Gastropatía por Antiinflamatorios no Esteroides: Algunas inquietudes en relación con estos nuevos fármacos

A estos fármacos, de reciente introducción para uso clínico, no se les conoce aún su papel sobre el riñon, en la formación de los huesos, la mitogénesis, el crecimiento, y la fisiología de la reproducción en la mujer (76).


  1. Wallace J. Nonsteroidal antiinflammatory drugs and gastroenteropathy: the second hundred years. Gastroenterology 1997; 112: 1000-16.
  2. Vane JR, Flower RJ, Botting RM. History of aspirin and its mechanism of action. Stroke 1990; 21 (Suppl) IV-12ÐIV-23.
  3. Dreser H. Pharmacologisches. ber aspirin (acetylsalicylsa. re). Pflugers Arch 1899; 76: 306-318.
  4. Douthwaite AH, Lintott GAM. Gastroscopic observation of effect of aspirin and certain other substances on stomach. Lancet 1938; 2: 1222-1225.
  5. Sun DC, Roth SH, Mitchell CS, Englund DW. Upper gastrointestinal disease in rheumatoid arthritis. Am J Dig Dis 1974; 19: 405-410.
  6. Lewis R. Cox Fighting Awarding of patent may only reflect who filed first. The Scientist; 2000: 14 [11 ]: 1.
  7. 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: 517-520.
  8. Larkai EN, Smith JL, Lidsky MD, Graham DY .Gastroduodenal mucosa and dyspeptic symptoms in arthritic patients during chronic steroidal antiinflammatory drug use. Am J Gastroenterol 1987; 82: 1153-1158.
  9. Singh G, Ramey DR, Morfeld D, Shi H, Hatoum HT, Fries JF. Gastrointestinal tract complications of nonsteroidal antiinflammatory drug treatment in rheumatoid arthritis: a prospective observational cohort study. Arch Intern Med 1996; 156: 1530 -1526.
  10. Singh G, Triadafilopoulus G. Epidemiology of NSAID-induced GI complications. J Rheumatol 1999; 26 (Suppl26) 18-24.
  11. Armstrong CP, Blower AL. Nonsteroidal antiinflammatory drugs and life threatening complications of peptic ulceration. Gut 1987; 28: 527-532.
  12. Singh G, Ramey DR, Terry R, Khraishi M, Triadafilopoulos G. NSAID-related effects on the GI tract: an ever widening spectrum.Arthritis Rheum 1997; 40 (Suppl) S93. abstract.
  13. Singh G. Recent considerations in nonsteroidal antiinflammatory drug gastropathy. Am J Med 1998; 105: 31S-38S.
  14. Bjorkman DJ. Nonsteroidal antiinflammatory druginduced gastrointestinal injury. Am J Med 1996; 101(Suppl) 1A: 25S-32S.
  15. Gabriel SE, Jaakkimainen L, Bombardier C. Risk for serious gastrointestinal complications related to use of nonsteroidal antiinflammatory drugs: a meta-analysis. Ann Intern Med 1991; 115: 787-796.
  16. 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: 257-263.
  17. Langman MJ, Weil J, Wainwright P, et al. Risks of bleeding peptic ulcer associated with individual non-steroidal anti-inflammatory drugs. Lancet 1994; 343: 1075-8. [Erratum, Lancet 1994; 343: 1302 ].
  18. García Rodríguez LA, Jick H. Risk of upper gastrointestinal bleeding and perforation associated with individual non-steroidal anti-inflammatory drugs. Lancet 1994; 343: 769-72. [Erratum, Lancet 1994; 343: 1048.]
  19. Hallas J, Lauritsen J, Villadsen HD, Gram LF. Nonsteroidal antiin- flammatory drugs and upper gastrointestinal bleeding, identifying high risk groups by excess risk estimates. Scand J Gastroenterol 1995; 30: 438-444.
  20. Hochain P, Berkelmans I, Czernichow P, et al. Which patients taking non-aspirin non-steroidal anti-inflammatory drugs bleed? A case-control study. Eur J Gastroenterol Hepatol 1995; 7: 419-426.
  21. Piper JM, Ray WA, Daugherty JR, Griffin MR. Corticosteroid use and peptic ulcer disease: role of nonsteroidal anti-inflammatory drugs. Ann Intern Med 1991; 114: 735-740.
  22. Shorr RI, Ray WA, Daugherty JR, Griffin MR. Concurrent use of nonsteroidal antiinflammatory drugs and oral anticoagulants places elderly persons at high risk for hemorrhagic peptic ulcer disease. Arch Intern Med 1993; 153: 1665 – 1670.
  23. Barkin J. The relation between Helicobacter pylori and nonsteroidal anti- inflammatory drugs. Am J Med 1998; 105: 22S – 27S.
  24. Goggin PM, Collins DA Jazrawi RP, et al. Prevalence of Helicobacter pylori infection and its effect on symptoms and non-steroidal anti-inflammatory drug induced gastrointestinal damage in patients with rheumatoid arthritis. Gut 1993; 34: 1677 -1680.
  25. Kim JG, Graham DY. Helicobacter pylori infection and development of gastric or duodenal ulcer in arthritic patients receiving chronic NSAID therapy. Am J Gastroenterol 1994; 89: 203-207.
  26. Thillainayagam AV, Tabaqchali S, Warrington SJ, Farthing MJ. Interrelationships between Helicobacter pylori infection, nonsteroidal anti-inflammatory drugs, and gastroduodenal disease:a prospective study in healthy volunteers. Dig Dis Sci 1994; 39: 1085-1089.
  27. Laine L, Cominelli F, Sloane R, Casini-Raggi V, Marin-Sorensen M, Weinstein WM. Interaction of NSAIDs and Helicobacter pylori on gastrointestinal injury and prostaglandin production:a controlled doubleblind study.Aliment Pharmacol Ther 1995; 9: 127-135.
  28. Bianchi Porro G, Parente F, Imbesi V, Montrone F, Caruso I. Role of Helicobacter pylori in ulcer healing and recurrence of gastric and duodenal ulcers in longterm NSAID users: response to omeprazole dual therapy. Gut 1996; 39: 22-26.
  29. Chan FK, Sung JJ, Chung SC, et al. Randomised trial of eradication of Helicobacter pylori before non-steroidal anti-inflammatory drug therapy to prevent peptic ulcers. Lancet 1997; 350: 975-979.
  30. Hawkey CJ, Tulassay Z, Szczepa Œski L, et al. Randomised controlled trial of Helicobacter pylori eradication in patients on nonsteroidal antiinflammatory drugs: HELP NSAIDs study. Lancet 1998; 352: 1016-1021. [Erratum, Lancet 1998; 352: 1634.]
  31. Schoen RT, Vender RJ. Mechanisms of nonsteroidal anti-inflammatory drug-induced gastric damage. Am J Med 1989; 86: 449 -458.
  32. Whittle BJR. Mechanisms underlying gastric mucosal damage induced by indomethacin and bile salts, and the actions of prostaglandins. Br J Pharmacol 1977; 60: 455-460.
  33. Wolfe MM, Soll AH. The physiology of gastric acid secretion. N Engl J Med 1988; 319: 1707-1715.
  34. Carson JL, Strom BL, Morse L, et al. The relative gastrointestinal toxicity of the nonsteroidal anti-inflammatory drugs. Arch Intern Med 1987; 147: 1054-1059.
  35. Soll AH, Weinstein WM, Kurata J, Mc Carthy D. Nonsteroidal anti-inflammatory drugs and peptic ulcer disease. Ann Intern Med 1991; 114: 307-319.
  36. Lanza FL, Royer GL Jr, Nelson RS. Endoscopic evaluation of the effects of aspirin, buffered aspirin, and entericcoated aspirin on gastric and duodenal mucosa. N Engl J Med 1980; 303: 136-138.
  37. Maliekal J, Elboim CM. Gastrointestinal complications associated with intramuscular ketorolac tromethamine therapy in the elderly. Ann Pharmacother 1995; 29: 698-701.
  38. Henry D, Dobson A, Turner C. Variability in the risk of major gastrointestinal complications from nonaspirin nonsteroidal anti-inflammatory drugs. Gastroenterology 1993; 105: 1078-1088.
  39. Lee M, Cryer B, Feldman M. Dose effects of aspirin on gastric prostaglandins and stomach mucosal injury. Ann Intern Med 1994; 120: 184-189.
  40. Masferrer JL, Seibert K, Zweifel B, Needleman P. Endogenous glu- cocorticoids regulate an inducible cyclooxygenase enzyme. Proc Natl Acad Sci USA 1992; 89: 3917-3921.
  41. Crofford LJ. COX-1 and COX-2 tissue expression:implications and predictions. J Rheumatol 1997; 24 (Suppl 49) 15-19.
  42. De Witt DL, Smith WL. Primary structure of prostaglandin G/H synthase from sheep vesicular gland determined from the complementary DNA sequence. Proc Natl Acad Sci USA 1988; 85: 1412-6. [Erratum, Proc Natl Acad Sci U S A 1988; 85: 5056.]
  43. Hla T, Neilson K . Human cyclooxygenase-2 cDNA. Proc Natl Acad Sci USA 1992; 89: 7384-7388.
  44. Needleman P, Isakson PC. The discovery and function of COX-2. J Rheumatol 1997; 24 (Suppl 49) 68.
  45. Lichtenstein DR, Syngal S, Wolfe MM. Nonsteroidal antiinflammatory drugs and the gastrointestinal tract: the double – edged sword. Arthritis Rheum 1995; 38: 5-18.
  46. Graham DY, Smith JL. Aspirin and the stomach. Ann Intern Med 1986; 104: 390-398.
  47. Graham DY, Agrawal NM, Roth SH. Prevention of NSAID-induced gastric ulcer with misoprostol: multicentre, double-blind, placebo-con-trolled trial. Lancet 1988; 2: 1277-1280.
  48. Bijlsma JW. Treatment of NSAID-induced gastrointestinal lesions with cimetidine:an international multicentre collaborative study. Aliment Pharmacol Ther 1988; 2 (Suppl 1) 85-95.
  49. Lanza FL, Aspinall RL, Swabb EA, Davis RE, Rack MF, Rubin A . A double-blind, placebo-controlled endoscopic comparison of the mucosal protective effects of misoprostol versus cimetidine on tolemetin-induced mucosal injury to the stomach and duodenum.Gastroenterology 1988; 95: 289-294.
  50. Saunders JHB, Oliver RJ, Higson DL. Dyspepsia:incidence of a nonulcer disease in a controlled trial of ranitidine in general practice.Br Med J 1986; 292: 665-668.
  51. Van Groenendael JHLM, Markusse HM, Dijkmans BAC, Breed- veld FC. The effect of ranitidine on NSAID related dyspeptic symptoms with and without peptic ulcer disease of patients with rheumatoid arthritis and osteoarthritis. Clin Rheumatol 1996; 15: 450-456.
  52. Taha AS, Hudson N, Hawkey CJ, et al. Famotidine for the prevention of gastric and duodenal ulcers caused by nonsteroidal antiinflammatory drugs. N Engl J Med 1996; 334: 1435-1439.
  53. Yeomans ND, Tulassay Z, Juh/sz L, et al. A comparison of omeprazole with ranitidine for ulcers associated with nonsteroidal antiinflammatory drugs. N Engl J Med 1998; 338: 719-726.
  54. Hawkey CJ, Karrasch JA, SzczepaŒski L, et al. Omeprazole compared with misoprostol for ulcers associated with nonsteroidal antiinflam- matory drugs.N Engl J Med 1998;338:727-734.
  55. McCarthy DM. Sucralfate. N Engl J Med 1991; 325: 1017-1025.
  56. Croker JR, Cotton PB, Boyle AC, Kinsella P. Cimetidine for peptic ulcer in patients with arthritis. Ann Rheum Dis 1980; 39: 275-278.
  57. O Laughlin JC, Silvoso GK, Ivey KJ. Resistance to medical therapy of gastric ulcers in rheumatic disease patients taking aspirin: a doubleblind study with cimetidine and follow-up. Dig Dis Sci 1982; 27: 976-980.
  58. Walan A, Bader J-P, Classen M, et al. Effect of omeprazole and ranitidine on ulcer healing and relapse rates in patients with benign gastric ulcer. N Engl J Med 1989; 320: 69-75.
  59. Agrawal N, Safdi M, Wruble L, Karvois D, Greski-Rose P, Huang B. Effectiveness of lansoprazole in the healing of NSAID-induced gastric ulcer in patients continuing to take NSAIDs. Gastroenterology 1998; 114: A52-A53.
  60. Caldwell JR, Roth SH, Wu WC, et al. Sucralfate treatment of nonsteroidal anti-inflammatory druginduced gastrointestinal symptoms and mucosal damage. Am J Med 1987; 83 (Suppl 3B) 74-82.
  61. Agrawal NM, Roth S, Graham DY, et al. Misoprostol compared with sucralfate in the prevention of nonsteroidal anti-inflammatory drug induced gastric ulcer: a randomized, controlled trial. Ann Intern Med 1991; 115: 195-200.
  62. Robinson MG, Griffin JW Jr, Bowers J, et al. Effect of ranitidine on gastroduodenal mucosal damage induced by nonsteroidal antiinflammatory drugs.Dig Dis Sci 1989; 34: 424-428.
  63. Ehsanullah RSB, Page MC, Tildesley G, Wood JR. Prevention of gastrointestinal damage induced by non-steroidal anti-inflammatory drugs: controlled trial of ranitidine. BMJ 1988; 297: 1017-1021.
  64. Oddsson E, Gudjonsson H, Thjodleifsson B. Comparison between ranitidine and omeprazole for protection against gastroduodenal damage caused by naproxen. Scand J Gastroenterol 1992; 27: 1045-1048.
  65. Scheiman JM, Behler EM, Loeffler KM, Elta GH. Omeprazole ameliorates aspirin-induced gastroduodenal injury. Dig Dis Sci 1994; 39: 97-103.
  66. Lanza FL. A guideline for the treatment and prevention of NSAID-induced ulcers. Am J Gastroenterol 1998; 93: 2037 -2046.
  67. Raskin JB, White RH, Jackson JE, et al. Misoprostol dosage in the prevention of nonsteroidal anti-inflammatory druginduced gastric and duodenal ulcers: a comparison of three regimens. Ann Intern Med 1995; 123: 344-350.
  68. Roth SH, Tindall EA, Jain AK, et al. A controlled study comparing the effects of nabumetone, ibuprofen, and ibuprofen plus misoprostol on the upper gastrointestinal tract mucosa. Arch Intern Med 1 993; 153: 2565-2571.
  69. Schattenkirchner M. An updated safety profile of etodolac in several thousand patients. Eur J Rheumatol Inflamm 1990; 10: 56-65.
  70. Distel M, Mueller C, Bluhmki E, Fries J. Safety of meloxicam:a global analysis of clinical trials. Br J Rheumatol 1996; 35 (Suppl 1) 68-77.
  71. Wolfe MM. Future trends in the development of safer nonsteroidal anti-inflammatory drugs. Am J Med 1998; 105 (Suppl 5A) 44S-52S.
  72. Vane JR, Botting RM. Mechanism of action of anti-inflammatory drugs. Scand J Rheumatol 1996; 25 (Suppl 102) 9 -21.
  73. Vane JR, Botting RM. Overview: the mechanism of action of anti-inflammatory drugs .In: Vane JR, Botting R, eds.Clinical significance and potential of selective Cox-2 inhibitors. London: William Harvey Press; 1998; 1-18.
  74. Bjarnason I, Macpherson A, Rotman H, Schupp J, Hayllar J. A randomized, double-blind, crossover comparative endoscopy study on the gastroduodenal tolerability of a highly specific cyclooxygenase-2 inhibitor, flosulide, and naproxen. Scand J Gastroenterol 1997; 32: 126-130.
  75. Lipsky PE, Isakson PC. Outcome of specific COX-2 inhibition in rheumatoid arthritis. J Rheumatol 1997; 24: Suppl 49: 9-14.
  76. Wolfe M, Lightenstein D, Singh G. Gastrointestinal toxicity of nonste roidal antiinflamatory drugs. N Engl J Med 1999; 340: 1888-1899.



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