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Drugs

, Volume 32, Issue 5, pp 445–457 | Cite as

Prostaglandins in Peptic Ulcer Disease

An Overview of Current Status and Future Directions
  • Stephen J. Sontag
Review Article

Summary

Naturally occurring prostaglandins almost certainly play an important role in maintaining the integrity of the gastrointestinal mucosa. Clinical evidence available to date indicates that synthetic analogues of prostaglandins heal gastroduodenal ulcer only in doses that suppress gastric acid. However, non-antisecretory doses of prostaglandins may eventually have a role in the treatment of ulcer disease by maintaining ulcer healing and preventing recurrence. This possibility along with the potential of prostaglandins to prevent gastroduodenal mucosal injury caused by NSAIDs, alcohol, aspirin and stress, if supported by the results of ongoing clinical trials, may prove to be a major therapeutic advance for the treatment of acid peptic disease.

Keywords

Prostaglandin Cimetidine Duodenal Ulcer Misoprostol Peptic Ulcer Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Abercrombie J. Pathological and practical researches on the disease of the stomach, 3rd ed., p. 320, Cases Lea & Blanchard, Philadelphia, 1838Google Scholar
  2. Agrawal N, Godiwala T, Arimura A, Dajani E. Cytoprotection by a synthetic prostaglandin against ethanol-induced gastric mucosal damage: a double-blind endoscopic study in human subjects. Gastrointestinal Endoscopy 32: 67–70, 1986PubMedCrossRefGoogle Scholar
  3. Agrawal NM, Saffouri B, Kruss DM, Callison DA, Dajani EZ. Healing of benign gastric ulcer a placebo controlled comparison of two dosage regimens of misoprostol, a synthetic analog of prostaglandin E1. Digestive Diseases and Sciences 30 (Suppl): 164–170, 1985CrossRefGoogle Scholar
  4. Ahlquist DA, Dozois RR, Zinsmeister AR, Malagelada JR. Duodenal prostaglandin synthesis and acid load in health and in duodenal ulcer disease. Gastroenterology 85: 522–529, 1983PubMedGoogle Scholar
  5. Aly A, Johansson C, Slezak P, Green K. Bioconversion of arachidonic acid in the human gastrointestinal tract. Biochemical Medicine 31: 309–313, 1984CrossRefGoogle Scholar
  6. Baron JH. The clinical use of gastric function tests. Scandinavian Journal of Gastroenterology 6 (Suppl.): 9–46, 1970Google Scholar
  7. Bergstrom S, Sjovall J. The isolation of prostaglandin F from sheep prostate glands. Acta Chimica Scandinavica 14: 1693–1700, 1960CrossRefGoogle Scholar
  8. Bettarello A. Anti-ulcer therapy: past to present. Digestive Diseases and Sciences 30 (Suppl.): 36–42, 1985CrossRefGoogle Scholar
  9. Brand DL, Roufail WM, Thomson ABR, Tapper EJ. Misoprostol, a synthetic PGE1 analog, in the treatment of duodenal ulcers: a multicenter double-blind study. Digestive Diseases and Sciences 30 (Suppl.): 147–158, 1985CrossRefGoogle Scholar
  10. Bright-Asare P, Sontag SJ, Gould RJ, Brand DL, Roufail WM. Efficacy of misoprostol (twice daily dosage) in acute healing of duodenal ulcer: a multicenter double-blind controlled trial. Digestive Diseases and Sciences 31 (Supply.): 63–67, 1986CrossRefGoogle Scholar
  11. Bynum L. Efficacy of enprostil vs placebo in gastric ulcer. American Journal of Medicine 81 (Suppl.), August, 1986Google Scholar
  12. Chaudhury TK, Jacobson ED. Prostaglandin cytoprotection of gastric mucosa. Gastroenterology 74: 58–63, 1978PubMedGoogle Scholar
  13. Cohen MM, Cheung G, Lyster DM. Prevention of aspirin-induced faecal blood loss by prostaglandin E2. Gut 21: 602–606, 1980PubMedCrossRefGoogle Scholar
  14. Cohen MM, Clark L, Armstrong L, D’Souza J. Reduced aspirin-induced faecal blood loss with simultaneous administration of misoprostol (PGE1 methyl analogue). Gastroenterology 84: A1126, 1983Google Scholar
  15. Cohen MM, McCreary D, Clark L, Sevelius H. Protection against aspirin-induced antral and duodenal damage with enprostil: a double-blind endoscopic study. Gastroenterology 88: 382–386, 1985PubMedGoogle Scholar
  16. Colton DG, Driskill DR, Phillips EL, Poy P, Dajani EZ. Effect of SC-29333, an inhibitor of gastric secretion, on canine gastric mucosal blood flow and serum gastrin levels. Archives of International Pharmacodynamiques et Therapie 236: 86–95, 1978Google Scholar
  17. Dajani EZ. Is peptic ulcer a prostaglandin deficiency disease? Human Pathology 17: 106–107, 1986PubMedCrossRefGoogle Scholar
  18. Dajani EZ, Callison DA, Bertermann RE. Effects of E prostaglandins on canine gastric potential difference. Digestive Diseases and Sciences 23: 436–442, 1978CrossRefGoogle Scholar
  19. Dajani EZ, Nissen, CH. Gastrointestinal cytoprotective effects of misoprostol: clinical efficacy overview. Digestive Diseases and Sciences 30 (Suppl.): 194–200, 1985CrossRefGoogle Scholar
  20. Dammann HG, Huttemann W, Kalek HD, Rohner HG, Simon B. A comparison of enprostil and ranitidine in the treatment of gastric ulcer. American Journal of Medicine 81 (Suppl.), August, 1986Google Scholar
  21. Debas HT, Cohen MM, Holubitsky IB, Harrison RC. Effect of cigarette smoking on gastric secretory responses. Gut 12: 93–96, 1971PubMedCrossRefGoogle Scholar
  22. Detweiler MK, Harrison CA, Rolling DE, Tolman KG, Mc-Cormack GH, et al. Effect of rioprostil on aspirin-induced gastrointestinal mucosal changes in normal volunteers. Gastroenterology 86: A1062, 1984Google Scholar
  23. Epstein M, Lifschitz M, Rappaport K. Augmentation of prostaglandin production by linoleic acid in man. Clinical Science 63: 565–571, 1982PubMedGoogle Scholar
  24. Friedman GD, Seiglaub AB, Seltzer CC. Cigarettes, alcohol, coffee and peptic ulcer. New England Journal of Medicine 290: 469–473, 1974PubMedCrossRefGoogle Scholar
  25. Gilbert DA, Surawicz CM, Silverstein FE, et al. Prevention of acute aspirin-induced gastric mucosal injury by 15-R-15 methyl prostaglandin E2: an endoscopic study. Gastroenterology 86: 339–345, 1984PubMedGoogle Scholar
  26. Hawkey CJ, Rampton DS. Prostaglandins and the gastrointestinal mucosa: are they important in its function, disease or treatment? Gastroenterology 89: 1162–1188, 1985PubMedGoogle Scholar
  27. Hawkey CJ, Simpson G, Sommerville KW. Reduction by enprostil of aspirin induced bleeding from human gastric mucosa. Gut 26: A560, 1985Google Scholar
  28. Herting RL, Clay GA. Overview of clinical safety with misoprostol. Digestive Diseases and Sciences 30 (Suppl.): 185–193, 1985CrossRefGoogle Scholar
  29. Hollander D, Tarnawski A, Ivey KJ, et al. Arachidonic acid protection of rat gastric mucosa against ethanol injury. Journal of Laboratory and Clinical Medicine 100: 296–308, 1982PubMedGoogle Scholar
  30. Hunt JN, Franz D. Effect of prostaglandin E2 on gastric mucosal bleeding caused by aspirin. Digestive Diseases and Sciences 26: 301–305, 1981PubMedCrossRefGoogle Scholar
  31. Hunt JN, Smith CL, Jiang CL, Kessler L. Effect of synthetic prostaglandin E1 analogue on aspirin-induced gastric bleeding and secretion. Digestive Diseases and Sciences 28: 897–902, 1983PubMedCrossRefGoogle Scholar
  32. Ippoliti A, Elashoff J, Valenzuela J, et al. Recurrent ulcer after successful treatment with cimetidine or antacid. Gastroenterology 85: 875–880, 1983PubMedGoogle Scholar
  33. Ito S, Lacy ER. Morphology of rat gastric mucosal damage, defense, and restitution in the presence of luminal ethanol. Gastroenterology 88: 250–260, 1985PubMedGoogle Scholar
  34. Ivy AC, Grossman MI, Bachrach WH. Peptic ulcer, p. 1088, The Blakiston Company, Philadelphia, 1950Google Scholar
  35. Jacobson ED, Chaudhury TK, Thompson WJ. Mechanism of gastric mucosal cytoprotection by prostaglandins. Gastroenterology 70: A897, 1976Google Scholar
  36. Kirsner JB, Palmer WL. Effect of various antacids on the hydrogen ion concentration of the gastric content. American Journal of Digestive Diseases 7: 85–93, 1940CrossRefGoogle Scholar
  37. Konturek SJ. Actions of nonsteroid anti-inflammatory compounds on gastric mucosal integrity and prostaglandin formation in healthy subjects and peptic ulcer patients. Advances in Inflammation Research 6: 29–37, 1984Google Scholar
  38. Konturek SJ, Kwiecien N, Swierczek J, et al. Comparison of methylated prostaglandin E2 analogues given orally in the inhibition of gastric responses to pentagastrin and peptone meal in man. Gastroenterology 70: 683–687, 1976PubMedGoogle Scholar
  39. Korman MG, Hansky J, Merrett AC, Schmidt GT. Ranitidine in duodenal ulcer: incidence of healing and effect of smoking. Digestive Diseases and Sciences 27: 712–715, 1982PubMedCrossRefGoogle Scholar
  40. Korman MG, Shaw RG, Hansky J, et al. Influence of smoking on healing rate of duodenal ulcer in response to cimetidine or high-dose antacid. Gastroenterology 80: 1451–1453, 1981PubMedGoogle Scholar
  41. Kurzrok R, Lieb CC. Biochemical studies of human semen. II. The action of semen on the human uterus. Proceedings of the Society of Experimental Biology and Medicine 28: 268–272, 1930Google Scholar
  42. Lam SK, Lau WY, Choi EK, et al. Prostaglandin E1 (misoprostol) overcomes the adverse effect of chronic cigarette smoking on duodenal ulcer healing. Digestive Diseases and Sciences 31 (Suppl.): 68–74, 1986CrossRefGoogle Scholar
  43. Lanza F. A double-blind study of prophylactic effect of misoprostol on lesions of gastric and duodenal mucosa induced by oral administration of tolmetin in healthy subjects. Digestive Diseases and Sciences 31 (Suppl.): 131–136, 1986CrossRefGoogle Scholar
  44. Larsen KR, Dajani EZ, Muka MA. Effects of misoprostol, 16,16-dimethyl PGE2 and cimetidine on mucosal blood flow and oxygen consumption in dog ex vivo gastric chamber. Digestive Diseases and Sciences 31 (Suppl.): 146, 1986Google Scholar
  45. Leung FW, Itoh M, Hirabayashi K, et al. Role of blood flow in gastric and duodenal mucosal injury in the rat. Gastroenterology 88: 281–289, 1985PubMedGoogle Scholar
  46. Lewis J. FDA GI Advisory Committee Summary. American Journal of Gastroenterology 80: 743–745, 1985PubMedGoogle Scholar
  47. Ligumsky M, Karmeli F, Rachmilewitz D. Sucralfate stimulation of gastric PGE2 synthesis — possible mechanism to explain its effective cytoprotective properties. Gastroenterology 86: A1164, 1984Google Scholar
  48. MacDonald CA, Goulston KJ. Effect of paracetamol and milk on aspirin induced gastric erosions in man. Medical Journal of Australia and New Zealand 12: 439, 1982Google Scholar
  49. Materia A, Jaffe BM, Money SR, Rossi P, DeMaarco M, et al. Prostaglandins in commercial milk preparations: their effect in the prevention of stress induced gastric ulcer. Archives of Surgery 119: 290–292, 1984PubMedCrossRefGoogle Scholar
  50. McCready DR, Clark L, Cohen MM. Cigarette smoking reduces human gastric luminal prostaglandin E2. Gut 26: 1192–1196, 1985PubMedCrossRefGoogle Scholar
  51. Miller TA. Protective effects of prostaglandins against gastric mucosal damage: current knowledge and proposed mechanisms. American Journal of Physiology 245: 601–623, 1983Google Scholar
  52. Moynihan B. Duodenal ulcer. Practitioner 76: 249, 1907Google Scholar
  53. Murthy SNS, Dinoso Jr VP, Clearfield HR, Chey WY. Simultaneous measurement of basal pancreatic, gastric acid secretion, plasma gastrin, and secretin during smoking. Gastroenterology 73: 758–761, 1977PubMedGoogle Scholar
  54. Nelson NA, Kelly RC, Johnson RA. Prostaglandins and the arachidonic acid cascade. Chemical and Engineering News 60: 30, 1982CrossRefGoogle Scholar
  55. Nicholson PA. A multicenter international controlled comparison of two dosage regimes of misoprostol and cimetidine in the treatment of duodenal ulcer in outpatients. Digestive Diseases and Sciences 30 (Suppl.): 171–177, 1985CrossRefGoogle Scholar
  56. Pliny C. The Historie of the World (commonly called The Natural Historie), P Holland (trans), Vol. 2, p. 329, London, Adam Islip, 1601Google Scholar
  57. Quimby GF, Bonnice CA, Burstein SH, Eastwood GL. Active smoking depresses prostaglandin synthesis in human gastroduodenal mucosa. Gastroenterology 88: A1548, 1985Google Scholar
  58. Rachmilewitz D, Chapman JW, Nicholson PA. A multicenter international controlled comparison of two dosage regimens of misoprostol with cimetidine in treatment of gastric ulcer in outpatients. Digestive Diseases and Sciences 31 (Suppl.): 75–80, 1986CrossRefGoogle Scholar
  59. Rask-Madsen J, Bukhave K, Madsen PER, Bekker C. Effect of carbenoxolone on prostaglandin E2 levels in patients with peptic ulcer disease following vagal and pentagastrin stimulation. European Journal of Clinical Investigation 13: 351–357, 1983PubMedCrossRefGoogle Scholar
  60. Riegel F. Diseases of the stomach. In Stockton CG (Ed.) Nothnagel’s Encyclopedia of Practical Medicine, WB Saunders Co., Philadelphia, 1905Google Scholar
  61. Robert A. Cytoprotection by prostaglandins. Gastroenterology 77: 761–767, 1979PubMedGoogle Scholar
  62. Robert A, Lancaster C, Davis JP, et al. Cytoprotection by prostaglandin occurs in spite of penetration of absolute ethanol into the gastric mucosa. Gastroenterology 88: 328–333, 1985PubMedGoogle Scholar
  63. Robert A, Nezamis JE, Lancaster C, et al. Cytoprotection by prostaglandins in rats: prevention of gastric necrosis produced by alcohol, HCl, NaOH, hypertonic NaCl, and thermal injury. Gastroenterology 77: 433–443, 1979PubMedGoogle Scholar
  64. Robert A, Nezamis JE, Phillips JP. Inhibition of gastric secretion by prostaglandins. American Journal of Digestive Diseases 12: 1073–1076, 1967PubMedCrossRefGoogle Scholar
  65. Samuelsson B. The structure of prostaglandin E3. Journal of the American Chemical Society 85: 1878–1879, 1963CrossRefGoogle Scholar
  66. Schlegel W, Wenk K, Dollinger HC, Raptis S. Concentrations of prostaglandin A-, E-, and F-like substances in gastric mucosa of normal subjects and of patients with various gastric diseases. Clinical Science and Molecular Medicine 52: 255–258, 1977PubMedGoogle Scholar
  67. Selling JA, Hogan DL, Koss MA, Isenberg JI. Human proximal versus distal duodenal bicarbonate secretion: effect of endogenous prostaglandin synthesis. Gastroenterology 88: A1580, 1985Google Scholar
  68. Sevelius H. Enprostil: an antisecretory and cytoprotective synthetic PGE2. Prostaglandins 27: 111, 1984Google Scholar
  69. Sevelius H. Overall safety of enprostil in clinical studies. American Journal of Medicine (Suppl.), in press, 1986Google Scholar
  70. Silverstein FE, Kimmey MB, Saunders DR, Levine DS. Gastric protection by misoprostol against 1300mg of aspirin. Digestive Diseases and Sciences 31 (Suppl.): 137–141, 1986CrossRefGoogle Scholar
  71. Sippy B. Gastric and duodenal ulcer: medical cure by an efficient removal of gastric juice corrosion. Journal of the American Medical Association 64: 1625–1630, 1915CrossRefGoogle Scholar
  72. Smith CL, Hillier K. Duodenal mucosa synthesis of prostaglandins in duodenal ulcer disease. Gut 26: 237–240, 1985PubMedCrossRefGoogle Scholar
  73. Soll AH. In Johnson (Ed.) Physiology of the gastrointestinal tract, pp. 673–691, Raven Press, New York, 1981Google Scholar
  74. Sonnenberg A, Muller-Lissner SA, Vogel E, et al. Predictors of duodenal ulcer healing and relapse. Gastroenterology 81: 1061–1067, 1981PubMedGoogle Scholar
  75. Sonnenberg A, Husmert N. Effect of nicotine on gastric mucosal blood flow and acid secretion. Gut 23: 532–535, 1982PubMedCrossRefGoogle Scholar
  76. Sontag SJ. Prostaglandins and the Universal Soldier. Journal of the American Medical Association 254: 605, 1985CrossRefGoogle Scholar
  77. Sontag SJ, Graham DY, Belsito A, et al. Cimetidine, cigarette smoking, and recurrence of duodenal ulcer. New England Journal of Medicine 311: 689–693, 1984PubMedCrossRefGoogle Scholar
  78. Sontag SJ, Mazure PA, Pontes JF, Beker SG, Dajani EZ. Misoprostol in the treatment of duodenal ulcer a multicenter double-blind, placebo controlled study. Digestive Diseases and Sciences 30 (Suppl.): 159–163, 1985aCrossRefGoogle Scholar
  79. Tesler M, Brand DL, Bright-Asare P, Krejs GJ, Van Zuiden PEA. A comparative study of enprostil and placebo in active duodenal ulcer (USA). American Journal of Medicine 81 (Suppl.), August, 1986Google Scholar
  80. Thomson ABR, Archambault AP, Halvorsen L, et al. Comparison of enprostil and placebo in active duodenal ulcer. American Journal of Medicine (Suppl.), August, 1986Google Scholar
  81. Vantrappen G, Janssens J, Popiela T, et al. Effect of 15(R)-15-methyl prostaglandin E2 (arbaprostil) on the healing of duodenal ulcer: a double-blind multicenter study. Gastroenterology 83: 357–363, 1982PubMedGoogle Scholar
  82. Von Euler US. On the specific vaso-dilating and plain muscle stimulating substances from accessory genital gland in man and certain animals (prostaglandin and vesiglandin). Journal of Physiology (London) 88: 213–234, 1936Google Scholar
  83. Watkinson G, Shroff NE, Akbar FA. Misoprostol in peptic ulcer disease. International conference on prostaglandins and related compounds, Florence, June 3–6, 1986Google Scholar
  84. Whittle BJR. Mechanisms underlying gastric mucosal damage induced by indomethacin and bile-salts, and the actions of prostaglandins. British Journal of Pharmacology 60: 455–460, 1977PubMedCrossRefGoogle Scholar
  85. Wilson DE, Levendoglu H, Adams A, et al. A new PGE1 analogue (CL115,574)III: effects of gastric acid and mucus secretion in man. Prostaglandins 28: 5–11, 1984PubMedCrossRefGoogle Scholar
  86. Wilson DE, Phillips C, Levine RA. Inhibition of gastric secretion in man by prostaglandin A1. Gastroenterology 61: 201–206, 1971PubMedGoogle Scholar
  87. Wilson DE, Winnan G, Quertermus J, et al. Effects of an orally administered prostaglandin analogue (16,16-dimethyl prostaglandin E2) on human gastric secretion. Gastroenterology 69: 607–611, 1965Google Scholar
  88. Winters L. Comparison of enprostil and cimetidine in active duodenal ulcer: summary of pooled European studies. Protective and therapeutic effects of gastrointestinal prostaglandins. American Journal of Medicine 81 (Suppl.), August, 1986Google Scholar
  89. Wright JP, Young GO, Klaff LJ, Weerss LA, Price SK, et al. Gastric mucosal prostaglandin E levels in patients with gastric ulcer disease and carcinoma. Gastroenterology 82: 63–67, 1982Google Scholar

Copyright information

© ADIS Press Limited 1986

Authors and Affiliations

  • Stephen J. Sontag
    • 1
    • 2
  1. 1.Departments of Ambulatory Care and MedicineEdward J. Hines Jr Veterans Administration HospitalHinesUSA
  2. 2.Department of MedicineLoyola University Medical CenterMaywoodUSA

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