Peculiarities of gastric acid production and motility in non-ulcer dyspepsia

The dissertation is devoted to the study of individual characteristics of gastric acid production and of the motor-evacuatory function of the upper gastrointestinal tract in patients with different clinical forms of non-ulcer dyspepsia. The work carries out a comprehensive dynamic examination of patients using 24-hour pH-metry, esophagogastroduodenoscopy with biopsy of the gastric mucosa and determination of Helicobacter pylori infection, as well as pharmacological tests. On the basis of the data obtained, differentiated treatment regimens are evaluated using prokinetics and proton pump inhibitors (omeprazole and rabeprazole), including as part of seven-day eradication regimens in H.pylori-associated non-ulcer dyspepsia.

The practical significance of the work is related to the development of a method for the comprehensive examination of patients and a scheme for analysing 24-hour pH-metry suitable for outpatient settings, as well as to the substantiation of an individual approach to prescribing antisecretory drugs, taking into account the characteristics of acid production and motor disorders. The results have been introduced into the practice of gastroenterological departments and are used in the educational process at the Department of Propaedeutics of Internal Diseases and Gastroenterology.

Relevance of the problem.

Non-ulcer dyspepsia (ND) is a highly prevalent pathology of the gastrointestinal tract (GIT). Dyspeptic complaints are reported both by patients with organic diseases and by those with functional disorders; therefore, establishing the diagnosis of ND requires a wide range of diagnostic measures. The substantial prevalence of ND and the marked decrease in quality-of-life indicators in patients with this pathology necessitate the development of criteria for individualised therapy based on the characteristics of the key components of pathogenesis. At present, in the pathogenesis of ND the leading role is assigned to the impairment of the motor-evacuatory function of the upper GIT, while gastric acid production is also of considerable importance. The influence of Helicobacter pylori (H.pylori) as a pathogenic agent in the onset of ND is not recognised by all researchers; however, there are studies that note improvement in the clinical condition of patients after the elimination of Helicobacter infection [85, 87, 94, 100, 107, 145, 146, 147, 151, 153].

The diagnostic techniques developed, which provide comprehensive examination of the patient, have made it possible to obtain reliable information on several parameters under study, thereby shortening the time required for patient examination and reducing economic costs. In our work we used the domestic device "Gastroscan-24" (AGM-24, "Istok-system" company, Fryazino, Russia), which performs pH monitoring at three different levels of the upper GIT for 24 hours or more.

The currently used regimens for ND include three principal groups of drugs: prokinetics, antisecretory agents, and antacids. However, thanks to the discovery of the mechanisms of action of the proton pump and to the development and introduction into clinical practice of new antisecretory drugs—substituted benzimidazole derivatives, that is, proton pump inhibitors (PPIs), which make it possible to achieve a stable and prolonged antisecretory effect—it has become possible to abandon the use of antacids in the treatment of patients with ND. The new PPIs suppress the final stage of hydrochloric acid synthesis by blocking H+,K+-ATPase. This advantageously distinguishes PPIs from other antisecretory agents, which block only one of the many mechanisms of hydrochloric acid secretion [27, 46, 56, 83, 91, 98].

It has been noted that in 60-70% of cases ND is associated with H.pylori, and according to the Maastricht Consensus adopted in 2000, the therapy of H.pylori-associated diseases includes first-line therapy (a three-component anti-Helicobacter regimen) and second-line therapy (a four-component regimen).

For the eradication of H.pylori, regimens are currently used that include two antibacterial drugs and a proton pump inhibitor [89]. It has been noted that PPIs, owing to their pronounced antisecretory action, which provides pH values close to neutral [51, 107, 134, 122], possess bactericidal activity against H.pylori and also enhance the effect of antibacterial drugs. These features of PPIs have made it possible to include them specifically in eradication regimens as antisecretory agents.

Aim of the study.

The aim of our study was to investigate the individual characteristics and to evaluate clinical criteria of changes in gastric acid production and the state of gastric motor activity in patients with different forms of ND, as well as methods of pharmacological correction of the identified disorders.

Objectives of the study:

1. To investigate the characteristics of intragastric acid production and the alkalinizing capacity of the antrum in patients with ND.

2. To investigate the characteristics of gastric and duodenal motility in patients with ND.

3. To assess the level of H.pylori infection in patients with ND.

4. To evaluate the effectiveness (onset rate, duration, and magnitude of the antisecretory effect) of the PPIs rabeprazole (Pariet) and omeprazole (Losec MUPS) and of prokinetics (Motilium) in different forms of ND.

5. To perform a comparative assessment of the dynamics of dyspeptic complaints and the rate of their relief during treatment with omeprazole and rabeprazole.

Scientific novelty of the work.

The scientific novelty is determined primarily by the fact that for the first time a comprehensive dynamic examination of patients with ND has been carried out. The state of the gastric mucosa (esophagogastroduodenoscopy, forceps biopsy of the gastric mucosa), the level of hydrochloric acid secretion (24-hour pH-metry), the degree of H.pylori infection of the gastric mucosa, and the influence of certain groups of drugs (antisecretory agents, prokinetics, anti-Helicobacter drugs) on the course of non-ulcer dyspepsia were studied. On the basis of the work performed, differentiated treatment regimens have been evaluated, taking into account the characteristics of GIT motility and the secretory and microbiological state of the mucosa in non-ulcer dyspepsia. A comparative assessment has been made of the antisecretory effect and the influence on the dynamics of dyspeptic syndrome and the rate of elimination of complaints of the new-generation proton pump inhibitor rabeprazole (Pariet), as well as of the new pharmaceutical form of omeprazole (Losec MUPS), as components of regimens for the treatment of different forms of ND, along with the degree of H.pylori eradication in patients with H.pylori-associated ND.

Practical significance of the work.

The relationship between disorders of motor and secretory function of the stomach and H.pylori dissemination with the pathogenesis of non-ulcer dyspepsia has been established, and treatment regimens have been evaluated with consideration of the clinical forms of non-ulcer dyspepsia. The necessity of assessing the individual characteristics of 24-hour intragastric acid production when prescribing antisecretory drugs as part of a comprehensive treatment regimen for patients with non-ulcer dyspepsia has been demonstrated.

The investigation performed revealed the characteristics of motor-evacuatory function of the upper GIT and acid production in the stomach in different forms of ND. The results of the study led to the conclusion that the use in patients with H.pylori-associated ND of 7-day eradication regimens based on the new-generation proton pump inhibitors omeprazole (Losec MUPS) and rabeprazole (Pariet), and including amoxicillin and clarithromycin as the antibacterial component, makes it possible to achieve high rates of relief of dyspeptic complaints and to durably improve the subjective condition of the patients. Compared with the omeprazole-based regimen, the rabeprazole-based regimen appears to be the most advantageous for clinical practice, since this regimen is highly effective and at the same time allows shortening the duration of ND treatment to one week and reducing treatment costs due to the comparatively lower cost of rabeprazole relative to omeprazole.

A technique for performing pharmacological tests in ND patients has been developed, which makes it possible to take into account not only the chronometric aspects when prescribing antisecretory agents, but also the individual characteristics of acid production in each specific patient.

A method for the comprehensive examination of ND patients and a scheme for analysing 24-hour pH-metry, convenient for use in outpatient settings, have been proposed.

Ways of implementing the results of the study.

The proposed ND treatment regimen has been introduced into the practice of the gastroenterological departments of the GKG MVD RF and the TsKB MPS RF. The results obtained have been incorporated into the work of the Department of Propaedeutics of Internal Diseases and Gastroenterology of MGMSU and are used in lectures, seminars, and practical classes with students and listeners of certification courses of the FPDO MGMSU.

Main propositions of the dissertation submitted for defence.

1. There are reliable differences in the levels of 24-hour intragastric acid production and in the motor-evacuatory capacity of the smooth musculature of the stomach and duodenum, as well as variants of their combinations, in different forms of ND.

2. Between the indicators of the antisecretory action of the two studied drugs—omeprazole (Losec MUPS) and rabeprazole (Pariet)—there are reliable differences in favour of rabeprazole (Pariet). Nevertheless, both drugs possess a pronounced antisecretory effect and make it possible to maintain an intragastric pH>4 on average for up to 15 hours (Pariet).

3. Eradication therapy regimens based on omeprazole (Losec MUPS) and rabeprazole (Pariet) used in the treatment of H.pylori-associated ND have shown comparably high results with respect to the rate of relief of dyspeptic syndrome and the degree of H.pylori eradication. However, the best results were obtained with the use of rabeprazole (Pariet).

4. One-week therapy for each of the three forms of ND, including rabeprazole (Pariet) 20 mg twice daily in the regimen, and—when H.pylori is detected—anti-Helicobacter therapy with clarithromycin 500 mg twice daily and amoxicillin 1000 mg twice daily, makes it possible not only to rapidly achieve a positive clinical effect and morphological dynamics, but also to shorten the duration of ND treatment, thereby reducing treatment costs and improving the patients' quality of life.