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Using Medication Wisely
Published in Melissa G. Hunt, Aaron T. Beck, Reclaim Your Life From IBS, 2022
Melissa G. Hunt, Aaron T. Beck
Linaclotide (Linzess) is a prescription medication that affects the transfer of water and electrolytes across membranes. It ends up making the stool softer and wetter. Unfortunately, linaclotide can sometimes cause severe diarrhea. You also have to drink LOTS of water when you take it, or you might end up quite dehydrated. It should never be taken by children, who can actually die from the dehydration associated with severe diarrhea. Linaclotide can also exacerbate bowel obstructions, which can be dangerous.
Severe functional constipation: Surgery and gastroenterologic collaboration
Published in Alejandra Vilanova-Sánchez, Marc A. Levitt, Pediatric Colorectal and Pelvic Reconstructive Surgery, 2020
Peter L. Lu, Desalegn Yacob, Carlo Di Lorenzo
Traditional pharmacological treatment for children with constipation has included osmotic laxatives, stimulant laxatives, and lubricants [17]. However, newer pharmacological treatments used in adults with constipation and IBS with constipation show promise for children with similar conditions, particularly when abdominal pain limits stimulant laxative use. Lubiprostone is a prostaglandin E1 derivative that promotes intestinal fluid secretion, softening stool and promoting intestinal motility through luminal distention [18]. Several randomized-controlled studies have demonstrated the efficacy and safety of lubiprostone in adults with constipation [19–21]. An open-label study of lubiprostone in children with functional constipation found it to be well tolerated and effective in improving bowel movement frequency, but improvements in abdominal pain were not significant [22]. Linaclotide is a peptide agonist of the intestinal guanylate cyclase-C receptor, which also promotes intestinal fluid secretion. Linaclotide not only softens stool and accelerates intestinal transit, but can also decrease visceral sensitivity in animal models [18,23]. Several randomized-controlled studies in adults have demonstrated improvements in constipation symptoms and abdominal pain [23–25]. Although research is ongoing, no studies have been published yet on the use of linaclotide for children with constipation-predominant IBS, and its use is contraindicated in children younger than 6 years of age because of the risk of severe dehydration.
Irritable Bowel Syndrome
Published in Peter Sagar, Andrew G. Hill, Charles H. Knowles, Stefan Post, Willem A. Bemelman, Patricia L. Roberts, Susan Galandiuk, John R.T. Monson, Michael R.B. Keighley, Norman S. Williams, Keighley & Williams’ Surgery of the Anus, Rectum and Colon, 2019
Constipation in IBS can be approached in much the same way as chronic constipation without the IBS diagnosis (see Chapter 17). Fibre supplementation may improve bowel symptoms in patients with IBS and constipation.40 Linaclotide, a gyanulate cyclase type-C receptor agonist, stimulates intestinal secretion, thereby improving constipation symptoms in patients with IBS (NNT = 6).43
Fabry disease – a multisystemic disease with gastrointestinal manifestations
Published in Gut Microbes, 2022
Some major GI symptoms in patients with FD can be treated with various concomitant drugs that are symptomatically effective. Patients with acute diarrhea can be treated with classical anti-diarrhea medication such as loperamid. By contrast, patients suffering from gastroparesis can benefit from treatments with pro-motility agents, such as metoclopramide, which increase the contractile force and accelerate intraluminal transit.68 Patients suffering from upper GI symptoms may benefit from proton pump inhibitors (e.g. omeprazole) or ondansetron if nausea is present.34 Medication against bloating and flatulence may include the administration of simethicone, which eliminates and prevents foam formation.69,70 Furthermore, linaclotide, which is an oligo-peptide agonist of guanylate cyclase 2C is used to treat IBS with constipation and chronic constipation with unknown cause.71,72 The antispasmodic dicyclomine, which blocks the action of acetylcholine on cholinergic receptors in smooth muscles in the GI tract, is used to treat spasms of the intestine in IBS,73 and might also be of relevance, although it should be used with caution, especially in patients with any unstable cardiac condition.
An update on guanylyl cyclase C in the diagnosis, chemoprevention, and treatment of colorectal cancer
Published in Expert Review of Clinical Pharmacology, 2020
Jeffrey A. Rappaport, Scott A. Waldman
Several potential obstacles to the translation of GUCY2C agonists for chemoprevention are worth noting. While oral GUCY2C agonists have been shown to reduce intestinal polyp burden in mice, it remains an open-ended question if the utility of these agents lies in tumor prevention or tumor therapy. In part, this question remains unanswered due to limitations of colon cancer mouse models, which do not fully recapitulate human disease progression; the most-widely used model, the APCmin/+ mouse, succumbs to disease before adenomas progress to invasive carcinoma. Pathologic reorganization of the epithelium and invasion beyond the basement membrane may make the GUCY2C ligand binding domain inaccessible to peptides in the intestinal lumen. Hence, while oral GUCY2C agonists have the potential to restore cGMP signaling in the colonic epithelium in the early stages of disease, their limited systemic absorption may restrict utility as the disease progresses. An additional obstacle is the relatively common side-effect of diarrhea in patients receiving linaclotide or plecanatide. A recent meta-analysis reported rates of diarrhea ranging from 3.2% to 22%, depending on the study’s definition of diarrhea [81]. This side-effect is consistent with their mechanism of action as anti-constipation agents, and dose-reduction may be a reasonable means of management [81]. Given these obstacles, at-risk patient populations, such as those with a genetic predisposition (i.e. FAP or Lynch syndrome), or a history of previous polyps, may be the best candidates for chemoprevention with GUCY2C agonists.
Recent advances in the pharmacological management of constipation predominant irritable bowel syndrome
Published in Expert Opinion on Pharmacotherapy, 2020
Karolina Niewinna, Anna Zielińska, Jakub Fichna
In 2012 the US Food and Drug Administration approved linaclotide (Linzess™) for the treatment of IBS-C in adults [54]. Linaclotide is a guanylate cyclase type-C (GC-C) agonist with a novel mechanism of action for the treatment of constipation. Both safety and efficacy for the indication of management of IBS-C were established in two double-blind studies. In those studies, patients were randomly assigned to take 290 μg of the drug or placebo for at least 12 weeks. Linaclotide was effective in reducing abdominal pain and increasing the number of complete, spontaneous bowel movements [55,56].