gastrins and roxatidine-acetate

H(2) antagonist premedication is common in surgical patients to control gastric pH and volume. However, several reports suggest that long-term medication may produce tolerance. Therefore, we studied the efficacy of a preanesthetic H(2) antagonist (oral roxatidine) in patients on regular H(2) antagonist therapy.. Forty-eight patients undergoing elective surgery were studied and grouped according to medication: those on no medication (control group) and those receiving H(2)-antagonists for less than two weeks (< or =2 w group), between two and four weeks (2-4 w group) and for longer than four weeks (> or =4 w group; n =12 each). All patients were given oral roxatidine as anesthetic premedication. Gastric volume and pH were measured after induction of anesthesia. Arterial blood was simultaneously collected for measurement of plasma gastrin levels using an enzyme-linked immunosorbent assay. We observed a significant decrease and increase in, respectively, gastric pH and volume (mL) in the < or =2 w group [6.50 +/- 0.43 (NS) and 11.6 +/- 10.3 (NS)], 2-4 w group [4.77 +/- 2.11 (P < 0.01) and 14.1 +/- 10.8 (P < 0.05)], > or =4 w group [2.32 +/- 1.46 (P < 0.01) and 22.2 +/- 14.2 (P < 0.01)] compared to patients in the control group (6.35 +/- 1.32 and 4.9 +/- 4.7). Plasma gastrin levels were decreased with increasing time on medication with a significant difference (46%) observed after two weeks' treatment. In addition, there was a significant correlation between gastric pH and plasma gastrin levels (r = 0.43, P < 0.01).. These data suggest that regular H(2) antagonist treatment for longer than two weeks may produce tolerance to pre-anesthetic H(2) antagonist administration.

Topics: Aged; Anesthesia; Bile; Drug Tolerance; Enzyme-Linked Immunosorbent Assay; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Histamine H2 Antagonists; Histamine Release; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Piperidines; Preanesthetic Medication; Stomach

We previously reported that H2-antagonist medication given for longer than 4 wk may produce complete tolerance to preanesthetic H2 antagonist therapy. In this study, we evaluated the efficacy of preanesthetic proton pump inhibitor (PPI; oral rabeprazol) use in patients receiving regular H2-antagonist (oral famotidine) therapy for more than 4 wk. Forty-eight patients with assumed complete tolerance to H2 antagonists undergoing elective surgery were recruited and randomly assigned to receive either a preanesthetic PPI (rabeprazol 20 mg; n = 24) or H2-antagonist (H2 group; roxatidine 75 mg; n = 24) at 9:00 pm on the day before surgery and 2 h before the induction of anesthesia. Volume of gastric contents and pH values were measured after the induction of anesthesia. Gastric pH value in the PPI group (5.38 +/- 2.42) was significantly higher than in the H2 group (3.27 +/- 1.98; P < 0.01). Gastric volume in the PPI group (8.6 +/- 1.5 mL) was significantly smaller than in the H2 group (15.4 +/- 2.8 mL; P < 0.05; cf. PPI). Fourteen patients in the H2 group were at risk of acid aspiration pneumonia (gastric pH <2.5 or volume >25 mL), whereas only four patients in the PPI group (P < 0.05) were at risk. These data suggest that in patients receiving H2-antagonist therapy for longer than 4 wk, prophylaxis for acid aspiration pneumonia should include preanesthetic PPI medication.. We previously reported that more than 4 wk of administration of H2-antagonists may produce a full tolerance to preanesthetic H2-antagonists. The present study suggests that a proton pump inhibitor may be effective for prophylaxis of acid aspiration pneumonia in patients showing the full tolerance to H2 antagonists.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Aged; Anti-Ulcer Agents; Benzimidazoles; Drug Tolerance; Famotidine; Female; Gastric Acidity Determination; Gastrins; Histamine H2 Antagonists; Humans; Male; Middle Aged; Omeprazole; Piperidines; Pneumonia, Aspiration; Preanesthetic Medication; Proton Pump Inhibitors; Rabeprazole

Therapy for the relief of symptoms of functional dyspepsia is unpredictable.. To identify which patients may benefit from antisecretory therapy.. Twenty-seven patients with functional dyspepsia were selected to receive H2-receptor antagonist (H2RA) treatment for 4 weeks. Serum pepsinogen A, pepsinogen C and gastrin were measured, and Helicobacter pylori status was determined. Symptoms were assessed at baseline and after H2RA treatment.. Fourteen patients were identified as H2RA responders and the remaining patients were non-responders. No differences were found between responders and non-responders with regard to serum pepsinogen A, pepsinogen C, gastrin and H. pylori status. However, the pepsinogen A/C ratio was significantly higher in responders than in non-responders. Ten of the 13 functional dyspepsia patients (77%) with a high value of the pepsinogen A/C ratio (> or = 4.5) achieved symptom resolution by H2RA, compared with only one of the eight patients (13%) with a low value of the pepsinogen A/C ratio (< or = 3.0).. The serum pepsinogen A/C ratio seems to identify those functional dyspepsia patients for whom acid control provides benefit. This ratio may be a practical tool for the management of functional dyspepsia patients.

Topics: Adult; Aged; Anti-Ulcer Agents; Biomarkers; Dyspepsia; Female; Gastrins; Helicobacter pylori; Histamine H2 Antagonists; Humans; Male; Middle Aged; Patient Selection; Pepsinogen A; Pepsinogen C; Piperidines; Treatment Outcome

In order to study structure-activity relationships of the previously reported dual histamine H2 and gastrin receptor antagonists and also to improve their low oral absorbability, we tried two chemical modifications. One tried to decrease the high hydrophobicity of the parent hybrid compounds to an appropriate level by incorporating a hydrophilic group into the molecule and the other by replacing the more hydrophobic groups with less hydrophobic ones. The former compounds (type I) involved hybrid compounds with a hydroxyl group at a position of a spacer, a piperidine moiety of H2A, or a phenyl ring at the C5 of the benzodiazepine skeleton as well as those with a free carboxyl group in the piperidine moiety of H2A. The latter (type II) involved hybrid compounds with the C5-phenyl group replaced with either a methyl group or hydrogen atom. Among them, only a type I compound, ([2-[3-(3-piperidin-1-ylmethylphenoxy)propylcarbamoyl] ethylcarbamoyl]methyl)carbamic acid 3-[3-[5-(3-hydroxyphenyl)-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiaz epin-3-yl]ureido]benzyl ester (18), showed potent dual histamine H2 and gastrin receptor antagonistic activity, whereas others resulted in a significant decrease of histamine H2 receptor antagonistic activity. The in vivo gastric acid antisecretory activity of 18 evaluated by Schild's rat method, however, did not suggest any notable improvement in oral absorbability.

Topics: Animals; Benzodiazepines; Chemical Phenomena; Chemistry, Physical; Gastric Acid; Gastrins; Guinea Pigs; Histamine H2 Antagonists; In Vitro Techniques; Mice; Piperidines; Rats; Receptors, Cholecystokinin; Solubility; Structure-Activity Relationship

1. Roxatidine acetate, a new histamine H2-receptor antagonist, was administered in the evening (75 mg p.o.) to eight patients with renal insufficiency (CLCR 8-17 ml min-1) for 12 days and plasma drug concentrations were measured. 2. Ambulatory intragastric pH was monitored following the last dose and values were compared with those on day 1 when all patients received a placebo. 3. The terminal elimination half-life (mean +/- s.d.) of roxatidine was 10.8 +/- 2.4 h and its oral clearance was 178 +/- 43 ml min-1. 4. During roxatidine treatment gastrin levels increased slightly (median 189 vs 289 ng l-1) and the hyperparathyroid status of the patients was almost normalized (parathyroid hormone levels: median 199 vs 132 ng l-1). 5. The mean latency to a gastric pH of at least 4 was 4.3 +/- 1.4 h. The duration of action (intragastric pH > 4) was 10.6 +/- 3.9 h. 6. As in a pilot study with six patients (CLCR < or = 17 ml min-1) the recommended dosage regimen (75 mg 48 h-1) was unable to maintain gastric pH > 4 for more than 6 h, daily nocturnal intake of 75 mg roxatidine acetate appears appropriate to elevate gastric pH > 4 for a sufficient period of time.

Topics: Adult; Drug Administration Schedule; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Histamine H2 Antagonists; Humans; Kidney Failure, Chronic; Male; Middle Aged; Parathyroid Hormone; Piperidines