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https://www.readbyqxmd.com/read/28448580/sildenafil-normalizes-bowel-transit-in-preclinical-models-of-constipation
#1
Sarah K Sharman, Bianca N Islam, Yali Hou, Margaux Usry, Allison Bridges, Nagendra Singh, Subbaramiah Sridhar, Satish Rao, Darren D Browning
Guanylyl cyclase-C (GC-C) agonists increase cGMP levels in the intestinal epithelium to promote secretion. This process underlies the utility of exogenous GC-C agonists such as linaclotide for the treatment of chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C). Because GC-C agonists have limited use in pediatric patients, there is a need for alternative cGMP-elevating agents that are effective in the intestine. The present study aimed to determine whether the PDE-5 inhibitor sildenafil has similar effects as linaclotide on preclinical models of constipation...
2017: PloS One
https://www.readbyqxmd.com/read/28423917/management-of-opioid-induced-constipation-in-hospice-patients
#2
Leah Sera, Mary Lynn McPherson
BACKGROUND: Constipation is a common symptom in patients with advanced disease taking opioids. Opioid-induced constipation (OIC) is commonly treated with laxatives and stool softeners. Recently, newer agents have come to market which broaden options for patients in whom first-line therapies are not effective. OBJECTIVE: To determine what pharmacologic regimens are currently used in hospice programs to prevent and treat OIC, whether those regimens have changed with the introduction of newer agents and evidence discouraging the use of docusate, and whether hospice programs are standardizing the management of OIC...
January 1, 2017: American Journal of Hospice & Palliative Care
https://www.readbyqxmd.com/read/28396341/bioactivity-of-oral-linaclotide-in-human-colorectum-for-cancer-chemoprevention
#3
David S Weinberg, Jieru E Lin, Nathan R Foster, Gary J Della'Zanna, Asad Umar, Drew K Seisler, Walter K Kraft, David M Kastenberg, Leo C Katz, Paul J Limburg, Scott A Waldman
Guanylate cyclase C (GUCY2C) is a tumor suppressing receptor silenced by loss of expression of its luminocrine hormones guanylin and uroguanylin early in colorectal carcinogenesis. This observation suggests oral replacement with a GUCY2C agonist may be an effective targeted chemoprevention agent. Linaclotide is an FDA approved oral GUCY2C agonist formulated for gastric release, inducing fluid secretion into the small bowel to treat chronic idiopathic constipation. The ability of oral linaclotide to induce a pharmacodynamic response in epithelial cells of the colorectum in humans remains undefined...
April 10, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28357122/therapeutically-targeting-guanylate-cyclase-c-computational-modeling-of-plecanatide-a-uroguanylin-analog
#4
Andrea Brancale, Kunwar Shailubhai, Salvatore Ferla, Antonio Ricci, Marcella Bassetto, Gary S Jacob
Plecanatide is a recently developed guanylate cyclase-C (GC-C) agonist and the first uroguanylin analog designed to treat chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C). GC-C receptors are found across the length of the intestines and are thought to play a key role in fluid regulation and electrolyte balance. Ligands of the GC-C receptor include endogenous agonists, uroguanylin and guanylin, as well as diarrheagenic, Escherichia coli heat-stable enterotoxins (ST)...
April 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28238460/-irritable-bowel-syndrome-with-constipation-and-functional-constipation-in-adults-treatment-part-2-of-2
#5
F Mearin, C Ciriza, M Mínguez, E Rey, J J Mascort, E Peña, P Cañones, J Júdez
In this Clinical practice guide we examine the diagnostic and therapeutic management of adult patients with constipation and abdominal discomfort, at the confluence of the spectrum of irritable bowel syndrome and functional constipation. Both fall within the framework of functional intestinal disorders and have major personal, health and social impact, altering the quality of life of the patients affected. The former is a subtype of irritable bowel syndrome in which constipation and altered bowel habit predominate, often along with recurring abdominal pain, bloating and abdominal distension...
February 23, 2017: Atencion Primaria
https://www.readbyqxmd.com/read/28236087/gastrointestinal-pharmacology
#6
Miguel Saps, Adrian Miranda
There is little evidence for most of the medications currently used to treat functional abdominal pain disorders (FAPDs) in children. Not only are there very few clinical trials, but also most have significant variability in the methods used and outcomes measured. Thus, the decision on the most appropriate pharmacological treatment is frequently based on adult studies or empirical data. In children, peppermint oil, trimebutine, and drotaverine have shown significant benefit compared with placebo, each of them in a single randomized clinical trial...
2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28162021/guanylate-cyclase-c-as-a-target-for-prevention-detection-and-therapy-in-colorectal-cancer
#7
Allison A Aka, Jeff A Rappaport, Amanda M Pattison, Takami Sato, Adam E Snook, Scott A Waldman
Colorectal cancer remains the second leading cause of cancer death in the United States, and new strategies to prevent, detect, and treat the disease are needed. The receptor, guanylate cyclase C (GUCY2C), a tumor suppressor expressed by the intestinal epithelium, has emerged as a promising target. Areas covered: This review outlines the role of GUCY2C in tumorigenesis, and steps to translate GUCY2C-targeting schemes to the clinic. Endogenous GUCY2C-activating ligands disappear early in tumorigenesis, silencing its signaling axis and enabling transformation...
May 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28116777/pharmacological-treatment-for-antipsychotic-related-constipation
#8
REVIEW
Susanna Every-Palmer, Giles Newton-Howes, Mike J Clarke
BACKGROUND: Antipsychotic-related constipation is a common and serious adverse effect, especially for people taking clozapine. Clozapine has been shown to impede gastrointestinal motility, leading to constipation, and has been reported in up to 60% of patients receiving clozapine. In rare cases, complications can be fatal. Appropriate laxatives should be prescribed to treat constipation in people taking antipsychotics, but there is a lack of guidance on the comparative effectiveness and harms of different agents in this population...
January 24, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28116695/update-on-the-management-of-chronic-constipation
#9
REVIEW
Jenna Koliani-Pace, Brian E Lacy
Chronic constipation (CC) is a highly prevalent disorder encountered by health care providers of all specialties. The diagnosis can be confidently made by taking a careful history, evaluating for warning signs and symptoms, performing an examination, including a digital rectal exam, and using the Rome IV criteria. Treatment should begin at the first visit; most patients require few diagnostic tests to make, or confirm, the diagnosis of CC. Assuming that the patient has persistent symptoms of constipation, despite using traditional therapy (fiber, osmotic agents), then patients should be offered one of the newer treatments, rather than repeating prior treatments, which is a common practice...
March 2017: Current Treatment Options in Gastroenterology
https://www.readbyqxmd.com/read/28070176/advances-in-ibs-2016-a-review-of-current-and-emerging-data
#10
Philip S Schoenfeld
Irritable bowel syndrome (IBS) is characterized by chronic intermittent abdominal pain and associated diarrhea (IBS-D), constipation (IBS-C), or both. IBS can significantly impact patient function and quality of life. The diagnosis of IBS is based on the presence of characteristic symptoms, the exclusion of concerning features, and selected tests to exclude organic diseases that can mimic IBS. The pathophysiology of IBS remains incompletely understood, and new contributing factors have been identified over the past decade...
August 2016: Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/27888862/functional-and-motor-gastrointestinal-disorders
#11
Fermín Mearin, Enrique Rey, Agustín Balboa
This article discusses the most interesting presentations at Digestive Disease Week, held in San Diego, in the field of functional and motor gastrointestinal disorders. One of the most important contributions was undoubtedly the presentation of the new Rome IV diagnostic criteria for functional gastrointestinal disorders. We therefore devote some space in this article to explaining these new criteria in the most common functional disorders. In fact, there has already been discussion of data comparing Rome IV and Rome III criteria in the diagnosis of irritable bowel syndrome, confirming that the new criteria are somewhat more restrictive...
September 2016: Gastroenterología y Hepatología
https://www.readbyqxmd.com/read/27815136/phenylquinoxalinone-cftr-activator-as-potential-prosecretory-therapy-for-constipation
#12
Onur Cil, Puay-Wah Phuan, Jung-Ho Son, Jie S Zhu, Colton K Ku, Niloufar Akhavan Tabib, Andrew P Teuthorn, Loretta Ferrera, Nicholas C Zachos, Ruxian Lin, Luis J V Galietta, Mark Donowitz, Mark J Kurth, Alan S Verkman
Constipation is a common condition for which current treatments can have limited efficacy. By high-throughput screening, we recently identified a phenylquinoxalinone activator of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel that stimulated intestinal fluid secretion and normalized stool output in a mouse model of opioid-induced constipation. Here, we report phenylquinoxalinone structure-activity analysis, mechanism of action, animal efficacy data in acute and chronic models of constipation, and functional data in ex vivo primary cultured human enterocytes...
April 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/27688649/guanylyl-cyclase-c-signaling-axis-and-colon-cancer-prevention
#13
REVIEW
Amanda M Pattison, Dante J Merlino, Erik S Blomain, Scott A Waldman
Colorectal cancer (CRC) is a major cause of cancer-related mortality and morbidity worldwide. While improved treatments have enhanced overall patient outcome, disease burden encompassing quality of life, cost of care, and patient survival has seen little benefit. Consequently, additional advances in CRC treatments remain important, with an emphasis on preventative measures. Guanylyl cyclase C (GUCY2C), a transmembrane receptor expressed on intestinal epithelial cells, plays an important role in orchestrating intestinal homeostatic mechanisms...
September 28, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27633684/peptide-therapeutics-and-the-pharmaceutical-industry-barriers-encountered-translating-from-the-laboratory-to-patients
#14
REVIEW
John Rafferty, Hema Nagaraj, Alice P McCloskey, Rawan Huwaitat, Simon Porter, Alyaa Albadr, Garry Laverty
Peptides are receiving increasing interest as clinical therapeutics. These highly tunable molecules can be tailored to achieve desirable biocompatibility and biodegradability with simultaneously selective and potent therapeutic effects. Despite challenges regarding up-scaling and licensing of peptide products, their vast clinical potential is reflected in the 60 plus peptide-based therapeutics already on the market, and the further 500 derivatives currently in developmental stages. Peptides are proving effective for a multitude of disease states including: type 2 diabetes (controlled using the licensed glucagon-like peptide-1 receptor liraglutide); irritable bowel syndrome managed with linaclotide (currently at approval stages); acromegaly (treated with octapeptide somatostatin analogues lanreotide and octreotide); selective or broad spectrum microbicidal agents such as the Gram-positive selective PTP-7 and antifungal heliomicin; anticancer agents including goserelin used as either adjuvant or monotherapy for prostate and breast cancer, and the first marketed peptide derived vaccine against prostate cancer, sipuleucel-T...
2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27486521/persistent-constipation-and-abdominal-adverse-events-with-newer-treatments-for-constipation
#15
Irene Sonu, George Triadafilopoulos, Jerry D Gardner
BACKGROUND: Clinical trials of several new treatments for opioid-induced constipation (OIC), chronic idiopathic constipation (CIC) and constipation-predominant irritable bowel syndrome (IBS-C) have focused on differences between subjects relieved of constipation with placebo and active treatment. Patients and clinicians however, are more interested in the probability these treatments provide actual relief of constipation and its associated symptoms. METHODS: We searched the medical literature using MEDLINE and Cochrane central register of controlled trials...
2016: BMJ Open Gastroenterology
https://www.readbyqxmd.com/read/27331917/modern-management-of-irritable-bowel-syndrome-more-than-motility
#16
REVIEW
Jan Tack, Tim Vanuytsel, Maura Corsetti
In the treatment of irritable bowel syndrome (IBS), loperamide seems efficacious for diarrhea and ispaghula for constipation, while musculotropic spasmolytics may relieve abdominal pain. Antidepressants were found to be efficacious for abdominal pain, but their tolerance may be problematic and the therapeutic effect varied largely between trials. While meta-analyses suggest efficacy of probiotics as a group, the quality of the trials is often suboptimal and there is large variability. Lubiprostone, a chloride channel activator, and linaclotide, a guanylyl cyclase-C agonist, showed favorable effects on multiple symptoms in IBS with constipation...
2016: Digestive Diseases
https://www.readbyqxmd.com/read/27230827/clinical-practice-guideline-irritable-bowel-syndrome-with-constipation-and-functional-constipation-in-the-adult
#17
REVIEW
Fermín Mearin, Constanza Ciriza, Miguel Mínguez, Enrique Rey, Juan José Mascort, Enrique Peña, Pedro Cañones, Javier Júdez
In this Clinical Practice Guideline we discuss the diagnostic and therapeutic approach of adult patients with constipation and abdominal complaints at the confluence of the irritable bowel syndrome spectrum and functional constipation. Both conditions are included among the functional bowel disorders, and have a significant personal, healthcare, and social impact, affecting the quality of life of the patients who suffer from them. The first one is the irritable bowel syndrome subtype, where constipation represents the predominant complaint, in association with recurrent abdominal pain, bloating, and abdominal distension...
June 2016: Revista Española de Enfermedades Digestivas
https://www.readbyqxmd.com/read/27165279/management-of-the-clinical-issue-of-constipation-with-abdominal-complaints-in-adults-a-national-survey-of-primary-care-physicians-and-gastroenterologists
#18
Enrique Rey Díaz-Rubio, Juan José Mascort Roca, Enrique Peña Forcada, Pedro Cañones Garzón, Jose María Tenias Burillo, Francisco Javier Júdez Gutiérrez
Irritable bowel syndrome and functional constipation represent a relevant and common health issue. However, real-world clinical practice includes patients with constipation who may or may not have other abdominal complaints (pain, bloating, abdominal discomfort) with variable frequency. The goal of the present study was to obtain information on the workload entailed by patients with constipation and associated abdominal complaints, predominant clinical behaviors, education needs, and potential daily practice aids both in Primary Care and gastroenterology settings...
June 2016: Revista Española de Enfermedades Digestivas
https://www.readbyqxmd.com/read/27158549/review-of-efficacy-and-safety-of-laxatives-use-in-geriatrics
#19
Manhal Izzy, Anju Malieckal, Erin Little, Sury Anand
AIM: To study the efficacy and safety of pharmacological treatment of constipation in geriatrics. METHODS: PubMed, MEDLINE, google scholar, and Ovid were searched to identify human studies performed on the use of laxatives in elderly with constipation, which were conducted between January 1990 and January 2013 using the specified keywords. Controlled studies that enrolled geriatric patients with a diagnosis of constipation and addressed the efficacy and/or the safety of pharmacological treatments were included...
May 6, 2016: World Journal of Gastrointestinal Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27134665/new-and-emerging-therapies-for-the-treatment-of-irritable-bowel-syndrome-an-update-for-gastroenterologists
#20
REVIEW
Amy E Foxx-Orenstein
Irritable bowel syndrome is a functional bowel disorder with gastrointestinal symptoms (e.g. abdominal pain, straining, urgency, incomplete evacuation, nausea, and bloating) that occur alongside bowel function alterations (i.e. constipation, diarrhea, or both). Patients with irritable bowel syndrome may also experience comorbid anxiety and depression. Irritable bowel syndrome is common, with a prevalence estimated between 3% and 28%, affecting patient health and quality of life. Patients with moderate or severe irritable bowel syndrome generally seek medical care, whereas those with milder symptoms may choose self-management...
May 2016: Therapeutic Advances in Gastroenterology
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