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)

In a randomized, double-blind, crossover trial, nabilone was compared to prochlorperazine for control of cancer chemotherapy-induced emesis in 30 children 3.5 to 17.8 years of age. All subjects received two consecutive identical cycles of chemotherapy with the trial antiemetics given in accordance to a body weight-based dosage schedule beginning eight to 12 hours before treatment. The overall rate of improvement of retching and emesis was 70% during the nabilone and 30% during the prochlorperazine treatment cycles (P = .003, chi 2 test). On completion of the trial, 66% of the children stated that they preferred nabilone, 17% preferred prochlorperazine, and 17% had no preference (P = .015, chi 2 test). Major side effects (dizziness, drowsiness, and mood alteration) were more common (11% v 3%) during the nabilone treatment cycles. CNS side effects appeared to be dose related and were most likely to occur when the nabilone dosage exceeded 60 micrograms/kg/d, but individual tolerance to nabilone varied considerably. Lower dosages of nabilone were associated with equivalent efficacy and no major side effects. Nabilone appears to be a safe, effective, and well-tolerated antiemetic drug for children receiving cancer chemotherapy. Although major side effects may occur at higher dosages, nabilone is preferable to prochlorperazine because of improved efficacy.
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PMID:Nabilone versus prochlorperazine for control of cancer chemotherapy-induced emesis in children: a double-blind, crossover trial. 303 79

Daily administration of diazepam (1.5 or 6 mg/kg) in Rhesus monkeys results in the progressive development of physical dependence, as evidenced by Ro15-1788 (5 mg/kg i.m.) precipitated withdrawal symptoms including retching, vomiting, face and limb tremors. Every third day administration of the benzodiazepine antagonist, Ro15-1788, during a similar period of continuous diazepam exposure, significantly decreases withdrawal behaviors. During the course of diazepam exposure (with or without periodic Ro15-1788 administration) effects of chronic diazepam on spontaneously elicited sedative and active behaviors were not altered. It is postulated that physical dependence reverts to a drug naive state after each exposure to the benzodiazepine antagonist. This treatment may represent a possible therapeutic approach for preventing the (time dependent) development of physical dependence and the accompanying severe withdrawal symptoms.
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PMID:Periodic benzodiazepine antagonist administration prevents benzodiazepine withdrawal symptoms in primates. 310 59

Baboons received continuous intragastric infusions of diazepam (20 mg/kg per day) for one or more months. While diazepam treatment continued, baboons received intragastric doses of Ro 15-1788 (0.032-32.0 mg/kg) or CGS 8216 (1.0-100.0 mg/kg) at intervals of two or more weeks. Baboons were observed following administration of these antagonists for the presence of precipitated withdrawal signs. The following results were obtained: (1) both Ro 15-1788 and CGS 8216 produced signs of precipitated withdrawal in the baboon; (2) a more severe overall withdrawal syndrome was precipitated with Ro 15-1788 than with CGS 8216 at testable doses; (3) Ro 15-1788 produced dose-related increases in the overall severity of withdrawal, while CGS 8216 did not produce a clear dose-related increase in the overall severity of withdrawal; (4) dose-effect curves for Ro 15-1788 for certain signs (e.g. limb-tremor) were monotonicly increasing, while for other signs dose-effect curves plateaued at lower doses of Ro 15-1788 (e.g. retching and vomiting) or were an inverted U-shape (e.g. scratching). CGS 8216 precipitated withdrawal signs were less clearly dose-dependent; (5) onset of Ro 15-1788 precipitated withdrawal signs were rapid (5-15 min) and reliable, while the onset of CGS 8216 precipitated withdrawal signs were generally slower (approximately 30 min) and more variable; (6) at doses of Ro 15-1788 and CGS 8216 that produced equal levels of vomiting and retching, Ro 15-1788 produced more limb-tremor than CGS 8216. These studies indicate that Ro 15-1788 and CGS 8216 may produce quantitatively and qualitatively different precipitated withdrawal syndromes.
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PMID:Effects of Ro 15-1788 and CGS 8216 in diazepam-dependent baboons. 312 66

Currently available treatments for radiation-induced nausea and vomiting either are ineffective or reduce performance. The new antiemetic and gastrokinetic agent zacopride was tested in rhesus monkeys to assess its behavioral toxicity and its ability to inhibit radiation-induced emesis. Zacopride (intragastric, 0.3 mg/kg) or a placebo was given blindly and randomly in the basal state and 15 min before a whole-body 800 cGy 60Co gamma-radiation dose (except for the legs which were partially protected to permit survival of some bone marrow). We determined (1) gastric emptying rates; (2) the presence and frequency of retching and vomiting; and (3) the effect of zacopride on the performance of a visual discrimination task in nonirradiated subjects. No vomiting, retching, or decreased performance was observed after either placebo or zacopride in the control state. Following irradiation plus placebo, 70 emeses were observed in 5 of 6 monkeys, and 353 retches were observed in all 6 monkeys. In contrast, only 1 emesis was observed in 1 of 6 monkeys and 173 retches were seen in 4 of 6 monkeys after irradiation plus zacopride (P less than 0.01). Zacopride also significantly inhibited radiation-induced suppression of gastric emptying. When given after the first vomiting episode in a separate group of irradiated monkeys, zacopride completely prevented any subsequent vomiting. The present results demonstrate that intragastric administration of zacopride significantly inhibited radiation-induced retching, vomiting, and suppression of gastric emptying in rhesus monkeys and did not cause detectable behavioral side effects when given to nonradiated monkeys. This observation has important implications in the treatment of radiation sickness.
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PMID:Prevention and treatment of the gastric symptoms of radiation sickness. 317 40

One-hundred and eighty patients undergoing elective abdominal hysterectomy were anaesthetized in random order with isoflurane, enflurane or fentanyl in combination with nitrous oxide and oxygen. Incidence and severity of emetic sequelae (none, nausea, retching or vomiting) were studied during the first 24 h after the operation. Patients who received isoflurane had significantly (P less than 0.01) less emetic sequelae (27%) during the first 2 h in the recovery room compared with patients who received enflurane (45%) or fentanyl (48%). There was no difference between the groups in the overall incidence of emetic sequelae during the time period of 2-24 h post-operatively (isoflurane 65%, enflurane 77% and fentanyl 77%). Significantly (P less than 0.02) more patients had emetic sequelae if they had experienced nausea or had vomited after previous anaesthetics.
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PMID:Nausea and vomiting after general anaesthesia with isoflurane, enflurane or fentanyl in combination with nitrous oxide and oxygen. 318 Nov 47

Alizapride 50 mg intravenously was compared with placebo in a double-blind trial on 170 women undergoing planned soft tissue surgery under general anesthesia. Alizapride or placebo was given intravenously about 20 minutes before the end of the operation. A second and a third prophylactic dose was administered 4 and 8 hours after the first injection. The patients were observed for 24 hours postoperatively. A therapeutic dose of alizapride 50 mg was administered intravenously in the two groups if retching or emesis occurred in the postoperative period. In the alizapride group there was less retching or emesis than in the placebo-group and the difference was statistically significant. However, there was still a significant incidence of 34% of postoperative vomiting in the alizapride group. There were no effects on heart rate or on respiratory rate but small changes of blood pressure after the first and second prophylactic injection of alizapride have been noted.
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PMID:Alizapride in the prevention of postoperative vomiting. A double-blind comparison. 323 97

Among the different types of esophageal wall injuries Boerhaave's syndrome is associated with the highest morbidity and mortality. The classical history of retching or vomiting and retrosternal splitting pain is indicative. Roentgenograms of the chest and esophagogram with a water soluble contrast medium are able to reveal the perforation in most cases. Esophagoscopy has been recommended for diagnosis, but its use is unnecessary and frequently contraindicated. Spontaneous perforation of the esophagus should be treated by prompt surgical intervention: left side thoracotomy, direct closure of the perforation by monolayer suture, and adequate mediastinal and pleural drainage. The treatment of esophageal perforation after late diagnosis is considerably more complicated and may consist in a drainage only.
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PMID:[Boerhaave syndrome]. 323 65

Nausea and vomiting can be induced by a wide variety of stimuli such as pregnancy, space travel, raised intracranial pressure, radiation and cytotoxic drugs. The mechanisms by which all these diverse stimuli culminate in a final common act is unknown. From studies in the 1950s a model of the emetic reflex emerged consisting of a chemoreceptor trigger zone in the area postrema and a vomiting centre in the brain stem. This concept has been reviewed and revised in the light of recent studies. Many discussions of emesis involve detailed descriptions of the gastrointestinal events associated with the act of vomiting only-nausea and retching receiving little attention. Here we have tried to give a broader view by considering the neurophysiology of such events and have included nausea and retching, phenomena that are usually inseparable from vomiting. The possible biological function of these events is also discussed. The involvement of visceral systems (such as the heart, airways and gut) is included, and particular attention is paid to vagal mechanisms underlying the changes in gut motor activity. Emesis has long been thought to be organized by a 'vomiting centre'; the possibility that this vomiting centre could be the parvocellular reticular formation is reviewed, as is the concept that the 'centre' is larger than an anatomically defined single group of cells. The mechanism of action of two clinically relevant emetic stimuli--radiation and cytotoxic drugs-is considered in detail. Recent studies of the antiemetic properties of novel 5-HT-3 receptor antagonists against radiation and cytotoxic drug-induced vomiting are discussed; these studies suggest that important advances will be made in the treatment of emesis induced by these and other related agents.
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PMID:The neurophysiology of vomiting. 328 38

Nineteen Chinese patients receiving chemotherapy for advanced cancer were studied for chemotherapy-induced acute nausea and vomiting. The chemotherapy consisted of cisplatinum 100 mg/m2 i.v. infusion over 4 h on day 1 and 5-fluorouracil (5-FU) 1000 mg/m2 120-h continuous infusion from day 2 to day 6, repeated every 3 weeks. At the first course of chemotherapy the patients were randomized to receive either low-dose metoclopramide and chlorpromazine or high-dose metoclopramide, and then crossed over for the second course. In the high-dose metoclopramide group there was a suggestion of an earlier onset of emesis, with slightly more frequent retching and vomiting and less food consumed. However, the duration of emesis was shorter in the high-dose group. These differences were not statistically significant. There were no major side effects. Mild salutary drowsiness was noticed in patients receiving low-dose metoclopramide and chlorpromazine. This trial suggests that, in the dosage, route and schedule described, high-dose metoclopramide is no more effective than low-dose metoclopramide together with chlorpromazine in preventing cisplatinum-induced nausea and vomiting. The low-dose scheme is more economic and suitable for patients with advanced cancer.
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PMID:A randomised cross-over trial comparing low-dose metoclopramide and chlorpromazine with high-dose metoclopramide in Chinese patients with advanced cancer receiving cisplatinum and 5-fluorouracil. 331 86

We have used the ferret as an animal model to investigate the emetic action of the cytotoxic drugs cyclophosphamide and cis-platin. Using selective nerve lesions, a crucial role for the abdominal innervation in the genesis of retching and vomiting in response to these agents has been demonstrated. A combination of bilateral abdominal vagotomy and greater splanchnic nerve section can totally abolish retching and vomiting in response to intraperitoneal cis-platin or intravenous cyclophosphamide. Intraperitoneal cyclophosphamide still produced retching but vomiting was markedly reduced, demonstrating complex and probably separate control mechanisms for retching and vomiting. The effect of a widely used anti-emetic, metoclopramide, was compared to that of nerve lesions. While effective this compound did not totally control retching or vomiting to either drug. Recent studies have attributed metoclopramide's action to its ability to antagonize 5-HT M-receptors (5-HT-3 receptors). Therefore we investigated BRL 24924, a gastro-kinetic agent with more specific 5-HT M-receptor antagonist properties. This agent was extremely potent in almost totally abolishing retching and vomiting in response to cyclophosphamide, given by either an intravenous or intraperitoneal route, and totally abolished cis-platin-induced vomiting for at least 4 h. Clearly the abdominal visceral innervation plays a complex and major role in the emesis produced by these two cytotoxic drugs; circumstantial evidence suggests that 5-HT M-receptors on visceral afferent nerves mediate this action, but other possibly central sites of action of the 5-HT M-receptor antagonists cannot be excluded.
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PMID:The role of the abdominal visceral innervation and 5-hydroxytryptamine M-receptors in vomiting induced by the cytotoxic drugs cyclophosphamide and cis-platin in the ferret. 334 98


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