Comparison of clinical and pharmacodynamic features of proton pump inhibitors efficacy in gastroesophageal reflux disease

The aim of review. To present literature data on clinical presentation, pharmacodynamic and economic efficiency of standard dozes of proton pump inhibitors (PPI) for gastroesophageal reflux disease (GERD).Summary. PPI are the most effective pharmaceuticals for treatment of acid-related diseases (ARD). Control of intragastric рН level is the key moment of healing of erosions and ulcers of the upper gastro-intestinal tract, as well as for Н. рylori eradication efficacy. Functional state of stomach mucosa and efficacy of antisecretory therapy was estimated by 24-hour pH or рН-impedance measurement. The standard dozes of PPI provided acid-suppressive effect for up to 18 hs. Already after the first dose intake at 24-hour рН monitoring the stomach рН>3 was recorded for 56,1% (±20,94) of total monitoring time, and рН>4 — for 44,0% (±18,72), that promoted rapid symptom relief. Terms of activation and efficacy of Н+/К+-ATPase inhibitors is determined by pH of the media and pKa values for each pharmaceutical. Intensity of acid-suppressive action of PPI depends on drug metabolic pathways and genetically determined features of cytochrome P450 system. Mutations of CYP2C19 alleles allow to divide the studied patients population into groups of rapid, mediun and slow «metabolizers» that it is necessary to take into account at prescription of the certain drug. At a choice of PPI dose or shift from one PPI to another it is necessary to be guided by the concept of equivalent dosages according to the instruction leaflet on the drug application. Long-term maintenance therapy by PPI for GERD enables reduction of expenses for treatment of disease preserving clinical efficacy.Conclusion. PPI are of the drugs of choice in ARD therapy. PPI should be applied in the least effective doze, including on demand treatment and intermittent treatment. The individual approach to PPI prescription, based on the careful analysis of clinical presentation, as well as on data of esophagogastroduodenoscopy, 24-hour pH or pH plus impedance measurement is required. Reasonable cost to efficacy ratio is no less important

Increase in treatment compliance reveals new options of treatment of gastroesophageal reflux disease

The aim of review. To present update on the causes of insufficient treatment response to proton pump inhibitors (PPI) at gastroesophageal reflux disease (GERD) and to inform on the options of increasing patients’ compliance.Summary. Decline of treatment compliance remains to be one of the principal causes of refractory course of gastroesophageal reflux disease. Existing PPIs have some limitations — necessity of intake strictly before meal and short action period. Dexlansoprazole in double delayed release form allows intake without relation to food intake that allows to increase compliance to treatment.Conclusion. The wide prevalence of GERD dictates necessity of search of new effective agents. Thus one of the principal causes of refractory course of disease is decreased adherence to treatment. Application of new PPI i.e. dexlansoprazole with once per day intake will allow to increase compliance to treatment and to reduce frequency and intensity of symptoms both at erosive esophagitis and non-erosive reflux disease

The role of esophageal and stomach motility disorders in pathogenesis of gastroesophageal reflux disease

The aim of review. To demonstrate that esophageal and stomach motility disorders play one of basic roles in pathogenesis of gastroesophageal reflux disease (GERD).Key points. Gastroesophageal reflux disease is related to the group of acid-related diseases, however esophageal and stomach motility disorders play important role in its development. In patients with GERD disorders of primary and secondary peristalsis of the esophagus, increase of frequency of transient lower esophageal sphincter relaxations and pathologic bile refluxes are common.Conclusion. Numerous studies are devoted to investigation of gastroesophageal reflux disease. The role of motility disorders of the esophagus and the stomach in its pathogenesis, and origin of symptoms of reflux disease and other gastro-intestinal functional diseases, in particular the functional dyspepsia is actively discussed. At upper gastro-intestinal motility disorders application of prokinetics is effective, e.g. itopride hydrochloride, that reduces frequency of transient lower esophageal sphincter relaxations due to decrease of intragastric pressure, activates propulsive stomach motility and eliminates duodenogastric and duodenogastroesophageal refluxes

New opinion on the issue of proton pump inhibitor-refractory gastroesophageal reflux disease

The aim of review. To present up-to-date data on the causes of proton pump inhibitor-refractory gastroesophageal reflux disease (GERD) development.Summary. The prevalence of GERD reaches 20–30% of population, and approximately 40–50% of patients do not respond to standard treatment by proton pump inhibitors (PPI). There is a disorder of the immune response as a disbalance between cellular and humoral components of immunity at GERD, that can be determined as phenotype of macrophages (М1 or М2), and other immune and non-immune cells.Conclusion. For the present moment it becomes clear, that low compliance of patients to PPI treatment, cytochrome Р450 isoenzyme CYP2C19 polymorphism and other known reasons are unable to explain growing number of refractory GERD cases. Therefore, studying of disease at cellular and tissue levels in relation to type of refluxate can disclose new mechanisms of refractory GERD and to increase treatment efficacy

Discussion of gastroesophageal reflux disease issue in World gastroenterological congress abstracts (Shanghai, 2013)

The aim of review. To demonstrate most pressing issues of diagnostics and treatment of gastroesophageal reflux disease (GERD), presented in abstracts of the World gastroenterological congress (China, 2013).Key points. Following tendencies and advances deserve the highest attention: wide introduction of new diagnostics methods of GERD in the last years, e.g.: рН-impedance measurement and high resolution manometry, development of new method of non-invasive GERD diagnostics at primary healthcare stage - GERD Q questionnaire, optimization of GERD treatment and its complications

European Society for Neurogastroenterology and Motility Consensus on Gastroparesis: What Issues Remain Unresolved?

Aim: to analyse the document of the European Society for Neurogastroenterology and Motility consensus on gastroparesis, held in 2020.Key findings. The evaluation of the voting results on the submitted statements of the consensus meeting shows that there is a high level of agreement among the experts regarding the definition of gastroparesis, the main diseases in which it occurs, and the existing diagnostic methods. At the same time, there is a divergence of views regarding the role of individual pathogenetic factors of gastroparesis and their relationship with clinical symptoms, as well as the effectiveness of drugs of various groups and other treatment methods.Conclusion. The pathophysiological mechanisms of gastroparesis and the effectiveness of various treatment methods need further research

Options of improvement of efficacy of gastroesophageal reflux disease treatment by dioctaedric smectite

Aim of investigation. To analyze efficacy of heartburn relief and pathological gastroesophageal reflux (GER) elimination as well as dynamics of endoscopic changes at gastroesophageal reflux disease (GERD) under dioctaedric smectite (Smecta) treatment in standard doze as monotherapy and within complex mode of treatment.Material and methods. Overall 45 case records of GERD patients (25 women and 20 men, mean age 43,06 years) were analyzed. All patients underwent esophagogastroduodenoscopy (EGDS) and 24-hour рН-impedance recording prior to the treatment onset and at the 14-th day of therapy. The first group included patients with erosive esophagitis (EE) of the I–II degree receiving combination of proton pump inhibitors (PPI) and Smecta, the second group included patients with EE, receiving PPI monotherapy, the third group — patients with non-erosive reflux disease (NERD) at Smecta monotherapy.Results. On a background of treatment by PPI + Smecta relief of heartburn was achieved at the 3rd day in 10 (66,7%) patients, at PPI monotherapy — in 4 (26,7%) patients with EE, at monotherapy by Smecta — in 6 (40%) patients. At the 5th day heartburn has been completely relieved in 11 (73,3%), 9 (60%) and 8 (53,3%), and at the 14-th day — in 13 (86,7%), 11 (73,3%) and 12 (80%) patients respectively. In the first group according to upper endoscopy data healing of erosions was confirmed in 13 (86,7%) patients, in the second — in 10 (66,7%). In the third group cessation of catarrhal signs was revealed in 13 (86,7%) patients. According to 24-hour рН-impedance esophageal recording prior at the beginning of therapy pathological acidic, weakly acidic and weakly alkalinic GERs were diagnosed in 34 (75,5%), 18 (40%) and 12 (26,7%) patients in group as a whole respectively. On a background of therapy by PPI + Smecta acidic refluxes have been eliminated in 14 (93%), at PPI monotherapy — in 11 (73%), at Smecta monotherapy — in 100% of patients. In the first group weakly acidic refluxes disappeared in 2 (67%), in the second — in 1 (50%), in the third – in 9 (69%) cases, weakly alkaline refluxes: in 4 (80%), in 2 (40%) and in 100% of cases respectively.Conclusions. Addition of Smecta in treatment mode at erosive form of GERD essentially increases treatment response rate, significantly reducing terms of clinical improvement onset. Dioctaedric smectite appears an effective drug as monotherapy of NERD. The chief advantage in treatment of GERD is ability of the drug to stop all reflux types: acidic, weakly acidic, and weakly alkalinic

Cardiac achalasia: modern concepts on etiology, pathogenesis, clinical presentation and diagnostics

The aim of review. To present up-to-date data on etiology, pathogenesis, clinical presentation and diagnostics of cardiac achalasia.Key points. Cardiac achalasia represents primary esophageal motor disease with involvement of myenteric plexus. Basic symptoms of achalasia include dysphagia, regurgitation, chest pain and weight loss. Esophageal manometry which allows to evaluate resting pressure and relaxation phenomenon of the lower esophageal sphincter and peristaltic activity of distal part of the esophagus is the «gold standard» of diagnostics. Genetic, autoimmune and infectious theories are considered for disease etiology.Conclusion. For the present moment pathogenesis, clinical presentation and diagnostics methods of cardiac achalasia are investigated in detail, however etiology of disease remains unknown, despite of centuries-old history. The major attention is drawn to autoimmune theory which requires further investigations

Efficacy of Topical Corticosteroid Monotherapy in Inducing and Maintaining Clinical and Histologic Remission in Adolescent and Adult Patients with Eosinophilic Esophagitis: a Systematic Review and Meta-Analysis

Background: Eosinophilic esophagitis (EoE) is the second most common cause of esophagitis. Topical steroids represent a promising group of drugs for inducing and maintaining clinical and histological remission in these patients.Objective. To evaluate the effectiveness of topical steroids in inducing and maintaining clinical and histological remission in adolescent and adult patients with EoE.Methods. A systematic literature search using defined keywords was performed up to March 20, 2021 in the MEDLINE / PubMed, EMBASE (Excerpta Medica), and Cochrane Central Register of Controlled Trials, ClinicalTrial.gov databases.Results. 390 patients from 5 studies were included in this systematic review with meta-analysis. The meta-analysis showed that topical steroids, compared with placebo, was more effective in inducing (odds ratio (OR) 75.77; 95 % confidence interval (CI): (21.8; 263.41), p < 0.001) and maintaining complete histological remission (OR 103.65; 95 % CI: (36.05; 298.01), p < 0.001) in patients with EoE. Also, topical steroids significantly relieved disease symptoms compared with placebo in inducing and maintaining clinical remission (OR 4.86; 95 % CI: (1.4; 16.86), p = 0.01) and (OR 11.06; 95 % CI: (4.62; 26.45), p < 0.001) respectively.Conclusions. Topical steroids represent an effective group of drugs for inducing and maintaining histologic and clinical remission in adolescent and adult patients with EoE

Systemic immune response at gastroesophageal reflux disease

Aim of investigation. To characterize the systemic immune response at patients various forms of gastroesophageal reflux disease (GERD).Material and methods. Overall 45 patients with GERD and 10 healthy volunteers were included in prospective study. All patients underwent following investigation: taking complaints and past history, detection of GERD risk factors; esophagogastroduodenoscopy and 24-hour рН-impedance recording. Levels of 7 cytokines were determined by flow cytofluorometry: two antiinflammatory: IL-4 and IL-10, three proinflammatory: IL-8, IFN-γ and TNF-α and two cytokines which can demonstrate both anti-inflammatory and proinflammatory activity in relation to conditions (bivalent) — IL-2 and IL-6.Results. Patients with erosive and/or ulcerative esophagitis in comparison to patients with non-erosive reflux disease (NERD), Barret's esophagus and healthy patients had increased expression of proinflammatory cytokines. In patients with Barret's esophagus in comparison to others GERD patients and healthy volunteers hyperproduction of anti-inflammatory cytokines was revealed. TNF-α and IL-8 levels correlated to total number of acidic refluxes and exposition of acidic bolus, while IL-4 and IL-10 level — with total number of weakly alkaline refluxes and exposition of weakly alkaline bolus. High level of IL-8 was associated with increased frequency of relapses of erosive esophagitis within 2 years, despite of carried out therapy.Conclusions. Relation of cytokine levels to the form of GERD was revealed. At erosive and/or ulcerative esophagitis in comparison to NERD and Barret's esophagus production of proinflammatory cytokines IL-8, the IFN-γ and TNF-α prevails, that indicates development of Th1-mediated immune response. At Barret's esophagus expression of anti-inflammatory cytokines IL-4 and IL-10 is increased, that indicates on development of Th2-immune response