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Gastro-oesophageal reflux disease
Published in Samar Razaq, Difficult Cases in Primary Care, 2021
Cases of severe GERD will require further assessment and management. A prokinetic agent, such as domperidone, used in combination with an H2-receptor antagonist, such as ranitidine, is common practice in the pharmacological management of GERD in children. PPIs have been shown to be very effective in the management of GERD and its complications. Omeprazole is licensed for use in children over the age of 1 year who have severe ulcerating oesophagitis. It is available in a multiple-unit pellet system that can be administered after mixing in fruit juice or yogurt. Surgical treatment, such as fundoplication and the placement of a percutaneous gastrojejunostomy tube, is reserved for the most severe and refractory cases.
Rational Medical Therapy of Functional GI Disorders
Published in Kevin W. Olden, Handbook of Functional Gastrointestinal Disorders, 2020
Richard M. Sperling, Kenneth R. McQuaid
Patients who are unresponsive to dietary fiber can be extremely difficult to manage. In these cases, constipation may arise from one of two pathophysiological processes: colonic inertia or rectosigmoid outlet delay (235). Before proceeding with further therapeutic trials, it is helpful to distinguish between these. A radioopaque-marker colon transit study is helpful both to confirm that constipation is truly present and to document colonic inertia. Patients with colonic inertia may respond to a trial of an osmotic laxative or the prokinetic agent cisapride. The diagnosis of outlet delay is based on the clinical history and may be confirmed by defecography or anal motility. This entity may be better approached with nonpharmacological means such as biofeedback and pelvic-floor retraining. These are reviewed in detail elsewhere (236).
Emesis
Published in Michael JG Farthing, Anne B Ballinger, Drug Therapy for Gastrointestinal and Liver Diseases, 2019
Gareth J Sanger, Paul LR Andrews
Vomiting in this setting may be unaffected by the gastric prokinetic agent and 5-HT4 receptor agonist cisapride,58 but is reduced or abolished by 5-HT3 receptor antagonism.37 In addition, improvement in pruritus by 5-HT3 receptor antagonism was also noted in one patient with terminal uraemia37 and in others with cholestasis.59 A causal relationship between 5-HT and the symptoms of emesis and pruritis in patients with uraemia has similarities to the 5-HT3 receptor mechanism in the aetiology of emesis in cancer patients receiving cytotoxic therapy, and with the symptoms of pruritis in cholestatic patients. It is suggested60 that the different combinations of emesis and/or pruritis are partly dependent on the source of 5HT but mostly dependent on the generation of other sensory nerve irritants in a disease-specific manner. Thus, the main action of the 5-HT3 receptors is to sensitize the nerve endings to excitatory actions of other substances.61 The expression of 5-HT3 receptor function is, therefore, dependent on the accessibility of a particular visceral afferent nerve (within the gut for emesis or skin for pruritis) to pathological amounts of 5-HT and other excitatory substances such as histamine, substance P.
Gastroparesis syndromes: emerging drug targets and potential therapeutic opportunities
Published in Expert Opinion on Investigational Drugs, 2023
Le Yu Naing, Matthew Heckroth, Prateek Mathur, Thomas L Abell
Mosapride is a selective 5-hydroxytryptamine type 4 (5-HT4) receptor agonist and 5-HT3 receptor antagonist. It is a prokinetic agent mostly used for gastroparesis, functional dyspepsia, gastroesophageal reflux, and it improves delayed gastric emptying. It is mostly used in Asian countries and South America for functional dyspepsia and is not currently available in the US. The Japan Mosapride Mega-Study (JMMS) in 2012 showed that a two-week treatment of mosapride significantly improved gastric stasis and epigastric pain[44]. A recent meta-analysis showed that mosapride was superior to placebo in improving gastric emptying time in patients with diabetic gastroparesis, but there was no statistically significant difference between mosapride and domperidone. The efficacy of mosapride combined with domperidone or mecobalamin was higher than mosapride alone[45]. However, another meta-analysis showed no statistically significant effect of mosapride on functional dyspepsia compared to placebo[46]. A randomized controlled trial of mosapride added to chronic hepatitis C treatment with pegylated interferon α-2b and ribavirin showed that the mosapride added group had total and distal gastric motility improvement in solid phase gastric emptying half-times within four weeks after the therapy compared to the control group.
Effect of anti-reflux treatment on gastroesophageal reflux-associated chronic cough: Implications of neurogenic and neutrophilic inflammation
Published in Journal of Asthma, 2020
Norihisa Takeda, Masaya Takemura, Yoshihiro Kanemitsu, Hisatoshi Hijikata, Kensuke Fukumitsu, Takamitsu Asano, Yusuke Yamaba, Motohiko Suzuki, Eiji Kubota, Takeshi Kamiya, Takashi Ueda, Akio Niimi
The present study focused on sensitization of esophageal-bronchial interconnecting neural pathways (5,26). In an animal model using guinea pigs, esophageal stimulation by hydrochloric acid caused neurogenic inflammation in the airways where neurokinin A (NK-A)-like substances were released and induced plasma extravasation (27,28). In agreement with these studies, SP levels were elevated in the sputum of chronic cough patients with co-existent acid reflux (9) and in the plasma of patients with both asthmatic and non-asthmatic cough (8). To address the relationship between SP and cough, SP protein levels were measured in plasma and sputum collected from the responder and poor responder groups before and after anti-reflux treatment. To the best of our knowledge, the present study is the first to demonstrate that the anti-reflux therapy resulted in lowered SP protein levels in plasma and sputum in the responder group than in the poor responder group (Figure 3A and B). These findings support the hypothesis that stimulation by acid influx into the lower esophagus causes neurogenic inflammation and increases SP release in the airways, which then sensitizes cough reflex neural pathways (27,28). PPI therapy, which suppresses acid reflux, may alleviate neurogenic inflammation and thereby reduce SP levels in the respiratory tract. However, the kinds of effects exerted by the prokinetic agent used in combination are not known.
Duodenal inflammation: an emerging target for functional dyspepsia?
Published in Expert Opinion on Therapeutic Targets, 2020
Lucas Wauters, Grace Burns, Matthias Ceulemans, Marjorie M Walker, Tim Vanuytsel, Simon Keely, Nicholas J Talley
Acotiamide is a mixed presynaptic muscarinic (M)-receptor-antagonist and cholinesterase inhibitor, leading to increased availability of acetylcholine in the synaptic cleft with improved gastric emptying and accommodation [129]. This first in class prokinetic agent was specifically developed for FD and showed beneficial effects in PDS patients from Japan [134] and Europe [135]. Moreover, preclinical studies have shown that acotiamide exerted effects on stress-impaired gastric function via decreased expression of stress-related genes in the brain stem of rats [136]. Treatment with 5-HT-1A receptor agonists (azapirones) such as buspirone and tandospirone also results in anxiolytic effects and improved accommodation, with a significant reduction of both overall and PDS-type symptoms in FD patients [137]. Thus, neuronal receptors and targets may overlap for gastric dysmotility and gut–brain interactions (Figure 2). We have shown that the effect of stress on the GI-tract involved increased permeability and immune activation [109] and that duodenal hyperpermeability in FD patients correlated with gastric emptying to solids, suggesting that gastric dysmotility can be secondary to duodenal pathology [138]. Whether targeting mucosal inflammation would not only improve symptoms and duodenal pathology but also gastric emptying and accommodation is subject of ongoing research.