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.     

Prevention of nausea and vomiting with granisetron, droperidol and metoclopramide during and after spinal anaesthesia for caesarean section: A randomized, double-blind, placebo-controlled trial

Background: Nausea and vomiting during and after spinal anaesthesia for caesarean section are distressing to the patient. This study was undertaken to evaluate the efficacy and safety of granisetron, droperidol and metoclopramide for the prevention of nausea and vomiting in parturients undergoing caesarean section under spinal anaesthesia.
Methods: In a randomized, double-blind, placebo-controlled trial, 120 patients received granisetron 3 mg, droperidol 1.25 mg, metoclopramide 10 mg or placebo (saline) ( n =30 of each) i. v. immediately after clamping of the foetal umbilical cord. Nausea, vomiting and safety assessments were performed during and after spinal anaesthesia for caesarean section.
Results: The incidence of intraoperative, post-delivery nausea and vomiting was 13%, 17%, 20% and 63% after administration of granisetron, droperidol, metoclopramide and placebo, respectively; the corresponding incidence during 0–3 h after surgery was 7%, 27%, 27% and 43%; the corresponding incidence during 3–24 h after surgery was 7%, 20%, 23% and 37% ( P <0.05; overall Fisher's exact probability test). No clinically important adverse events were observed in any of the groups.
Conclusion: Granisetron is highly effective for preventing nausea and vomiting during and after spinal anaesthesia for caesarean section. Droperidol and metoclopramide are effective for the prevention of intraoperative, post-delivery emesis, but are ineffective for the reduction of the incidence of postoperative emesis.     

Inhibition in carotid body chemoreceptors mediated by D-2 dopaminoceptors: Antagonism by benzamides

Inhibition of chemosensory nerve impulses in the cat is evoked by dopamine (DA) applied to carotid body chemoreceptors. Pharmacological characterization of the dopaminoceptors involved in this action was determined through their blockade with benzamides, selective antagonists of D-2 receptors. Both metoclopramide and sulpiride were effective blockers of DA-induced chemosensory inhibition. Furthermore, both drugs induced an immediate increase in the frequency of carotid nerve chemosensory impulses, suggesting the presence of previous tonic inhibition of chemoreceptor discharges by endogenous DA released from glomus cells.     

Treatment of post-operative nausea and vomiting: comparison of propofol,droperidol and metoclopramide

Purpose  

To compare the efficacy of propofol in a subhypnotic dose (10 mg iv), droperidol (1.25 mg iv), or metoclopramide (10 mg iv) in the treatment of PONV in the post anaesthesia care unit (PACU).     

Single-dose pharmacokinetics of metoclopramide

Summary The time courses of plasma metoclopramide concentrations were followed in six subjects after oral and intravenous single dose administration. Plasma concentration-time data following i.v. administration in each subject were found to fit a two compartment model with a mean terminal half-life of 4.55 h±0.80 h and a mean distribution half-time of 0.35 h±0.09 h. Volumes of distribution were high (3.43±1.181 · kg^–1), and clearances (0.53±0.191 · kg^–1h^–1) approached liver plasma flow. This suggests that metoclopramide occurs at higher concentrations in tissues than in plasma, and that its clearance is probably limited by liver blood flow rather than liver metabolic capacity. The post-absorption decline in metoclopramide plasma levels after oral administration was also biexponential in each subject. The terminal half-life was 5.17 h±0.98 h. Mean volume of distribution and mean clearance were similar to intravenous values (after adjustment for bioavailability). Oral absorption was rapid with peak plasma concentrations being reached at a mean time of 0.93 h. A mean bioavailability of 0.77 was calculated for the six subjects, and it was postulated that this incomplete availability is due to a first-pass effect. The inter-individual variation in the degree of first-pass was considerable (0.47–1.14).     

甲磺酸托烷司琼预防化疗药物引起恶心、呕吐的Ⅱ期临床研究

目的　观察甲磺酸托烷司琼 (Trop)对顺铂引起的恶心、呕吐、食欲不振的疗效和安全性。方法　应用随机、自身交叉对照方法将恶性肿瘤患者随机分为 2组 ,治疗组采用Trop(第 1周期 )→胃复安 (第 2周期 )止吐方法 ,对照组采用胃复安 (第 1周期 )→Trop(第 2周期 )止吐方法。观察 2组恶心、呕吐、食欲不振改善情况及药物不良反应。结果　化疗第 1天 ,治疗组对化疗药物引起的呕吐完全控制率明显优于对照组 (P <0 .0 1) ,对恶心、食欲不振的有效控制率略高于对照组 (P >0 .0 5 ) ;化疗第 2～ 6d治疗组疗效稍优于对照组 ,但无显著性差异 (P >0 0 5 ) ,Trop的主要不良反应有头痛、头晕、口干、便秘、疲倦、嗜睡及失眠 ,均较轻微。结论　Trop在控制强致吐化疗药物引起的急性呕吐方面疗效较好 ,不良反应少。     

不同性别大鼠创伤失血性休克后多形核白细胞反应的差异及胃复安干预的实验研究

本研究在以下几个方面具有创新：（1）将腺苷引入心肺复苏治疗中，观察腺苷与肾上腺素合用对心跳停搏后A主循环恢复率和复苏成功率的影响，结果表明合用腺苷可明显提高自主循环恢复率和复苏成功率；（2）观察腺苷在心肺复苏中对兔心、脑组织病理结构和超微结构的影响，结果表明腺苷可以明显减轻心脑组织的损害；（3）观察腺苷窒息大鼠心脏和肠系膜微循环的影响，并观察到肾上腺素对微循环无明显改善作用，联合应用腺苷可以改善微循环；（4）将激光多普勒血流量图象仪引入心肺复苏中，动态观察窒息大鼠肠壁组织血液灌流量变化，并观察到腺苷可以增加肠壁组织血流灌注量。[编者按]     

Education initiative improves the evidence‐based use of metoclopramide following morphine administration in the emergency department

Objective: We aimed to evaluate a multifaceted education initiative designed to reduce the prophylactic use of metoclopramide. Methods: This was a pre‐ and post‐intervention trial undertaken in a single ED. All ED doctors and nurses were targeted. The intervention comprised a specifically designed, 19‐slide ‘e‐learning module’, accessible via the ED intranet, supplemented by in‐service training and a range of reminder techniques (posters, emails and drug room flyers). The primary end‐point was the proportion of patients administered metoclopramide prophylactically with their initial morphine dose. Data were collected on random samples of patients who received morphine, using explicit medical chart review. Results: Both pre‐ and post‐intervention periods were of 3 month duration. The charts of 146 cases were reviewed in each period. In the post‐intervention period: ? The proportion of patients administered metoclopramide prophylactically decreased from 22.6% to 4.1% (difference 18.5% [95% CI 10.3–26.7], P < 0.001) ? The proportion of patients administered metoclopramide appropriately (for known morphine sensitivity, established nausea and rescue anti‐emesis) rose marginally from 28.8% to 32.9% (difference 4.1% [95% CI ?7.2–15.4], P = 0.53) ? There was a 12.7% decrease in the number of ampoules of metoclopramide issued to the ED without a concurrent rise in the issue of other anti‐emetic drugs Conclusion: The education initiative resulted in a significant improvement in the evidence‐based use of metoclopramide.     

Metoclopramide is metabolized by CYP2D6 and is a reversible inhibitor,but not inactivator,of CYP2D6

Abstract

1. Metoclopramide is a widely used clinical drug in a variety of medical settings with rare acute dystonic events reported. The aim of this study was to assess a previous report of inactivation of CYP2D6 by metoclopramide, to determine the contribution of various CYPs to metoclopramide metabolism, and to identify the mono-oxygenated products of metoclopramide metabolism.

2. Metoclopramide interacted with CYP2D6 with Type I binding and a K_s value of 9.56?±?1.09?µM. CYP2D6 was the major metabolizer of metoclopramide and the two major products were N-deethylation of the diethyl amine and N-hydroxylation on the phenyl ring amine. CYPs 1A2, 2C9, 2C19, and 3A4 also metabolized metoclopramide.

3. While reversible inhibition of CYP2D6 was noted, CYP2D6 inactivation by metoclopramide was not observed under conditions of varying concentration or varying time using Supersomes^TM or pooled human liver microsomes.

4. The major metabolites of metoclopramide were N-hydroxylation and N-deethylation formed most efficiently by CYP2D6 but also formed by all CYPs examined. Also, while metoclopramide is metabolized primarily by CYP2D6, it is not a mechanism-based inactivator of CYP2D6 in vitro.