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A detailed search strategy was used to find a relevant meta-analyses, systematic reviews and randomized double-blind controlled trials. Recommendations were graded with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group, using a consensus group. In addition, a general literature review and expert consensus were used for aspects of acute therapy for which randomized controlled trials were not available.
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The release of metoclopramide hydrochloride (a very water soluble cationic drug) and diclofenac sodium (a sparingly soluble anionic drug) from pellets coated with Surelease containing hydroxypropylmethylcellulose (HPMC) at different coating loads was investigated. The release rates of either drug at each coating composition decreased as the coating load increased. Inclusion of HPMC E15 increased the release rates of both drugs compared to pellets coated only with Surelease. This was thought to be due to the leakage of the soluble part of the film (HPMC E15) during dissolution, which left pores for drug release. The Surelease:HPMC E15 ratio had a major role in the release rates of drugs. Addition of HPMC E15 into Surelease did not change the release mechanism for metoclopramide hydrochloride (the mean value of n approximately 0.57) from that of Surelease alone, and diffusion remained the main mechanism controlling the release. However, the release exponent (approximately 1.28) increased for diclofenac sodium on addition of HPMC E15, indicating a dissolution-controlled mechanism. Despite its lower water solubility, diclofenac sodium was released slightly faster than metoclopramide hydrochloride from pellets coated with Surelease containing HPMC E15 at equivalent coating loads.
Nausea and vomiting are common complaints in the postoperative period and contribute to patient distress and delay of discharge for outpatient surgical procedures. Laparoscopic procedures are associated with a high incidence of postoperative nausea and vomiting (PONV) episodes. Parenteral use of metoclopramide prevents and treats PONV. The intranasal route provides rapid and complete absorption of metoclopramide without many of the adverse effects observed with parenteral administration of the drug. We performed a prospective, double-blinded, randomized, placebo-controlled study to evaluate the safety and efficacy of metoclopramide 20 mg administered intranasally for emetic prophylaxis in laparoscopic surgery patients. The results from 109 patients enrolled in the study showed that this intranasal dose of metoclopramide may be ineffective in preventing the occurrence of PONV. The poor performance of the intranasal metoclopramide formulation in this study cannot be attributed to patient-specific and perioperative factors. It may be due to an inadequate dose or slow absorption of the drug. The small sample size, however, may also have been a factor.
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Certain drugs, particularly clozapine and clonidine, have been reported to increase selectively the latency to initiate brain stimulation (the ON latency) in a shuttlebox test of self-stimulation, suggesting a preferential attenuation of the "reward" component. The pharmacological selectivity of this reported effect was systematically evaluated. At doses that blocked bar-pressing self-stimulation, metoclopramide (3 mg/kg), prazosin (3 mg/kg) clonidine (0.1mg/kg), clozapine (3 mg/kg)and haloperidol (0.3 mg/kg), all elevated the ON latency to a greater extent than the OFF latency. Methocarbamol (200 mg/kg), and a muscle relaxant, also elevated the ON latency preferentially but the magnitude of this preferential effect was smaller than that produced by the other drugs. A hurdle in the center of the shuttlebox increased the ON and OFF latencies nonselectively. The shuttlebox procedure does not clearly discriminate among various substances that interfere with noradrenergic or dopaminergic neurotransmission, but the common profile produced by the these substances is distinguishable to some degree from simple motor disruption.
Four to 6 weeks of a proton-pump inhibitor alone or in combination with a prokinetic agent successfully diagnoses and treats four of five patients with GERD-related cough. Twenty-four-hour esophageal pH monitoring will confirm the diagnosis in the others. These patients may be candidates for fundoplication. Nonresponders often aspirate as an additional aggravating factor.
A study was carried out in 10 healthy volunteers, aged between 22 and 28 years, to investigate the pharmacokinetics of an aspirin-metoclopramide combined preparation compared with those of the individual components given alone. Blood levels were determined before and after administration of a single dose of the three medications given at weekly intervals. No significant difference was found in the bioavailability of either the aspirin or metoclopramide from the combination as compared to the individual components.
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Only a few studies have been carried out in children on the prevention of chemotherapy-induced acute emesis. 5-HT3 antagonists have been shown to be more efficacious and less toxic than metoclopramide, phenothiazines and cannabinoids. The optimal dose and scheduling of the 5-HT3 antagonists has not been identified. Combinations of a 5-HT3 antagonist and dexamethasone show increased efficacy with respect to 5-HT3 antagonists alone. All pediatric patients receiving chemotherapy of high or moderate emetogenic potential should receive a combination of a 5-HT3 antagonist and dexamethasone to prevent acute emesis. No studies have specifically evaluated antiemetic drugs in the prevention of chemotherapy-induced delayed and anticipatory emesis in children.
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Modified resuscitation regimens and cytokine blockade/receptor antagonism after trauma have not been successful in decreasing the mortality rates from sepsis in trauma patients; therefore, an alternative approach using endocrine targets as modulators or inhibitors may be useful. Information regarding the influence of gender and hormones on immune and cardiovascular responses after nonthermal trauma-hemorrhagic shock is, on the one hand, considerable but, on the other hand, disappointingly incomplete. Trauma-hemorrhagic shock produces gender dimorphic immune and cardiovascular responses; men exhibit cardiovascular depression and are immunosuppressed, whereas proestrus women do not show cardiovascular or immunologic depression under those conditions. Furthermore, experimental studies have demonstrated the use of hormones, hormone antagonists, sex steroids, and receptor antagonists as salutary adjuncts, without any adverse effects on gastrointestinal, hepatic, and renal functions, for restoring the depressed immune and cardiovascular responses after trauma-hemorrhage. Thus, flutamide, dehydroepiandrosterone, metoclopramide, and 17beta-estradiol, which are readily availably clinically and do not produce any adverse hemodynamic effects, appear to be safe and novel agents/hormones for the treatment of immune and cardiovascular depression after severe blood loss in male and female trauma victims.
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The palonosetron-dexamethasone combination was more effective as compared to only palonosetron for reducing PONV after laparoscopic cholecystectomy.
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The response of plasma aldosterone, cortisol and adrenocorticotropin (ACTH) to the dopamine antagonists metoclopramide and domperidone, administered intravenously in a dose of 1 mg/kg, was investigated in healthy volunteers. Within 15 min after metoclopramide administration, plasma aldosterone (+ 99%), cortisol (+ 75%) and ACTH (+ 55%) increased (p less than 0.001), whereas the plasma levels of these hormones were not altered after domperidone. The differential responses of plasma aldosterone and cortisol to high doses of metoclopramide and domperidone are therefore, at least partially, mediated via the enhanced adrenal stimulation by ACTH after metoclopramide.
In 10 untreated epileptic patients, we evaluated the functional integrity of the hypothalamic-pituitary axis before and during chronic treatment with sodium valproate, a gamma-aminobutyric acid-mimetic compound. The GH response to L-dopa (250-500 mg po) was absent in 3 and severely impaired in 2 of the 10 patients though being, on the average, only slightly lower in the epileptic subjects than in normal controls. Conversely, the GH rise following GHRH (0.5 micrograms/kg body weight, iv) was normal in 9 of the patients. A significant blunting of the GH response to L-dopa occurred in the 7 patients initially responsive after 6 month of sodium valproate (P less than 0.05). The GH response to GHRH also underwent an evident though not significant attenuation. The ACTH and the ACTH/cortisol elevations elicited by metyrapone (35 mg/kg body weight infused over 4 h), and by CRH (1 microgram/kg body weight, iv), respectively, normal before treatment, were significantly impaired (P less than 0.05, less than 0.01) during antiepileptic therapy. Prolactin and TSH dynamics following metoclopramide (0.1 mg/kg body weight, iv) and TRH (200 micrograms iv) remained normal over the whole study period. Growth arrest ensued in 1 patient after 6 months of sodium valproate and disappeared after drug withdrawal. These observations point to a defective hypothalamic control of GH secretion in some epileptic patients. They also indicate that chronic administration of sodium valproate, hence activation of central gamma-aminobutyric acid system, results in a blunting of the stimulated GH and ACTH secretion. Occasionally, a reversible arrest of skeletal growth may also ensue.
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Tyrosine hydroxylase (TH) deficiency is associated with a broad phenotypic spectrum. Based on severity of symptoms/signs as well as responsiveness to levodopa therapy, clinical phenotypes caused by TH pathogenic variants are divided into (1) TH-deficient dopa-responsive dystonia (DRD: the mild form of TH deficiency [DYT5b]), (2) TH-deficient infantile parkinsonism with motor delay (the severe form), and (3) TH-deficient progressive infantile encephalopathy (the very severe form). In individuals with TH-deficient DRD, onset is between age 12 months and six years; initial symptoms are typically lower-limb dystonia and/or difficulty in walking. Diurnal fluctuation of symptoms (worsening of the symptoms toward the evening and their alleviation in the morning after sleep) may be present. In most individuals with TH-deficient infantile parkinsonism with motor delay, onset is between age three and 12 months. In contrast to TH-deficient DRD, motor milestones are overtly delayed in this severe form. Affected infants demonstrate truncal hypotonia and parkinsonian symptoms and signs (hypokinesia, rigidity of extremities, and/or tremor). In individuals with TH-deficient progressive infantile encephalopathy, onset is before age three to six months. Fetal distress is reported in most. Affected individuals have marked delay in motor development, truncal hypotonia, severe hypokinesia, limb hypertonia (rigidity and/or spasticity), hyperreflexia, oculogyric crises, ptosis, mental retardation, and paroxysmal periods of lethargy (with increased sweating and drooling) alternating with irritability.
Functional Gastrointestinal disorders are not serious ailments but have a key impact on quality of life. overall dyspeptic symptom relief rates were significantly high in the Levosulpiride group (p<0.004) as compare to Domperidone and Metoclopramide groups. A proper understanding of disease process by health care personnel and by sufferer is obligatory to enhance the quality of life and daunting the self/over the counter medication in this condition.
The effectiveness of metoclopramide in reducing gastrointestinal-induced artifacts in myocardial perfusion imaging (MPI) is a subject of debate. We examined the significance of this pharmacological intervention in the quality of images obtained from MPI studies.
Information on the significance of an elevated urinary dopamine is limited and can lead to misinterpretation of the cause of such a finding. This laboratory-based study examines the associations with elevated dopamine gathered from a significant number of patients.
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A 38-year-old man was admitted for arthroscopic repair of a right shoulder injury. An interscalene block was attempted in the preoperative area and combined with general anesthesia for surgery. The procedure lasted 5(1/4) hours. After transfer to the recovery room, the patient complained of severe right shoulder pain and had no discernible sensory or motor block. He was noted to be hiccuping. The patient was discharged home the following morning but returned 2 days later complaining of persistent hiccups since surgery, with associated insomnia and nausea. He was readmitted and given chlorpromazine 50 mg intravenously every 8 hours and metoclopramide 10 mg intravenously every 6 hours. The patient was discharged 4 days later on chlorpromazine 25 mg by mouth every 8 hours and baclofen 5 mg by mouth every 12 hours, with hiccups greatly reduced in both intensity and frequency. Hiccups ceased 1 day after discharge. Eighteen days after surgery, he was off all medication with no return of his hiccups; 1 month later he remains hiccup free.
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Dopamine decreases gastric tone in a dose-related manner and 10 mg of the dopamine-antagonist metoclopramid is not enough to fully reverse these effects.
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Metoclopramide (MCP), a dopamine antagonist, was recently used as the pharmacological test for the diagnosis of pheochromocytoma. There have been no reports involving false negative cases in the MCP test. We experienced a rare case of pheochromocytoma which showed a negative MCP test, and it caused a failure of the diagnosis. A 51-year-old man visited our hospital with a sudden onset of headache and palpitation. Blood pressure was 218/98 mmHg at another hospital. When he came to our hospital, blood pressure returned to normal (120/80 mmHg), and both serum adrenaline (E) and noradrenaline (NE) were within normal limits. A computed tomography, magnetic resonance imaging, and angiography demonstrated a 1.8 x 1.8 cm right adrenal mass. No changes in blood pressure and plasma catecholamine were observed following the injection of 10 mg of MCP. The pathologically resected right adrenal gland contained a typical pheochromocytoma which was 1.0 x 1.0 cm in size and weighed 8 g. The detailed mechanism of the negative MCP test in this case was not known but might be related to the small size of the tumor.
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The problem of classifying benzamides is, in general, the same as classifying neuroleptics. A pharmacological classification of neuroleptics can be established on the basis of the following criteria: specificity of action on dopaminergic receptors; penetration into the CNS; dopaminergic profile in the CNS; relative binding with respect to subclasses of DA; preferential antagonism of certain effects of apomorphine; preferential affinity for dopaminergic structures; activating effects on DA systems at low doses; different clinical effects: antiemetic, psychiatric (antihallucinatory and disinhibitory), neurologic. A relationship between biochemical, behavioural and clinical effects is proposed: antihallucinatory effect: decrease of dopaminergic function; disinhibitory effect: increase of dopaminergic function. We emphasize the problem of doses used because the different effects occurred for a given drug at different doses. This hypothesis suggests that positive symptomatology of schizophrenia is related to hyperdopaminergic activity, negative symptomatology is related to hypodopaminergic activity. Classification of benzamides: metoclopramide: peripheral dopaminolytic activity antiemesis without psychiatric or neuroleptic effects with low doses. sulpiride, tiapride, DAN 2163: peripheral effects + preferential blockade of D3 and D4 receptors, central DA activation with low doses, disinhibitory effects. With high doses, decrease of specificity for subclasses of DA receptors, central DA inhibition, antihallucinatory effects but little extrapyramidal symptomatology and sedation. sultopride: central DA inhibition, antihallucinatory effects, sedative and neurological effects.
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The determination of metoclopramide hydrochloride is spectrophotometrically determined by the Bratton-Marshall method in a flow injection assembly. The required nitrite is prepared on-line in the flow assembly by reducing a nitrate solution with the aid of a copperised cadmium solid-phase reactor. The calibration graph is linear over the range 0.5-85 mg l(-1), with a relative standard deviation (RSD) of 0.89%, and sample throughput of 51 samples h(-1). The method is easy and simple, and it is applied to determination of metoclopramide in some pharmaceutical formulations. The method eliminates the need for frequent preparation of unstable nitrite solutions.
5-Hydroxytryptamine-3 RAs are superior to placebo and other antiemetics for prevention of emesis, but little benefit was identified for nausea prevention. 5-Hydroxytryptamine-3 RAs are suggested for prevention of emesis. Limited evidence was found regarding delayed emesis, adverse events, quality of life, or need for rescue medication. Future randomized, controlled trials should evaluate different 5-HT3 antiemetics and new agents with novel mechanisms of action such at the NK(1) receptor antagonists to determine the most effective drug. Delayed nausea and vomiting should be a focus of future study, perhaps concentrating on the palliative cancer population.
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N(2)O increases the incidence of postoperative nausea after gynecologic laparoscopic surgery. This preliminary finding indicates that N(2)O may increase PONV in a dose-dependent fashion. A study with a sample size of >400 patients in each group would be necessary to demonstrate a statistically significant difference among each of these three groups. We do not recommend using a high concentration of N(2)O in this clinical setting.