Ranitidine-treated Group Research Articles

Pharmacoepidemiological Research on N-Nitrosodimethylamine-Contaminated Ranitidine Use and Long-Term Cancer Risk: A Population-Based Longitudinal Cohort Study.

Simple SummaryThere is a lack of published data regarding the association between N-nitrosodimethylamine and human cancer risks. Hence, this study answers several questions using propensity score matching with a large population size selected from a high-quality nationwide and population-based database with a long follow-up period to assess the relationship between the cumulative individual cancer incidence and long-term ranitidine use.N-Nitrosodimethylamine (NDMA), a carcinogenic chemical, has recently been identified in ranitidine. We conducted a population-based study to explore ranitidine use and cancer emergence over time. Using the Taiwan National Health Insurance Research Database, a population-based cohort study was conducted. A total of 55,110 eligible patients who received ranitidine between January 2000 and December 2018 were enrolled in the treated cohort. We conducted a 1:1 propensity-score-matching procedure to match the ranitidine-treated group with the ranitidine-untreated group and famotidine controls for a longitudinal study. The association of ranitidine exposure with cancer outcomes was assessed. A multivariable Cox regression analysis that compared cancer risk with the untreated groups revealed that ranitidine increased the risk of liver (hazard ratio (HR): 1.22, 95% confidence interval (CI): 1.09–1.36, p < 0.001), lung (HR: 1.17, CI: 1.05–1.31, p = 0.005), gastric (HR: 1.26, CI: 1.05–1.52, p = 0.012), and pancreatic cancers (HR 1.35, CI: 1.03–1.77, p = 0.030). Our real-world observational study strongly supports the pathogenic role of NDMA contamination, given that long-term ranitidine use is associated with a higher likelihood of liver cancer development in ranitidine users compared with the control groups of non-ranitidine users treated with famotidine or proton-pump inhibitors.

Gastroprotective Effect of Capparis spinosa on Indomethacin-induced Gastric Ulcer in Rats.

Peptic ulcer is an acid-induced lesion that is usually found in the stomach and duodenum. It is usually a case of imbalance between the acid (and other injurious factors) and the mucosal defense mechanisms. Indomethacin is one of the most ulcerogenic drugs that is prescribed over-the-counter for the management of musculoskeletal problems. Capparis spinosa is one of the most important species in the Capparidaceae family, which has a wide range of diversity. Caper (Capparis spinosa L.) is a common member of the genus Capparis (Capparidaceae family). The present study was designed to compare the effect of C. spinosa extract as a gastroprotective agent with indomethacin as an induction agent and ranitidine as a standard drug. To this aim, 40 adult male Wistar rats were randomly divided into 4 groups (n=10 each), including Control +: indomethacin-treated group, Control -: receiving physiological saline solution, C.S: C. spinosa-treated group; and ranitidine-treated group (50 mg/kg) as a standard agent for the treatment of the gastric ulcer. After the experimental period, all the animals were sacrificed by anesthesia overdose and their stomachs were removed. The gastroprotective effect of C. spinosa was investigated by studying prostaglandin E2 (PGE2), Gastrin, anti-tumor necrosis factor alpha (TNF-α), and Interleukin 1 beta (IL1-β), along with histopathological examination. The results showed a significant increase in PGE2 levels in the ranitidine-treated group with a significant reduction in Gastrin, TNF-α, and IL1-β. The recorded data obtained from the histopathological study showed a significant improvement in the treated group with the extract of C. spinosa. The study concluded that C. spinosa had gastroprotective properties possibly through enhancing PGE2 which was acting as anti-inflammatory inhibiting neutrophil infiltration.

ANTI-ULCER ACTIVITY OF HYDROALCOHOLIC EXTRACT OF PIPER BETLE LEAF ON EXPERIMENTAL ANIMALS

Objective: The main objective of this study is to establish the anti-ulcer activity of hydroalcoholic extract of Piper betle leaf on experimental animals based on previously existing aspects such as antioxidant, antihistaminic, and antimicrobial properties of P. betle leaf.&#x0D; Methods: The leaves were collected, shed dried, and extracted by the Soxhlet apparatus using 70% ethanol. The anti-ulcer activity of the extract was evaluated in albino Wistar rats employing pyloric ligation and stress-induced antiulcer models. Ranitidine was served as a standard drug in both the models. The significance of activity was assessed using a one-way analysis of variance followed by Dunnett’s post-parametric test.&#x0D; Results: In the pyloric ligation model, the untreated control has shown 4.3 mEq/l of acidity, whereas the ranitidine-treated standard group shown 2 mEq/l and P. betle has shown 2.5 mEq/l acidity, respectively. In the stress-induced antiulcer model, the activity was more prominent, in the untreated control, there was 26 number of sores present, whereas the standard group showed only one number of ulcer sore, and in the P. betle treated group, there was four number of ulcer sores present.&#x0D; Conclusion: In the present study, P. betle exhibited potent antiulcer potential while compared with the untreated control and the activity is comparable with standard ranitidine. From the above findings, it can correlate the use of betel leaf as a digesting or gastroprotective agent.

Effect of jianpiyiqi prescription on the expression of heat shock proteins in acetic acid-induced chronic gastric ulcer rats.

To investigate the effect of Jianpiyiqi prescription on the expression of heat shock proteins (HSPs) and the changes of HSPs in gastric-ulcerated rats, the rat model of chronic gastric ulcer was induced by acetic acid. The SABC immunohistochemical method was used to observe HSP70 of mucosa around the gastric ulcer. Imaging analysis was performed. Western dot blot was used to detect HSPs contents in the plasma and gastric mucosal homogenate in each group. The results showed that HSP70 contents of the mucosa around the gastric ulcer in the model group and ranitidine-treated group were increased as compared with control group (P < 0.01). Jianpiyiqi could increase the expression of HSP70 of the mucosa around the gastric ulcer further as compared with that in the model group and ranitidine-treated group (P < 0.01). The HSP70 contents in the serum and mucosa in the model group and ranitidine-treated group were increased as compared with control group (P < 0.01, P < 0.05 respectively). HSP70 of serum and mucosa in the Jianpiyiqi-treated group was higher than in the model group and ranitidine-treated group (P < 0.05, P < 0.01 respectively). It was concluded that HSP might play a role in the process of pathophysiology of gastric ulcer. Jianpiyiqi could enhance gastric ulcer-healing through the protective mechanism of HSPs.

IgE levels in surgery: effect of ranitidine and prednisolone

Immunoglobulin E (IgE) is important in allergic reactions and in host defense against parasites. IgE may also participate in the acute-phase response to physical stress. This study aimed to determine whether major abdominal surgery induced increased serum IgE levels, and whether treatment with ranitidine or prednisolone influenced the IgE response to surgery. For assessment of the IgE response to surgery and the effect of ranitidine, 24 patients scheduled for major abdominal surgery were randomized to receive either perioperative treatment with ranitidine or no treatment. To evaluate the effect of glucocorticoids, 24 patients undergoing major elective abdominal surgery were randomized to receive preoperative treatment with either prednisolone or placebo. IgE levels were determined in serum samples drawn pre- and postoperatively. In the ranitidine study, both the control group and the ranitidine-treated group displayed a postoperative increase (P<0.001) of serum IgE. In the prednisolone study, a postoperative increase (P<0.05) of serum IgE was detected in the placebo group. No significant increase was found in the prednisolone-treated group. Major abdominal surgery induces an increase of serum IgE. This increase can be prevented by preoperative treatment with prednisolone, but not with ranitidine.

Comparative efficacy of cimetidine, famotidine, ranitidine, and mylanta in postoperative stress ulcers: Gastric pH control and ulcer prevention in patients undergoing coronary artery bypass graft surgery

To determine the comparative efficacy of several histamine (H2)-receptor antagonists (cimetidine, famotidine, and ranitidine) and the antacid Mylanta-II (Stuart Pharmaceuticals, Wilmington, DE) in gastric pH control and the prevention of postoperative stress ulceration, a prospective, randomized study was performed in a homogeneous population of patients with elective coronary artery bypass. None of the 57 patients in the study population had a documented history of ulcer disease. There were four treatment groups, each with similar demographics (age and sex). Cimetidine-treated group consisted of 15, famotidine-treated group of 18, ranitidine-treated group of 19, and antacid-treated group of 5 patients. There was no hemodynamically significant postoperative gastrointestinal bleeding in any of the patients. When the agents were compared for efficacy of gastric pH control, statistically better pH control was found in the famotidine- and ranitidine-treated groups (P < 0.003) than in the cimetidine-treated group (pH ≤ 4.0) during the 20-hour observation period. Side effects (hematologic and neurological) were noted only in the cimetidine-treated group. The results of this study indicate that in patients in postoperative intensive care, better gastric pH control, and thus prevention of gastric stress ulcers, is achieved with either famotidine or ranitidine rather than cimetidine or antacid.

Gastric tonometry in healthy volunteers

To determine if intraluminal production of CO2 leads to underestimation of gastric intramural pH (pHi) by tonometry. Nonrandomized controlled study. Healthy volunteers. NG tonometers were placed in healthy volunteers. Some of the volunteers (n = 11) were pretreated with ranitidine to prevent secretion of protons into the gastric lumen. Others (n = 13) were untreated (i.e., gastric acid secretion was uninhibited). Gastric pHi was calculated from the arterial (HCO3-) and the tonometrically determined intraluminal PCO2 using the Henderson-Hasselbalch equation. Intraluminal PCO2 was significantly higher in the control group (54 +/- 14 torr [7.2 +/- 1.9 kPa]) than in the ranitidine-treated group (42 +/- 4 torr [5.6 +/- 0.4 kPa], p = .02). Mean gastric luminal pH was 1.9 +/- 0.6 in the control group as compared with 6.7 +/- 0.7 in volunteers treated with ranitidine (p less than .01). Mean calculated gastric pHi was 7.30 +/- 0.11 in the untreated group and 7.39 +/- 0.03 in the ranitidine-treated group (p less than .03). These data suggest that intraluminal production of CO2 from the titration of gastric HCO3- by secreted H+ can result in the underestimation of gastric pHi by tonometry. This phenomenon can be eliminated by H2-receptor blockade.

The influence of a histamine2‐receptor antagonist on the healing of an experimentally induced gastric mucosal lesion

The effect of an H2-receptor antagonist (ranitidine) on the healing of gastric mucosal lesions was studied. Mucosal lesions were induced by a standardized thermo-mechanical technique. The healing process was assessed by macro- and light microscopical examination. It was further evaluated by measurements of the tissue contents of hydroxyproline, a chemical compound reflecting collagen, and of DNA and RNA, reflecting cell frequency and protein synthesis respectively, in the gastric wall from both injured and wound-free areas. The healing process was more rapid in ranitidine-treated animals than in controls. After four weeks, however, the lesion in nine out of ten animals had healed in the ranitidine-treated group and seven of nine rats in the control group. At that time the amounts of hydroxyproline, DNA and RNA did not differ between the two groups. These findings may be taken as an indication that the tissue components of the healed lesions were similar in ranitidine-treated rats and in the saline controls, i.e. the different speeds of the healing process did not seem to influence the components of the scar tissue.

Acid-secretory response and parietal cell sensitivity in patients with duodenal ulcer before and after treatment with sucralfate or ranitidine

Patients with endoscopically proved duodenal ulcer were randomly assigned to treatment with either ranitidine 300 mg at bedtime or sucralfate 2 g twice daily for six weeks. Acid-secretory studies were performed before commencement and 60 to 84 hours after cessation of treatment and endoscopic healing was confirmed. Patients were randomly assigned to receive a constant infusion of secretory stimulant: either, pentagastrin 0.1 and 6.0 μg/kg/hour or histamine acid phosphate 4.0 and 40 μg/kg/hour. Acid output in mmol/hour was measured for basal, low dose, and high dose output. Parietal cell sensitivity (PCS) was calculated as the ratio of low-dose acid output:high-dose acid output and expressed as a percentage. Values before and after treatment were compared and significance of differences was determined using the Student paired t test. There was an apparent decrease in basal acid output, low-dose acid output, high-dose acid output, and PCS with ulcer healing, regardless of treatment or stimulant used. Basal acid output, low-dose acid output, high-dose acid output, and PCS were significantly in the sucralfate-treated group, but only high-dose acid output decreased significantly in the ranitidine-treated group. These differences may be relevant to early duodenal ulcer relapse in ranitidine-treated patients.

Ranitidine Therapy for Gastroesophageal Reflux Disease

In a multicenter, double-blind trial, 284 patients with gastroesophageal reflux disease were evaluated before, during, and after six weeks of treatment with either placebo or ranitidine (150 mg twice daily). Randomization resulted in two comparable patient groups. Ranitidine treatment was significantly more effective than placebo treatment in decreasing the frequency and the severity of heartburn during both daytime and nighttime assessment periods. There was a significant correlation between improvement in heartburn symptoms and decrease in antacid consumption; hence, patients receiving ranitidine consumed significantly fewer antacid tablets. Among patients with endoscopic esophagitis at baseline, the overall change in endoscopic classification after six weeks of therapy was significantly better for the ranitidine-treated patients. The ranitidine-treated group had less evidence of erosions and ulcerations as well as greater healing. There were no differences between the groups with respect to changes in esophageal mucosal sensitivity to acid perfusion or changes in histologic grading of esophageal mucosal biopsy specimens. The ranitidine safety profile was similar to that of previous studies. We conclude that, in patients with gastroesophageal reflux disease, ranitidine therapy, 150 mg twice daily, markedly reduced the heartburn symptoms of reflux disease and significantly improved the endoscopic appearance of the esophageal mucosa.

Effects of intravenous administration of ranitidine hydrochloride to the pregnant rat in organogenesis period

The effects of ranitidine hydrochloride, a histamine H2-receptor antagonist, on development and general behavior of F1 generation of Crj: CD (SD) rats were examined. Ranitidine hydrochloride was intravenously administered once daily from day 7 to 17 of gestation at dose levels of 5, 15 and 40 mg/kg in base weight respectively. Two-thirds of females were killed on day 20 of gestation to examine the development of fetuses, the remaining females were allowed to litter naturally and the postnatal development of the offsprings was observed. Tachypnea, prone position and transient tremor were observed for approximately 15 from 30 seconds directly after an intravenous administration of ranitidine hydrochloride in the dose of 40 mg/kg, which were probably induced by a rapid fall in blood pressure. During the gestation period, there occurred a slight depression of the maternal body weight gain in the ranitidine-treated groups. At the stage of lactation, the body weights of dams showed slightly lower levels than control and their liver weights of dams were also inclined to decrease in 15 and 40 mg/kg groups. In the observation of the fetuses, there were no significant differences between the control and ranitidine-treated groups concerning fetal growth and development, external, skeletal and internal anomalies in fetuses. In delivery and postpartum observation, no influence of ranitidine administration was observed on the litter size, mortality rate of F1 pups. There was a tendency towards decrease in body weight in males of the ranitidine-treated groups. But no significant changes were observed in general behavior, postnatal development, various functions such as reflex response, learning and reproductive performances of F1 generation. Therefore, it was concluded that ranitidine hydrochloride had no effects on fetal and postnatal development, general behavior and various functions of F1 generation at the dose of 40 mg/kg/day or less.