M.Sechenov First Moscow State Medical University of the Ministry of Health of Russia (Sechenov University) RABEPRAZOLE IN THE TREATMENT OF DUODENAL ULCER DESEASE AND FUNCTIONAL DYSPEPSIA The review aims to provide a contemporary view of the pathogenesis and treatment of the most common duodenum diseasesduodenal ulcer disease (DUD) and functional dyspepsia (FD).Due to its unique structure and functions, the duodenum that anatomically represents the initial section of the small intestine differentiates itself from others. The prevalence of DUD is declining in many Western countries due to the widespread introduction of effective anti-Helicobacter therapy and a significant decrease in the prevalence of H pylori infection. However, the ideas about the poly-biological nature of DUD persists and additional risk factors continue to be studied. DUD is manifested by pain/burning feeling in the epigastric region, as well as by symptoms such as early satiety, epigastric filling after eating in the absence of obvious organic changes in the digestive system. The diagnosis of FD is based on the Rome IV criteria. The duodenum plays an important role in its pathogenesis (disorders of gastric accommodation, motor and visceral hypersensitivity). Most patients with FD have microscopic signs of inflammation of the mucous membrane of the postbulbar part of the duodenum -an increased amount of intraepithelial lymphocytes, eosinophils, and signs of increased permeability of the mucous membrane. In all likelihood, these changes are provoked by infection and / or nutritional factors, as well as by exposure to hydrochloric acid. Proton pump inhibitors (prokinetics in postprandial distress syndrome) form the basis of treatment of peptic ulcer and epigastric pain syndrome; all patients with DUD and dyspepsia syndrome infected with H. pylori receive antihelicobacter therapy. Rabeprazole that is characterized by a long and powerful effect and minimal interaction with the cytochrome 2C19 system stands out from the proton pump inhibitors. Conclusion: acid aggression plays a very important role in the pathogenesis of duodenal ulcers diseases and FD; proton pump inhibitors form the basis for the treatment of such patients both in the form of monotherapy and as part of eradication regimens.
Резюме Проблеме сочетания двух или нескольких функциональных заболеваний (ФЗ) органов пищеварения посвящено немало публикаций и крупных популяционных исследованиях. В материалах Римского консенсуса IV термин «перехлест ФЗ» применяется по отношению к случаям сочетаний в пределах одного органа и подчеркивается, что по современным представлениям синдром раздраженного кишечника в любой его форме следует скорее рассматривать как «континуум различных клинических вариантов». В качестве возможного объяснения существования перехлеста ФЗ рассматривают нарастание степени висцеральной гиперчувствительности, расширение зоны гиперчувствительности, прогрессирование моторных нарушений. При сочетании ФЗ число и интенсивность жалоб увеличиваются, снижаются показатели качества жизни, растет среднее число сопутствующих соматических симптомов и принимаемых препаратов. В составе сочетаний ФЗ чаще встречается функциональная диспепсия. При этом постпрандиальный дистресс-синдром чаще сочетается с синдромом раздраженного кишечника с запором, синдром эпигастральной боли-с синдромом раздраженного кишечника с диареей, а также с эндоскопически негативной гастро-эзофагеальной рефлюксной болезнью. Помимо пищевых компонентов, особую роль в развитии висцеральной сенситизации отводят персистенции воспаления после перенесенной инфекции, воздействию глютена, нарушениям кишечного микробиома, условиям депрессии и тревоги. При сочетании двух или нескольких ФЗ органов пищеварения целесообразно выбирать методы лечения, направленные на устранение действия внутрипросветных раздражителей и формирование «болевой памяти». Применяются препараты, нормализующие кишечную перистальтику и секрецию, выбор которых определяется клиническим вариантом течения, пробиотики, а также средства, влияющие на состояние центральной нервной системы. При сочетании двух или нескольких ФЗ органов пищеварения целесообразно выбирать препараты, которые воздействуют на их общие патогенетические механизмы. Ключевые слова: функциональные заболевания органов пищеварения, висцеральная гиперчувствительность, сочетание функциональных заболеваний, «болевая память», гистамин
Introduction. Constipation is a derangement of the motor, secretory and/or evacuation function of the colon. The same symptoms are recorded in at least 20% of the population in the developed countries – as those occurring sporadically or for a long period.Basic content. The secretory function of the colon significantly affects stool consistency and its free movement. The secretion increases by 8–10 times in the presence of local mechanical irritation. Intestinal mucus is produced by colonic goblet cells. The frequency, time of defecation and stool consistency is in large part determined by the motor function of the colon. The relation of various types of contraction varies depending on the main function – propulsion or mixing. Rhythmic phasic contractions in the colon generate a pendular movement with slow propulsion of the contents and absorption of water. The tonic contractions enhance the mixing effect of weak rhythmic contractions. The propulsive contractions are specifically attributed to the lower gastrointestinal tract and occur spontaneously. They occur quite regularly, from 2 to 10 times a day, and ensure the propulsion of intestinal contents over great distances in the colon. When reaching the sphincter area, such wave causes its relaxation by mechanisms of descending inhibition. The dietary regime and adequate intake of carbohydrates with various chain lengths, including dietary fiber, as well as flavonoids and other components that modify peristaltic activity and secretion, play an important role in the regulation of intestinal secretion and peristalsis. The drugs enhancing intestinal secretion and peristalsis, such as bisacodyl and sodium picosulfate, are also used to treat constipation. These substances hydrolyse into bis-(p-hydroxyphenyl)-pyridyl-2-methane in the intestine, which, upon contact with the receptors in colonic mucosa, stimulates propulsive activity and increases intestinal secretion. The selective action of sodium picosulfate is confined to the colon.Conclusion. Pharmacological and non-pharmacological treatments for constipation are aimed at maintaining and enhancing the natural propulsive contractions of the colon and intestinal secretion.
Aim. This review aims to describe the nature of changes in the intestinal microbiota in irritable bowel syndrome (IBS) and provide a pathogenetic justification of the feasibility of a therapeutic impact on microbiota. General findings. An important aspect of the interaction of intestinal bacteria with the “host” cells is their contact with pattern recognition receptors of enterocytes, dendritic cell receptors, as well as a transcellular transport of antigens in the region of Peyer’s patches. The area of interaction of intestinal bacteria and the human body is not limited to the intestines. Intestinal bacteria demonstrate a significant humoral effect due to signalling molecules, some of which exhibit neurotransmitter properties. The study of the bacterial cross-feeding for various species, i.e. mutual use of nutrient substrates produced by bacteria of various species, is of a great interest. The development of a lowactivity inflammation in IBS can partly be explained by the increased interaction of flagellin with the corresponding receptor, as well as the influx of excess bacteria from the small intestine. The majority of studies on IBS have demonstrated the predominance of intestinal bacteria with pro-inflammatory potential (Enterobacteriaceae) and the lack of bacteria with a pronounced anti-inflammatory, antimicrobial and enzymatic action (Lactobacillus and Bifidobacterium), as well as increased mucus degradation. Similar changes are observed in inflammatory bowel diseases. Reduced microbial diversity increases susceptibility to intestinal infections and parasitoses, including those caused by protozoa conditionally pathogenic for adults, such as Blastocystis hominis hominis, Dientamoeba fragilis, Giardia lamblia. With the help of nutrition correction, the use of probiotics and functional foods containing certain probiotic strains, plant fibres (primarily psyllium) and, in some cases, nonabsorbable antibiotics, a positive effect can be achieved in a significant number of IBS patients. Recent works have shown that clinical improvement is accompanied by a change in the composition of the intestinal microbiota.Conclusion. For the pathogenetic treatment of irritable bowel syndrome, the use of non-drug treatment is justified, such as diet optimization and prescription of plant fibres and probiotic bacterial strains. The positive effect of such an approach is largely determined by modification of the intestinal microbiota composition. This opens up prospects for a further, more targeted impact on the intestinal microbiome.
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