Gastric Acid Secretion In Patients Research Articles

Use of omeprazole in patients with Zollinger-Ellison syndrome

Omeprazole, a substituted benzimidazole, has been shown to be a potent inhibitor of gastric acid secretion in patients with Zollinger-Ellison syndrome (ZES). We review our experience, as well as the published data on 210 patients with ZES who have required omeprazole for control of gastric acid hypersecretion over the past seven years. The dose of omeprazole required in individual patients ranged from 10 to 180 mg/24 hr with 20-60% requiring a split dosage regimen. Omeprazole was effective in approximately 99% of the patients over a period ranging from 0.5 to 54 months. Twenty-four percent of patients required an increase in omeprazole dose, while 26% required a decrease in dose. Adverse effects attributable to omeprazole were reported in 2% of patients, and in all cases, they were mild (ie, rash, constipation, headache). There was no effect of omeprazole on serum gastrin concentration or on gastric endocrine cells in three studies. Although one patient with multiple endocrine neoplasia, type-I syndrome (MEN-I) in this series developed a gastric carcinoid while taking omeprazole, evidence is presented that suggests the presence of MEN-I per se may be important in determining the development of gastric carcinoid in patients with ZES. It is concluded that omeprazole is safe and effective in patients with ZES, and in these patients, it is the drug of choice for the management of gastric acid hypersecretion. However, yearly assessment is indicated to clearly evaluate the long-term risk of gastric carcinoid as well as therapy directed at the gastrinoma itself.

Stress ulceration in the intensive care unit: use of H2‐receptor antagonists

H2-receptor antagonist drug therapy is the mainstay of peptic ulcer treatment in the USA. About 75% of patients in intensive care units receive parenteral H2-antagonists. The rationale for their use is that parenteral H2-antagonists offer about a four-fold protective effect compared with placebo against significant upper gastrointestinal haemorrhage. Parenteral administration of H2-receptor antagonists appears to be preferred to oral antacid or sucralfate regimens because of ease of administration and, perhaps, lower treatment costs. Recommended dosage schedules for intravenously administered H2-receptor antagonists are at fixed intervals, 6- to 8-h intervals for cimetidine and ranitidine and 12-h intervals for famotidine. These dosage schedules assume a fixed dose-response relationship (i.e. a given dose of H2-antagonist results in equivalent acid suppression throughout the circadian, or 24-h, period). However, human basal gastric acid secretion exhibits circadian variation, with peak rates occurring during the evening hours. Recent evidence from 24-h continuous intragastric pH studies in fasting patients with healed duodenal ulcer suggests that larger doses of intravenous H2-antagonists are required in the evening than in the morning to achieve equivalent acid suppression. These findings are consistent with a changing H2-antagonist dose/acid-inhibiting response over the circadian period. Continuous infusion has the advantage of providing consistent and sustained suppression of gastric acid secretion in patients at risk for stress ulceration. Results of a double-blind, randomized, crossover study indicated that equally effective suppression of acidity and time-to-onset of pharmacological effect can be achieved with and without priming bolus doses of ranitidine, and presumably other H2-receptor antagonists as well.(ABSTRACT TRUNCATED AT 250 WORDS)

Elevated gastric acid secretion in patients with Barrett's metaplastic epithelium.

Gastric acid secretion in response to a protein meal and to exogenously administered synthetic human gastrin 17-I was measured in patients with Barrett's esophagus, patients with uncomplicated gastroesophageal reflux, and normal age- and sex-matched controls. Acid secretion, both basally and in response to gastrin 17-I, was significantly greater in patients with Barrett's esophagus compared to normal individuals without reflux. Basal gastrin levels and meal-stimulated levels of the hormone were similar among all three groups. Sensitivity to gastrin, expressed as the concentration causing half-maximal acid secretion, was also similar among the study groups. It is speculated that elevated basal acid production in Barrett's esophagus may contribute to the pathogenesis of the disorder.

Effect of smoking on gastric acid secretion in patients with duodenal ulcer

The effect of smoking on gastric secretion was studied in 15 consecutive patients with duodenal ulcer--six normosecretors (basal acid output less than or equal to 3 mEq/h), and nine hypersecretors (basal acid output greater than 3 mEq/h). The volume, acid output, acid concentration, and pH of the gastric juice measured before, during and after 1 h of smoking did not show any significant difference in these patients taken as a single group, or when the normosecretors and hypersecretors were analysed as separate groups (P greater than 0.05 for each parameter in each group). The higher acid output before and during smoking in hypersecretors than in normosecretors was due to the higher acid concentration in the gastric juice (P less than 0.01). Study of the pH curves of the gastric juice after acute smoking showed that hypersecretors had a lower pH for a longer duration compared with normosecretors. This could make the hypersecretors with a history of chronic smoking more prone to developing duodenal ulcer.

Gastrointestinal transit and gastric acid secretion in patients with achalasia

Previous studies suggest that patients with achalasia exhibit degenerative changes of extraesophageal nerve fibers. We investigated whether these morphological alterations are associated with functional abnormalities of the gastrointestinal tract. Patients with achalasia had a normal acid secretory response (5.5 +/- 1.5 mmol/hr) to vagal stimulation when compared to controls (6.0 +/- 5.3 mmol/hr). However, the half time of gastric emptying of liquids was significantly shorter in patients with achalasia (10.4 +/- 1.8 min) than in control subjects (19.3 +/- 11.3 min) (P less than 0.01). Although there was a tendency towards a more rapid gastrointestinal transit in patients with achalasia, these changes failed to reach statistical significance. It is concluded that patients with achalasia have a gastric emptying disorder that could either be explained by a selective defect of extraesophageal vagal inhibitory nerve fibers or as an epiphenomenon occurring as a consequence of impaired esophageal emptying.

Loss of Efficacy of Famotidine in the Control of Gastric Acid Secretion in Patients with Zollinger-Ellison Syndrome Reversed by Omeprazole

(1989). Loss of Efficacy of Famotidine in the Control of Gastric Acid Secretion in Patients with Zollinger-Ellison Syndrome Reversed by Omeprazole. Scandinavian Journal of Gastroenterology: Vol. 24, No. sup166, pp. 180-180.

Gastropathy and ketoconazole malabsorption in the acquired immunodeficiency syndrome (AIDS).

To correlate oral ketoconazole absorption with gastric acid secretion in patients with the acquired immunodeficiency syndrome (AIDS). Prospective measurement of maximal acid output and oral ketoconazole absorption with and without 0.1-N hydrochloric acid. Hospital in-patients in university medical center. Ten consecutive male patients with AIDS. Maximal acid output was determined after pentagastrin stimulation in all patients. Serum ketoconazole levels were measured the day after ingestion of a 200-mg ketoconazole tablet in the fasted state. On the final day, ketoconazole was ingested with 200 mL of 0.1-N hydrochloric acid. Maximal acid output was below 15 mEq/h in 7 of 10 patients. In all 7, the area under the serum ketoconazole concentration-time curve was below normal (1.4 +/- 0.9 mg/h.L; mean +/- SE), and absorption was normalized by hydrochloric acid (9.9 +/- mg/h.L). Two of three patients with maximal acid outputs above 15 mEq/h had normal ketoconazole absorption (15.1 +/- 6.7 mg/h.L). The bioavailability of oral ketoconazole is reduced in patients with AIDS, largely as a result of gastric hypochlorhydria. Ketoconazole tablets should therefore be given with acid in these patients.

Peptic ulcer and gastric acid secretion in patients with insulinoma.

We evaluated the incidence of associated peptic ulcers and the gastric acid secretion in our 20 series of insulinoma, and obtained the following results: 1) Four out of 20 patients (20%) with insulinoma were associated with peptic ulcers. 2) Except for the maximum acid concentration, the preoperative gastric secretion tests, such as the basal acid output and maximum acid output, failed to indicate hyperacidity in those patients. And patients with a short duration of illness by insulinoma neither showed hyperacidity nor were associated with peptic ulcers. 3) A tendency of reduced gastric acid secretion and the amelioration of peptic ulcers was observed in those who underwent the extirpation of insulinoma. 4) In the most recent case received gastric analysis with continuous monitoring of blood glucose level, an increase of basal acid output was observed during the hypoglycemic period in which the blood glucose levels reduced to around 30 mg/100 ml. These results indicate that the low blood glucose level and the high gastric acid secretion produced under the condition on an empty stomach, may be important factors related to the high association rates of the peptic ulcers in patients with insulinoma.

Trimoprostil: inhibits meal-stimulated gastric acid secretion in patients with duodenal ulcer

Trimoprostil: inhibits meal-stimulated gastric acid secretion in patients with duodenal ulcer

Sensitivity of gastric acid secretion in patients with chronic renal failure.

By means of a dose-response secretion test the sensitivity of gastric acid secretion was investigated in 85 patients with chronic renal failure and in 85 age- and sex-matched controls. The renal patients were also gastroscoped, with biopsy specimens taken from the gastric body. The examinations were repeated on 18 patients undergoing regular dialysis and 8 patients after successful transplantation. The acid secretion sensitivity of the stomach among the non-dialyzed patients was decreased when compared with the controls (p less than 0.01) but tended to normalize during the intermittent dialysis treatment (p less than 0.05) and particularly after transplantation (p less than 0.01). The low secretion responses were independent of gastric body histology and were also seen in patients with normal body mucosa. The maximum theoretic acid output did not differ significantly from that of the controls. It is concluded that there is an inhibition of gastric acid secretion in chronic renal failure. This inhibition depends on the decreased sensitivity to stimulation and is diminished by treatment of renal failure by dialysis or transplantation.

Total 24-Hour Gastric Acid Secretion in Patients With Duodenal Ulcer: Comparison With Normal Subjects and Effects of Cimetidine and Parietal Cell Vagotomy

The purposes of these studies were as follows: (a) to compare gastric acid secretion throughout an entire 24-h period in 8 patients with duodenal ulcer disease and in 7 normal subjects, and (b) to determine in duodenal ulcer patients to what extent total, 24-h acid secretion was reduced by oral cimetidine (n = 7) or parietal cell vagotomy (n = 7). Basal, interprandial, and nocturnal acid secretion were measured by gastric aspiration, whereas acid secretion in response to breakfast, lunch, and dinner was measured by in vivo intragastric titration. Total, 24-h acid secretion averaged 408.3 +/- 61.7 mmol in duodenal ulcer patients and 208.3 +/- 18.5 mmol in normal subjects (p less than 0.02). Acid secretion was higher in duodenal ulcer patients than in normal subjects during both day (p less than 0.01) and night (p less than 0.05). Cimetidine (400 mg twice daily) significantly (p less than 0.001) reduced total, 24-h acid secretion in duodenal ulcer patients to 235.3 +/- 58.6 mmol, a rate that was not significantly different from 24-h acid secretion in normal subjects. On the other hand, total, 24-h acid secretion averaged only 86.7 +/- 20.7 mmol after parietal cell vagotomy, a rate that was significantly lower than 24-h acid secretion in normal subjects (p less than 0.001) and in duodenal ulcer patients receiving cimetidine (p less than 0.05). These studies indicate that patients with duodenal ulcer disease secrete excessive amounts of gastric acid during the day and night and throughout an entire 24-h period. A twice-daily 400-mg dose of cimetidine reduces 24-h acid secretion in duodenal ulcer patients to nearly normal rates, whereas parietal cell vagotomy reduces acid secretion to well below normal rates.

Oesophagitis, signs of reflux, and gastric acid secretion in patients with symptoms of gastro-oesophageal reflux disease.

In a study comprising 100 patients referred to a surgical clinic with symptoms suggestive of gastro-oesophageal reflux disease the value of different diagnostic procedures was investigated. Positive acid perfusion and 24-h pH tests were the commonest findings. Forty-nine per cent showed a normal oesophageal mucosa or diffuse oesophagitis at endoscopy. The severity of heartburn and regurgitation did not differ between patients with normal oesophageal mucosa and oesophagitis of various severities. The severity of macroscopic oesophagitis was significantly correlated to the total reflux time, the presence of reflux or a hiatal hernia at radiology, an open cardia or reflux at endoscopy, pressure transmission or reflux and low lower oesophageal sphincter pressure at manometry. Gastric hypersecretion was found in 66% of the patients. Gastric acid secretion was not correlated to the severity of oesophagitis or to the findings at 24-h pH test. In patients with severe oesophagitis the sensitivity for radiologic, manometric, and endoscopic signs of incompetence of the gastro-oesophageal junction was 94%.

Lack of pharmacokinetic interaction between cimetidine and pirenzepine

The oral administration of pirenzepine (PRZ), an antimuscarinic agent, has a variable effect on gastric acid secretion in patients with duodenal ulcer, and it seems to potentiate cimetidine-induced inhibition of secretion. The possibility of a pharmacokinetic interaction between these drugs was examined in eight patients who received cimetidine and PRZ alone and in combination in a crossover fashion. Cimetidine, 600 mg b.i.d., PRZ, 50 mg b.i.d., or combination therapy were each given for 1 week before the study. Serum samples were serially drawn during each dosing interval for determination of cimetidine and PRZ concentrations by HPLC and RIA, respectively. Cimetidine given alone or with PRZ exhibited diurnal variation, as the peak serum concentration was lower after the nighttime dose than after the morning dose. PRZ showed intersubject variation. However, each drug failed to alter the pharmacokinetic indices of the other. The times to attain the peak serum concentration were not significantly different for cimetidine alone or with PRZ, arguing against an effect of PRZ on gastric motility in the doses we used. The greater and prolonged acid inhibition with the combination of cimetidine and PRZ, therefore, may stem from a synergistic action of both drugs on receptor sites on gastric parietal cells.

Gastric acid secretion in patients with typhoid fever.

Gastric secretory studies were carried out in the following groups of patients: group A, 30 Salmonella typhi positive enteric patients, group B, 15 non-enteric fever patients and group C, 20 healthy controls. Patients with typhoid were divided into two subgroups on the basis of the severity of the disease: group A1 (17) consisted of uncomplicated cases of enteric fever and group A2 (13) comprised of those who had associated complications. During convalescence both groups of typhoid patients showed significantly lower basal acid output (BAO) and maximal acid output (MAO) levels compared with controls and patients with non-enteric fever. Patients in group A2 had significantly lower MAO levels compared with group A1 but the BAO levels showed no such difference. In contrast BAO and MAO levels during convalescence in patients with non-enteric fever were similar to those in the control group. After two months, there was a significant increase in both the BAO and MAO levels in groups A1 and A2. The levels in group A2, however, remained significantly lower compared with group A1, controls and patients with non-enteric fever. Histologically, the gastric mucosa did not show any significant abnormality in either group of typhoid patients. The results suggest that depressed gastric secretion is the result of enteric infection and is related to the severity of the disease process.

Omeprazole: Effective, Convenient Therapy for Zollinger—Ellison Syndrome

The acute and long-term effects of omeprazole on gastric acid secretion were examined in 11 patients with Zollinger-Ellison syndrome. Basal gastric acid secretion was inhibited by 50% 3 h after a single 60-mg dose of omeprazole and 78% 4 h after administration of omeprazole. Patients were treated with a single daily dose of omeprazole, and the dose requirement was defined as the lowest dose of omeprazole that would reduce gastric acid secretion to less than 10 mEq/h during the last hour before the next dose. The mean daily dose requirement was 70 mg (range 20-160 mg). Ten of the 11 patients were given omeprazole once a day and 1 patient required omeprazole every 12 h. When omeprazole was discontinued after several months of therapy, mean basal gastric acid secretion was inhibited by greater than 50% 48 h after administration of omeprazole. Omeprazole continued to inhibit gastric acid secretion during 1-9 mo of therapy and patients remained free of toxicity or side effects related to omeprazole. Omeprazole is a highly effective inhibitor of gastric acid secretion in patients with Zollinger-Ellison syndrome. Because of its potency and long duration of action, omeprazole offers an advance in convenient medical therapy for Zollinger-Ellison syndrome compared with the histamine H2-receptor antagonists.

Antisecretory effect and oral pharmacokinetics of omeprazole in patients with chronic renal failure.

The inhibitory effect of omeprazole on gastric acid secretion was tested in a group of patients on haemodialysis for chronic renal failure. Single 30 mg doses almost totally inhibited basal acid output on both dialysis and non-dialysis days. Plateau acid output was reduced by a mean of 77% and 90% on non-dialysis and dialysis days respectively. The absorption and pharmacokinetic profile of omeprazole were not affected by dialysis. Omeprazole was not recoverable from dialysis fluid. It is concluded that omeprazole is a potent inhibitor of gastric acid secretion in patients with chronic renal failure, and its effect is not influenced by haemodialysis.

Abnormally processed gastrins in active duodenal ulcer disease

In contrast to healthy subjects, duodenal ulcer patients in the active phase contain large amounts of a peptide in serum and antrum which react with antiserum specific for the N-terminus, but not the C-terminus of gastrin-17. The immunochemical and chromatographic properties were similar to that of the N-terminal tridecapeptide sequence of gastrin-17. The peptide follows the clinical course of duodenal ulcer disease, as it disappears when the ulcer heals. The N-terminal tridecapeptide - lacking the bioactive tetrapeptide of gastrin-17 - is a potent inhibitor of gastric acid secretion, presumably by way of competitive antagonism to gastrin. It is suggested to participate in the regulation of gastric acid secretion in patients with active duodenal ulcer disease. To confirm the chemical structure of the peptide, antral and gastrinoma extracts were used for isolation, purification and amino acid analysis. We found two different peptides with the same N-terminus as gastrin-17, namely the previously known N-terminal tridecapeptide fragment of gastrin-17 and a new gastrin component, identical with a C-terminal glycine extended gastrin-17. Furthermore, a C-terminal glycine extended component, corresponding to each of the other molecular forms of gastrin were present. Thus, a variety of abnormally processed gastrins are synthesized and released to the circulation during the active period of duodenal ulcer disease.

The N-terminal tridecapeptide fragment of gastrin-17 inhibits gastric acid secretion

After a meal the serum concentrations of the N-terminal tridecapeptide-like fragment of gastrin-17, (1–13)G-17, increased markedly in patients with active duodenal ulcer, but less so in healthy subjects. Consequently the synthetic (1–13)G-17 was infused intravenously in doses that resulted in concentrations similar to those measured in duodenal ulcer patients in order to examine whether the N-terminal fragment influences gastric acid secretion. Doses of 125 and 400 pmol (1–13)G-17/kg per h inhibited the meal-stimulated acid secretion by 36% ( P < 0.05) and 66% ( P < 0.05) respectively. The release of endogenous C-terminal gastrin immunoreactivity was not influenced. The infusion of (1–13)G-17 also inhibited the acid response to exogenous gastrin-34, gastrin-17 and Peptavlon®, but not to gastrin-4. The results suggest that the N-terminal gastrin-17 fragment — although devoid of the hitherto considered only active site of gastrin — plays a significant role in the regulation of the gastric acid secretion in patients with active duodenal ulcer.

The Effect of a Gastrin-Receptor Antagonist on Gastric Acid Secretion and Serum Gastrin in the Zollinger-Ellison Syndrome

We studied the effect of intravenous administration of a gastrin-receptor antagonist (proglumide) on gastric acid secretion and serum gastrin in three patients with Zollinger-Ellison syndrome. Proglumide administered as a bolus injection (50 mg/kg) or as an infusion (50 mg/kg hour and 100 mg/kg hour) or as a combination of bolus injection and infusion (50 mg/kg I.V. followed by 50 mg/kg hour) inhibited gastric acid secretion by 13-62%. Cimetidine (2 mg/kg I.V. followed by 2 mg/kg hour) inhibited gastric acid secretion by 83-86%. Neither proglumide nor cimetidine significantly influenced serum gastrin concentrations. We conclude that proglumide is a relatively weak inhibitor of gastric acid secretion in patients with the Zollinger-Ellison syndrome.

Reliability of Symptoms in Assessing Control of Gastric Acid Secretion in Patients With Zollinger-Ellison Syndrome

In the present study we explored whether the presence or absence of symptoms could provide a reliable way of assessing the adequacy of control of gastric secretion in patients with Zollinger-Ellison syndrome who were treated medically. Over a 5-yr period, 26 Zollinger-Ellison syndrome patients were entered into a prospective study which examined the presence or absence of symptoms that are associated with gastric hypersecretion, the presence of absence of upper gastrointestinal pathology, and the degree of control of gastric acid secretion. During their last admission, 15 of the 26 patients (58%) were symptomatic, but post-drug gastric acid secretion for the 2 h before the next dose of medication was not significantly different from that in asymptomatic patients. This lack of correlation between the presence or absence of symptoms and post-drug gastric acid secretion was evident for the group as a whole, as well as for 8 to 12 patients who underwent multiple admissions. Of 23 patients who underwent upper gastrointestinal endoscopy of x-ray, or both, on their last admission, 12 had pathology. Post-drug gastric acid secretion was less in patients without pathology than in those with pathology. Furthermore, in patients in whom post-drug gastric acid secretion was less than or equal to 10 mEq/h, the criterion of acceptable control used in this study, pathology did not occur. These findings demonstrate that the presence or absence of symptoms cannot be used to assess the adequacy of medical control of gastric acid secretion in patients with Zollinger-Ellison syndrome. In our opinion, maintenance of post-drug gastric acid secretion less than or equal to 10 mEq/h for the 2 h before the next dose of medication is an acceptable criterion for long-term control of gastric secretion in patients with Zollinger-Ellison syndrome.