatment of peptic ulcer and its complications — can we estimate risk? Agents Actions. 1985;17:105–17.

    CAS  Google Scholar 

  49. Strom BL. Sample size considerations for pharmacoepidemiologic considerations. In: Strom BL, ed. Pharmacoepidemiology. New York: Churchill-Livingstone; 1989:27–37.

    Google Scholar 

  50. Moore JG, Bjorkman DJ. NSAID-induced gastropathy in the elderly: understanding and avoidance. Geriatrics. 1989;44:51–7.

    PubMed  CAS  Google Scholar 

  51. Rainsford KD, Velo GP, eds. Side Effects of Anti-Inflammatory Drugs. Pt. 1. Clinical and Epidemiological Studies. Lancaster: MTP Press; 1987.

    Google Scholar 

  52. Van Staa T-P, Abenhaim L, Leufkens H. Selective prescribing of non-steroidal anti-inflammatory drugs — implications for postmarketing surveillance. Post Marketing Surveillance. 1992;5:339–49.

    Google Scholar 

  53. Leufkens HG, Urquart J, Stricker BHCh, Bakker A, Petri H. Channeling of controlled release formulation of ketoprofen (Oscorel) in patients with a history of gastrointestinal problems. J Epidemiol Commun Health. 1992;46:428–32.

    CAS  Google Scholar 

  54. Lanas A, Sekar MC, Hirschowitz BI. Objective evidence of asprin use in both ulcer and non-ulcer and lower gastrointestinal bleeding. Gastroenterology. 1992;103:862–9.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  56. Cox NL, Doherty SM. Non-steroidal anti-inflammatory: outpatient audit of patient preferences and side-effects in different diseases. In: Rainsford KD, Velo GP, eds. Side Effects of Anti-Inflammatory Drugs. Vol.1. Clinical and Epidemiological Aspects. Lancaster: MTP Press; 1987:137–50.

    Google Scholar 

  57. Pemberton RE, Strand LJ. A review of upper gastrointestinal effects of the newer nonsteroidal anti-inflammatory agents. Dig Dis Sci. 1979;24:53–64.

    Article  PubMed  CAS  Google Scholar 

  58. Rainsford KD. An analysis of gastrointestinal side-effects of non-steroidal anti-inflammatory drugs, with particular reference to comparative studies in man and laboratory species. Rheumatol Int. 1982;2:1–10.

    Article  PubMed  CAS  Google Scholar 

  59. Rainsford KD, Velo GP, eds. Side effects of anti-inflammatory/analgesic drugs. New York: Raven Press; 1984.

    Google Scholar 

  60. Rainsford KD. Interplay between anti-inflammatory drugs and eicosanoids in gastrointestinal damage. In: Hiller K, ed. Eicosanoid and the Gastrointestinal Tract. Lancaster: MTP Press; 1988:111–28.

    Google Scholar 

  61. Rainsford KD, ed. Azapropazone: Over 20 Years of Clinical Use, 2nd edn. Lancaster: Kluwer Academic Publishers; 1991.

    Google Scholar 

  62. Rainsford, KD, James C, Johnson DM et al. Effect of chronic NSAIDs on gastric mucosal injury related to mucosal, prostanoids, and plasma drug concentrations in human volunteers. Agents Actions. 1993;39:C21–3.

    Article  PubMed  CAS  Google Scholar 

  63. Rainsford KD, Velo GP, eds. Side-Effects of Anti-Inflammatory Drugs. 3. Lancaster: Kluwer Academic Publishers; 1992.

    Google Scholar 

  64. Weber JCP. Epidemiology in the United Kingdom of adverse drug reactions from non-steroidal anti-inflammatory drugs. In: Rainsford KD, Velo GP, eds. Side-Effects of Anti-Inflammatory Drugs. Pt. 1. Clinical and Epidemiological Aspects. Lancaster: MTP Press; 1987:27–35.

    Google Scholar 

  65. Wiholm BE, Myrhed M, Ekman E. Trends and patterns in adverse drug reactions to non-steroidal anti-inflammatory drugs reported in Sweden. In: Rainsford KD, Velo GP, eds. Side-Effects of Anti-Inflammatory Drugs. Pt. 1. Clinical and Epidemiological Aspects. Lancaster: MTP Press; 1987:55–70.

    Google Scholar 

  66. Lamy PP. Non-steroidal anti-inflammatories in the elderly. In: Rainsford KD, Velo GP, eds. Side-Effects of Anti-Inflammatory Drugs. Pt. 1. Clinical and Epidemiological Aspects. Lancaster: MTP Press; 1987:151–74.

    Google Scholar 

  67. Gabriel SE, Jaakkimainen RL, Bombardier C. The cost-effectiveness of misoprostol for nonsteroidal anti-inflammatory drug-associated adverse gastrointestinal events. Arth Rheum. 1993;36:447–59.

    Article  CAS  Google Scholar 

  68. Kent TH, Cardelli RM, Stamler FW. Small intestinal ulcers and intestinal flora in rats given indomethacin. Am J Pathol. 1969;54:237–49.

    PubMed  CAS  Google Scholar 

  69. Fang WF, Broughton A, Jacobson ED. Indomethacin induced intestinal inflammation. Am J Dig Dis. 1977;22:749–60.

    Article  PubMed  CAS  Google Scholar 

  70. Robert A, Asano T. Resistance of germ-free rats to indomethacin-induced intestinal lesions. Prostaglandins. 1977;14:333–41.

    Article  PubMed  CAS  Google Scholar 

  71. Shriver DA, Dove PA, White CB, Sandor A, Rosenthale ME. A profile of the gastrointestinal toxicity of aspirin, indomethacin, oxaprozin, phenylbutazone and fentiazac in arthritic and Lewis normal rats. Toxicol Appl Pharmacol. 1977;42:75–83.

    Article  PubMed  CAS  Google Scholar 

  72. Duggan DE, Hooke KF, Noll RM, Kwan KC. Enterohepatic circulation of indomethacin and its role in intestinal irritation. Biochem Pharmacol. 1975;25:1749–54.

    Article  Google Scholar 

  73. Rainsford KD. A comparison of the gastric ulcerogenic activity of benoxaprofen with other non-steroidal anti-inflammatory drugs in rats and pigs. Eur J Rheumatol Inflamm. 1982;5:148–64.

    PubMed  CAS  Google Scholar 

  74. Rainsford KD. Mechanisms of intestinal mucosal damage by non-steroidal anti-inflammatory drugs. In: Phillips SF, Barbara L, Paoletti R, eds. Gastroenterology: New Trends in Pathophysiology and Therapy of the Large Bowel. Amsterdam, North Holland: Elsevier; 1983:207–20.

    Google Scholar 

  75. Brune K, Dietzel K, Nurnberg B, Schneider HTh. Recent insight into the mechanism of gastrointestinal tract ulceration. Scand J Gastroenterol. 1987;(suppl.65):135–40.

  76. Rainsford KD. Mucosal lesions induced in the rat intestinal tract by the anti-inflammatory drug. Wy 41,770, a weak inhibitor of prostaglandin synthesis, contrasted with those from the potent prostaglandin inhibitor, indomethacin. Toxicol Pathol. 1988;16:366–76.

    Article  PubMed  CAS  Google Scholar 

  77. Ruelius HW, Young EM, Kirkman SK, Schillings RT, Sisenwine SF, Janssen FW. Biological fate of acyl glucuronides in the rat. The role of rearrangement, intestinal enzymes and reabsorption. Biochem Pharmacol. 1985;34:2115–6.

    Article  PubMed  Google Scholar 

  78. Bjarnason I, Williams P, Smethurst P, Peters TJ, Levi AJ. Effect of non-steroidal anti-inflammatory drugs and prostaglandins on the permeability of the human small intestine. Gut. 1986;27:1292–7.

    PubMed  CAS  Google Scholar 

  79. Bjarnason I, Peters TJ. Intestinal permeability, non-steroidal anti-inflammatory drugs enteropathy and inflammatory bowel disease: an overview. Gut Festscrift. 1989;22–8.

  80. Bjarnason I, Zanelli G, Smith T, Prouse P, Williams P, Smethurst P, Delacey G, Gumpel MJ, Levi AJ. Non-steroidal anti-inflammatory drug-induced intestinal inflammation in humans. Gastroenterology. 1987;93:480–9.

    PubMed  CAS  Google Scholar 

  81. Bjarnason I. NSAID-induced small intestinal inflammation in man. Recent Adv Gastroenterol. 1988;7:23–46.

    Google Scholar 

  82. Bjarnason I, Zanelli G, Prouse P et al. Effect of non-steroidal anti-inflammatory drugs on the human small intestine. Drugs. 1986;32(Suppl.1):35–41.

    PubMed  Google Scholar 

  83. Bjarnason I, Williams P, Smethurst P et al. The effect of non-steroidal anti-inflammatory drugs and prostaglandins on the permeability of the human small intestine. Gut. 1986;27:1292–7.

    PubMed  CAS  Google Scholar 

  84. Jenkins RT, Rooney PJ, Bienenstock J, Goodacre RL. Increased intestinal permeability in patients with rheumatoid arthritis: a side-effect of oral non-steroidal anti-inflammatory drug therapy? Br J Rheumatol. 1987;26:103–7.

    Article  PubMed  CAS  Google Scholar 

  85. Jenkins AP, Trew DR, Crump BJ, Nukajam WS, Foley JA, Menzies IS, Creamer B. Do non-steroidal anti-inflammatory drugs increase colonic permeability? Gut. 1991;32:66–9.

    PubMed  CAS  Google Scholar 

  86. Mielants H, Veys EM, Goemaere S, DeVos M, Cuvelier C, Maerteus M, Ackerman K. Intestinal mucosal permeability in inflammatory rheumatic diseases. In: Rainsford KD, Velo GP, eds. Side-Effects of Anti-Inflammatory Drugs. 3. Lancaster: Kluwer Academic Publishers; 1992:80–8.

    Google Scholar 

  87. TerLaag B, Hermann U. Biliary elimination of indomethacin in man. Eur J Clin Pharmacol. 1986;29:691–5.

    Article  Google Scholar 

  88. Shack MW. Drug induced ulceration and perforation of the small intestine. Arizona Med. 1966;23:517–23.

    PubMed  CAS  Google Scholar 

  89. Davies DR, Brightmore T. Idiopathic and drug-induced ulceration of the small intestine. Br J Surg. 1970;57:134–9.

    Article  PubMed  CAS  Google Scholar 

  90. Wijdeveld PGAB. Some clinical and therapeutic aspects of the nephrotic syndrome in the adult (with special emphasis on the effects of indomethacin and related substances). Folia Med Neerl. 1971;14:4–31.

    PubMed  CAS  Google Scholar 

  91. Sturges HF, Krone CL. Ulceration and stricture of the jejunum in a patient on long-term indomethacin therapy. Am J Gastroenterol. 1973;59:162–9.

    PubMed  CAS  Google Scholar 

  92. Coutrou S, Roland D, Barbier J, Van der Marq P, Alcalay M, Matuchansky C. Acute perforation of colonic diverticula associated with short-term indomethacin. Lancet. 1978;2:134–9.

    Google Scholar 

  93. McQueen EG. New Zealand Committee on Adverse Drug Reactions: Fifteenth Annual Report. NZ Med J. 1981;93:194–8.

    CAS  Google Scholar 

  94. Langman MJS, Morgan L, Worral A. Use of anti-inflammatory drugs by patients admitted with small or large bowel perforation and haemorrhage. Br Med J. 1985;290:347–9.

    CAS  Google Scholar 

  95. Banerjee AK. Enteropathy induced by non-steroidal anti-inflammatory drugs. Often subclinical but may mimic Crohn’s disease. Br Med J. 1989;298:1539–40.

    Article  CAS  Google Scholar 

  96. Dabakken L, Osnes M. Non-steroidal anti-inflammatory drug-induced disease in the distal ileum and large bowel. Scand J Gastroenterol. 1989;24(Suppl.163):48–55.

    Google Scholar 

  97. Lang J, Price AB, Levi AJ, Burke M, Gumpel JM, Bjarnason I. Diaphragm disease: pathology of disease of the small intestine induced by non-steroidal anti-inflammatory drugs. J Clin Pathol. 1988;41:516–26.

    Article  PubMed  CAS  Google Scholar 

  98. Bjarnason I, Macpherson A. The changing gastrointestinal side effect profile of non-steroidal anti-inflammatory drugs. A new approach for the prevention of a new problem. Scand J Gastroenterol. 1989;24(Suppl.163):56–64.

    Google Scholar 

  99. Huber T, Ruchti C, Halter F. Nonsteroidal antiinflammatory drug-induced colonic strictures: a case report. Gastroenterology. 1991;100:1119–22.

    PubMed  CAS  Google Scholar 

  100. Whitcomb DC, Martin SP, Trellis DR, Evans BA, Becich MJ. ‘Diaphramlike’ stricture and ulcer of the colon during diclofenac treatment. Archiv Intern Med. 1992;1552:2341–3.

    Article  Google Scholar 

  101. Halter F, Weber B, Huber T, Eigenmann F, Frey MP, Ruchti C. Diaphragm disease of the ascending colon. Association with sustained-release diclofenac. J Clin Gastroenterol. 1993;16:74–80.

    Article  PubMed  CAS  Google Scholar 

  102. Hudson N, Wilkinson MJ, Swannell AJ, Steele RJ, Hawkey CJ. Ileo-caecal ulceration associated with the use of diclofenac slow release. Aliment Pharmacol Ther. 1993;7:197–200.

    Article  PubMed  CAS  Google Scholar 

  103. Meddings JB, Sutherland LR, Byles NI, Wallace JL. Sucrose: a novel permeability marker for gastroduodenal disease. Gastroenterology. 1993;104:1619–26.

    PubMed  CAS  Google Scholar 

  104. Borda IT, Koff RS, eds. NSAIDs: A Profile of Adverse Effects. Philadelphia: Hanley and Belfus; 1992.

    Google Scholar 

  105. Allison MC, Howatson AG, Torrance CJ, Lee FD, Russell RI. Gastrointestinal damage associated with the use of nonsteroidal antiinflammatory drugs. N Engl J Med. 1992;327:749–54.

    Article  PubMed  CAS  Google Scholar 

  106. Fleming JL, Ahlquist DA, McGill DB, Zinsmeister AR, Ellefson RD, Schwartz S. Influence of aspirin and ethanol on fecal blood levels as determined by using the Hemoquant assay. Mayo Clin Proc. 1987;62:159–63.

    PubMed  CAS  Google Scholar 

  107. St John DJB, Young GP, Alexeyett MA, Deacon MC, Cuthbertson AM, Macrea FA, Penford JCB. Evaluation of new occult blood tests for the detection of colorectal neoplasia. Gastroenterology. 1993;104:1661–8.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Biomedical Sciences and Health Research Centre, Sheffield Hallam University, S1 1WB, Sheffield, UK

    K. D. Rainsford

  2. Department of Biomedical Sciences, McMaster University, L8N 3Z5, Hamilton, Ontario, Canada

    K. D. Rainsford & M. Quadir

Authors
  1. K. D. Rainsford
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Quadir
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rainsford, K.D., Quadir, M. Gastrointestinal damage and bleeding from non-steroidal anti-inflammatory drugs. I. Clinical and epidemiological aspects. Inflammopharmacology 3, 169–190 (1995). https://doi.org/10.1007/BF02674920

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02674920

Keywords

Search

Navigation