Current Trends in Treatment for Acid-Dependent Diseases: Clinical Efficacy and Safety of Rabeprazole

Aim. A comparative review of the rabeprazole properties vs. other PPIs, its efficacy and safety in treatment for aciddependent diseases.Key points. Rabeprazole provides a rapid proton pump blockade in parietal cells due to its high dissociation constant (pKa). A lower rabeprazole metabolic dependence on cytochrome P-450 enzyme system renders its antisecretory effect predictable and reduces the risk of interactions with other drugs metabolised through this system. A faster antisecretory effect and higher acid-suppressive activity of rabeprazole determine its better clinical efficacy in treatment for such acid-dependent diseases as gastroesophageal reflux disease and peptic ulcer. This makes rabeprazole (Pariet) a preferred drug in course and maintenance therapies for acid-dependent diseases, as well as in H. pylori eradication.Conclusion. The rabeprazole properties of high acid suppression potential, persistent antisecretory effect from first day of therapy, non-enzymatic metabolism and pleiotropic action determine its high efficacy in treatment for a wide range of acid-dependent diseases at a minimal risk of drug interaction.

Effects of Cola anomala (K. Schum.) water/ethanol pods extract on the inflammation and intestinal secretion in lipopolysaccharide-induced diarrhea

Diarrhea is one of the leading causes of death among children in low and low-middle income countries and the management of this pathology is still a problem in these regions. The water/ethanol extract of the pods of Cola anomala (KEO) has been shown to possess antimicrobial and antidiarrheal effects in Shigella flexneri-induced diarrhea, but whether KEO is active on the toxemic part of this diarrhea is unknown. This study was undertaken to evaluate the effects of KEO on the intestinal secretion and inflammation induced by intraperitoneal administration of lipopolysaccharide (LPS). KEO obtained by maceration in water/ethanol (1:1) was administered orally (25, 50 and 100 mg/kg of body weight) against LPS-induced diarrhea in mice. The mass of feces, the intestinal nitric oxide (NO) and prostaglandin (PGE2) contents as well as myeloperoxidase (MPO) activity were assessed. KEO was also tested on LPS-induced enteropooling in rats. In this experiment, the intestinal fluid and its electrolytes (Na+, K+ and Cl-) contents were determined as well as NO, PGE2, TNF-α and IL-1β levels in the small intestine homogenate. Indomethacin (5 mg/kg) was used as reference drug. KEO significantly (p < 0.001) reduced stools excretion, NO content and MPO activity in intestine but did not affect PGE2 in LPS-induced diarrhea. On the enteropooling model, KEO showed no effect on the intestinal fluid and electrolyte excretion, PGE2, TNF-α and IL-1β contents, but significantly (p < 0.05) reduced the NO production. This study suggests that KEO does not have antisecretory effect, but has anti inflammatory activities. It can be concluded that the anti-toxemic effect of KEO contributes less to its antidiarrheal activity in infectious diarrhea.

Differentiated approach to the choice of PPI in a patient with GERD in the practice of an outpatient (with a clinical case)

Gastroesophageal reflux disease (GERD) is a widespread disease. Despite the fact that different approaches to the treatment and prevention of recurrence of this disease have been developed, the number of patients with GERD, including refractory form of GERD, is only increasing. To date, well studied and described the possible links of the pathogenesis of this disease, which predetermine certain approaches to the treatment of various variants of GERD. Effective drug therapy of GERD includes the appointment of proton pump inhibitors (PPI). However, doctors are often faced with the problem of ineffective use of PPI in patients with GERD or with the so-called refractory form of GERD. The reasons for the ineffectiveness of therapy of PPI can be associated not only with the pathogenetic features of GERD and therapy, but also with the patient himself. Daily pH monitoring allows to determine the cause of the ineffectiveness of the treatment of PPI if the patient complies with all prescriptions. With ineffective acid suppression in the stomach, it is necessary to increase the dose of PPI or replace it. It is important to prescribe both effective and safe means of correcting the symptoms of GERD, and also take into account the possibility of long-term maintenance of remission when using them. These requirements are met by PPI, created in the form of enantiomers, having an improved pharmacokinetic profile. An example of this differentiated approach is dexlansoprazole, a law-converting monoisomer of lansoprazole with double release technology and the ability to maintain the antisecretory effect for a long time, which appeared relatively recently on the Russian pharmaceutical market. The use of this drug is presented in a clinical case.

Deprescribing and Optimal Selection of Proton Pump Inhibitors (Contributions of the 26th United Russian Gastroenterology Week)

Aim. Presentation of the Forum “Deprescribing and optimal selection of proton pump inhibitors” held in Moscow on 29 September 2020 during the 26th United Russian Gastroenterology Week.Key points. The Forum was aimed at discussing issues associated with improving the proton pump inhibitor (PPIs) therapy in treatment and prevention of acid-related diseases and upper gastrointestinal tract (GIT) disorders induced by non-steroidal anti-inflammatory drugs (NSAIDs) and antiplatelet medications. Deprescribing is considered to be an effective strategy of a motivated reduction of the PPI dosage, duration of therapy and the patient’s transfer from a regular to on-demand intake regimen. The choice of PPI may condition an optimal therapy for acid-related diseases.Conclusion. PPIs prevail in therapies for acid-related diseases and NSAID-induced upper GIT lesions. PPI deprescribing should be a strategy of choice if medically indicated. A non-enzymatic metabolism, high acid suppression, stable antisecretory effect from day 1 of therapy and cytoprotective action justify the application of rabeprazole (Pariet®) for optimising therapies for acid-related diseases and implementing the deprescribing strategy.

Cytoprotective and antisecretory properties of methanolic extract of Distemonanthus benthamianus (Caesalpiniaceae) stem bark on acute gastric ulcer in rats

ObjectivesIn African traditional medicine, Distemonanthus benthamianus (Caesalpiniaceae) is used to treat many diseases including gastric ulcers. We evaluated in this study, the cytoprotective and antisecretory properties of the methanolic extract of the stem bark of this plant using different technics of gastric lesion induction.MethodsCytoprotective and antisecretory activity of the methanolic extract of D. benthamianus stem bark was evolved through six methods of gastric lesion induction in experimental Wistar male rats (150–200 g): (1) gastric lesions induced by HCl/ethanol, (2) gastric lesions induced by Indomethacin- HCl/ethanol, (3) gastric lesion induced by Indomethacin, (4) gastric lesions induced by Pylorus ligation, (5) gastric lesions induced by histamine-Pylorus ligation, (6) gastric lesions induced by carbachol-Pylorus ligation. Mucus and gastric mucosal ulceration were evaluated. pH, gastric volume, and acidity were quantified in all pylorus ligation induction technics. Nitric oxide (NO) level was determined in indomethacin induced gastric ulcers.ResultsAt different doses (125, 250 and 500 mg/kg), extract reduced significantly the ulcer index. In all models used, that is 100.00% with HCl/ethanol; 100.00% with HCl/ethanol/indomethacin; 95.70% with Indomethacin; 74.79% with pylorus ligation, 95.94% histamine-Pylorus ligation, 99.54% carbachol-Pylorus ligation at the highest dose of 500 mg/kg. The lesion formation reduces in all the methods used followed by a significant increase of mucus production. The pylorus ligation technic revealed that the extract has an antisecretory activity.ConclusionsThe methanolic extract of D. benthamianus stem bark has both cytoprotective and antisecretory effects. This extract exerts its antisecretory effect trough cholinergic and histaminergic pathways.

STUDY OF ANTISECRETORY ACTIVITY OF DINITRATE 2-PHENYL-9-DIETHYLAMINOETHYLimidazo[1,2-A] BENZIMIDAZOLE BY METHOD OF CONTINUOUS PERFUSION OF RATS’ STOMACHS

Nowadays, effective pharmacotherapy of acid-dependent gastrointestinal diseases remains an urgent problem of modern gastroenterology. In this regard, the search for new drugs with a pronounced antisecretory activity still continues; their aim is to keep the control over the acid production safe and effective.The aim of this study was an experimental study of the antisecretory activity of the substance and the finished dosage form (FDF) of dinitrate 2-phenyl-9-diethylaminoethylimidazo[1,2-a]benzimidazole.Materials and Methods. The study of antisecretory activity was performed by method of a continuous perfusion of rats’ stomachs. The studied substance was administered at the doses of 3, 10 and 30 mg/kg, and the FDF – at the doses of 13 and 26 mg/kg. The substance of Ranitidine (Sigma Аldrich, USA) was used as a reference object in the study of the antisecretory activity of the substance under study, and Ranitidine (Hemofarm A.D., Serbia) was used as a reference drug in the study of the FDF. In order to determine the stimulated secretion immediately before collecting the samples of the perfusate, histamine was administered subcutaneously at the dose of 5 mg/kg. The content of hydrochloric acid in the perfusate was determined by titration of a 0.01 M sodium hydroxide solution. The acidity value was determined in terms of the debit-hour of hydrochloric acid.Results and discussion. The obtained experimental data showed that the studied substance at the dose of 30 mg/kg decreased the basal hydrochloric acid secretion by 54%, which significantly exceeded the antisecretory effect of Ranitidine by 1.8 times. The FDF at the dose of 26 mg/kg, statistically reliable relative to the control and the group treated with Ranitidine, decreased the basal secretion of gastric juice by 33%. The substance at the dose of 30 mg/kg reliably suppressed the stimulated secretion of hydrochloric acid by 80%, while Ranitidine did it by 56%. The FDF at the dose of 26 mg/kg decreased the histamine-stimulated secretion by 66%, and Ranitidine did it by 52%, which was statistically reliable.Сonclusions. The studied substance and its dosage form are more effective in suppressing basal activities and exceed the anisecretory activity of H2 -histamine antagonists of Ranitidine under the conditions of the secretion stimulated by histamine.