Rational Medical Therapy of Functional GI Disorders
Kevin W. Olden in Handbook of Functional Gastrointestinal Disorders, 2020
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).
Pathophysiology and Management of Diabetic Gastropathy
Emmanuel Opara in NUTRITION and DIABETES, 2005
Cisapride, a prokinetic agent with a mixed 5-HT3 antagonist and 5-HT4 agonist activity, has been extensively evaluated in those patients with gastrointestinal dysmotility and gastroesophageal-reflux disease. Its effects on gastric emptying are likely due to stimulation and coordination of antral-pyloro-duodenal motility and possibly due to changes in gastric-outlet resistance.130–135 Although cisparide has been shown to accelerate gastric emptying in multiple studies, the correlation between improved gastric emptying and control of patient symptoms has remained less convincing.136–139 Reports of arrythmias and sudden death related to prolongation of the QT interval resulted in significant restrictions on the routine use of cisapride in the United States.140–142 Most of these adverse events occurred in the context of concomitant systemic diseases or drugs that could prolong cisapride metabolism.
Emesis
Michael JG Farthing, Anne B Ballinger in Drug Therapy for Gastrointestinal and Liver Diseases, 2019
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.
Mucoadhesive thermoreversible formulation of metoclopramide for rectal administration: a promising strategy for potential management of chemotherapy-induced nausea and vomiting
Published in Pharmaceutical Development and Technology, 2020
Mahmoud M. El-Sonbaty, Hatem R. Ismail, Alaa A. Kassem, Ahmed M. Samy, Mohamed A. Akl
Metoclopramide hydrochloride (MCP HCl) is a dopamine receptor antagonist. It is a potent prokinetic agent commonly used for the management of gastrointestinal (GI) disorders. Also, it is an effective antiemetic agent in the management of nausea and vomiting that related to migraine, cancer chemotherapy, pregnancy, or post-surgery (Zaki et al. 2007; Zuheir et al. 2013). Although MCP HCl is an inexpensive medication, there was no significant difference between it and Ondansetron in the prevention of postoperative vomiting (Isazadehfar et al. 2017). MCP HCl gains a renewed research interest regard it's in vitro and in vivo chemosensitizing properties. MCP HCl has a short half-life of 5 ± 1 h which required frequent administration (Henzi and Tramèr 2003; De Oliveira et al. 2012). However, oral forms of MCP HCl are rapidly absorbed in the GIT, it isn’t appropriate for children or elderly patients, as they are often vomited out before systemic absorption. In addition, MCP HCl oral bioavailability ranges from 32% to 98% due to extensive first-pass metabolism (Abdel-Rahman et al. 2009). The difficulty of repeated oral dosing and maintaining parenteral access for extensive periods besides poor patient compliance of injection route due to associated pain make it necessary and of the greatest need for an alternative to the oral or parenteral route is required. In this regard, the rectal delivery of MCP HCl-LS seems to be an attractive approach.
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.
Comparative pharmacokinetic evaluation of extended release itopride HCl pellets with once daily tablet formulation in healthy human subjects: a two treatment, four period crossover study in fasted and fed condition
Published in Drug Development and Industrial Pharmacy, 2019
Muhammad Iqbal Nasiri, Rabia Ismail Yousuf, Muhammad Harris Shoaib, Fahad Siddiqui, Faaiza Qazi, Kamran Ahmed, Sohail Anwer, Kamran Zaheer
However, the test product (Itopride HCl 150 mg ER pellets) meeting the criteria for bioequivalence to the reference (Ganaton 150 mg OD Tablet) product in fed condition. Table 7 shows comparative mean PK log-transformed parameters of test versus reference product. Geometric mean ratios (90% CI), exhibited no considerable differences in the Cmax, AUC0–t and AUC0–∞ between the two formulations i.e. 0.997 to 1.064, 0.984–1.042, and 0.991–1.052, respectively and their values were within the bioequivalence range (0.8–1.25) (Table 7). Yoon et al. assessed the effect of food on the bioavailability of ER Itopride formulation and reported insignificant change in the oral bioavailability, although food related delayed absorption of ER Itopride formulation was reported [11]. Metoclopramide is also a prokinetic agent used for the treatment of gastroparesis, dyspepsia and reflux etc. [34]. A crossover study (4-way) was conducted in male volunteers (16) and insignificant food effect was reported for absorption of sustained release Metoclopramide formulations [35].
Related Knowledge Centers
- Abdominal Pain
- Bloating
- Constipation
- Gastrointestinal Tract
- Heartburn
- Irritable Bowel Syndrome
- Vomiting
- Nausea
- Motility
- Gastrointestinal Disease