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Serotonin Modulation of Gastrointestinal Motility
Published in T.S. Gaginella, J.J. Galligan, SEROTONIN and GASTROINTESTINAL FUNCTION, 2020
Marcello Tonini, Fabrizio De Ponti
The findings from human studies resemble those obtained in conscious dogs, where neither tropisetron nor granisetron affected liquid or solid emptying delayed by an α2-adrenoceptor agonist.188 In the same canine model of gastroparesis, SC-49518 was found to enhance gastric emptying by a 5-HT4 receptor mechanism.189 In good agreement, in dogs with a gastric fistula, the gastric emptying of a liquid test meal was accelerated by the 5-HT4 receptor agonist renzapride, but unaffected by granisetron.190 The only situation where 5-HT3 receptor antagonists were found to accelerate gastric emptying in dogs was after lipid-induced slowing of gastric emptying.191 Interestingly, cilansetron and ondansetron, but not granisetron, were more effective after intraduodenal than after intravenous administration, as if they were acting in part locally on the mucosal sensory afferents of the duodenum (see also the section on small bowel transit below).
Fecal Incontinence: Office-Based Management
Published in Laurence R. Sands, Dana R. Sands, Ambulatory Colorectal Surgery, 2008
Tisha Lunsford, Jonathan Efron
After an appropriate work-up has excluded organic disease, the first step in treatment is the initiation of bulking agents such as psyllium or methylcellulose (Metamucil® or Citrucel®), partially hydrolyzed guar gum (Benefiber®), and previously attapulgite (Kaopectate®). Due to concerns of high lead levels, the makers of Kaopectate have recently reformulated the drug so that its primary ingredient is bismuth salicylate (the primary ingredient in Pepto Bismal®). When using bulking agents, modifying stool consistency is the primary goal because formed stool is much easier to control than loose stool. The formulations of psyllium, methylcellulose and guar gum are available in both powder and tablet form. Tablets, in a recommended dose of one to two tablets twice daily, are preferred in the case of loose or diarrheal stools, as fiber may procure more benefit as a bulking agent when taken with only sips of a noncaffeinated clear beverage. Bismuth salicylate may also be used; however, unlike the fiber formulations, this medication should only be used for temporary relief of symptoms. Pharmacotherapy with agents such as loperamide, diphenoxylate/atropine, alosetron, clonidine, cholestyramine, colestipol, probiotics, tincture of opium, and amytriptyline are usually reserved for patients with more persistent diarrhea that does not respond to conservative bulking agents. Intuitively, the subsequent decreased stool frequency produced by these agents should lessen the frequency of incontinent episodes. Applications and dosing guidelines for the aforementioned pharmacologic agents are outlined in Table 5. However, special concerns may arise in patients with IBS-Diarrhea (IBS-D) predominant as conservative fiber therapy may exacerbate abdominal bloating and discomfort and may precipitate poor compliance. If these bothersome symptoms do not abate after 7 days of use, initiation of pharmacotherapy, including loperamide, amytriptyline, probiotics (specifically those that contain Bifidobacterium), alosetron (limited to certified prescribers), or cilansetron (currently in phase III clinical development), may provide more effective relief for the subset of patients with IBS-D (11–17).
How can we develop better antispasmodics for irritable bowel syndrome?
Published in Expert Opinion on Drug Discovery, 2019
Sheyda Ranjbar, Seyed Afshin Seyednejad, Shekoufeh Nikfar, Roja Rahimi, Mohammad Abdollahi
Serotonin (5-HT) is a dominant molecule in GI, exhibiting characteristics of both an NT and a local hormone. Serotonin plays an important role in modulating GI functions including motility [39]. Seven subtypes of serotonin receptors have been identified but currently, 5-HT3 and 5-HT4 subtypes have the greatest potential in drug discovery approaches especially in gut disorders [40]. 5-HT3 antagonists inhibit the excitatory cholinergic motor neurons and SMCs contraction leading to a decrease in GI motility [41]. Alosetron, the serotonin 5-HT3 receptor antagonist, was approved in 2000 but its use due to lethal adverse effects is now restricted to a refractory subgroup of IBS-D patients [42]. Other drugs in this group ramosetron, cilansetron and ondansetron also reduce discomfort in IBS-D patients [43].