Gastric Antisecretory Drugs Research Articles

Omeprazole: a new drug for the treatment of acid-peptic diseases

Omeprazole is the first of a new class of gastric antisecretory drugs, proton pump inhibitors. It inhibits the H+,K(+)-adenosinetriphosphatase enzyme of the gastric parietal cell, resulting in potent, long-lasting suppression of basal and stimulated acid secretion. The drug is currently approved for treatment of gastroesophageal reflux disease and Zollinger-Ellison syndrome. In clinical trials, treatment with omeprazole results in rapid healing of duodenal ulcers; it is also effective in treating gastric ulcer disease. It is uniformly well tolerated without significant adverse effects, although animal studies linked profound long-term suppression of gastric acid secretion with the development of gastric carcinoids. Potential future uses include the prophylaxis of ulceration secondary to stress or use of nonsteroidal anti-inflammatory drugs, and the prophylaxis of recurrent peptic ulcer disease.

Jejunal efflux in short bowel syndrome

24 h oral intake and intestinal output were studied in 15 patients with a short residual length of jejunum and no colon. 8 patients showed a net secretory, and 7 a net absorptive response to food. In secretors, daily intestinal output exceeded oral intake (mean 2·3 kg wet weight, and 233 mmol sodium). Long-term parenteral fluid and electrolyte replacements were needed only in those with a secretory response. Jejunal length inversely correlated with net intestinal output of fluid, sodium, potassium, and with percentage energy absorption. A secretory response was observed if jejunal length was less than 100 cm and was reduced by gastric antisecretory drugs and octreotide.

Use of a five-day test to predict the long-term effects of gastric antisecretory agents on serum gastrin in rats

It has been hypothesized that prolonged achlorhydria causes compensatory elevation of serum gastrin, and that there is an association in rats between sustained hypergastrinemia, hyperplasia of gastric enterochromaffin-like cells, and subsequent formation of gastric carcinoids in 2-year carcinogenicity studies. The present study examined whether daily administration of gastric antisecretory drugs in rats for 4 days could cause hypergastrinemia associated with inhibition of acid output. Rats were dosed orally for 4 days with the histamine H 2-receptor antagonist ranitidine or the H +K +sensitive ATPase inhibitor omeprazole, and examined on day 5 for effects on gastric acid secretion and serum gastrin. Omeprazole (138 mg/kg/day significantly inhibited gastric acid secretion and increased serum gastrin levels. Large, single daily doses of ranitidine (1000–2000 mg/kg/day) had no effect on 24-hr acid or gastrin secretion; however, ranitidine did inhibit next-day acid secretion with associated increases in serum gastrin when administered in three divided doses. These results with ranitidine support the hypothesis that a sustained gastric antisecretory action will cause a compensatory hypergastrinemia, regardless of the antisecretory agent used. The ability to detect increased serum gastrin levels associated with inhibition of acid secretion, after administration of antisecretory agents for only 4 days, suggests that this short 5-day test may be useful for determining the potential of antisecretory agents to cause hypergastrinemia due to 24-hr inhibition of acid secretion and may be predictive of long-term hyperplastic changes.

The effects of cigarette smoking on plasma concentrations of gastric antisecretory drugs.

Plasma concentrations of cimetidine and ranitidine were measured after oral administration (n = 5 for cimetidine, n = 5 for ranitidine) or intravenous administration (n = 6 for cimetidine, n = 4 for ranitidine) in habitual smokers, once when cigarettes were smoked and again on a separate day when cigarettes were prohibited. After oral administration plasma concentrations of both drugs rose more rapidly and peak plasma concentrations were achieved earlier when cigarettes were smoked. However, plasma concentrations of the drugs subsequent to the peak were significantly lower when cigarettes were smoked. Cigarette smoking had no effect on plasma blood concentrations of either drug when administered intravenously. In eight healthy smokers cigarette smoking increased the gastric emptying of a liquid test meal by 28% compared with non-smoking control rates. In habitual smokers cigarette smoking alters the blood concentrations of antisecretory drugs in a manner which appears attributable to an increase in the rate of gastric emptying. The observed changes in drug disposition may contribute to the loss of gastric secretory inhibition observed in duodenal ulcer patients who are smokers.

Gastric carcinoids and antisecretory drugs

Gastric carcinoids and antisecretory drugs

Some Factors in the Assessment of Gastric Antisecretory Drugs by a Sampling Technique

Samples of gastric contents from patients with duodenal ulcer were more often highly acid when they drank 120 ml. of milk-cream mixture every hour than when they ate a bland diet. The volume of the drinks and the timing of the samples determined this apparent difference. Long-acting propantheline bromide reduced gastric acidity a little when the patients ate the diet and more when they took the drinks of milk-cream alone. It is concluded that the clinical usefulness of gastric antisecretory drugs can only be assessed under the actual conditions of use.