A Clinician’s View of Strategies for Preventing Nsaid-Induced Gastrointestinal Ulcers

  • J. Huang
  • R. H. Hunt


Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed drugs in the world. Each year approximately 100 million NSAID prescriptions are dispensed in the United States [1]. In Canada in 1989, there were 10.7 million prescriptions for NSAIDs [2], a growth rate of 6% per year [3]. In the United Kingdom, nearly 22 million prescriptions for NSAIDs were issued in 1985 [4]. Despite the undoubted efficacy of NSAIDs in pain relief in patients with arthritis and musculoskeletal pain, all have the potential to cause a number of clinically significant gastrointestinal (GI) adverse effects. Although these effects are generally restricted to minor injury to the gastrointestinal mucosa, epidemiological studies have indicated a three- to fourfold increase in gastric ulceration, upper GI bleeding and complicated duodenal ulcer [5], especially in a high-risk population; the sequelae of using NSAIDs may result in life-threatening complications and these may occur without any warning symptoms [6]. The purpose of this article is to review, from a clinician’s point of view, the wide spectrum of GI damage induced by NSAIDs, the possible mechanism of action of NSAIDs and strategies for treating and preventing NSAID-induced GI lesions.


gastrointestinal NSAIDs ulcers 


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  1. 1.
    ACG Primary Care News for the GI Patients. Effect of NSAIDs on the upper gastrointestinal tract. 1995;1(1):1.Google Scholar
  2. 2.
    Hunt RH. NSAID-induced gastric ulcers: exploring the silent dilemma. Can J Gastroenterol. 1990;4(3):89–90.Google Scholar
  3. 3.
    Gabriel SE, Bombardier C. NSAID induced ulcers: an emerging epidemic? J Rheumatol. 1990;17:1–4.PubMedGoogle Scholar
  4. 4.
    Walt R, Logan R, Katschinski B, Ashley J, Langman M. Rising frequency of ulcer perforation in elderly people in the United Kingdom. Lancet. 1986;i:489–92.CrossRefGoogle Scholar
  5. 5.
    Hawkey CJ. Non-steroidal anti-inflammatory drugs and peptic ulcers. Facts and figures multiply, but do they add up? Br Med J. 1990;300:278–84.CrossRefGoogle Scholar
  6. 6.
    Armstrong CP, Blower AL. Non-steroidal anti-inflammatory drugs and life-threatening complications of peptic ulceration. Gut. 1987;28:527–32.PubMedCrossRefGoogle Scholar
  7. 7.
    Douthwaite AH, Lintott GAM. Gastroscopic observation of the effect of aspirin and certain other substances on the stomach. Lancet. 1938;ii:1222–4.CrossRefGoogle Scholar
  8. 8.
    Roth SH. Nonsteroidal anti-inflammatory drug gastropathy: we started it - can we stop it? Arch Intern Med. 1986;146:1075–6.PubMedCrossRefGoogle Scholar
  9. 9.
    Fries JF, Miller SR, Spitz PW, Williams CA, Hubert HB, Bloch DA. Toward an epidemiology of gastropathy associated with nonsteroidal antiinflammatory drug use. Gastroenterology. 1989;96:647–55.PubMedGoogle Scholar
  10. 10.
    Guess HA, West R, Strand LM, et al. Fatal upper gastrointestinal hemorrhage or perforation among users and nonusers of nonsteroidal anti-inflammatory drugs in Saskatchewan, Canada, 1983. J Clin Epidemiol. 1988;41(1):35–45.PubMedCrossRefGoogle Scholar
  11. 11.
    Roth SH, Bennet RE. Nonsteroidal anti-inflammatory drug gastropathy. Recognition and response. Arch Intern Med. 1987;147:2093–100.PubMedCrossRefGoogle Scholar
  12. 12.
    Hochberg MC. Association of nonsteroidal antiinflammatory drugs with upper gastrointestinal disease: epidemiologic and economic considerations. J Rheumatol. 1992;19(supp1.36):63–7.Google Scholar
  13. 13.
    Lockard O, Ivey KJ, Butt JH, Silvoso G, Sisk C, Holt S. The prevalence of duodenal lesions in patients with rheumatic disease on chronic aspirin therapy. Gastrointest Endosc. 1980;26:5–7.PubMedCrossRefGoogle Scholar
  14. 14.
    O’Laughlin JC, Hoftiezer JW, Ivey KJ. Effect of aspirin on the human stomach in normals: endoscopic comparison of damage produced one hour, 24 hours, and 2 weeks after administration. Scand J Gastroenterol. 1981; 16(supp1.67):211–14.Google Scholar
  15. 15.
    Lanza FL. A review of gastric ulcer and gastroduodenal injury in normal volunteers receiving aspirin and other non-steroidal anti-inflammatory drugs. Scand J Gastroenterol. 1989;24(supp1.163):24–31.CrossRefGoogle Scholar
  16. 16.
    Savage RL, Moller PW, Ballantyne CL, Wells JE. Variation in the risk of peptic ulcer complications with nonsteroidal antiinflammatory drug therapy. Arthritis Rheum. 1993;36(1):84–90.PubMedCrossRefGoogle Scholar
  17. 17.
    Kaufman DW, Kelly JP, Sheehan JE, et al. Nonsteroidal anti-inflammatory drug use in relation to major upper gastrointestinal bleeding. Clin Pharmacol Ther. 1993;53:485–94.PubMedCrossRefGoogle Scholar
  18. 18.
    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. A gastroscopic and photographic study. Dig Dis Sci. 1979;24(11):823–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Lanza FL. Endoscopic studies of gastric and duodenal injury after the use of ibuprofen, aspirin, and other nonsteroidal anti-inflammatory agents. Am J Med. 1984;17:19–24.CrossRefGoogle Scholar
  20. 20.
    Willet LR, Carson JL, Strom BL. Epidemiology of gastrointestinal damage associated with nonsteroidal anti-inflammatory drugs. Drug Safety. 1994;10(2):170–81.CrossRefGoogle Scholar
  21. 21.
    Collier DSJ, Pain JA. Non-steroidal antiinflammatory drugs and peptic ulcer perforation. Gut. 1985;26:359–63.PubMedCrossRefGoogle Scholar
  22. 22.
    Somerville K, Faulkner G, Langman M. Non-steroidal anti-inflammatory drugs and bleeding peptic ulcer. Lancet. 1986;1:462–4.PubMedCrossRefGoogle Scholar
  23. 23.
    Lapote J, Carne X, Vidal X, Moreno V, Juan J. Upper gastrointestinal bleeding in relation to previous use of analgesics and non-steroidal anti-inflammatory drugs. Lancet. 1991;337:85–9.CrossRefGoogle Scholar
  24. 24.
    Silvoso GR, Ivey KJ, Butt JH, et al. Incidence of gastric lesions in patients with rheumatic disease on chronic aspirin therapy. Ann Intern Med. 1979;91(4):517–20.PubMedCrossRefGoogle Scholar
  25. 25.
    Larkai EN, Smith JL, Lidsky MD, Graham DY. Gastroduodenal mucosa and dyspeptic symptoms in arthritic patients during chronic non-steroidal anti-inflammatory drug use. Am J Gastroenterol. 1987;82(11):1153–8.PubMedGoogle Scholar
  26. 26.
    Elliot SL, Yeomans ND, Buchanan RRC, Smallwood RA. Efficacy of 12 months misoprostol as prophylaxis against NSAID-induced gastric ulcers. Scand J Rheumatol. 1994;23:171–6.CrossRefGoogle Scholar
  27. 27.
    Geis GS, Stead H, Wallemark C, Nicholson PA. Prevalence of mucosal lesions in the stomach and duodenum due to chronic use of NSAID in patients with rheumatoid arthritis or osteoarthritis, and interim report on prevention by misoprostol of diclofenac associated lesions. J Rheumatol. 1991;18(supp1.28):11–14.Google Scholar
  28. 28.
    Caruso I, Biachi Porro G. Gastroscopic evaluation of anti-inflammatory agents. Br Med J. 1980;280:75–8.PubMedCrossRefGoogle Scholar
  29. 29.
    Graham DY, Smith JL, Dobbs SM. Gastric adaptation occurs with aspirin administration in man. Dig Dis Sci. 1983;28:1–6.PubMedCrossRefGoogle Scholar
  30. 30.
    Shorrock CJ, Rees WDW. Mucosal adaptation to indomethacin induced gastric damage-studies on morphology, blood flow, and prostaglandin E2 metabolism. Gut. 1992;33:164–9.PubMedCrossRefGoogle Scholar
  31. 31.
    Bahrt KM, Korman LY, Nashel DJ. Significance of a positive test for occult blood in stools of patients taking anti-inflammatory drugs. Arch Intern Med. 1984;144:2165–6.PubMedCrossRefGoogle Scholar
  32. 32.
    Collins AJ, du Toit JA. Upper gastrointestinal findings and faecal occult blood in patients with rheumatic disease taking nonsteroidal anti-inflamamtory drugs. Br J Rheumatol. 1987;26:295–8.PubMedCrossRefGoogle Scholar
  33. 33.
    Graham DY, Smith JL. Aspirin and the stomach. Ann Intern Med. 1986;104:390–8.PubMedCrossRefGoogle Scholar
  34. 34.
    CSM Update. Non-steroidal anti-inflammatory drugs and serious gastrointestinal adverse reactions -1. Br Med J. 1986;292:614.CrossRefGoogle Scholar
  35. 35.
    Fries JF. NSAID gastropathy: the second most deadly rheumatic disease? Epidemiology and risk appraisal. J Rheumatol. 1991; 18(Supp1.28):6–10.Google Scholar
  36. 36.
    Mitchell DM, Spitz PW, Young DY, Bloch DA, McShane DJ, Fries JF. Survival, prognosis, and causes of death in rheumatoid arthritis. Arthritis Rheum. 1986;29(6):706–14.PubMedCrossRefGoogle Scholar
  37. 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.PubMedCrossRefGoogle Scholar
  38. 38.
    Smedley FH, Taube M, Leach R, Wastell C. Non-steroidal anti-inflammatory drug ingestion: retrospective study of 272 bleeding or perforated peptic ulcer. Postgrad Med J. 1989;65:892–5.PubMedCrossRefGoogle Scholar
  39. 39.
    Gabriel SE, Jaakkimainen L, Bombardier C. Risk for serious gastrointestinal complications related to use of nonsteroidal antiinflammatory drugs. Ann Intern Med. 1991;115:787–96.PubMedCrossRefGoogle Scholar
  40. 40.
    Vandenbroucke JP, Hazevoet HM, Cats A. Survival and cause of death in rheumatoid arthritis: a 25-year prospective follow-up. J Rheumatol. 1984;11:158–61.PubMedGoogle Scholar
  41. 41.
    Quader K, Logan RFA. Peptic ulcer (PU) deaths: how many occur at home or after non-steroidal antiinflammatory drug (NSAID) prescribing? Gut. 1988;29:A1443.Google Scholar
  42. 42.
    Agrawal NM, Patel R, Mahatama M, Dajani EZ. Non-steroidal antiinflammatory drugs and acute upper gastrointestinal bleeding: a prospective study. J Assoc Acad Minor Phys. 1991;2:64–6.PubMedGoogle Scholar
  43. 43.
    Somerville K, Faulkner G, Langman M. Non-steroidal anti-inflammatory drugs and bleeding peptic ulcer. Lancet. 1986;1(i):462–4.PubMedCrossRefGoogle Scholar
  44. 44.
    Hudson N, Wilkinson Mi, Swannell AJ, Steele RJ, Hawkey CJ. Ileo-caecal ulceration associated with use of diclofenac slow release. Aliment Pharmacol Ther. 1993;7:197–200.PubMedCrossRefGoogle Scholar
  45. 45.
    Pucius RJ, Charles AK, Adair HM, Rowe RCG, Hacking JC. Diaphragm-like stricture of the colon induced by non-steroidal anti-inflammatory drugs. Br J Surg. 1993;80:39–6.CrossRefGoogle Scholar
  46. 46.
    Robinson MHE, Wheatley T, Leach IH. Nonsteroidal antiinflammatory drug-induced colonic stricture: an unusual cause of large bowel obstruction and perforation. Dig Dis Sci. 1995;40(2):315–9.PubMedCrossRefGoogle Scholar
  47. 47.
    Langman MJS, Morgan L, Worrall A. Use of anti-inflammatory drugs by patients admitted with small or large bowel perforations and hemorrhage. Br Med J. 1985;290:347–9.CrossRefGoogle Scholar
  48. 48.
    Allison MC, Howatson AG, Torrance CJ, Lee FD, Russel RI. Gastrointestinal damage associated with use of nonsteroidal anti-inflammatory drugs. N Engl J Med. 1992;327(11):749–54.PubMedCrossRefGoogle Scholar
  49. 49.
    Wilson RG, Smith AN, Macintyre IMC. Complications of diverticular disease and non-steroidal anti-inflammatory drugs: a prospective study. Br J Surg. 1990;77:1103–4.PubMedCrossRefGoogle Scholar
  50. 50.
    Campbell K, Steele RJC. Non-steroidal anti-inflammatory drugs and complicated diverticular disease: a case-control study. Br J Surg. 1991;78:190–1.PubMedCrossRefGoogle Scholar
  51. 51.
    Riddell RH, Tanaka M, Mazzoleni G. Non-steroidal anti-inflammatory drugs as a possible cause of collangenous colitis: a case-control study. Gut. 1992;33:683–6.PubMedCrossRefGoogle Scholar
  52. 52.
    Gibson GR, Whitacre EB, Ricotti CA. Colitis induced by nonsteroidal anti-inflammatory drugs. Report of four cases and review of the literature. Arch Intern Med. 1992;152:625–32.PubMedCrossRefGoogle Scholar
  53. 53.
    Bjarnason I, Macpherson MS. Intestinal toxicity of non-steroidal anti-inflammatory drugs. Pharmac Ther. 1994;62:145–57.CrossRefGoogle Scholar
  54. 54.
    Debenham GP. Ulcer of the caecum during oxyphenbutazone (Tanderil) therapy. Can Med Assoc J. 1966;94:1182–4.PubMedGoogle Scholar
  55. 55.
    Hall RI, Petty AH, Cobden I, Lendrum R. Enteritis and colitis associated with mefenamic acid. Br Med J. 1983;287:1182.CrossRefGoogle Scholar
  56. 56.
    Philips MS, Fehilly B, Stewart S, Dronfield MW. Enteritis and colitis associated with mefenamic acid. Br Med J. 1983;287:1626–7.Google Scholar
  57. 57.
    Williams R, Glazer G. Enteritis and colitis associated with mefenamic acid. Br Med J. 1983;287:1627.CrossRefGoogle Scholar
  58. 58.
    Doman DB, Goldberg HJ. A case of meclofenamate sodium-induced colitis. Am J Gastroenterol. 1986;81:1220–1.PubMedGoogle Scholar
  59. 59.
    Coutrot S, Roland D, Barbier J, Marcq PVD, Alcalay M, Matuchansky C. Acute perforation of colonic diverticula associated with short-term indomethacin. Lancet. 1978;2:1055–6.PubMedCrossRefGoogle Scholar
  60. 60.
    Day TK. Intestinal perforation associated with osmotic slow release indomethacin capsules. Br Med J. 1983;287:1671–2.CrossRefGoogle Scholar
  61. 61.
    Bridges AG, Marshall JB, Diaz-Arias AA. Acute eosinophilic colitis and hypersensitivity reaction associated with naproxen therapy. Am J Med. 1990;89:526–7.PubMedCrossRefGoogle Scholar
  62. 62.
    Gentric A, Pennec YL. Diclofenac-induced pseudomembraneous colitis. Lancet. 1992;340:126–7.PubMedCrossRefGoogle Scholar
  63. 63.
    Giardiello FM, Hansen FC, Lazenby M. Collangenous colitis in the setting of nonsteroidal anti-inflammatory drugs and antibodies. Dig Dis Sci. 1990;35:257–60.PubMedCrossRefGoogle Scholar
  64. 64.
    Carson J, Notis WM, Orris ES. Colonic ulceration and bleeding during diclofenac therapy. N Engl J Med. 1990;323:135.PubMedCrossRefGoogle Scholar
  65. 65.
    Rampton DS, Hawkey CJ. Prostaglandins and ulcerative colitis. Gut. 1984;25:1399–413.PubMedCrossRefGoogle Scholar
  66. 66.
    Hawkey CJ, Rampton DS. Prostaglandins and the gastrointestinal mucosa: are they important in its function, disease or treatment? Gastroenterology. 1985;89:1162–88.PubMedGoogle Scholar
  67. 67.
    Kaufmann HJ, Taubin HL. Nonsteroidal anti-inflammatory drugs activate quiescent inflammatory bowel disease. Ann Intern Med. 1987;107:513–6.PubMedCrossRefGoogle Scholar
  68. 68.
    Bjarnason I, Zanelli G, Prouse P, et al. Blood and protein loss via small intestinal inflammation induced by non-steroidal anti-inflammatory drugs. Lancet. 1987;2:711–14.PubMedCrossRefGoogle Scholar
  69. 69.
    Bjarnason I, Smethurst P, Hayllar J, Levi AJ. NSAID enteropathy: the main site of blood loss in patients on NSAIDs. Gut. 1990;31:Al203.CrossRefGoogle Scholar
  70. 70.
    Lang J, Price AB, Levi AJ, Burke M, Gumpel JM, Bjamason I. Diaphragm disease: pathology of disease of the small intestine induced by non-steroidal anti-inflammatory drugs. J Clin Pathol. 1988;41:516–26.PubMedCrossRefGoogle Scholar
  71. 71.
    Morris AJ, Wasson LA, MacKenzie JF. Small bowel enteroscopy in undiagnosed gastrointestinal blood loss. Gut. 1992;33:887–9.PubMedCrossRefGoogle Scholar
  72. 72.
    Davenport HW, Warner HA, Code CF. Functional significance of gastric mucosal barrier to sodium. Gastroenterology. 1964;47:142–52.PubMedGoogle Scholar
  73. 73.
    Kimmey MB. NSAID, ulcers, and prostaglandin. J Rheumatol. 1992;19(Supp1.19):68–73.Google Scholar
  74. 74.
    Garner A, Flemstrom G, Allen A. Current concepts of gastroduodenal mucosal protection. Scand J Gastroenterol. 1984;19(Supp1.92):78–80.Google Scholar
  75. 75.
    Rees WDW, Turnberg LA. Mechanisms of gastric mucosal resistance: a role for the ‘mucus-bicarbonate’ barrier. Clin Sci. 1982;62:343–8.PubMedGoogle Scholar
  76. 76.
    Scarpignato C. Nonsteroidal anti-inflammatory drugs: How do they damage gastroduodenal mucosa? Dig Dis Sci. 1995;13(Suppl.l):9–39.Google Scholar
  77. 77.
    Feldman M, with the technical assistance of Barnett CA. Gastric bicarbonate secretion in humans: Effect of pentagastrin, bethanechol and 11,16,16-trimethyl prostaglandin E 2J Clin Invest. 1983;72: 295–303.PubMedCrossRefGoogle Scholar
  78. 78.
    Isenberg JI, Hogan DL, Koss MA, Selling JA. Human duodenal bicarbonate secretion. Gastroenterology. 1986;91:370–8.PubMedGoogle Scholar
  79. 79.
    Konturek SJ, Pawlik W. Physiology and pharmacology of prostaglandin. Dig Dis Sci. 1986;31:6s–19s.PubMedCrossRefGoogle Scholar
  80. 80.
    Hollander D, Tamawski A. Gastric cytoprotection - a clinician’s guide. New York: Plenum Publishing, 1989.CrossRefGoogle Scholar
  81. 81.
    Abramson SB, Weissmann G. The mechanisms of action of nonsteroidal anti-inflammatory drugs. Arthritis Rheum. 1989;32:1–9.PubMedCrossRefGoogle Scholar
  82. 82.
    Hollander D, Dadufalza D, Fairchild PA. Intestinal absorption of aspirin, influence of pH, taurocholate, ascorbate and ethanol. J Lab Clin Med. 1981;98:591–8.PubMedGoogle Scholar
  83. 83.
    Ivey KJ. Mechanisms of nonsteroidal anti-inflammatory drug-induced gastric damage. Actions of therapeutic agents. Am J Med. 1988;84(Supp1.2A):41–8.PubMedCrossRefGoogle Scholar
  84. 84.
    Schmassmann A, Tarnawski A, Peskar BM, Varga L, Flogerzi B, Halter F. Influence of acid and angiogenesis on kinetics of gastric ulcer healing in rats interaction with indomethacin. Am J Physiol. 1995;268(2: 1):G276–85.PubMedGoogle Scholar
  85. 85.
    Fries JF, Miller SR, Spitz PW, Williams CA, Hubert HB, Bloch DA. Identification of patients at risk for gastropathy associated with NSAID use. J Rheumatol. 1990;17(Supp1.20):12–9.Google Scholar
  86. 86.
    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;114:257–63.PubMedCrossRefGoogle Scholar
  87. 87.
    Holvoet J, Terriere L, Van Hee W, Verbist L, Fierens E, Hautekeete ML. Relation of upper gastrointestinal bleeding to non-steroidal anti-inflammatory drugs and aspirin: a case-control study. Gut. 1991;32:730–4.PubMedCrossRefGoogle Scholar
  88. 88.
    Bretagne J, Raoul J. Management of nonsteroidal anti-inflammatory drug-induced upper gastrointestinal bleeding and perforation. Dig Dis. 1995;13(Suppl.1):89–105.PubMedCrossRefGoogle Scholar
  89. 89.
    Kim JG, Graham DY and the Misoprostol Group. Helicobacter pylori infection and development of gastric and duodenal ulcer in arthritic patients receiving chronic NSAID therapy. Am J Gastroenterol. 1994;89(2):203–7.Google Scholar
  90. 90.
    Graham DY, Lidsky MD, Cox AM, et al. Long-term nonsteroidal anti-inflammatory drug use and Helicobacter pylori infection. Gastroenterology. 1991;100:1653–7.PubMedGoogle Scholar
  91. 91.
    Loeb D, Ahlquist D, Carpenter H, Talley N. Role of helicobacter pylori (Hp) in non-steroidal anti-inflammatory drug (NSAID)-induced gastroduodenopathy. Am J Gastroenterol. 1990;85(9):1236.Google Scholar
  92. 92.
    Taha AS, Nakshabendi I, Lee FD, Sturrock RD, Russell RI. Chemical gastritis and Helicobacter pylori related gastritis in patients receiving non-steroidal anti-inflammatory drugs: comparison and correlation with peptic ulceration. J Clin Pathol. 1992;45:135–9.PubMedCrossRefGoogle Scholar
  93. 93.
    Heresbach D, Raoul JL, Bretagne JF, et al. Helicobacter pylori: a risk and severity factor of non-steroidal anti-inflammatory drug-induced gastropathy. Gut. 1992;33:1608–11.PubMedCrossRefGoogle Scholar
  94. 94.
    Semble EL, Wu WC. Anti-inflammatory drugs and gastric mucosal damage. Semin Arthritis Rheum. 1987;16:271–86.PubMedCrossRefGoogle Scholar
  95. 95.
    Coles LS, Fries JF, Kraines RG, Roth SH. From experiment to experience: side effects of nonsteroidal anti-inflammatory agents. Am J Med. 1983;74:820–8.PubMedCrossRefGoogle Scholar
  96. 96.
    Mellem H, Stave R, Myren J, et al. Symptoms in patients with peptic ulcer and hematemesis and/or melena related to the use of non-steroidal anti-inflammatory drugs. Scand J Gastroenterol. 1985;20:1246–8.PubMedCrossRefGoogle Scholar
  97. 97.
    Bradley JD, Brandt KD, Katz BP, Kalisinski LA, Ryan SI. Comparison of an antiinflammatory dose of ibuprofen and acetaminophen in the treatment of patients with osteoarthritis of the knee. N Engl J Med. 1991;325:87–91.PubMedCrossRefGoogle Scholar
  98. 98.
    Bijlsma JWJ. Treatment of endoscopy-negative NSAID-induced upper gastrointestinal symptoms with cimetidine: an international multicentre collaborative study. Aliment Pharmacol Ther. 1988;2S:75–83.Google Scholar
  99. 99.
    Bijlsma JWJ. Treatment of NSAID-induced gastrointestinal lesions with cimetidine: an international multicentre collaborative study. Aliment Pharmacol Ther. 1988;25:85–96.Google Scholar
  100. 100.
    Wallin BA, Frank WO, Fox MJ, et al. The effects of cimetidine on the healing of nonsteroidal antiinflammatory drug-induced gastroduodenal damage while continuing NSAID therapy. Am J Gastroenterol. 1988;83:1076.Google Scholar
  101. 101.
    Lancaster-Smith MJ, Jaderberg ME, Jackson DA. Ranitidine in the treatment of non-steroidal anti-inflammatory drug associated gastric and duodenal ulcers. Gut. 1991;32:252–5.PubMedCrossRefGoogle Scholar
  102. 102.
    Ehsanullah RSB, Page MC, Tildesley G, Wood JR. Prevention of gastroduodenal damage induced by non-steroidal anti-inflammatory drugs: controlled trial of ranitidine. Br Med J. 1988;297:1017–21.CrossRefGoogle Scholar
  103. 103.
    Sontag SJ, Schnell TG, Budiman-Mak E, et al. Healing of NSAID-induced gastric ulcers with a synthetic prostaglandin analog (enprostil). Am J Gastroenterol. 1994;89(7):1014–20.PubMedGoogle Scholar
  104. 104.
    Manniche C„ Malchow-Moller A, Andersen JR, et al. Randomized study of the influence of non-steroidal anti-inflammatory drugs on the treatment of peptic ulcer in patients with rheumatic disease. Gut. 1987;28:226–9.PubMedCrossRefGoogle Scholar
  105. 105.
    Caldwell JR, Roth SH, Wu WC, et al. Sucralfate treatment of nonsteroidal anti-inflammatory drug-induced gastrointestinal symptoms and mucosal damage. Am J Med. 1987;83(Suppl.3B):74–82.PubMedCrossRefGoogle Scholar
  106. 106.
    Eriksson S. Effect of omeprazole and ranitidine on ulcer healing and relapse rates in patients with benign gastric ulcer. N Engl J Med. 1989;320(2):69–75.PubMedCrossRefGoogle Scholar
  107. 107.
    Koch M, Capurso L, Dezi A, Ferrario F, Scarpignato C. Prevention of NSAID-induced gastroduodenal mucosal injury: meta-analysis of clinical trials with misoprostol and H2-receptor antagonists. Dig Dis Sci. 1995;13(Supp1.1):62–74.Google Scholar

Copyright information

© Springer Science+Business Media Dordrecht 1997

Authors and Affiliations

  • J. Huang
    • 1
  • R. H. Hunt
    • 1
  1. 1.Department of Medicine, Division of GastroenterologyMcMaster University Medical CentreCanada

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