Efficacy of ondansetron and metoclopramide for preventing postoperative emesis following strabismus surgery in children

A double-blind, randomised, placebo-controlled trial was conducted to compare the efficacy of metoclopramide with the 5-HT₃ antagonist, ondansetron, for the prevention of postoperative emesis in children undergoing elective strabismus surgery. None of the children received any premedication and a similar anaesthetic technique was used for all. Ondansetron 0.15 mg.kg⁻¹, metoclopramide 0.25 mg.kg⁻¹ or saline placebo were administered following intravenous catheter placement. Episodes of emesis were recorded for the first 24 h for the intervals of 0–2, 2–6 and 6–24 h. The incidence of emesis in the first 24 h was observed to be 71.7% in the placebo group, 34.4% in the ondansetron group (p < 0.001) and 61.4% in the metoclopramide group (p = NS). The severity of vomiting was less in the ondansetron group as compared with metoclopramide (p < 0.01) and placebo (p < 0.001). Recovery room scores were comparable in all the groups. No serious side-effects were observed in the ondansetron group. We conclude that prophylactic ondansetron is effective and superior to metoclopramide in the prevention of postoperative emesis in children following elective strabismus surgery.     

Cisplatin-induced long-term dynorphin A-immunoreactivity in cell somata of rat area postrema neurons

We evaluated long-term dynorphin A-immunoreactivity in the rat area postrema (AP) after the administration of cisplatin. First, rats were given 1, 5 and 10 mg/kg body weight cisplatin (i.p.) and their behavior was monitored for 72 h. We observed a delayed increase in pica 24-72 h after injection, compared to the 24 h before injection. We attributed this to the cisplatin injection. Pica was defined as an increase in the intake of non-nutritional matter such as kaolin. Administration of 1, 5 and 10 mg/kg cisplatin led to an increase in kaolin intake on day 1. Administration of 5 and 10 mg/kg of cisplatin led to decreased intake of laboratory chow (MF) on days 1–3, but 10 mg/kg cisplatin causes an excessive aggravation of their condition. Following this behavioral experiment, we immunohistochemically examined the induction of dynorphin A in the AP at 24, 48 and 72 h post-administration of 1 and 5 mg/kg cisplatin. Administration of 5 mg/kg cisplatin caused dynorphin A to accumulate gradually in the neurosoma of the AP neurons, and the numbers of positive AP neurosomata at 48 and 72 h post-administration were higher than following an equal dosage of 0.9% NaCl. These findings suggest that dynorphin A increases in the central nervous system for a long time following administration, and causes certain behavioral and clinical changes, including those related to appetite and nausea.     

Glucose-Dependent Insulinotropic Polypeptide and Substance P Mediate Emetic Response Induction by Masked Trichothecene Deoxynivalenol-3-Glucoside through Ca2+ Signaling

Deoxynivalenol (DON), the most naturally-occurring trichothecenes, may affect animal and human health by causing vomiting as a hallmark of food poisoning. Deoxynivalenol-3-glucoside (D3G) usually co-occurs with DON as its glucosylated form and is another emerging food safety issue in recent years. However, the toxicity of D3G is not fully understood compared to DON, especially in emetic potency. The goals of this research were to (1) compare emetic effects to D3G by oral and intraperitoneal (IP) routes and relate emetic effects to brain-gut peptides glucose-dependent insulinotropic polypeptide (GIP) and substance P (SP) in mink; (2) determine the roles of calcium-sensing receptor (CaSR) and transient receptor potential (TRP) channel in D3G’s emetic effect. Both oral and IP exposure to D3G elicited marked emetic events. This emetic response corresponded to an elevation of GIP and SP. Blocking the GIP receptor (GIPR) diminished emetic response induction by GIP and D3G. The neurokinin 1 receptor (NK-1R) inhibitor Emend^® restrained the induction of emesis by SP and D3G. Importantly, CaSR antagonist NPS-2143 or TRP channel antagonist ruthenium red dose-dependently inhibited both D3G-induced emesis and brain-gut peptides GIP and SP release; cotreatment with both antagonists additively suppressed both emetic and brain-gut peptide responses to D3G. To summarize, our findings demonstrate that activation of CaSR and TRP channels contributes to D3G-induced emesis by mediating brain-gut peptide exocytosis in mink.     

Tachykinin NK1 receptor antagonists for the control of chemotherapy-induced nausea and vomiting

The treatment of neoplastic disease with chemotherapeutic cytotoxic drugs has long been associated with profound nausea and vomiting (emesis). This became the most feared side effect of this type of treatment and was so severe that some patients would withdraw from further treatment, thus jeopardising their clinical outcome and possibly life expectancy. The introduction of the 5-HT₃ receptor antagonists had a significant impact in this area, offering substantial reductions in emesis, largely through prophylactic treatment. Unfortunately, some forms of emesis were resistant to treatment with these drugs, so the search has continued to identify new chemical entities with a higher level of efficacy and a broader spectrum of activity. Data generated in animals has identified tachykinin NK₁ receptors as highly important in the emetic reflex and experimental evidence strongly supports NK₁ receptor antagonists as highly efficacious anti-emetic agents, with unparalleled broad spectrum activity. Several novel antagonists have recently entered clinical development and data are emerging to support their anti-emetic activity. This area continues to attract substantial medicinal chemical research effort. Most major pharmaceutical companies are seeking new matter through structural refinement of early leads or discovery of novel compounds from library screening. The scope of chemical lead matter has advanced from early piperidine and quinuclidines to a spectrum of templates that improve expectations for a well-tolerated therapeutic agent. Recent success in combining 5-HT₃ and NK₁ antagonists in emesis treatment is expected to greatly advance clinical outcomes with newer and safer agents.     

Substituted indazole derivatives and their use as inhibitors of PDE4 and the production of tumour necrosis factor

This patent discloses indazole derivatives that exhibit activity as inhibitors of phosphodiesterase Type 4 (PDE4) and also inhibit the production of tumour necrosis factor (TNF). These compounds are expected to have utility in the treatment of inflammatory diseases such as asthma and rheumatoid arthritis.     

格拉司琼联合地塞米松防治顺铂所致呕吐的疗效观察

目的 观察格拉司琼联合地塞米松防治顺铂所致呕吐的疗效.方法 回顾性分析格拉司琼防联合地塞米松防治顺铂所致急性与迟发性呕吐疗效以及副反应.结果 格拉司琼联合地塞米松防治顺铂所致急性、迟缓性呕吐的有效控制率分别为90%、78%,完全控制率为76%、68%,发生1-2级常见副反应分别为便秘、厌食、腹胀、焦虑、失眠,几率分别为48%、42%、36%、40%、26%,未见3级以上副反应.结论 格拉司琼联合地塞米松防治顺铂所致的急性与迟发性呕吐均具有较好的临床效果,但有一些副反应,更加有效、副反应更小的止吐方案有待进一步研究.     

Clinical usefulness of oral granisetron hydrochloride for alleviation of delayed nausea and vomiting induced by CPT-11

This open label pilot study evaluated the safety and efficacy of the oral 5-HT3 receptor antagonist granisetron for prophylaxis of delayed chemotherapy-induced nausea and vomiting (CINV) in 30 patients with advanced or recurrent colorectal cancer. Patients were studied during two cycles of a 5-week regimen with irinotecan (CPT-11) and UFT. Patients received prophylactic anti-emetic therapy that included intravenous granisetron. If Grade 1 or higher severity gastrointestinal symptoms occurred during 6 days after CPT-11 administration in Cycle 1, then oral granisetron was administered daily for the following 5 days of CPT-11 in Cycle 2. Sixteen patients (53.3%) experienced delayed CINV in Cycle 1. The incidence of Grade 2 or higher vomiting was 32.1% and 27.7% in Cycles 1 and 2 in males (P = 0.554) respectively, and 54.6% and 32.4% in females (P = 0.001) respectively. Granisetron is effective against delayed Grade 2 or higher vomiting induced by CPT-11/UFT in female patients, although granisetron alone may not sufficiently control nausea induced by this regimen.     

Strategies for postoperative nausea and vomiting

Significant improvement towards a better control of postoperative nausea and vomiting have been achieved in recent years. Today, we understand better who is likely to vomit or to be nauseous after surgery. Significant amounts of the huge literature on anti-emetic interventions have been systematically reviewed, critically appraised and quantitatively synthesized. Thus, we know what anti-emetic interventions work, and how well they work, and we know their adverse effect profile. We also know which interventions have no worthwhile efficacy. A rational approach to postoperative nausea and vomiting includes three steps: identification of patients at risk, keeping the baseline risk low, and prophylactic administration of anti-emetics in those patients who are most likely to need them. For patients who are identified as high-risk patients, all measurements should be simultaneously initiated (multimodal anti-emesis).     

Chemotherapy-induced nausea and vomiting in routine practice: a European perspective

Goals of work The aim of this study was to evaluate the occurrence of chemotherapy-induced nausea and vomiting (CINV) and its effect on patients ability to carry out daily life activities following moderately to highly emetogenic, first-cycle chemotherapy in routine practice in cancer centers of four different European countries.Patients and methods This was a prospective, cross-sectional, nonrandomized, self-assessment study in 249 patients enrolled from cancer centers in Spain, Austria, Germany, and Switzerland. The study population consisted of 78% women, with a mean age of 54. Breast, lung, and ovarian cancers made up 75% of all cancers in the study. Patients received a mean of 2.0 chemotherapy agents and 2.5 antiemetic drugs.Main results A total of 450 emetic episodes experienced by 243 patients was recorded over 5 days following chemotherapy, with an average of 1.8 episodes per patient (range: 0–28). A higher percentage of patients (38%) suffered from delayed compared to acute emesis (13%). Between 42% and 52% of all patients suffered from nausea (visual analogue scale 5 mm) on any one day, peaking at day 3. Using the Functional Living Index for Emesis (FLIE) questionnaire, 75% of patients with nausea and 50% with vomiting reported a negative impact of these conditions on performance of daily living.Conclusions CINV remains a significant problem in routine practice, particularly in the delayed phase posttreatment. Overall, CINV had a negative impact on patients daily life.