昂丹司琼和甲氧氯普胺在肿瘤化学疗法时作为止吐剂的对比

用自身随机交替对照法，观察昂丹司琼和甲氧氯普胺对６２例（男性４３例，女性１９例：年龄４９±ｓ１２ａ）肿瘤化学疗法（化疗）患者的止吐作用。采用昂丹司琼８ｍｇ，ｉｖ，ｔｉｄ×３ｄ后改８ｍｇ，ｐｏ，ｔｉｄ×４ｄ或甲氧氯普胺２０ｍｇ，ｉｍ，ｔｉｄ×３ｄ后改１０ｍｇ，ｐｏ，ｔｉｄ×４ｄ。结果：对顺铂的止恶心和止吐，昂丹司琼优于甲氧氯普胺，有效率分别为９５％和５０％，但对阿霉素无显著差别。前者未发生锥体外系症状，后者则有３例。     

Different effects of metoclopramide and domperidone on arginine-vasopressin secretion in man.

This study was performed in order to investigate the dopaminergic mechanism involved in the control of arginine-vasopressin (AVP) secretion in normal men. Plasma AVP concentrations were measured before and after the administration of an i.v. bolus of 10 mg metoclopramide or domperidone to twelve healthy males. Metoclopramide, a cerebral and peripheral antagonist of dopaminergic receptors, significantly stimulated AVP secretion, whereas domperidone, a dopamine antagonist which does not cross the blood-brain barrier, was without effect. These data suggest that metoclopramide stimulates the release of AVP by blocking dopaminergic receptors in structures located inside the blood-brain barrier. Alternatively, it is possible that the stimulation of AVP release induced by metoclopramide does not occur through inhibition of dopamine receptors but rather through interaction with other neuroendocrine pathways.     

多潘立酮和甲氧氯普胺治疗呃逆的临床观察

目的探讨呃逆的治疗方法。方法将呃逆患者73例按咨询顺序随机分为2组,多潘立酮组37例,给予多潘立酮10mg顿服,如1h后无效再服1次;甲氧氯普胺组36例,给予甲氧氯普胺10mg,如1h后无效再服1次。2组疗程均为1d,比较2组临床疗效。结果多潘立酮组治疗呃逆显效时间快于甲氧氯普胺组,而且疗效优于甲氧氯普胺组,差异均有统计学意义（P〈0.01）。结论多潘立酮治疗呃逆效果优于甲氧氯普胺。     

Comparison of the effects of metoclopramide and domperidone on HERG channels

Torsades de pointes (TdP) is a potentially fatal form of ventricular arrhythmia that occurs under conditions where cardiac repolarization is delayed (as indicated by prolonged QT intervals from electrocardiographic recordings). A likely mechanism for QT prolongation and TdP is blockade of the rapid component of the cardiac delayed rectifier K(+) current (I(Kr)), which is encoded by HERG (human ether-a-go-go-related gene). The gastroprokinetic agent cisapride is a potent blocker of HERG currents and serious cardiac arrhythmias and deaths from TdP and ventricular fibrillation have been reported in patients taking cisapride. The aim of the present study was to compare the effects of the gastroprokinetic agents domperidone and metoclopramide on HERG channels transiently expressed in human embryonic kidney (HEK 293) cells using the whole-cell configuration of the patch-clamp technique. Both domperidone and metoclopramide concentration-dependently blocked HERG currents, and the following values were calculated for IC(50) (the concentrations causing half-maximal inhibition) and n (the Hill coefficient): 57.0 nmol/l and 0.99 for domperidone, 5.4 micromol/l and 0.95 for metoclopramide. The observation that the extent of block of HERG currents by domperidone increased at more positive membrane potentials whereas block of HERG currents by metoclopramide displayed a smaller degree of voltage dependency seems to indicate that domperidone and metoclopramide have distinct binding sites on HERG channels. In conclusion, the potency for block of HERG currents is about 100-fold lower for metoclopramide when compared to domperidone.     

Use of metoclopramide, domperidone, and cisapride in the management of diabetic gastroparesis

The pathophysiology, diagnosis, and treatment of diabetic gastroparesis are reviewed, and the mechanisms of action, pharmacokinetics, clinical efficacy, adverse effects, and dosage of metoclopramide, domperidone, and cisapride are described. Diabetic gastroparesis is a state of delayed gastric emptying that reportedly affects 20-30% of diabetic patients. Symptoms include nausea, early satiety, postprandial bloating and fullness, and vomiting. Diabetic gastroparesis has been managed most successfully with drugs that stimulate gastric emptying. Of the three agents studied--metoclopramide, domperidone, and cisapride--only metoclopramide is commercially available in the United States. The clinical efficacy of metoclopramide, domperidone, and cisapride has been well documented in several placebo-controlled trials. Metoclopramide effectively decreases mean gastric emptying time, although tolerance to this stimulation of gastric emptying may develop with long-term therapy. However, symptomatic relief persists with long-term therapy because of metoclopramide's antiemetic properties. Domperidone, which has also been shown to stimulate gastric motility and to possess antiemetic properties, improves symptoms in patients suffering from diabetic gastroparesis. Cisapride appears to have continued beneficial effects on gastric motility with long-term therapy. All three agents have favorable adverse-effect profiles. Although metoclopramide is currently the first-line agent for the management of gastroparesis, domperidone and cisapride both possess properties that may make them useful alternatives in patients who are unresponsive to or cannot tolerate metoclopramide therapy.     

Effects of oral domperidone on gastric emptying and motility. A double-blind comparison with placebo and metoclopramide

The effects of an oral treatment with domperidone on the gastric motor function were investigated in a double-blind study, including 129 patients, referred to the department of radiology for barium meal examination. None of them had an organic obstruction or had had previous gastrointestinal surgery. The patients received either domperidone (50, 20 or 10 mg), metoclopramide (20 mg) or a placebo. The medication was given 30 min before the intake of the barium meal in order to stimulate therapeutic conditions. During the barium meal examination, an assessment was made of the peristaltic activity of the antrum, the gastric emptying and the small bowel transit time. As to these parameters, 50 mg and 20 mg domperidone and 20 mg metoclopramide were significantly superior to the placebo.     

Effects of exepanol-HCl, metoclopramide and domperidone on the lower esophageal sphincter of dogs

The actions of rac. 3,5-cis-2,3,4,5-tetrahydro-3-methylamino-1-benzoxepine-5-ol hydrochloride (prop. INN exepanol-HCl, KC 2450), metoclopramide and domperidone on the resting pressure of the lower esophageal sphincter (LES) were studied in anesthetized and conscious beagle dogs using pull-through manometrical methods. Exepanol-HCl proved to enhance the LES pressure (LESP) significantly both in anesthetized and conscious dogs. The action of domperidone which was used as reference compound in the anesthetized dog experiments was less pronounced. In conscious dogs the actions of exepanol-HCl and metoclopramide were comparable. Domperidone was not active in this test.     

Effects of metoclopramide and domperidone on cholinergically mediated contractions of human isolated stomach muscle

The experiments examine the actions of metoclopramide and domperidone on the responses evoked by electrical field stimulation or by acetylcholine, in longitudinal muscle strips obtained from human stomach. Electrical field stimulation evoked contractions which were predominantly cholinergically mediated; metoclopramide 0.28-28 microM caused a concentration-dependent increase in the height of these contractions. In the presence of atropine and barium chloride, electrical stimulation evoked relaxations of the stomach muscle, probably by stimulating non-adrenergic, non-cholinergic inhibitory nerves; metoclopramide 28 microM had no effect on these relaxations. Metoclopramide 0.003-2.8 microM had no effect on contractions evoked by exogenous acetylcholine, although higher concentrations of the drug increased the contractions. The results suggest that in human isolated stomach, low concentrations of metoclopramide may increase electrically evoked cholinergic activity by increasing the release of neuronal acetylcholine. Stimulation by metoclopramide of cholinergic activity in the gut may therefore be an important mechanism by which the drug increases gastrointestinal motility during therapy. Cholinergically mediated contractions were not increased by domperidone, and other mechanism(s) of action may therefore be important for this drug.     

The pharmacokinetics of high dose metoclopramide in patients with neoplastic disease.

High dose metoclopramide infusions (10 mg/kg) were administered to nineteen patients with bronchial carcinoma who were receiving intravenous cyclophosphamide as single agent chemotherapy. Considerable interindividual variability in metoclopramide disposition was observed. Mean clearance was 0.33 +/- 0.13 (s.d.) l h-1 kg-1, mean volume of distribution at steady state was 3.8 +/- 1.2 (s.d.) l/kg and mean elimination half-life was 8.3 +/- 4.4 (s.d.) h. These results were significantly different from mean values previously reported for young healthy volunteers given conventional doses (0.70 l h-1 kg-1, 2.2 l/kg and 2.6 h respectively). Significant correlations were found between serum urea, serum creatinine and metoclopramide clearance. The metoclopramide regimens were well tolerated and, with the exception of two patients, were completely effective in the prevention of nausea and vomiting. To achieve and maintain target serum metoclopramide concentrations of 1 microgram/ml, we now administer a loading infusion of 3.61 mg/kg over 30 min followed by a maintenance infusion of 0.36 mg kg-1 h-1 for 10 h. Cyclophosphamide is normally administered concurrently with the second infusion. For patients with evidence of mild renal impairment, the maintenance infusion rate of metoclopramide hydrochloride should be adjusted according to the predicted individual clearance value; CL (l h-1 kg-1) = 0.57 - [0.036 X urea (mmol/l)].     

Pharmacokinetics of metoclopramide in patients with liver cirrhosis.

The pharmacokinetics of metoclopramide were investigated after intravenous and oral administration in eight patients with severe alcoholic cirrhosis and in eight healthy volunteers. As a consequence of a 50% lower clearance (0.16 +/- 0.07 vs 0.34 +/- 0.09 l h-1 kg-1, plasma drug concentrations and the half-life of metoclopramide were greater in patients following both routes of drug administration. Volume of distribution (3.1 +/- 0.8 vs 3.4 +/- 1.2 l kg-1) and absolute bioavailability (79 +/- 19 vs 84 +/- 15%) were similar in the two groups. The adverse effects of metoclopramide observed in patients with marked hepatic impairment are likely to result from increased accumulation of the drug as a result of impaired clearance. Consequently a reduction in dose of 50% is recommended in patients with severe liver cirrhosis.     

Overview of supportive care in patients receiving chemotherapy: antiemetics, pain management, anemia, and neutropenia

With advancements in the field of oncology, more and more people are living with cancer. The prevalence of invasive cancer in the United States is estimated to be almost 12 million. The treatment of cancer as well as the malignancy itself can cause an immense number of side effects and other complications. This article explores the fundamentals of supportive care in patients receiving chemotherapy and radiation treatment including prevention of nausea and vomiting, pain management, treatment of anemia and neutropenia. Proper supportive care can help improve clinical outcomes, reduce medical costs, and help patients with cancer live longer, happier, and healthier lives. For these reasons, it is important for pharmacists to possess a solid understanding of how to prevent and treat the adverse effects of chemotherapy and radiation treatment.     

Inappropriate prescribing in patients accessing specialist palliative day care services

Background For patients accessing specialist palliative care day services, medication is prescribed routinely to manage acute symptoms, treat long-term conditions or prevent adverse events associated with these conditions. As such, the pharmacotherapeutic burden for these patients is high and polypharmacy is common. Consequently, the risk of these patients developing drug-related toxicities through drug–drug interactions is exacerbated. Medication use in this group should, therefore, be evaluated regularly to align with achievable therapeutic outcomes considering remaining life expectancy. Objective To (1) assess the prevalence of inappropriate medication use; (2) identify potential drug–drug interactions; and, (3) determine how many potential drug–drug interactions could be prevented by discontinuing inappropriate medication. Setting A specialist tertiary care palliative care centre in Northern England serving a population of 330,000. Main outcome measure Prescribing of inappropriate medication. Method Medication histories for patients accessing a specialist palliative day care centre were established and a modified Delphi method was used to reach consensus of medication appropriateness. The Delphi method utilized a framework considering the following factors: remaining life expectancy of the patient, time until benefit of the treatment, goals of care and treatment targets. Potential drug interactions were established using drug interaction recognition software and categorised by their ability to cause harm. Results A total number of 132 patients were assessed during the study period who were prescribed 1,532 (mean = 12/patient) medications; 238 (16 %) were considered inappropriate in the context of limited life expectancy. The most common class of medications considered inappropriate were the statins, observed in 35 (27 %) patients. A total of 267 potential drug–drug interactions were identified; 112 were clinically significant and 155 were not considered clinically significant. Discontinuation of inappropriate medication would reduce the total number of medications taken to 1,294 (mean = 10/patient) and prevent 31 clinically significant potential drug–drug interactions. Conclusion Patients accessing specialist palliative day care services take many inappropriate medications. These medications not only increase the pharmacotherapeutic burden for the patient but they also contribute to potential drug–drug interactions. These patients should have their medication reviewed in the context of life limiting illness aligned with achievable therapeutic outcomes.     

多潘立酮口腔崩解片的处方优化及体外评价

目的:优化多潘立酮口腔崩解片的处方并评价其质量。方法:以直接粉末压片法制备多潘立酮口腔崩解片,采用HPLC法测定其含量,以崩解时限和体外溶出度为指标优化处方。结果:以6%的交联聚维酮作为崩解剂,制备的多潘立酮口腔崩解片外观圆整光洁,硬度为(3.3±0.8)kg/cm2,脆碎度<1%,体外崩解时限和口腔内崩解时限分别为(9.00±0.56),(17.00±2.00)s,15min的累积溶出度为(99.22±0.38)%。结论:按最优处方制备的多潘立酮口腔崩解片符合《中华人民共和国药典》2010年版的要求,质控方法准确可靠。     

胃复安致小儿锥体外系反应94例

胃复安广泛用于治疗恶心,呕吐,反流性食管炎和放射性胃肠检查等,为临床常用胃肠道药物,但可引起锥体外系症状,尤以小儿多见,现将近年本组94例报告如下。     

Preparation and in-vitro evaluation of sustained-release metoclopramide hydrochloride microspheres

Abstract

Sustained-release metoclopramide microspheres were successfully prepared using cellulose propionate polymer at 1:2 drug to polymer ratio employing solvent evaporation technique and using acetone as the polymer solvent. The prepared microspheres at three stirring speeds were characterized with regard to their drug content, particle size distribution, surface topography using SEM and their release profiles at two different pHs at 37°C. The surface of all samples was smooth with very few irregular elevations or depressions. The average particle size decreases as the rotational speed increases and was found to be 1320, 774 and 345 μm at 600, 900 and 1200rpm, respectively. The average % drug entrapped was found to be 90.5, 100.1 and 60.0% at 600, 900 and 1200 rpm, respectively. Small differences in the release rate were observed due to different rotation speeds with an apparent lower dissolution for batches produced at 1200 rpm probably due to the properties of the coat. The effect of storage under accelerated conditions for 10 weeks on the release characteristics of these microspheres was also studied. The release properties of the microspheres did not change after storing them at 40°C/80% relative humidity for 10 weeks.     

Pharmacokinetics of high-dose metoclopramide in cancer patients

The introduction of new cytotoxic drug regimens has been associated with an increase in the incidence and severity of adverse effects. This in turn has highlighted the need for more effective adjuvant therapy. The use of metoclopramide for the prophylaxis of nausea and vomiting, in high intravenous doses (50 to 1000 mg), has become established since 1981. As a lipid-soluble drug, metoclopramide has a large volume of distribution. The reported mean values after high doses range between 2.8 and 4.6 L/kg. The mean values for total body clearance and terminal half-life range from 0.31 to 0.69 L/kg/h and from 4.5 to 8.8 hours, respectively. The values of these pharmacokinetic parameters are essentially similar to those obtained after conventional doses (less than 50mg). Pharmacokinetic parameters appear unaffected by age, although no high-dose study has been conducted in children. Bodyweight is apparently correlated with clearance. An influence of renal function indices on terminal half-life and clearance has been shown, which is rather surprising since renal clearance accounts for only 20% of the total clearance. No thorough investigations exist which examine the influence of hepatic disease, cancer type and cytotoxic drug regimen on the disposition of metoclopramide. A relationship between dose (or concentration) and therapeutic or adverse effects of metoclopramide is outlined. The therapeutic benefit of high doses (up to 14 mg/kg) may be dependent on age, and on the combination of cytotoxic drugs. The advantages of high doses of metoclopramide are most apparent when the drug is used as protection against the adverse effects of high doses of cisplatin (greater than 60 mg/m2). Despite considerable pharmacokinetic variability, intravenous administration of high doses of metoclopramide is relatively safe due to its large therapeutic index.     

无痛人工流产患者围术期护理分析

目的探讨采用无痛人工流产终止妊娠的临床效果及围术期护理方法。方法将本院收治的236例患者随机分为对照组和观察组,两组患者均采用无痛人工流产术终止妊娠。对照组采用常规护理方法,观察组采用综合护理措施。分析两组护理效果及手术并发症发生情况。结果观察组患者对护理服务满意度显著高于对照组,差异有统计学意义(P<0.05)。观察组患者术后并发症发生情况显著少于对照组,差异有统计学意义(P<0.05)。结论采用综合护理患者满意度高,手术并发症少,值得临床推广应用。     

The absorption and elimination of metoclopramide in three animal species.

The absorption and elimination of metoclopramide have been studied in the rat, rabbit and dog. Thin-layer chromatography followed by photodensitometry was used for the analysis of the unchanged drug and its metabolites. N-De-ethylation is an important Phase I metabolic reaction and conjugation with glucoronic acid and sulphate is a major route of metabolism, particularly in the rabbit. The pharmacokinetic parameters after intravenous administration showed little interspecies variation. First order elimination kinetics with short half-lives and high apparent volumes of distribution (greater than 1.1 kg(-1)) were observed. Major interspecies variations were seen after oral administration of high doses of the drug. Metoclopramide was eliminated slowly after oral administration to rats. The findings in the rabbit and in the dog suggest that the liver plays an active role reducing the systemic availability of unchanged metoclopramide after oral administration.