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Safety Pharmacology and the GI Tract
Published in Shayne C. Gad, Toxicology of the Gastrointestinal Tract, 2018
Drugs increasing colonic propulsion and excretion, either to activity on motility or increase fluid content (inhibition of absorption/ increase secretion), can be easily detected [47]. Serotonin and a serotonin3 receptor agonist, 2-methyl-5-HT, dose-dependently increased fecal pellet output in conscious rats. The selective 5-HT3 receptor antagonists GK-128, granisetron, ramosetron, azasetron and ondansetron depressed the increase in fecal pellet output caused by 2-methyl-5-HT. Granisetron and ramosetron dose-dependently reduced the spontaneous excretion of fecal pellets. Croci and Bianchetti [48] showed the effects of several alpha-adrenoceptor antagonists on fecal output and water content in rats. The rat colon appears to be under tonic inhibitory control of prejunctional alpha2-adrenergic receptors, whose blockage by specific antagonists induces fecal excretion. The alpha2A-receptor subtype appears to be the most likely candidate for controlling fecal excretion through inhibition of acetylcholine release.
Different effects of intravenous and local anesthesia in patients undergoing ultrasound-guided radiofrequency ablation of thyroid nodules: a prospective cohort study
Published in International Journal of Hyperthermia, 2022
Shuhang Gao, Yalin Zhu, Mengying Tong, Lina Wang, Shuangsong Ren, Liu Rui, Fang Yang, Zhiqing Lian, Ying Che
The IV group was anesthetized by an anesthesiologist. The patients were instructed to fast before the treatment, and venous access was established through the forearm cephalic, brachial or noble vein. The nasal oxygen flow was 3 L/min. Intravenous midazolam (initial dose, 0.03 mg/kg) was inducted. Propofol (4–12 mg/kg/h) and remifentanil (1.2–7.2 μg/kg/h) intravenous pump was inducted until the end of the procedure. According to the Ramsay Sedation Scale (RSS), the sedation effect was controlled using the RSS scores of 2–3, keeping the patient cooperative, oriented and tranquil during the procedure and maintaining a quick response to gentle taps or commands. The cough reflex of the patient was maintained throughout the course of anesthesia. Ramosetron was routinely administered to prevent nausea and vomiting [25–26]. Intravenous medication was stopped at the end of the treatment so that the patients quickly awakened after the procedure.
Current and emerging pharmacological approaches for treating diarrhea-predominant irritable bowel syndrome
Published in Expert Opinion on Pharmacotherapy, 2020
Akhil Munjal, Bhavtosh Dedania, Brooks D. Cash
Ramosetron is a selective 5-HT3 receptor antagonist approved for IBS-D in parts of Southeast Asia and Japan and has been shown to have a lower side effect profile compared to alosetron. A randomized, controlled phase IV study of ramosetron that included 98 patients diagnosed with IBS-D per the Rome III criteria evaluated 5 mcg of ramosetron vs placebo daily for 12 weeks. In this trial, 53.2% of patients receiving ramosetron had better relief of IBS-D symptoms vs 42% in the placebo group, with the greatest improvement noted in the stool consistency changes [16]. Another study in 576 women with IBS-D found that a significantly higher proportion of patients treated with ramosetron 2.5 mcg daily reported global IBS-D symptom improvement vs placebo (50.7% vs 32%, p < 0.001) [6]. Finally, a recent meta-analysis including four RCTs (n = 1623 patients) demonstrated overall IBS-D symptom improvement in both males and females vs placebo (RR; 95% CI 1.94; 1.58–2.38 and 1.49; 1.25–1.79) with no serious adverse events reported [17], although there is a paucity of post-marketing safety data. Unlike alosetron, ramosetron has not been linked to CI. Contraindications to ramosetron include a history of severe or chronic constipation, GI tract strictures, history of GI perforation or known symptomatic adhesions, CI, diverticulitis, inflammatory bowel disease, or severe hepatic impairment [5,7,18].
An overview of 5-HT3 receptor antagonists as a treatment option for irritable bowel syndrome with diarrhea
Published in Expert Opinion on Pharmacotherapy, 2023
Karolina Merecz, Mikołaj Hirsa, Olga Biniszewska, Jakub Fichna, Aleksandra Tarasiuk
There are several drugs that are currently under development or already in use for the treatment of different types of IBS. These include ramosetron and granisetron, selective 5-HT3 receptor antagonists, which are used to relieve symptoms in a variety of conditions. Ramosetron alone is commonly used as an antiemetic in chemotherapy, to prevent postoperative nausea and vomiting, and in patients with IBS-D. Also, it has been shown that ramosetron inhibits defecation, colonic dysfunction, and colonic nociception in vivo, while clinical studies have emphasized significant improvements in stool consistency, overall IBS symptoms as well as IBS-related quality of life in IBS-D patients. Granisetron is an antiemetic drug which inhibits 5-HT3 receptors in animal tissues such as heart, ileum, and vagus nerve. In clinical trials in IBS patients, granisetron has been shown to desensitize the rectum and reduce postprandial motility. Ondansetron is the drug used the most for the treatment of IBS-D – it has been shown to improve stool consistency, bowel movements, and bloating. Additionally, ondansetron is most commonly used as an anti-vomiting drug in patients that undergo chemo- and radiotherapy with nausea. Animal studies, performed on mice, have shown that ondansetron reduces also intestinal peristalsis. Another 5-HT3 antagonist, alosetron, is an FDA-approved drug for the treatment of IBS-C as it may prolong colonic transit. Of note, it is currently recommended for women with IBS-D. Alosetron is a gender-dependent drug and has better effects for women, e.g. improved stool consistency. However, adverse effects, as constipation or headaches, are also more frequent in females than in men. According to a network meta-analysis of RCTs of pharmacological therapies for IBS-D and IBS-M, Black et al. found that all drugs such alosetron, ramosetron, rifaximin, and eluxadoline are superior to placebo, but alosetron and ramosetron appeared to be the most effective [61–63].