gastrins and Substance-Withdrawal-Syndrome

Our previous study demonstrated rebound nocturnal acid hypersecretion after a 4-week course of nizatidine. Nocturnal acid output was increased by 77% two days after discontinuing treatment compared with pretreatment values. To confirm this effect with other H2-blockers we assessed daytime intragastric pH, fasting and meal-stimulated plasma gastrin and nocturnal acid output in 9 duodenal ulcer patients in remission before, during and two days after treatment with three different drugs. Each patient received 4-week courses of 300 mg ranitidine, 40 mg famotidine or 300 mg nizatidine, taken at 20.00 hours in randomized order with a 'washout' period of 4 weeks between each course of drug. Median nocturnal acid output (mmol/10 h) decreased during treatment with ranitidine to 3 (range 0-17), famotidine to 4 (1-12) and nizatidine 6 (0-40) compared with the respective pre-treatment values, 49 (20-126; P less than 0.01), 52 (22-105; P less than 0.01) and 32 (23-114; P less than 0.01). Two days after discontinuing treatment nocturnal acid output was increased after ranitidine at 77 (28-237; P less than 0.04) and after nizatidine at 64 (17-130; P less than 0.05) compared with pre-treatment values. There was no significant change in nocturnal acid output after famotidine at 57 (27-107) compared with the pre-treatment value. There was no change in daytime intragastric pH with any drug during or after treatment compared with the pre-treatment values. Fasting and meal-stimulated plasma gastrin concentrations were increased on the final treatment day with ranitidine and famotidine but had returned to pretreatment levels two days after treatment. The rebound acid hypersecretion may contribute to the high ulcer relapse rate after discontinuation of H2-receptor antagonists.

Topics: Adult; Aged; Duodenal Ulcer; Famotidine; Gastric Acid; Gastric Acidity Determination; Gastric Mucosa; Gastrins; Histamine H2 Antagonists; Humans; Male; Middle Aged; Nizatidine; Ranitidine; Substance Withdrawal Syndrome

Dyspepsia develops in healthy volunteers after withdrawal of proton-pump inhibitors. This phenomenon, attributed to rebound acid hypersecretion, is thought to be mediated by reflex hypergastrinemia.. To measure fasting and postprandial gastrin in patients on long-term proton-pump inhibitor treatment and correlate gastrin levels with the duration of treatment and other potential predictors.. In this cross sectional study patients, with erosive esophagitis, on long-term proton-pump inhibitor treatment and healthy controls underwent gastrin measurements at baseline and four times following a meal and Helicobacter pylori status was determined.. A total of 100 patients and 50 controls were studied. Pre- and postprandial gastrin levels were higher in patients (p<0.001). No significant correlation was found between the area under the gastrin-curve and the treatment duration. Female patients had significantly higher gastrin levels than males pre- and postprandial, whereas such differences was not found in the control group. Female gender was the only independent predictor of s-gastrin levels (OR 2.50 compared to males, 95% CI: 1.08-5.76, p=0.032) in the patient group.. Gastrin values were higher in patients compared to controls. There was no correlation between gastrin levels and treatment duration. Female patients had significantly higher gastrin values than males.

Topics: Aged; Case-Control Studies; Chromogranin A; Cross-Sectional Studies; Dyspepsia; Esophagitis, Peptic; Female; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Postprandial Period; Proton Pump Inhibitors; Sex Factors; Substance Withdrawal Syndrome

In the following study the function of gastric mucosa after withdrawal of 4-week suppression of acid secretion was examined. Rats were treated orally for 4 weeks with omeprazole (CAS 73590-58-6, 150 mg/kg/day). While elevated plasma gastrin levels during the treatment returned to normal 4 days after the last dosing, exogenously applied pentagastrin induced higher acid secretion compared with the vehicle-treated controls. Acetylsalicylic acid induced mucosal lesion 3.6-fold over the control as well. In contrast, the HCl-induced lesion was inhibited by 24.4%. These results indicate that not only the acid secretion but also the mucosal protection is enhanced after 4-week treatment with omeprazole in rats.

Topics: Analgesics, Non-Narcotic; Animals; Anti-Ulcer Agents; Aspirin; Gastric Acid; Gastric Mucosa; Gastrins; Histamine; Male; Omeprazole; Rats; Rats, Sprague-Dawley; Substance Withdrawal Syndrome

Nizatidine (N-[2-[[[2-[(dimethylamino)methyl]- 4-thiazolyl]methyl]thio]ethyl]-N'-methyl-2-nitro-1,1-ethenediamine , CAS 76963-41-2) is a new histamine H2-receptor antagonist which shows suppression of gastric acid secretion and antiulcer activity. In the present experiment, the effects of single s.c. administration of nizatidine, cimetidine and ranitidine on serum gastrin levels were studied in fasted rats. Nizatidine at 100 mg/kg increased serum gastrin level 3 h after administration, which however, returned to basal level 6 h after administration. Cimetidine and ranitidine at respective doses of 250 and 100 mg/kg markedly increased serum gastrin levels 3 and 6 h after administration. In a previous study, the suppressive effect of nizatidine on basal gastric acid secretion was 82.8% at a dose of 100 mg/kg s.c. in rat pylrus-ligated model. On the basis of these findings, changes in basal gastric acid secretion and serum gastrin level after withdrawal of nizatidine, cimetidine and ranitidine administered for 14 consecutive days were studied. One day after withdrawal, nizatidine at 100 mg/kg showed a tendency to increase the basal gastric acid secretion. However, 3 and 7 days after administration, almost no changes were obtained. Cimetidine at 250 mg/kg showed a tendency to increase the basal gastric acid secretion 7 days after withdrawal of the drug. Ranitidine at 100 mg/kg induced no changes in basal gastric acid secretion after withdrawal. No obvious influences of all drugs on serum gastrin level after withdrawals were obtained. These results indicate that consecutive administration of nizatidine may cause only a transient increase of gastric acid secretion but no hypergastrinaemia after its withdrawal.

Topics: Animals; Cimetidine; Gastric Acid; Gastrins; Male; Nizatidine; Pylorus; Ranitidine; Rats; Rats, Inbred Strains; Substance Withdrawal Syndrome