Omeprazole: is it the answer of peptic ulcer disease?

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 cell 1. A single 20mg dose of omeprazole inhibits acid secretion by 65% after 4-6 hours and by 25% after 24 hours 2 , but with subsequent doses inhibition increases, reaching a plateau after 4 doses 3. When the treatment is stopped, secretion returns to the pretreatment levels in 3 days without rebound phenomenon 4,5. 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 animals 6. 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 dose 7-10. All doses of more than 10mg/day showed healing rates of 90-100% at 4 weeks 7,9. 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 weeks 11-14. 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 omeprazole 12,14,15. 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 antagonista 11-16. Omeprazole has also shown its efficacy in the healing of resistant duodenal ulcers-which failed to heal …