Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cisplatin (cis-diammine-dichloro-platinum) administered at a dose of 3 mg/kg iv induced a reproducible and characteristic emetic response in the dog. It was characterized by a latency period (90-120 min) and multiple emetic episodes occuring within 5 hours following drug administration with sporadic delayed emesis later within the first 24 hours. There was a qualitative similarity between the emetic response of Cisplatin seen in dogs and cancer patients. Metoclopramide (1, 3 mg/kg sc) was found to be the most effective antagonsit of Cisplatin emesis in the dog while haloperidol (1 mg/kg sc) and chlorpromazine (0.3, 1, 3 mg/kg sc) offered a less complete protection. Nabilone (0.1 mg/kg iv) and AL-1612 (1 mg/kg sc) failed to to demonstrate any significant activity. A relationship between antagonism patterns of emetic responses induced by Cisplatin and apomorphine was discussed.
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PMID:Antagonism of cisplatin induced emesis in the dog. 44 17

Metoclopramide or placebo was administered postoperatively in a randomized, double-blind fashion to 115 patients undergoing laparotomy. The effect of metoclopramide on postoperative adynamic ileus (PAI) was evaluated. The patients were stratified into two groups: Group A--those with laparotomy without a gastrointestinal anastomosis or ostomy procedure, and group B--those with laparotomy undergoing an anastomosis or ostomy procedure. Metoclopramide reduced nausea and emesis postoperatively. However, the only significant effect on postoperative adynamic ileus was an earlier return to tolerance of solid foods in the patients in Group A.
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PMID:The effects of metoclopramide on postoperative ileus. A randomized double-blind study. 58 60

Metoclopramide, 4-amino-5-chloro-2-methoxy-N-(2-diethyl-aminoethyl) benzamide, is advocated for use in gastro-intestinal diagnostics, and in treating various types of vomiting and a variety of functional and organic gastro-intestinal disorders. Published data have indicated that metoclopramide assists radiological identification of lesions in the small intestine, facilitates duodenal intubation and small intestine biopsy, and eases emergency endoscopy in upper gastro-intestinal haemorrhage. Metoclopramide reduces post-operative vomiting and radiation sickness, and ameliorates some types of drug-induced vomiting. It may provide symptomatic relief in dyspepsia and possibly in vertigo, reflux oesophagitis and hiccups, but further controlled trials are needed to confirm the efficacy of metoclopramide in these proposed areas of use. It promotes gastric emptying prior to anaesthesia. Its effects in healing gastric ulcer and preventing relapse of duodenal ulcer remain unproven. Side-effects are few and transient, though alarming extrapyramidal reactions can occur in a small proportion of patients receiving therapeutic doses but more usually following excessive doses in young subjects. They respond rapidly to withdrawal of the drug.
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PMID:Metoclopramide: a review of its pharmacological properties and clinical use. 78 7

Thirty-seven patients with Parkinsonism were treated with bromocriptine 2.5-300 mg daily. Bromocriptine, alone or combined with levodopa, caused a 20-30% reduction in disability scores in 11 patients treated for one year. Tolerance did not develop during this period. Bromocriptine treatment was not of value in six patients who had previously not responded or who had lost their response to levodopa. However, in four of five patients with response swings on levodopa due to rapid changes in plasma dopa levels, the addition of bromocriptine caused a more stable response. Dose response curves to bromocriptine 12.5, 25, 50, and 100 mg and to levodopa 250, 500, 1000, and 2000 mg were studied in seven patients. Levodopa 2 g had a greater therapeutic effect and caused a greater rise in plasma growth hormone concentration than bromocriptine 100 mg. Levodopa caused emesis more commonly and hallucinations less commonly than bromocriptine. Bromocriptine appears to be a less potent stimulant than dopamine, and has both pre- and post-synaptic effects. Metoclopramide 60 mg oral was given 30 minutes before bromocriptine or levodopa to establish whether this caused dopamine-receptor blockade. Metoclopramide acted as a competitive antagonist to the anti-Parkinsonism and growth hormone effect of both drugs and in individual cases prevented emesis and hallucinations. The fall in blood pressure due to bromocriptine or levodopa was not antagonised by metoclopramide. Central and peripheral vascular dopamine receptors may be different in nature.
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PMID:Bromocriptine in Parkinsonism: long-term treatment, dose response, and comparison with levodopa. 103 99

Reserpine (0.5 mg/kg i.m.) produced emesis in pigeons with 60% of the animals responding. Metoclopramide HCl at 10, 20 and 40 mg/kg p.o. administered 30 min before or after reserpine injection was effective in blocking reserpine emesis. Metoclopramide was unable to antagonize reserpine-induced sedation and hypotension in rats, thus inviting discussion of its possible mechanism in blocking reserpine emesis.
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PMID:Blockade of reserpine emesis in pigeons by metoclopramide. 114 17

Delayed gastric emptying, gastroparesis, is one of the sequelae of diabetes mellitus. Symptoms may include postprandial nausea, epigastric pain, bloating, vomiting, early satiety and unpredictable blood sugar fluctuations. Nowadays diagnosis is made by the measurement of gastric emptying with a radionuclide test meal. Using this technique some 50% of diabetic patients show signs of disordered gastric emptying. Relief is best delivered by agents promoting gastric emptying. In phase II single-dose studies metoclopramide, domperidone, cisapride, erythromycin and renzapride were all able to enhance gastric evacuation of solid and liquid meals in patients with diabetic gastroparesis. A few short term studies support the efficacy of domperidone and renzapride, but long term trials are lacking. Erythromycin, mimicking the potent gastrokinetic effect of motilin, may hold considerable promise for the future. Experience with erythromycin in diabetic gastroparesis is nonetheless very limited. To some extent the therapeutic effectiveness of metoclopramide and cisapride has been established in placebo-controlled trials. In trials with a placebo-controlled crossover design, however, only metoclopramide showed a sustained positive effect. Metoclopramide, which combines gastrokinetic and antiemetic properties seems, so far, the best therapeutic option in diabetic gastroparesis. Cisapride may be considered as a good alternative in cases where limited efficacy or side effects preclude the use of metoclopramide.
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PMID:Diabetic gastroparesis. A critical reappraisal of new treatment strategies. 128 Oct 70

The availability of radiolabelled ligands selective for various putative neurotransmitter receptor sites and the development of quantitative autoradiography has led to a greater understanding of the neuronal pathway and receptor subtypes involved in the vomiting reflex induced by various mechanisms both within the central nervous system and the periphery. Receptors for acetylcholine, dopamine, histamine and serotonin have been detected in a number of brain regions associated with the vomiting reflex, and provide a rational basis for the antiemetic action of drugs that inhibit receptor subtypes for these neurotransmitters. The basis of the antiemetic action of other drugs such as dexamethasone and the cannabinoids is still obscure. Some drugs act on more than 1 receptor subtype. Metoclopramide may inhibit both dopamine D2- and 5-HT3 receptors in producing its antiemetic effect. Both metoclopramide and domperidone appear to have additional peripheral actions that contribute to their effectiveness. The cannabinoids are effective in cytotoxic-induced vomiting, perhaps acting via endorphin receptors or by inhibiting prostaglandin synthesis. The effectiveness of 5-HT3 receptor antagonists may depend on the block of both central and peripheral neuronal 5-HT3 receptors. Vomiting constitutes a major disadvantage to the use of many drugs; vomiting induced by aminoglycoside antibiotics appears to be due to ototoxicity and is relieved by histamine H1-receptor antagonists. The protracted vomiting associated with the use of some cytotoxics in cancer chemotherapy may involve psychic components, the chemoreceptor trigger zone and peripheral sensory neurons. Both 5-HT3 and dopamine D2-receptor antagonists exert some control, the former being more effective with cytotoxics of high emetogenic potential, such as cisplatin. Serotonin 5-HT3 receptor antagonists or high doses of metoclopramide in combination with anxiolytics and steroids as well as greater attention to pharmacokinetic profiles of the drugs involved would appear to offer improved control. The use of dopamine receptor antagonists in controlling emesis induced by dopamine agonists used in Parkinson's disease poses theoretical problems which can be overcome by using drugs with selectivity for the chemoreceptor trigger zone, such as domperidone or metoclopramide. However, higher doses of these drugs may produce some impairment of therapeutic responses to the agonists. Muscarinic and nicotinic agonists currently under investigation in Alzheimer's disease pose another therapeutic dilemma as emesis is due to a central action of these compounds. Several sites may be involved including the chemoreceptor trigger zone and frontal lobes. Opiates may act through dopamine receptors or mu-receptors on dopaminergic nerves, but serotonergic mechanisms may also be involved in the action of some opiates.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pharmacological agents affecting emesis. A review (Part I). 137 16

A logical outgrowth of the early clinical success with ondansetron in phase I and phase II trials has been an interest in comparative antiemetic trials using conventional agents. Metoclopramide is generally acknowledged to be the single most effective conventional drug for the prevention of acute cisplatin-induced emesis and, therefore, was considered an appropriate agent for inclusion in comparative trials with ondansetron. Three phase III trials comparing metoclopramide with ondansetron for the prevention of acute nausea and vomiting associated with cisplatin administration have been completed to date. One was a single-blind, parallel-group trial conducted in the United States, and the other two were double-blind, crossover trials performed in Europe. The efficacy results of these studies demonstrated either a consistent trend or clear superiority of ondansetron in comparison with metoclopramide. Treatment failure consistently developed much later with ondansetron than with metoclopramide. Less antiemetic toxicity was noted with ondansetron. With the exception of headache, there was a lower incidence of neurologic adverse events in the ondansetron group. No dystonic reactions were observed with ondansetron in any of the trials. In all three trials, patients expressed greater overall satisfaction with ondansetron for emesis control.
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PMID:Comparative trials of ondansetron versus metoclopramide in the prevention of acute cisplatin-induced emesis. 138 48

The incidence of postoperative nausea and vomiting and requirements for anti-emetic medication were assessed in 80 female patients undergoing day-case anaesthesia during assisted conception therapy. Anaesthesia was induced with alfentanil 50 micrograms.kg-1 and propofol 1 mg.kg-1; atracurium 0.5 mg.kg-1 was given to facilitate tracheal intubation. The patients were allocated to receive either total intravenous maintenance of anaesthesia with an infusion of propofol and increments of alfentanil (Group P) or inhalational maintenance of anaesthesia with nitrous oxide and enflurane (Group E). Postoperative nausea, retching, vomiting, requirements for anti-emetic therapy, and unplanned admission for overnight stay in hospital were recorded. Overall incidence of nausea was 64% in group E and 39% in Group P (P less than 0.05). Incidence of vomiting was 67% in Group E and 34% in Group P (P less than 0.05). Metoclopramide was requested by 62% of patients in Group E, and 32% of those in Group P (P less than 0.05); 21% of the patients in Group E were admitted to hospital overnight, while only 5% of the patients in Group P required unscheduled admission to hospital (P less than 0.05). We conclude that total intravenous anaesthesia with propofol and alfentanil is superior to inhalational maintenance with nitrous oxide and enflurane in that it is associated with less nausea and vomiting, less requirement for anti-emetic medication, and a lower probability of unplanned admission to hospital after day-care gynaecological surgery.
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PMID:Total intravenous anaesthesia with propofol and alfentanil protects against postoperative nausea and vomiting. 153 Nov 18

Nausea and vomiting are common clinical problems in patients receiving cancer chemotherapy. Metoclopramide is often used but frequently causes extrapyramidal reactions. As an alternative, prochlorperazine is prescribed but no data on its pharmacokinetics in paediatric patients are available to guide the choice of suitable dosages. The primary objective of this study was to evaluate the pharmacokinetics and safety of intravenous prochlorperazine in paediatric patients receiving cancer chemotherapy. Eleven patients (ages 1-9 years) who received high doses of cisplatin or cyclophosphamide were given three to four intermittent doses of 0.2 mg/kg prochlorperazine i.v. over a period of 6-9 h. Multiple blood samples were collected and prochlorperazine was quantified by a specific gas-liquid chromatographic method. The peak serum concentrations ranged from 402 to 5,608 ng/ml. The total clearance and elimination half-life ranged from 0.03 to 0.28 (mean: 0.12) litre/kg/h, and from 1.2 to 15.5 (mean: 5.6) h, respectively. No adverse effects were observed in our patients. Three patients had uncontrolled episodes of vomiting during prochlorperazine therapy. These data suggest: (i) that there was a substantial interpatient variability in prochlorperazine pharmacokinetics thus the dose requirement differed among patients; and (ii) that prochlorperazine appeared safe at the doses used but higher doses may be required to control nausea and vomiting in some paediatric patients receiving high-dose cisplatin or cyclophosphamide therapy.
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PMID:Pharmacokinetics and safety of prochlorperazine in paediatric patients receiving cancer chemotherapy. 158 79


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