scholarly journals Pharmacology of Antispasmodic Drugs Used in Management of Irritable Bowel Syndrome

Doctor Ru ◽  
2021 ◽  
Vol 20 (4) ◽  
pp. 46-54
Author(s):  
Е.N. Kareva ◽  
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Objective of the Review: To describe and compare some pharmacodynamic and pharmacokinetic parameters of antispasmodic drugs used in complex management of irritable bowel syndrome (IBS) in the Russian Federation. Key Points. IBS is a chronic recurrent disease associated with abdominal pain and bowel disorders. The key factors of IBS pathogenesis include intestinal motility disorders and visceral hypersensitivity. Both processes are controlled by endocrine and neural systems. In a target cell, voltage-operated calcium channels mediate neuronal signals for unstriped muscles to contract and for glands to start secreting. Antispasmodic drugs are a group of products that have been used for IBS management for decades. The review describes contemporary idea of molecular mechanisms to control contraction of GIT muscle cells and a comparison of antispasmodic drugs used in complex therapy of IBS in the Russian Federation. Their key pharmacodynamic and pharmacokinetic characteristics are discussed. Conclusion. The fundamental difference of mebeverine (Duspatalin) is its ability to normalise bowel motility in patients with IBS without the need in complete motility suppression. Also, its inability to block muscarinic receptors and stimulate opioid receptors is another advantage in improving the quality of life of patients. Keywords: pharmacodynamics, pharmacokinetics, antispasmodic drugs, therapy of irritable bowel syndrome, mebeverine.

2016 ◽  
Vol 311 (5) ◽  
pp. G777-G784 ◽  
Author(s):  
Michael Camilleri ◽  
Ibironke Oduyebo ◽  
Houssam Halawi

Several chemical and molecular factors in the intestine are reported to be altered and to have a potentially significant role in irritable bowel syndrome (IBS), particularly in IBS with diarrhea. These include bile acids; short-chain fatty acids; mucosal barrier proteins; mast cell products such as histamine, proteases, and tryptase; enteroendocrine cell products; and mucosal mRNAs, proteins, and microRNAs. This article reviews the current knowledge and unanswered questions in the pathobiology of the chemical and molecular factors in IBS. Evidence continues to point to significant roles in pathogenesis of these chemical and molecular mechanisms, which may therefore constitute potential targets for future research and therapy. However, it is still necessary to address the interaction between these factors in the gut and to appraise how they may influence hypervigilance in the central nervous system in patients with IBS.


2021 ◽  
Author(s):  
Jun-wei LIANG ◽  
Wen-jun BAI ◽  
Xiao-yan WANG ◽  
Li-li CHI

Abstract Background:Many studies on long chain non-coding RNAs (lncRNAs) are published in recent years. But the roles of lncRNAs in diarrhea irritable bowel syndrome (IBS-D) are still unclear and should be further examined. The present work focused on determining the molecular mechanisms underlying lncRNAs regulation in IBS-D on the basis of the lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network.Methods:This study collected the mRNAs (GSE36701) expression data within human tissue samples with IBS-D group and normal group based on Gene Expression Omnibus (GEO) database and collected the differentially expressed lncRNAs (DELs) and differentially expressed miRNAs (DEmiRs) based on PubMed.Functional enrichment analysis of DEGs was performed on the DAVID database. Then the interaction network was constructed and visualized using STRING database and Cytoscape.Results: This study identified 3192 DEmRNAs (1437 with up-regulation and 1755 with down-regulation),29 DEmiRs (18 upregulated and 11 downregulated)and 2 DELs(one upregulated and one downregulated) between IBS-D and control samples.Furthermore,we constructed a lncRNA-miRNA-mRNA network through two DELs (lncRNA TUG1 with up-regulation and lncRNA H19 with down-regulation), four DemiRs (hsa-miR-148a-3p,hsa-miR-342-3p,hsa-miR-149-5p with up-regulation and hsa-miR-219a-5p with down-regulation)and 24 DEGs (4 with up-regulation and 20 with down-regulation) with 42 axes. Simultaneously, we conducted functional enrichment and pathway analyses on genes within the as-constructed ceRNA network. According to our PPI/ceRNA network and functional enrichment analysis results, two critical genes were found (BCL2L11 and QKI). Conclusion:In conclusion, the ceRNA interaction axis we identified is a potentially critical target for treating IBS-D.BCL2L11 axis(LncH19-hsa-miR-148a-3p-BCL2L11) may via interaction with PI3K/AKT pathways in IBS-D.Our results shed more lights on the possible pathogenic mechanism in IBS-D using a lncRNA-associated ceRNA network.


2022 ◽  
Vol 2 ◽  
Author(s):  
Rui-Sheng Wang ◽  
Anthony J. Lembo ◽  
Ted J. Kaptchuk ◽  
Vivian Cheng ◽  
Judy Nee ◽  
...  

Background and Aims: Irritable bowel syndrome (IBS), a functional pain disorder of gut-brain interactions, is characterized by a high placebo response in randomized clinical trials (RCTs). Catechol-O-methyltransferase (COMT) rs4680, which encodes high-activity (val) or low-activity (met) enzyme variants, was previously associated with placebo response to sham-acupuncture in an IBS RCT. Examining COMT effects and identifying novel genomic factors that influence response to placebo pills is critical to identifying underlying mechanisms and predicting and managing placebos in RCTs.Methods: Participants with IBS (N = 188) were randomized to three placebo-related interventions, namely, double-blind placebo (DBP), open-label placebo (OLP), or simply trial enrollment without placebo treatment [no placebo (i.e., no pill) treatment control (NPC)], for 6 weeks. COMT rs4680, gene-set, and genome-wide suggestive (p < 10−5) loci effects on irritable bowel symptom severity score (IBS-SSS) across all participants were examined.Results: Participants with IBS homozygous for rs4680 met (met/met) had the greatest improvement across all arms, with significantly greater improvement compared to val/val in DBP (beta (SE), −89.4 (42.3); p = 0.04). Twelve genome-wide suggestive loci formed a gene regulatory network highly connected to EGR1, a transcription factor involved in placebo-related processes of learning, memory, and response to stress and reward. EGR1 gene expression in peripheral blood mononuclear cells (PBMC) was significantly reduced at the endpoint across all treatment arms (log fold-change, −0.15; p = 0.02). Gene-set enrichment analysis returned three genome-wide significant ontology terms (GO:0032968, GO:0070934, and GO:0070937) linked to transcription regulation and GO:0003918 associated with DNA topoisomerase regulation.Conclusion: These results suggest common molecular mechanisms in response to varying forms of placebo that may inform personalized IBS treatment and placebo response prediction.Clinical Trial Registration:ClinicalTrials.gov, Identifier: NCT0280224.


2010 ◽  
pp. 2384-2388
Author(s):  
D.G. Thompson

Case History—A 42 yr old woman presenting with increased bowel frequency, loose stools and urgency after treatment of Campylobacter sp.. Symptoms suggestive of disturbed lower gastrointestinal function without adequate explanation are very common in adults in the Western world, up to 15% of whom experience such symptoms at any one time, although most do not seek medical advice. It is not clear whether the symptoms of those individuals who do seek medical help have a different pathophysiological basis from those who do not, and whether the seeking of medical advice is more an indication of a worried individual than of disturbed gut function....


Author(s):  
Jenny Gordon

The aim of this chapter is to provide nurses with the knowledge to be able to assess, manage, and care for people with the group of conditions often described as functional bowel disorders (FBD)—see definitions below—in an evidence-based and person-centred way. The chapter will provide an overview of the causes and impact of FBDs, before exploring best practice to deliver care, as well as to prevent or to minimize further ill-health. Nursing assessments and priorities are highlighted throughout, and the nursing management of the symptoms and common health problems associated with FBDs can be found in Chapters 16, 23, 24, and 25, respectively. This chapter discusses the group of conditions often described as functional bowel disorders (FBDs). The term ‘functional gastrointestinal disorders’ is also used in the literature, but, for the purpose of this book, the term FBDs will be adopted. This refers to a group of disorders that are characterized by chronic gastrointestinal symptoms that currently have an unknown structural or biochemical cause that could explain those symptoms. Rome III is an internationally agreed set of diagnostic criteria and related information on functional gastrointestinal disorders (Longstreth et al., 2006). It includes six major domains for adults: oesophageal; gastro/duodenal; bowel; functional abdominal pain syndrome; biliary; and anorectal. This chapter will cover the FBDs that specifically relate to chronic abdominal symptoms. General abdominal symptoms include functional dyspepsia, non-cardiac chest pain, which may mimic functional abdominal symptoms, chronic abdominal pain, functional constipation, functional diarrhoea, functional bloating, and irritable bowel syndrome (IBS). The chapter will concentrate on irritable bowel syndrome. Coeliac disease and Crohn’s disease are included: to give an understanding of these disorders, and to differentiate between inflammatory and non-inflammatory conditions; to highlight the impact of the symptoms on the people who suffer from them; and to give an insight into the contribution that effective nursing makes. The amount of research and the number of publications concerning FBDs has risen considerably since the mid 1990s, and has contributed to the increasing legitimacy of these conditions as disorders in their own right and not simply by virtue of exclusion of all other possibilities.


2015 ◽  
Vol 53 (1) ◽  
pp. 65-74
Author(s):  
F. Rusu ◽  
Dan L. Dumitraşcu

Abstract There is little data on the long term evolution of patients with irritable bowel syndrome (IBS) and of associated conditions. We therefore studied the evolution of IBS patients in a single tertiary center during a long interval of time. Methods. We carried out a retrospective study based on the survey of patients records. We analyzed the records of symptoms, therapy, associated diseases, as consigned at follow-up visits for an interval of 4 years in average (2008-2011). Results. A cohort of 114 patients with IBS diagnosed based on Rome III criteria were included (29 men and 85 women), age 19-85 years (mean age: 43.45 years). Urban patients were predominant. The main three symptoms were: abdominal pain, bowel disorders (constipation, diarrhea) and bloating. IBS - constipation (IBS - C) is associated with a favorable course of symptoms (increasing the number of stools, decrease intensity of abdominal pain and bloating) after treatment and IBS - diarrhea (IBS - D) is associated with variable symptoms after treatment (p = 0.031). Using trimebutin or mebeverin in association with other drugs for one month correlates with a favorable evolution of symptoms after treatment and monotherapy is associated with fluctuating symptoms ( p< 0.001). Favorable symptoms are associated with the use of probiotics in combination, but not in monotherapy (p< 0.001). Favorable evolution of symptoms is also associated with the use of anxiolytics in combination. Persistence of symptoms after treatment was correlated with the presence or absence of depression. The absence of depression was correlated with a favorable evolution of symptoms (p = 0.005). IBS-C is associated at limit (marginal significance) with hemorrhoidal disease (p = 0.56). 33 patients (29%) - received monotherapy (trimebutin or mebeverin or probiotics); 81 patients (71%) - received combined therapy: (trimebutin or mebeverin or probiotics) + anxiolytics or proton pump inhibitors (PPI) or nonsteroidal anti-inflammatory (NSAI) or spasmolitics. The most common associated diseases observed in patients with IBS were: depression (27.19%), dyslipidemia (25.43%), hemorrhoidal disease (22.80%) and fibromyalgia (21%). Conclusions. The highest response rate was obtained with trimebutin or mebeverin + anxiolitics + probiotics. The most frequent disease associated with IBS was depression. Other diseases with a high incidence: dyslipidemia, hemorrhoidal disease and fibromyalgia. Further studies are needed to analyze the link between IBS and some associated diseases.


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