Side effects of anti-emetics: results of a class experiment

A number of standard anti-emetic drugs (perphenazine, promethazine, propiomazine, thiethylperazine, hyoscine, cyclizine, dimenhydrinate, metoclopramide) and a placebo were given by intramuscular injection to students in a clinical pharmacology class to allow them to study side effects. Students proved to be sensitive detectors of the subjective side effects and the placebo response rate was low. Drowsiness was the commonest and most marked side effect; the extra-pyramidal effects were confined to the phenothiaziness, and dizziness and dryness of mouth were frequent only after hyoscine. Cardiovascular effects were trivial and only slight bradycardia was noted with all substances administered. The undesired actions of the phenothiazines lasted longer than those of cyclizine and hyoscine. The frequency of side-effects of anti-emetic drugs is so high that they must be balanced against efficacy in choosing an anti-emetic for a particular situation.     

Preventing prolonged post-operative ileus in gastric cancer patients undergoing gastrectomy and intra-peritoneal chemotherapy

AIM: To assess the efficacy of metoclopramide (Met) for prevention of prolonged post-operative ileus in advanced gastric cancer patients undergoing D2 gastrectomy and intra-peritoneal chemotherapy (IPC). METHODS: Thirty-two advanced gastric cancer patients undergoing D2 gastrectomy and IPC were allocated to two groups. Sixteen patients received Met immediately after operation (group A), and 16 did not (group B). Another 16 patients who underwent D2 gastrectomy without IPC were enrolled as the control group (group C). All patients had received epidural pain control. The primary endpoints were time to first post-operative flatus and time until oral feeding with a soft diet without discomfort. Secondary endpoints were early complications during hospitalization. RESULTS: Gender, the type of resection, operating time, blood loss, tumor status and amount of narcotics were comparable in the three groups. However, the group C patients were older than those in groups A and B (67.5±17.7 vs 56.8±13.2,57.5±11.7 years, P= 0.048). First bowel flatus occurred after 4.35±0.93 d in group A, 4.94±1.37 d in group B, and 4.71±1.22 d in group C (P>0.05). Oral feeding of a soft diet was tolerated 7.21±1.92 d after operation in group A, 10.15±2.17 d in group B, and 7.53±1.35 d in group C (groups A and C vs group B, P<0.05). There was no significant difference in respect to the first flatus among the three groups. However, the time of tolerating oral intake with soft food in groups A and C patients was significantly shorter than that in group B patients. Levels of C-reactive protein (CRP) were significantly lower in group C and there was a more prominent and prolonged response in CRP level in patients undergoing IPC. The incidence of post-operative complications was similar in the three groups except for prolonged post-operative ileus. There was no increased risk of anastomotic leakage in patients receiving Met. CONCLUSION: The results suggest that a combination of intravenous Met and epidural pain control may be required to achieve a considerable decrease in time to resumption of oral soft diet in advanced gastric cancer patients who underwent gastrectomy and IPC. Furthermore, the administration of Met did not increase anastomotic leakage. Met has a role in the prevention of prolonged post-operative ileus.     

肌肉注射胃复安预处理对食管心房调搏检查结果阳性率及假阳性率的影响

目的 探讨肌肉注射胃复安预处理对食管心房调搏检查结果阳性率及假阳性率的影响.方法 拟行食管心房调搏检查的患者120例,随机分为试验组(n=63)和对照组(n=57),试验组食管心房调搏前20 min肌注10 mg胃复安注射液,对照组肌注等体积生理盐水,比较两组食管心房调搏检查结果的阳性率和假阳性率.结果 两组患者窦房结功能不良阳性率、房室折返性心动过速阳性率比较,差异无统计学意义(P>0.05).试验组房室结双径路阳性率、房室结折返性心动过速(AVNRT)阳性率和总阳性率高于对照组;可疑窦房结功能不良假阳性率、房室前传功能障碍假阳性率低于试验组(均P<0.05).结论 肌肉注射胃复安预处理能提高食管心房调搏的房室结双径路和AVNRT诊断阳性率,降低可疑窦房结功能不良假阳性率和房室传导功能障碍假阳性率,值得在临床推广.     

Post-Laparoscopic Vomiting in Females versus Males: Comparison of Prophylactic Antiemetic Action of Ondansetron versus Metoclopramide

Background and Objectives:

The incidence of postoperative vomiting in patients undergoing laparoscopic cholecystectomy is compared in females versus males. The report also compares the prophylactic action of ondansetron versus metoclopramide.

Methods:

A total of 85 American Society of Anesthesiologists (ASA) I and II patients were enrolled in the study. Patients were divided into two groups according to sex: Group I 53 females, and Group II 32 males. After anaesthetic induction, subjects received intravenously either 4 mg ondansetron or 10 mg metoclopramide.

Results:

The incidence of vomiting as well as the frequency of emetic episodes over 24 hours were analyzed in each group using X2 analysis. Data analysis revealed a significantly higher incidence (P<0.05) of postoperative emesis in females 10:53 (18.9%) as compared to males 0:32 (0%). In the male group, no patient vomited postoperatively, whether prophylactic ondansetron or metoclopramide was used. While the incidence of emesis in the female group was lower (P<0.05) in the ondansetron group (17.6%) than the metoclopramide group (29.6%).

Conclusion:

These results may indicate prophylactic antiemetic therapy in female patients undergoing laparoscopic cholecystectomy; ondansetron appears to be superior to metoclopramide.     

耳穴贴压提高肿瘤危重症患者鼻肠管置管成功率临床观察

目的 观察耳穴贴压法对肿瘤重症患者留置鼻肠管成功率的影响。方法 将120例肿瘤危重症患者根据随机数字表法分为耳穴贴压组、甲氧氯普胺组和对照组,每组40例。统计分析3组患者置管成功率、置管时间、2次置管率、置管并发症等,监测患者置管前、置管中、置管后1 h的心率（heart rate,HR）、呼吸频率（respiratory rate,RR）、平均动脉压（mean arterial pressure,MAP）、指端血氧饱和度（percutaneous oxygen saturation,SpO2）变化。结果 耳穴贴压组、甲氧氯普胺组置管成功率均高于对照组（P＜0.05）,两者的二次置管率均明显低于对照组（P＜0.05）。3组患者置管时间比较,差异均有统计学意义（P＜0.05）,甲氧氯普胺组与耳穴贴压组置管时间较对照组明显缩短（P＜0.05）;3组患者置管深度比较,差异无统计学意义（P＞0.05）。与置管前比较,置管中3组患者HR、RR均明显加快（P＜0.05）,MAP明显增高（P＜0.05）,SpO2均无明显变化（P>0.05）;与置管中比较,置管后1 h,3组患者HR、MAP、RR均明显降低（P＜0.05）;与置管前比较,置管后1 h,3组患者HR、MAP、RR、SpO2均无明显变化（P>0.05）。置管中,甲氧氯普胺组和耳穴贴压组患者HR明显低于对照组（P＜0.05）。结论 耳穴贴压法可提高肿瘤危重症患者鼻肠管的置管成功率,无明显并发症发生。     

Antagonism of the effects of 5-hydroxytryptamine on the rabbit isolated vagus nerve by BRL 43694 and metoclopramide

Summary Depolarization and reduction in the C fibre compound action potential (C spike) in response to 5-HT were recorded simultaneously from rabbit isolated vagus nerve. 5-HT (0.1–100 mol/l) was applied cumulatively and EC₅₀ and IC₅₀ values measured from individual concentration-response curves. Blockade of 5-HT responses by the 3-indazole carboxamide, BRL 43694, was investigated and compared with the blocking action of metoclopramide. BRL 43694 was a selective antagonist of 5-HT responses. A concentration of 10 nmol/l BRL 43694, which nearly abolished the depolarization and reduction of the C spike evoked by 5-HT (100 mol/l), had no effect on similar responses evoked by DMPP (100 mol/l) or GABA (100 mol/l). Blockade of 5-HT responses by BRL 43694 (0.3 nmol/l) was slow in onset, a plateau blockade occurring after equilibrium of tissue with antagonist for 2 to 3 h. Metoclopramide induced a blockade of rapid onset. The maximal blockade was apparent within 30 min of application. Full recovery in the responsiveness of the tissue to 5-HT was observed within 30 min of washing out metoclopramide. BRL 43694 at concentrations of 0.3, 1, 3 and 10 nmol/l caused a progressive rightward shift of the concentration-response curves to 5-HT. At the highest concentration of antagonist, there was some depression of the maximal 5-HT response. The apparent pA₂ estimated from the Schild equation was 10.03 ± 0.09 (mean ± SEM, n = 20) against 5-HT depolarization and 10.31 ± 0.1 against C spike reduction. Schild plots had slopes not significantly different from 1.0. The slopes and extrapolated pA₂ fitted by linear regression were 0.91 (0.58 – 1.24) and pA₂ 10.16 (9.74–10.58; mean and 95% confidence levels) for the depolarizations. For reduction in C spikes the slope was 0.74 (0.39–1.08) with a pA₂ of 10.86 (10.24–11.49). There was no apparent use-dependent element to the blockade by BRL 43694. Blockade of 5-HT depolarization or C spike reduction by BRL 43694 (0.3 nmol/l) was not significantly different on repeated testing in the presence of the antagonist or without testing of 5-HT until 3 h incubation had elapsed. Metoclopramide at concentrations of 0.3, 1, 3, or 10 mmol/l progressively shifted concentration-response curves to the right. However, the response maximum, especially that for depolarization, was enhanced in the presence of the antagonist. The apparent pA₂ values from the Schilde equation were 7.04 ± 0.04 (n = 20) against 5-HT depolarization and 7.13 ± 0.06 (n = 16) against C spike reduction. Schild plots had slopes significantly less than unity. The lines fitted to the relationship gave pA₂ values of 7.41 (7.25–7.57) with a slope of 0.79 (0.69–0.9) against depolarization and 7.63 (7.28–7.97) with a slope of 0.74 (0.54–0.93) against C spike reduction. Metoclopramide at concentrations above 30 mol/l directly reduced C spike amplitude; the IC₅₀ for the local anaesthetic action was 158 ± 40 mol/l (mean ± SEM). It is concluded that BRL 43694 is a potent and selective antagonist of 5-HT₃ receptors on the rabbit vagus nerve. At concentrations below 10 nmol/l, BRL 43694 appeared to behave as a competitive antagonist while at 10 nmol/l the antagonism was unsurmountable, suggesting a pseudo-irreversible antagonism due to slow dissociation of antagonist from the receptor. Although metoclopramide behaved as a surmountable antagonist, the low slope of the Schild plots and the increase in maximal response amplitude in the presence of the antagonist are unexplained features of its blocking action.Send offprint requests to D. I. Wallis at the above address     

Metoclopramide to augment lactation,does it work? A randomized trial

Objectives.?The objective of this study was to investigate the efficacy of metoclopramide on augmentation of milk production in mothers of premature newborns.

Methods.?This was a randomized, double-blind, placebo-controlled trial. Women who delivered at?≤34 weeks of gestation, with no prior breastfeeding experience, singleton pregnancy, and no contraindications to using metoclopramide were eligible for entry. Twenty-five women were randomly assigned to receive 10?mg of metoclopramide or placebo three times daily for 8 days starting within 36?h of birth. Certified lactation nurses provided breastfeeding education. Breast milk expressed at each pumping session over the 8 days of treatment was recorded.

Results.?Data from 18 patients were available for analysis. Milk production in both groups increased rapidly during the first 4 days and then more gradually to an average for the last 4 days of 633?±?168 (9) ml/day [mean?±?SEM (n)] for the placebo group and 459?±?91 (10) ml/day for the metoclopramide group. Analysis with a repeated-measures ANOVA indicated a significant increase in milk production during the 8-day measurement period [within subjects p?<?0.001]; however, there was no significant difference in milk production between the two groups [between subjects p?=?0.427]. Side effects were similar between groups.

Conclusion.?In mothers with preterm babies, metoclopramide treatment does not augment (sample size had 80% power for detection of 50% difference) the breast milk production. Maternal interest, education, and support are recognized as mainstay in accomplishing successful lactation.     

胃复安对胶囊内镜检查影响的临床研究

目的:研究胃复安对胶囊内镜检查的影响。方法:将2009年6月至2010年6月期间接受胶囊内镜检查的116例患者随机分成2组,干预组患者在吞服胶囊后立即肌注胃复安针10 mg,对照组患者不予注射胃复安针。观察2组患者的胶囊胃通过时间、小肠通过时间、全小肠检查完成率等项目。结果:各有58例患者进入干预组和对照组。干预组有51例完成全小肠检查,全小肠检查完成率为87.9%,对照组有48例完成全小肠检查,全小肠检查完成率为82.8%。对照组和干预组胶囊平均胃通过时间分别为(32.45±29.63)min和(45.81±40.01)min,组间比较有统计学差异(P<0.05);小肠通过时间分别为(252.69±113.29)min和(258.75±83.83)min,组间比较无统计学差异(P>0.05)。结论:吞服胶囊内镜后肌注胃复安针10 mg可明显缩短胶囊胃通过时间,不影响小肠通过时间,可提高全小肠检查完成率。     

Metoclopramide as pharmacological tool to assess vasopressinergic co-activation of the hypothalamus–pituitary–adrenal (HPA) axis: A study in healthy volunteers

The synthetic vasopressin (AVP) analogue desmopressin (dDAVP) has been used as pharmacological function test to quantify vasopressinergic co-activation of the hypothalamus–pituitary–adrenal (HPA) axis in the past. Such exogenous vasopressinergic stimulation may induce confounding cardiovascular, pro-coagulatory and anti-diuretic effects and low endogenous corticotrophin-releasing-hormone (CRH) levels may limit its potential to reliably assess co-activation. Alternatively, the dopamine-2-(D2)-antagonist metoclopramide is believed to induce co-activation indirectly by releasing endogenous AVP. We investigated this indirect co-activation with metoclopramide under conditions of low and enhanced endogenous CRH release in healthy volunteers. A randomized, double-blind, placebo-controlled, four-way crossover study was performed in 12 healthy males. CRH release was induced by administering an oral 5-hydroxytryptophan (5-HTP) 200 mg function test. Co-activation was investigated by administering metoclopramide 10 mg intravenously around the expected maximal effect of 5-HTP. The neuroendocrine effects were compared to those of metoclopramide alone, the 5-HTP test alone and matching placebo. Metoclopramide safely induced HPA-axis activation by itself, and potently synergized 5-HTP-induced corticotrophinergic activation of the HPA axis. These findings are indicative of vasopressinergic co-activation and suggest a role for metoclopramide as a practical function test for co-activation of the HPA axis. However, its application will be hampered pending clarification of the exact pharmacological mechanism by which metoclopramide induces co-activation of the HPA axis.