- Evidence-based management of irritable bowel syndrome with diarrhea. [Journal Article]
- AJAm J Manag Care 2018; 24(3 Suppl):S35-S46
- Irritable bowel syndrome (IBS), a complex disorder of the gastrointestinal tract, is characterized by abdominal pain associated with defecation or changes in stool form or frequency. IBS is associate...
Irritable bowel syndrome (IBS), a complex disorder of the gastrointestinal tract, is characterized by abdominal pain associated with defecation or changes in stool form or frequency. IBS is associated with substantial burden, including direct medical costs and indirect costs. Direct costs associated with IBS in the United States have been estimated to exceed $1 billion. However, indirect costs, such as negative effect on quality of life (QOL) and work productivity, are difficult to quantify. There are 3 main subtypes: IBS with prominent diarrhea (IBS-D), IBS with constipation, and IBS with mixed symptoms of both constipation and diarrhea. A number of pharmacologic agents have been used to treat IBS-D despite lack of approval by the FDA for this indication. The pharmacologic agents that are indicated by the FDA for the treatment of IBS-D include alosetron, eluxadoline, and rifaximin. The negative impact of IBS-D symptoms on QOL reported by patients indicate there is an unmet need for therapies that effectively treat and manage the symptoms of this condition. Addressing gaps in treatment is an important priority.
- Medical Therapies in the Pipeline for Irritable Bowel Syndrome. [Journal Article]
- GHGastroenterol Hepatol (N Y) 2017; 13(9):550-552
- Toluene exposure enhances acute and chronic formalin-induced nociception in rats: Participation of 5-HT3receptors. [Journal Article]
- NNeurotoxicology 2017; 63:97-105
- The purpose of this study was to evaluate the effect of acute toluene exposure on formalin (0.5% and 1%)-induced acute and long-lasting nociceptive hypersensitivity in rats. In addition, we sought to...
The purpose of this study was to evaluate the effect of acute toluene exposure on formalin (0.5% and 1%)-induced acute and long-lasting nociceptive hypersensitivity in rats. In addition, we sought to investigate the role of peripheral 5-HT3receptors in the pronociceptive effect of toluene. Toluene exposure (6000ppm) for 30min enhanced 0.5% or 1% formalin-induced acute nociception and long-lasting secondary allodynia and hyperalgesia. In contrast, exposition to toluene for 30min in rats previously injected (six days before) with 1% formalin did not affect long-lasting hypersensitivy. Local peripheral pre-treatment with alosetron (5-HT3receptor antagonist, 10-100 nmol) reduced the pronociceptive effect of toluene in acute nociception and long-lasting secondary allodynia and hyperalgesia. Alosetron (100nmol) was also able to reduce the nociceptive effects of 1% formalin in absence of toluene. Moreover, local peripheral injection of m-CPBG (5-HT3receptor agonist, 300 nmol) enhanced 0.5% formalin-induced acute and long-lasting nociception in air- and toluene-exposed rats. Alosetron (10nmol) blocked the pronociceptive effects of m-CPBG (300nmol) on 0.5% formalin-induced acute and long-lasting hypersensitivity in rats exposed to toluene. Alosetron (at 10nmol) did not modify formalin-induced nociceptive behaviors. Finally, local peripheral pre-treatment with methiothepin (non-selective 5-HT receptor antagonist, 1.5nmol), did not affect the pronociceptive effect of toluene on 1% formalin-induced acute and long-lasting hypersensitivity. Our data demonstrate that acute exposure to toluene has pronociceptive effects in formalin-induced acute nociception and long-lasting hypersensitivity. Our data suggest that this pronociceptive effect depend on activation of peripheral 5-HT3, but not methiothepin-sensitive 5-HT, receptors.
- The place of eluxadoline in the management of irritable bowel syndrome with diarrhea. [Review]
- TATherap Adv Gastroenterol 2017; 10(9):715-725
- Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder characterized by abdominal pain associated with defecation with altered stool frequency or stool form. The global preva...
Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder characterized by abdominal pain associated with defecation with altered stool frequency or stool form. The global prevalence of IBS ranges from 10% to 15% and total healthcare cost attributable to IBS is significant. Among individuals with IBS, the condition has dramatic effects on health-related quality of life, work and school productivity, and activities of daily living. It may be diagnosed with confidence, based on symptom-based diagnostic criteria, exclusion of alarm features and directed diagnostic testing. Management of IBS typically begins with dietary and lifestyle modifications, progressing to over-the-counter therapies, and then to prescription medications, both approved and nonapproved for IBS. This narrative summarizes the efficacy and safety of three US Food and Drug Administration (FDA)-approved prescription therapies for IBS with diarrhea (IBS-D), with a focus on the most recently marketed agent, eluxadoline, and its role in the treatment IBS-D.
- Review of Rifaximin: Latest Treatment Frontier for Irritable Bowel Syndrome Mechanism of Action and Clinical Profile. [Journal Article]
- CMClin Med Insights Gastroenterol 2017; 10:1179552217728905
- Irritable bowel syndrome is classified as a functional gastrointestinal disorder with the primary symptom of abdominal pain in conjunction with bloating and bowel movement disorder. It affects up to ...
Irritable bowel syndrome is classified as a functional gastrointestinal disorder with the primary symptom of abdominal pain in conjunction with bloating and bowel movement disorder. It affects up to 15% of the world's population. Among its subtypes, the most common is diarrhoea predominant. However, the current treatment options for diarrhoea-predominant irritable bowel syndrome have had not very promising results; most, such as antispasmodics, only provide partial symptomatic relief. Treatment with antidepressants and alosetron (a 5HT3 antagonist) has shown the most promise to date. The latest drug to be approved for the treatment of irritable bowel syndrome-diarrhoea is rifaximin, which was approved in May 2015. It is a minimally absorbed antibiotic that is used to change the gut microbiota. Small intestinal bacterial overgrowth is one of the causes suggested for irritable bowel syndrome, particularly for the diarrhoea-predominant type. There are various methods for detecting bacterial overgrowth, the simplest of which is breath tests. Rifaximin has been shown to be of benefit to these patients.
- Palladium-Catalyzed Dehydrogenative Difunctionalization of Aminoalkenes with Aminals as Oxidants and Electrophiles. [Journal Article]
- OLOrg Lett 2017 Sep 01; 19(17):4600-4603
- A novel palladium-catalyzed aminomethylamination of aminoalkenes with an aminal, functioning not only as an aminomethylation reagent but also as an oxidant, was developed. This direct and operational...
A novel palladium-catalyzed aminomethylamination of aminoalkenes with an aminal, functioning not only as an aminomethylation reagent but also as an oxidant, was developed. This direct and operationally simple protocol provides a fundamentally novel and unique approach toward the synthesis of 2-(2-aminoethyl)indoles and 2-(2-aminoethyl)pyrrolidines, which are important building blocks in synthetic organic chemistry. The unity of this method was highlighted by the rapid synthesis of Alosetron, a drug used for the treatment of irritable bowel syndrome.
- Pharmacological Approach for Managing Pain in Irritable Bowel Syndrome: A Review Article. [Review]
- APAnesth Pain Med 2017; 7(2):e42747
- CONCLUSIONS: Conventional pain managing drugs are in general not suitable for treating IBS pain. Medications that target the GI tract and peripheral nerves have better therapeutic profiles by limiting adverse CNS effects.
- SYMPOSIUM REPORT: An Evidence-Based Approach to IBS and CIC: Applying New Advances to Daily Practice: A Review of an Adjunct Clinical Symposium of the American College of Gastroenterology Meeting October 16, 2016 • Las Vegas, Nevada. [Journal Article]
- GHGastroenterol Hepatol (N Y) 2017; 13(2 Suppl 1):1-16
- Many nonpharmacologic and pharmacologic therapies are available to manage irritable bowel syndrome (IBS) and chronic idiopathic constipation (CIC). The American College of Gastroenterology (ACG) regu...
Many nonpharmacologic and pharmacologic therapies are available to manage irritable bowel syndrome (IBS) and chronic idiopathic constipation (CIC). The American College of Gastroenterology (ACG) regularly publishes reviews on IBS and CIC therapies. The most recent of these reviews was published by the ACG Task Force on the Management of Functional Bowel Disorders in 2014. The key objective of this review was to evaluate the efficacy of therapies for IBS or CIC compared with placebo or no treatment in randomized controlled trials. Evidence-based approaches to managing diarrhea-predominant IBS include dietary measures, such as a diet low in gluten and fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs); loperamide; antispasmodics; peppermint oil; probiotics; tricyclic antidepressants; alosetron; eluxadoline, and rifaximin. Evidence-based approaches to managing constipation-predominant IBS and CIC include fiber, stimulant laxatives, polyethylene glycol, selective serotonin reuptake inhibitors, lubiprostone, and guanylate cyclase agonists. With the growing evidence base for IBS and CIC therapies, it has become increasingly important for clinicians to assess the quality of evidence and understand how to apply it to the care of individual patients.
- Effects of intranasal treatment with slow (GYY4137) and rapid (NaHS) donors of hydrogen sulfide in lipopolysaccharide-induced airway inflammation in mice. [Journal Article]
- PPPulm Pharmacol Ther 2017; 45:170-180
- We have investigated the effects of slow (GYY4137) and rapid (NaHS) hydrogen sulfide (H2S) releasing donors in lipopolysaccharide (LPS)-induced airway inflammation in mice. LPS (0.1 mg/ml) in 60 μl P...
We have investigated the effects of slow (GYY4137) and rapid (NaHS) hydrogen sulfide (H2S) releasing donors in lipopolysaccharide (LPS)-induced airway inflammation in mice. LPS (0.1 mg/ml) in 60 μl PBS was administered by the intranasal (i.n.) route and control group received vehicle, whereas the subgroups of mice were treated with i.n. GYY4137 or NaHS. The tracheal reactivity, inflammatory cell count in bronchoalveolar lavage (BAL) fluid and lung histopathology were evaluated in all groups 48 h after LPS/PBS applications. 5-Hydroxytryptamine (5-HT)-induced contraction response in isolated tracheas was enhanced after LPS treatment but carbachol response was not altered. Incubation with atropine (10-6 M), 5-HT2Areceptor antagonist ketanserin (10-9-10-7 M) and 5-HT3receptor antagonist alosetron (10-8and 10-7 M) prevented 5-HT-induced hyperreactivity whereas 5-HT4receptor antagonist GR113808 (10-7 M, 10-6 M) did not have any effect in LPS-treated group. Electrical field stimulation (EFS) of isolated tracheas elicited frequency-dependent contractile response, which was not altered by LPS treatment alone but was enhanced in the presence of 5-HT (10-9-10-4 M). This data indicated that 5-HT2Aand 5-HT3receptors, and acetylcholine released from cholinergic nerves were contributing to 5-HT-induced hyperreactivity in the present experiments. The increase in neutrophil count along with cytokine (IL-1β, TNF-α) levels in bronchoalveolar lavage (BAL) fluid and histopathological changes like paranchymal inflammation and interalveolar thickening were determined in LPS-treated mice. H2S production in lung homogenates were determined by the methylene blue assay, and found to be similar in both LPS and control groups. The experiments conducted after i.n. treatment with H2S donors has shown that only GYY4137 (1 mg/kg) inhibited 5-HT-induced hyperreactivity, and both GYY4137 and NaHS (1 mg/kg) prevented the neutrophil increase in BAL fluid in LPS-induced airway inflammation. IL-1β increase in BAL fluid was abolished by both GYY4137 and NaHS treatments whereas TNF-α levels remained unchanged. Furthermore, GYY4137 treatment did not have any effect in LPS-induced changes of lung pathology whereas NaHS prevented the paranchymal inflammation. The different H2S releasing pattern of these donors may explain the difference of their effects in this model. Compounds that provide stable H2S levels via local application may be a new therapeutic approach in airway inflammation.
New Search Next
- Efficacy and safety of 5-hydroxytryptamine 3 receptor antagonists in irritable bowel syndrome: A systematic review and meta-analysis of randomized controlled trials. [Review]
- PlosPLoS One 2017; 12(3):e0172846
- CONCLUSIONS: Ramosetron, cilansetron, ondansetron, and alosetron are effective for treating non-constipated IBS and IBS-D. Our systematic review found rare serious adverse events.