June 1993, Volume 43, Issue 6


Omeprazole: Is it the Answer of Peptic Ulcer Disease?

Waquaruddin Ahmed  ( PMRC Research Centre, Jinnah Postgraduate Medical Centre, Karachi. )

Omeprazole, the acid pump inhibitor, is a new approach to the regulation of gastric acidity. Its discovery has led to new insights into the mechanism of gastric secretion, pathogenesis of certain gastrointestinal tu­mours and the development of new treatments for peptic ulcer. Recently this product has been marketed in Pakistan with promising results, but is yet to be evaluated in terms of long term safety and efficacy. Omeprazole inhibits acid secretion by inhibiting H+/K+ -AT Pase enzyme in the parietal cell1. A single 20mg dose of omeprazole inhibits acid secretion by 65% after 4-6 hours and by 25% after 24 hours2, but with subse­quent doses inhibition increases, reaching a plateau after 4 doses3. When the treatment is stopped, secretion returns to the pretreatment levels in 3 days without rebound phenomenon4,5. The long term administration of omeprazole causes inhibition of gastric acid secretion leading to an increased plasma gastrin concentration, which, in turn, produces carcinoid tumours of the body of stomach and hyperplasia of certain oxyntic mucosal endocrine cells, the entero chromaffin- like cells in experimental animals6. These results led the Food and Drug Administration to restrict the length of omeprazole treatment to 8 weeks except in patients with Zollinger­ Ellison syndrome. Initial studies examining the efficacy of omeprazole in the healing of duodenal ulcer indicate 20mg/day as the most effective minimum dose7-10. All doses of more than 10mg/day showed healing rates of 90-100% at 4 weeks7,9. Later randomized controlled trials of omeprazole (20 mg/day) and H2 receptor antagonists (ranitidine 300 mg/day) showed healing rates of 42- 83% and 34-65% respectively at 2 weeks, while 82-97% and 63-96% respectively at 4 weeks11-14. This shows a significant advantage for omcprazole both at 2 and 4 weeks. Other studies lasting for 6-8 weeks and with doses of more than 20 mg/day have shown even larger differences in favour of omeprazole12,14,15. However, no significant difference was found in the healing rates both at 2 and 4 weeks in a similar study conducted at our centre, appearing in this issue of JPMA. In the same study we could not find any significant difference in the rate of pain relief, while in the earlier studies omeprazole has been shown to be more effective in relieving symptoms as compared to H2 receptor antagonista11-16. Omeprazole has also shown its efficacy in the healing of resistant duodenal ulcers - which failed to heal after atleast two months of treatment with H2 receptor antagonists in standard or high doses. The healing rates with 40 mg omeprazole/day reached up to 98% at 4-8 weeks in these cases17. Although few follow-up studies have demonstrated similar relapse rates in omeprazole and H2 antagonists treated cases but most of others have shown less recurrence (41-44%) with omeprazole18,19 as compared to ranitidine (50-60%), in six months20,21. However, the relapse rate was significantly higher (100%) in the former group as compared to the latter (90%) ­within three months in our series appearing in this issue of the journal. Gastric ulcer like duodenal ulcer, also responded better with omeprazole as compared to H2 receptor antagonist. Meta-analysis showed that 20 mg om­eprazole/day was significantly better than H2 receptor antagonists only after 8 weeks and 30-40 mg of om­eprazole after 4 weeks therapy22-24. Resistant gastric ulcers not healing with H2 receptor antagonists showed healing upto 96% with 40 mg omeprazole/day at 8 weeks25,26. Although omeprazole offers a little advantage over H2 receptor antagonists for large and resistant gastric ulcers, the rate of relapse was similar24,27. In contrast to the slight advantage of omeprazole in the healing of duodenal and gastric ulcer, omeprazole is much more effective than H2 receptor antagonists for the relief of symptoms and healing of refluxoesophagitis. The healing rate up to 74% and 87% with omeprazole vs 43% and 56% with ranitidine has been reported at 4 and 8 weeks respectively28-30. Omeprazole 40 mg has also shown better healing rates in resistant oesophagitis (90%) than ranitidine 300 mg B.D. (47%)31, but unfortu­nately 80-90% of the healed oesophagitis relapses within 6 months after cessation of therapy29,32. Inspite of high relapse rates omeprazole has its real advantage in the treatment of patients with oesophagitis and Zollinger­ Ellison syndrome who failed to respond with H2 receptor antagonists even in higher doses and longer duration33,34. The benefits of omeprazole therapy have to be weighed against its potential risks. Cases of gynecomastia and impotence are emerging due to its inhibitory effect on the synthesis of adrenal steroids35. It interacts with the cytochrome P-450 system in the liver36 and inhibits metabolism of some drugs like warfarin37, phenytoin, diazepam38. antipyrine and aminopyrine39. Long term treatment may produce sufficient hypergastrinemia to cause hyperplasia of enterochromaffin-like cells and possibly carcinoid tumours in some patients41. Marked anti-secretory effect of omeprazole increases the bacte­rial-cell counts and nitrosamine levels in the stomach41. Such changes could theoretically lead to an increased risk of both gastric cancer and gastrointestinal infec­tions42,43 especially in tropical countries where helmin­thic, protozoal and bacterial infections are common due to poor hygienic conditions. Although this magic drug has proven its efficacy in the rapid healing of all types of peptic ulcer disease, its high cost, rapid relapse and potential risks of developing adverse effects has to be balanced against the risk/ benefits of other treatments.


1. Sacha, G., Carlsson, E., Lindberg, P., Wallmark, B. Gastric H, K- ATPsseas therapeutic target. Annu. Rev. Pharmacol. Toxicol., 1988;28:269-84.
2. Clissold, S.P. and Campoli-Richards, D.M. Omeprazole; a preliminary review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in peptic ulcer disease and Zollinger-Ellison syndrome. Drugs, 1986;32:15-47.
3. Lind, T., Cedeberg, c., Ekenved, 0., Haglund, U. and Olbe, L. Effectof omeprazole a gastric proton pump inhibitorS on pentagastrin stimulated acid secretion in man. Gut, 1983:24:270- 76.
4. Sharma, B.K., Walt, R.P., Pounder, RE., Gomcs, M.D., Wood, E.C. and Logan, L.H. Optimal dose of oral omeprazole for maximal 24 hour decrease of intragastric acidity. Gut, 1984;25:957-64.
5. Lanzon-Miller, S., Pounder, RE., Hamilton, M.R. et al. Twenty- four-hour intragastric acidity and plasma gastrin concentration before and during treatment with either ranitidine oromeprazole. Ailment Pharmacol. Ther., 1987;1:239-51.
6. Havu, N. Enterochromaffin-like carcinoids of gastric mucosa in rats after lifelong inhibition ofgastric aecretion.Digestion, 1986;35:Suppl. 1:42-55.
7. Prichard, P.J., Rubinstein, D., Jones, D.B. et al. Double blind comparative study of omeprazole 10 mgand 30mg daily forhealingduodenal ulcers. Br.Med., J., 1985;290:601­
8. Huttemann, W., Rohner, HG., duBosque, 0. et at 20versus 30mg omeprazole once daily: effect of healingrates in 115 duodenal ulcer patients. Digestion, 1986;33:117-20.
9. Belgian Multicentre Group. Rate of duodenal healing during treatment with om­eprazole: a double-blind comparison of a daily dose of 30mg versus 60 mg. Scand. J. GastroenteroL, Suppl. 1986;118:175-76.
10. Lauritaen, K., Anderson, B.N., Havelund,T. etal. Effectof 10 mgand 20 mgomeprazole daily on duodenal ulcer: double blind comparative trial. Aliment Pharmacol. Ther., 1989;3:59-67.
11. Classen, M., Dammann, H.G., Domschke, W. et al. Short-term therapy of duodenal ulcerwith omeprazoleand ranitidine: results of a German multicentre study. Dtsh. Med. Wochenschr., 1985;110:210-15.
12. Banthan, LCD., Bianchi-Porro, 0., Bose, K et at A comparison of two differentdosesof omeprazole versus ranitidine in treatment of duodenal ulcers. 3. Clin. Gastroenterot, 1986;8:408-13.
13. Hallberg, D., Backman, L., Hellstrom, M. et al. The effect of omeprazole and ranitidine on ulcer healing in treatment of duodenal ulcer patients. Dig. Dis. Sci., 1986;31:Suppl. 10:280S. abstract
14. Barbara, L., Blasi, A., cheli, R. et at Omeprazole va ranitidine in the short-term treatment of duodenal ulcer: an Italian multicenter study. Hepatogastroenterology, 1987;34:229-32.
15. Archambault, A.P., Pare, P., Bailey, R.J. et at Omeprazole (20 mg daily) versua cimetidine (1200 mgdaily) in duodenal ulcer healing and pain relief. Gastroenterology, 1988;94:1130-34.
16. Lauritsen, K, Rune, S.J., Bytzer, P. et al Effect of omeprazole and cimetidine on duodenal ulcer: a double-blind comparative trial. N.Engl.J.Med., 1985;312:958-61.
17. Bardhan, KD., Naesdal, 3., Bianchi-Porro, 0. et al. Omeprazole (OM) in the treatment of refractory peptic ulcer (RPU). Gastroenterology, 1988;94:A22. abstract
18. cooperative study. Omeprazole in duodenal ulceration: acid inhibition, symptom relief, endoacopic healing and recurrence. Br.Med. 3., 1984;289:525-28.
19. Farup, P.O., Rosseland, A.R., Halvoraen, L, Anderson, O.K and Bernklev, T. Duodenal ulcer treated with omeprazole: healing and relapae rates: dose treatment duration influence subsequent remission? Scand.J.Gastroenterol., 1989;24:1107-12.
20. Grant, S.M., Langtry, H.D. and Brogden, RN. Ranitidinc: an updated review of its pharmacodynamic and pharmacolcinecic properties and therapeutic use in peptic ulcer disease and other allied diseases. Drugs, 1989;37:801-7.
21. McLean, A.J., Harcourt, 5.M. and McNeil, J.J. Relapse rate as a major determinant of drug selection in peptic ulcer therapy. Drugs, 1988;35:329-33.
22. Barbara, L., Saggioro, A., Olsson,J., Ciaternino, M. and Franceschi, M. Omeprazole 20 mg om and ranitidine 150 mg bd in the healing of benign gastric ulcers - an Italian multicentre study. Gut, 1987;28:A1341. abstract
23. Bate, CM., Wilkinson, S.P., Bradby, G.V.H. etal. Randomised, doubleblind comparison of omeprazole and eimetidine in the treatment of symptomatic gastric ulcer. Gut, 1989;30:1323-28.
24. Walan, A., Bader, IF., Claaaen, M. et at 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.
25. Tytgat, G.N.J., Lamera, C.B.H.W., Hammeceman, W.,Jansen, 1M.B.J. and Wilson,3.A. Omeprazole in peptic ulcera resistant to histamine H2 receptor antagonista. Aliment Pharmaeol. Ther., 1987;1:31-38.
26. Brunner, 0., Crueszfelds, W., Harke, U. and Lambersa, it Therapywith omeprazole in patients with peptic ulcerations resistant to extended high-dose ranitidine treatment Digestion, 1988;39:80- 90.
27. DanishOmeprazole StudyGroup. Omeprazoleand cimetidine inthetreatmencofulcers ofchebodyofthestomach: a double-blind comparativetrial. Br.Med.3., 1989;298:645-47.
28. Klinkenberg-Knol, E.C., Jansen, J.B.M.J., Festen, H.P.M., Meuwissen, S.G.M. and Lamera, C.B.H.W. Double-blind multicentre comparison of omeprazole and ranitidine in the treatment of reflux oesophagitia. Lances, 1987;1:349-51.
29. Sandmark, S., Carlason, R., Fausa, 0. and Lundell, L. Omeprazole or ranitidine in the treatment of reflux esophagitis: results of a double-blind, randomized, Scandinavian mulsicentre study. Scand.J. Gaatroenterot, 1988;23:625-32.
30. Havelund, T., Laursen, 1_S., Skoubo-Kristensen, E. et al. Omeprazole and ranitidine in treatment of reflux oesophagitis: double-blind comparative tnal. Br.Med. 3., 1988;296:89-92.
31. Lundell, L., Backman, L., Elcatrom, P. et at Omeprazole or high dose ranitidine in the treatment of patients with reflux esophagitis not responding to standard doses of H2-receptor antagonists. Aliment Pharmacol. Ther., 1990;4:145-56
32. Hetzel, D.J., Dent, 3., Reed, W.D. et al. Healing and relapseof severe pepticesophagitis after treatmentwith omeprazole. Gastroenterology, 1988;95:903-12.
33. McArthur, KE., Collen, M.3., Maton, P.N. et al. Omeprazole: effective, convenient therapy for Zollinger-Ellison syndrome. Gastroenterology, 1985;88:939-44.
34. Maton, P.N., Vinayek, R., Frucht, H. etal. Long-term efficacy and safety of omeprazole in patients with Zollinger-Ellison syndrome: a prospective study. Gastroenterology, 1989;97:827.36.
35. Lindquist, M.and Edwards, I.R. Endocrine adverse effects of omeprazole. Br.Med.3., 1992;305:451-52.
36. Din, D., Fabre, L, Daujas, M. et at Omeprazole is an aryl hydrocarbon-like inducer of human hepaticcytochrome P450. Gastroenterology, 1990;99:737-47.
37. Sutfin, T., Balmer, K, Bostrom, H; Erikason, S., Hoglund, P. and Paulsen, 0. Stereoselective interaction of omeprazole with warfarin in healthy men.Ther. Drug Monit, 1989;11:176-84.
38. Gugler, R. and Jensen, J.C. Omeprazole inhibits oxidative drugmetabolism: studiedwitb diazepam and phenytoin in vivo and 7- ethoxycoumarin in vitro. Gastroenterology. 1985;89:1235-41.
39. Henry, D.A., Somerville, K.W., Kitchingman, 0. and Langman, M.3. Omeprazole: effects on oxidative drug metabolism. Br.J.Clin. Pharmacol., 1984; 18: 195-200.
40. Solda, E., Rindi, 0., Havu, N. and Elm, 0. Oualitative studies of gastric endocrine cells in patients treated long-term with omeprazole. Scand. 3. Gastroencerol. Suppl., 1989;166:129-37.
41. Sharma, BK, Santana, L.A., Wood, E.C. cc al. Lntragastric bacterial activity and nitrosstion before, during and after treatment with omeprazole. Br. Med. J., 1984;289:717-19.
42. Howden, C.W. and Hunt, RH. Relationship between gastric secretion and infection. Gut, 1987; 28:96-107.
43. Wormsley, KG. Assessing the safety of drugs for the long-term treatment of peptic ulcers. Gut, 1984;25:1416-23.

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