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Adverse events of dopamine-blocking agents include acute dystonic reactions and oculogyric crises (OGCs). OGCs may be recurrent on maintenance of or re-exposure to the drug. Thus, complete withdrawal is recommended. Recurrent episodes of acute dystonia despite withdrawal and the lack of further exposure to antidopaminergic agents are usually not seen. Here, we report three cases with recurrent OGCs despite complete withdrawal of neuroleptics. Triggering or priming factors were a single dose of haloperidol in two cases and a single dose of metoclopramide in one case. Episodes reoccurred spontaneously, but responded to anticholinergics. The pathomechanisms of acute dystonic reactions and OGCs remain unclear. Parallels to levodopa-induced dyskinesias in Parkinson's disease, as well as to dopa-responsive dystonia, paroxysmal dyskinesias, and channelopathies are discussed here. Whether there is a genetic susceptibility or some other reason for only some patients developing this phenomenon remains unclear.
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Forty-seven infants and children suffering from chronic vomiting or regurgitation, participated in a two-week double-blind trial comparing 1% drops of domperidone, 1% metoclopramide drops or placebo. The dose was 0.3 mg/kg given t.d.s. before meals. Both active medicaments were significantly more effective than placebo in controlling the symptoms and domperidone was also significantly superior to metoclopramide. It is concluded, in view of the good safety margin with domperidone, that this drug could become the treatment of choice in such cases.
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In 20 patients with diagnosis of functional dyspepsia due to dysmotility and/or reflux, the effectivity and tolerance of two prokinetic drugs--metochlopramide (MCP) (10 mg. three daily doses, vo) and cinitrapide (CTP) (1 mg., 3 daily doses, vo)--were assessed using a protocol of a propective and cross-sectional study after a blank period. Following the treatment with MCP and CTP, statistically significant improvements were observed in the intensity/severity of postprandial epigastric fullness, flatulence, epigastralgia, pyrosis, active regurgitations and anorexia. The MCP was more effective for the improvement of vomiting in these patients; however, the number of defecations per week increased significantly only after the CTP therapy. The therapeutical effectivity of both drugs, according to a subjective and objective global assessment was similar, with good results of 60-65% for MCP and 55-60% for CTP. Tolerance of both drugs was good. None of the patients spontaneously referred to the presence of side effects and only 3 patients (15%) treated with MCP and 2 patients (10%) treated with CTP mentioned some of the suggested side effects, which were absent before the onset of treatment. Both drugs produced an increase in the levels of Prolactine, but their average values were within the normal range. Only in two patients treated with MCP and in one patient treated with CTP, values slightly higher than the upper normal limit were observed. No significant differences were observed when comparing the results obtained with MCP therapy and CTP therapy.
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The authors studied whether metoclopramide decreases the incidence of emesis after spinal anesthesia supplemented with subarachnoid morphine.
Tropisetron is a serotonin (5-hydroxytryptamine; 5-HT) antagonist that is primarily used in the prevention of chemotherapy-induced nausea and vomiting. Antagonism of 5-HT3 binding sites in the peripheral and central nervous system is the probable mechanism of prevention of acute nausea and vomiting. Effects on delayed nausea and vomiting are less well understood as these are probably not mediated solely by 5-HT3 receptors. Tropisetron monotherapy is effective for the control of acute, and to a lesser extent delayed, nausea and vomiting in patients receiving moderately to severely emetogenic chemotherapy. The combination of dexamethasone and tropisetron is more effective than monotherapy. Complete control of cisplatin-induced nausea and vomiting was obtained in 69 to 97% of patients receiving the combination compared with 46 to 80% receiving tropisetron monotherapy in randomised trials. There were generally no significant differences between the control of acute or delayed nausea and vomiting provided by tropisetron, ondansetron or granisetron in randomised, comparative trials. The antiemetic efficacy of tropisetron was maintained over multiple cycles of chemotherapy. Most comparative studies showed tropisetron monotherapy to be more effective than metoclopramide in controlling acute nausea and vomiting, with the exception of 1 study which showed similar efficacy. However, high dose metoclopramide plus dexamethasone provided similar control of delayed emesis to tropisetron plus dexamethasone. Tropisetron is also effective in children, including those who responded poorly to previous antiemetic treatment. Tropisetron and ondansetron generally have similar efficacies in this population. The drug enhanced patients' quality of life and was well tolerated by adults and children alike. The recommended oral and IV dosage of tropisetron is 5 mg once daily; there is no increase in efficacy with doses >5 mg.
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Nausea and vomiting are the most distressing and common side effects of cancer chemotherapy which often result in patient noncompliance. In the present study, standardized methanolic and n-butanolic fractions of Bacopa monnieri were evaluated against cisplatin-induced emesis in the pigeon in relation to their activity on central and intestinal neurotransmitters levels. Cisplatin (7.0 mg/kg, i. v.) induced reproducible emesis without lethality in healthy pigeons. The methanolic (10-40 mg/kg) and the bacoside-rich n-butanolic fractions of B. monnieri (5-20 mg/kg), as well as the antioxidant N-(2-mercaptopropionyl) glycine (10 mg/kg), attenuated cisplatin-induced emesis by 66.3% (p < 0.05), 71.6% (p < 0.001), and 76.5% (p < 0.001), respectively, where the standard antiemetic metoclopramide (30 mg/kg) produced a 48.9% reduction (p < 0.01). The methanolic and n-butanolic fractions of B. monnieri at all of the doses tested significantly reduced the serotonin concentration (p < 0.001) in the brain stem and intestine 3 h after cisplatin administration, while at the 18th h, B. monnieri treatments attenuated not only the dopamine upsurge in the area postrema and brain stem (p < 0.05-0.001), but also the intestinal 5-HT concentration (p < 0.01-0.001). B. monnieri treatments alone did not alter the basal neurotransmitters or their metabolites in the brain areas and intestine. The prolonged suppressive effect of B. monnieri treatments on the behavioral signs of cisplatin-induced emesis, the subsequent supportive neural evidence, and the safety and tolerability profile suggest that B. monnieri methanolic and bacoside-rich n-butanolic fractions might be a valuable adjunct in the treatment of emetogenic chemotherapy, and this warrants further study in other models of emesis.
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This study suggests that metoclopramide may reduce the rate of pneumonia and may improve other clinical outcomes in patients with subacute stroke fed via nasogastric tube. These findings need to be confirmed in larger randomized and blinded trials.
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Because all consults were included, feeding tube placements occurred in surgical and medical patients in the intensive care unit and on the ward. Of the 135 tube placements performed, 129 (95%) were successfully placed postpylorically, with 84% (114 of 135) placed at or beyond D3. Average time for tube placement was 28 min (10 to 90 min). One radiograph was required for 92% of the placements; eight of 135 (6%) required two radiographs. No acute complications were associated with the tube placements.
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Recent studies have shown that administration of the anterior pituitary hormone, prolactin, after hemorrhage restored the depressed immune responses that are observed under those conditions. Because metoclopramide (MCP) is known to increase prolactin secretion and ultimately plasma prolactin levels, we attempted to determine whether administration of metoclopramide after hemorrhage produces any beneficial effects on the depressed splenocyte and peritoneal macrophage immune function after severe hemorrhage.
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The effect of metoclopramide has been studied on the emptying of solid meals labelled with (51)Cr and monitored with a gamma camera. Metoclopramide, 10 mg iv or a dummy injection, was given randomly and double blind to 10 normal subjects and to 10 patients within three months of a truncal vagotomy and pyloroplasty. All were tested in the recumbent position. Metoclopramide had no effect on emptying rates in the normal subjects nor in four postvagotomy patients who had emptying within the normal range (T(1/2) 30-150 min). In six patients with abnormally delayed emptying (mean T(1/2) 369 min) metoclopramide produced a significant improvement (mean T(1/2) 194 min, p < 0.01).
A sharp increase in serum and CSF prolactin (PRL) values after acute metoclopramide (10 mg i.m.) administration was found in six male patients without endocrine diseases. Peak values occurred simultaneously in serum and in CSF. This finding suggests the possibility that CSF PRL content depends also on the retrograde transport from pituitary gland.
To evaluate the prophylactic effect of low-dose dexamethasone (5 mg) on postoperative nausea and vomiting (PONV) in women undergoing ambulatory laparoscopic surgery. Metoclopramide and saline served as controls.
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All the tissues revealed AT2R1, MC2R, AVPR, and 5-HT4R mRNA expression. LHR mRNA was found in normal adrenals and 13 adrenal tumors. By contrast with normal adrenals tumorous adrenal tissue expressed GnRHR mRNA (4/15) and TSHR mRNA (1/15). Both the patients and controls responded to posture, ACTH, glucagon, AVP, and MCP. Specific responses were seen in one patient following TRH and three patients following GnRH stimulation.
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BACKGROUND AND PURPOSE The substituted benzamide, metoclopramide, is a dopamine receptor antagonist and is widely prescribed in the symptomatic treatment of nausea and vomiting, although it can cause adverse motor and non-motor side effects. The effects of metoclopramide on brain metabolism have not been investigated to date. EXPERIMENTAL APPROACH To determine the effects of metoclopramide on brain function, cerebral perfusion changes after a single oral dose were assessed in healthy volunteers using magnetic resonance imaging (MRI) techniques. Arterial spin labelling (ASL) perfusion MRI was used to measure cerebral blood flow before and after metoclopramide. Blood haemodynamics in the vertebral and internal carotid arteries were evaluated using phase-contrast MRI. KEY RESULTS Metoclopramide altered haemodynamics in the carotid arteries and the cerebral perfusion. Perfusion increased bilaterally in the putamen, consistent with antagonism of dopamine D(2) receptors by metoclopramide and possibly related to its motor side effects. In contrast, reduced perfusion was observed in the insular cortices and anterior temporal lobes. In addition, functional connectivity between the insular cortex and the dorsolateral prefrontal cortex was decreased. These cortical changes affecting neural circuits between high-order association areas may underlie certain neuropsychiatric conditions occasionally reported after metoclopramide administration. CONCLUSIONS AND IMPLICATIONS The present results show the sensitivity of ASL to detect small changes in regional blood flow, closely related to brain function, after a single pharmacological challenge, highlighting the potential of this technique for human pharmacological studies.
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IV lidocaine (0.5 mg/kg) should be given with a rubber tourniquet on the forearm, 30 to 120 s before the injection of propofol; lidocaine will prevent pain in approximately 60% of the patients treated in this manner.
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The effect of metoclopramide on cardiac repolarization was evaluated in 10 healthy male volunteers in the supine position. Metoclopramide (10 mg) or placebo was administered intravenously at random in a double-blind, cross-over manner to the participants during continuous electrocardiographic recording in the supine position. The 30-min stationary segments of the recordings before and after drug administration were used to investigate QT dynamicity.
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These results thus indicate, that ICS 205-930 is a very effective antiemetic for cancer chemotherapy-induced emesis in man. Given as a single dose prior to the chemotherapeutic agent, ICS 205-930 inhibits emesis and nausea for at least 24 hr. Together with the lack of extrapyramidal side-effects, these properties of ICS 205-930 indicate a clear superiority to the current therapeutic standard metoclopramide.
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The efficacy of ondansetron 4 mg was compared with metoclopramide 10 mg for the prevention of post-operative nausea and vomiting in patients after major gynaecological abdominal surgery. Anaesthesia was standardized using thiopentone, atracurium and methadone for induction followed by isoflurane in nitrous oxide-oxygen mixture. Fifty patients were randomized in a double-blind fashion to either receive intravenous (i.v.) ondansetron 4 mg or metoclopramide 10 mg during closure of the pelvic peritoneum. The incidence and frequency of vomiting, and the incidence of severe nausea was recorded for 24 h after surgery. One patient was excluded because of respiratory depression. In the first 4 h after surgery, five patients (20%) in the ondansetron group (n = 25) and eight patients (33%) in the metoclopramide group (n = 24) vomited, whereas at 4-12 h, this increased to 11 patients (44%) and nine patients (37.5%) respectively. The incidence was 52 and 37.5% respectively in the subsequent 12-24 h. The highest incidence of nausea was in the first 4 h after surgery, being 56 and 37.5% in the ondansetron and the metoclopramide groups respectively. This decreased to less than 25% in both groups in the 12-24 h period. Ondansetron 4 mg and metoclopramide 10 mg had similar but short lasting efficacy for the prevention of vomiting in patients who received continued opioid analgesia after major gynaecological surgery.
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There is no agreed technique for minimizing PONV (Postoperative Nausea and Vomiting) although some techniques are associated with low rate. Best practice involves identifying high risk patients and surgeries and use of prophylactic antiemetic where appropriate. Laparoscopic gynaecological surgery has high incidence of PONV (54-92%). An audit on the practice of antiemetic use in diagnostic laparoscopic gynaecological surgery was done in the department of anaesthesia of Aga Khan University Hospital from 1st January to 30th June 2006. We included all the patients scheduled for this procedure lasting less than 90 minutes. Anaesthetist involved in the audit identified the patient falling into the predetermined risk factors. The following facts about antiemetic were noted; whether the patients received any antiemetics or not, if it was prophylactic or rescue, type, dose route and timing of antiemetic. Patients were rated for any signs of nausea and vomiting (retching) after extubation in the operating room by the anaesthetist and in the recovery room or surgical day care unit (SDC) by the nurse who was briefed about it and was cross checked by the anaesthetist involved in the audit. This was done for two hours postoperatively. Our results showed that only 75% of patients with risk factors received an antiemetic. The most commonly used antiemetic was Metoclopramide. Eight percent of the patients had vomiting and all of them had received a prophylactic antiemetic. They received the same rescue antiemetic. This audit recommended institutional guidelines for the management of PONV. These should be based on evidence obtained from the published peer-reviewed studies. These guidelines could be communicated to health care workers involved in postoperative management of patients to help them achieve an optimal management strategy for this uncomfortable postoperative complication.
Twenty untreated HIV infected men category C2 or C3, mean (SD) age 26.9 (6.3) years, were compared to 14 clinically healthy HIV-negative men, age 25.4 (2.3) years.
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Gastroparesis, or delayed gastric emptying, is a common cause of chronic nausea and vomiting as seen in a gastroenterology practice. Diabetic, postsurgical, and idiopathic causes remain the three most common forms of gastroparesis. In addition to nausea and vomiting, symptoms of gastroparesis may include early satiety, postprandial fullness, and abdominal pain. Physiologic changes that may explain symptoms in patients with gastroparesis, in addition to delayed gastric emptying, include impaired fundic accommodation, antral hypomotility, gastric dysrhythmias, pylorospasm, and perhaps visceral hypersensitivity. Diagnosis of gastroparesis is best determined using a radioisotope-labeled solid meal with scintigraphic imaging for at least 2 hours, and preferably 4 hours, postprandially. Most commonly, a 99mTc sulfur colloid-labeled egg sandwich with imaging at 0, 1, 2, and 4 hours is used. Extension of the gastric emptying test to 4 hours improves the accuracy of the test, but unfortunately, this is not commonly performed at many centers. Emptying of liquids remains normal until the late stages of gastroparesis and is less useful. The aims of treatment should be to control symptoms and maintain adequate nutrition and hydration. Patients should be advised to eat small meals and to limit their intake of fat and fiber. Additional dietary recommendations may include increasing caloric intake in the form of liquids. For diabetic patients, control of blood glucose levels is important, as symptom exacerbation is frequently associated with poor glycemic control. Specific treatment often begins with metoclopramide, 10 mg, up to four times daily, after a discussion of possible side effects with the patient. An antiemetic agent, such as prochlorperazine, 5 to 10 mg orally or 25 mg by suppository, can be added on an as-needed basis every 4 to 6 hours to control nausea. If these antiemetic medications are not effective, or if side effects develop, orally dissolving ondansetron, 8 mg every 8 to 12 hours, can be tried on an as-needed basis. If this regimen is unsuccessful, then alternative prokinetic agents--erythromycin, 125 mg, or tegaserod, 6 mg, prior to meals--can be tried. For cases refractory to these treatments, referral to a center with US Food and Drug Administration permission to use domperidone should be considered. Alternatively, symptom modulators such as low-dose tricyclic antidepressants can be tried to reduce symptoms, but these do not improve gastric emptying. In patients for whom all medical therapy fails, other options that are tried at experienced centers include the injection of botulinum toxin into the pylorus, placement of a feeding jejunostomy, and/or placement of a gastric electrical stimulator.
The maximum PONV percentages were 41.1%, 32.7%, and 37% in groups 1, 2, and 3, respectively. The consumption of antiemetics was similar in all groups. The number of patients who needed one or more additional antiemetics during the first 24 hours after surgery was 112 (56.6%), 57 (58%), and 60 (60%) in groups 1, 2, and 3, respectively.