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

There is interest in the development of antiemetics other than dopamine receptor antagonists for the treatment of postoperative nausea and vomiting. A ferret model of morphine-induced emesis may have wider application in evaluating newer agents than the apomorphine dog model. This study describes the conditions for morphine-induced emesis in ferrets and evaluates five antiemetics that are prototypical of three different mechanisms. The average numbers of vomiting and retching episodes induced by morphine (0.1-2.5 mg/kg s.c.) were distributed as a bell-shaped curve. Maximum number of vomits occurred at 0.3 mg/kg (11.8 +/- 2.1 vomits; 45 +/- 12.5 retches). Antiemetics or vehicle were given i.v. 5 min prior to morphine while each ferret was maintained under isoflurane-O2 anesthesia. Ondansetron, a 5-HT3 receptor antagonist, reduced vomiting episodes by 47% and 70% (3 and 10 mg/kg). Granisetron, a 5-HT3 receptor antagonist was inactive at doses of 0.1, 1.0, 3.0 and 10 mg/kg. Metoclopramide reduced vomiting episodes by 48% and 82% (3 and 10 mg/kg). Droperidol reduced vomiting episodes by 84% at 3 mg/kg. Naloxone reduced vomiting episodes by 91% and 43% at doses of 0.1 and 1.0 mg/kg. In most cases, prolonged latency times to the first episodes accompanied the reduction in total numbers of episodes. The significant reduction of morphine-induced emesis in the ferret by ondansetron, metoclopramide and droperidol is consistent with the reduction of postoperative emesis in man by these compounds when morphine was a component of the anesthetic regimen. These results suggested that the morphine ferret model may be useful for evaluating compounds having the potential for preventing and treating postoperative vomiting.
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PMID:The effects of different antiemetic agents on morphine-induced emesis in ferrets. 822 24

Postoperative nausea and vomiting (PONV) is still a common perioperative complication and ondansetron has proved to be an effective antiemetic substance in its prevention. The antiemetic effect of single and repetitive application was evaluated in this study. Fifty-one female patients who underwent gynaecological surgical procedures took part in a random double-blind study. Before the start of anaesthesia, 21 patients (group 1) received either a placebo (six patients), 8 mg ondansetron orally (seven patients) or 16 mg orally (eight patients). The remaining 30 patients (group 2), split into subgroups of ten, were given the same preoperative medication as group 1 plus further doses of the same strength 8 and 16 hours after the first intake of the study medication. Metoclopramide was given intravenously if patients had more than one emetic episode or if they asked for it. Nausea and vomiting were documented up to 24 hours after finishing anaesthesia. Metoclopramide had only to be given to patients who had received a placebo. Nausea was felt by 57% (4/7) of the patients after a single dose of 8 mg ondansetron and by 40% (4/10) of the patients after three doses of 8 mg. One patient (14%, 1/7) with a single dose and two patients (20%, 2/10) with a repetitive dose of 8 mg ondansetron vomited. Following a single dose of 16 mg ondansetron, no patient (0/8) had to vomit and 25% (2/8) of the patients had nausea. There were no complications reported by the patients. Ondansetron was shown to be a well-tolerated antiemetic and seems to have a higher reductive effect on PONV when given in a single dose and not repetitively. The prophylaxis of vomiting seems to be more effective than the reduction of nausea. Follow-up studies will have to clarify our findings.
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PMID:[Prevention of postoperative nausea and vomiting with single and repeat administration of ondansetron--review of the literature on different administration forms]. 904 56

Metoclopramide, a drug used for the relief of nausea and emesis, is currently under development as a radio- and chemosensitizing agent. Its usefulness in high doses, however, is limited by its central nervous system side effects. Neu-metoclopramide (Neu-Sensamide), a novel, concentrated, phosphate-buffered, pH-adjusted (pH = 6.5-7.0) formulation of metoclopramide, has been shown to have an improved side-effect profile in animal studies. The present double-blind, four-way crossover study compared the central nervous system effects and pharmacokinetics of neu-metoclopramide (intravenously and intramuscularly at 1.8 mg/kg) with intravenous metoclopramide and intramuscular placebo in 19 healthy male volunteers. Eight participants withdrew from the study, one because of noncompliance and seven because of adverse events. A total of 28 central nervous system events were observed with intravenous metoclopramide administration, whereas 16, 15, and 6 such events were attributed to intravenous neu-metoclopramide, intramuscular neu-metoclopramide, and placebo, respectively. Extra-pyramidal effects occurred on 10 occasions: 7 after intravenous metoclopramide, 2 after intravenous neu-metoclopramide, and 1 after intramuscular neu-metoclopramide. No significant differences were observed in the pharmacokinetic profiles of the three formulations of metoclopramide. It may be speculated, therefore, that the molecular conformational changes inherent to neu-metoclopramide result in a reduced side-effect profile compared with conventional metoclopramide formulations.
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PMID:Comparative central nervous system effects and pharmacokinetics of neu-metoclopramide and metoclopramide in healthy volunteers. 908 24

The incidence of postoperative nausea and vomiting (PONV) has not decreased significantly for decades. This study was done to evaluate whether there is a standard method or a preferred substance in German hospitals in the prophylaxis and treatment of PONV. Twenty-one randomly selected hospitals were asked to give details about substances, doses and application times and forms in PONV prophylaxis and treatment. Most of the patients with a high risk of emesis were treated prophylactically with droperidol. Dosage and time of application were different in each hospital. Metoclopramide was the second most frequently used substance for both prophylaxis and treatment. Dimenhydrinate, triflupromaxzine, promethazine and acupuncture were used less commonly in prophylaxis. Alizapride and ondansetron were used to treat PONV in only two hospitals. Summarising, this study found no routine standard in the prophylaxis and therapy of PONV. Droperidol and metoclopramide were the most frequently used antiemetics. An overview of the antiemetics involved is given.
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PMID:[Clinical use of antiemetic drugs for prevention and therapy of postoperative nausea and vomiting]. 909 Sep 49

The aim of the study was to verify whether the combination of an antiserotoninergic, metoclopramide, and a steroid could improve the complete control (CC) of delayed emesis, a contraversial issue, 105 patients undergoing highly-emetogenic chemotherapy, receiving Ondansetron (O) 8 mg + Dexamethasone 20 mg i.v. for the prevention of acute emesis, were randomly treated p.o for three further days with a) Metoclopramide 10 mg x 3 b) the same as a) + Methylprednisolone 4 mg c) the same as b) + O 8 mg x 3. CC (acute+delayed emesis) over three cycles was: a) 0.b) 12.5%, c) 38.5% (p = 0.02). Days with nausea/vomiting: 59%, 51%, 29.7% of the total observed period, respectively (b vs c p = 0.0000). CC of acute emesis was similar in the first cycle (about 85%), remained unchanged in the following cycles (c) and decreased to 30% and 68% in the third cycle (a and b) (p = 0.01). The three drug combination significantly improved complete control of acute and delayed emesis over successive chemotherapy cycles.
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PMID:The combination of metoclopramide, methylprednisolone and ondansetron against antiblastic-delayed emesis: a randomised phase II study. 913 96

In the past few years important progress in the prevention of chemotherapy-induced nausea and vomiting has been made mainly thanks to the introduction of the 5-HT3 receptor antagonists in clinical practice (ondansetron, granisetron, tropisetron). In the prevention of acute emesis induced by cisplatin, an intravenous combination of a 5-HT3 receptor antagonist plus single dose dexamethasone (20 mg) should be considered the treatment of choice. This is also the case in the prevention of acute emesis induced by moderately emetogenic chemotherapy (intravenous cyclophosphamide, doxorubicin, epirubicin, carboplatin, used alone or in combination), but high and repeated doses of dexamethasone should be used (8 mg intravenously plus 4 mg orally every 6 hours for four doses starting contemporarily to chemotherapy administration). Several-well conducted double-blind comparative studies among intravenously administered 5-HT3 receptor antagonists have been carried out. Almost all showed that they have identical antiemetic activity and tolerability. Therefore, the choice among 5-HT3 receptor antagonists should be based only on their acquisition cost in each country. In the prevention of delayed emesis (from day 2 to day 4) induced by cisplatin oral metoclopramide (0.5 mg/kg or 20 mg every 6 hours for four doses daily) and oral ondansetron (8 mg twice daily), both combined with dexamethasone, showed similar antiemetic efficacy. Metoclopramide plus dexamethasone should be considered the antiemetic regimen of choice due to its lower cost. Ondansetron plus dexamethasone is a valid alternative regimen that should be preferred in patients who not tolerate metoclopramide and in patients who suffer from acute vomiting. In the prevention of delayed emesis induced by moderately emetogenic chemotherapy oral dexamethasone or oral ondansetron showed a good antiemetic efficacy, but the results from a recently published study seem suggest the necessity to treat only patients who present acute vomiting or moderate-severe nausea. In fact, patients obtaining complete protection from vomiting and nausea (or at most mild acute nausea) have a very low incidence of delayed emesis.
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PMID:[Recent improvements in antiemetic therapy]. 923 27

Ondansetron 4 mg was compared with metoclopramide 10 mg for prevention of post-operative nausea and emesis in in-patients undergoing major gynaecological surgery in this double-blind, randomized, placebo-controlled, multicentre study. A total of 1044 patients received a single intravenous (i.v.) injection of study medication immediately before induction of anaesthesia. Nausea and emesis were assessed over the 24 h post-operative period. Significantly more patients who received ondansetron experienced no emetic episodes (44%) compared with those who received metoclopramide (37%, P = 0.049) or placebo (25%, P < 0.001). No nausea was experienced by significantly more patients who received ondansetron (32%) than with patients who received metoclopramide (24%, P = 0.009) or placebo (16%, P < 0.001). In addition, fewer emetic episodes, less severe nausea and a reduced need for rescue antiemetics were also observed with ondansetron (P < 0.05 vs. metoclopramide and placebo). Metoclopramide and placebo-treated patients were also 1.5 times (95% Cl 1.5-4.2) and 2.5 times (95% Cl 1.1-2.0) more likely, respectively, to experience nausea post-operatively. Overall, ondansetron was the most effective antiemetic in this patient population.
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PMID:International, multicentre, placebo-controlled study to evaluate the effectiveness of ondansetron vs. metoclopramide in the prevention of post-operative nausea and vomiting. 952 45

The severity of nausea and vomiting in patients undergoing radiotherapy is lower than that associated with chemotherapy regimens, but its duration may be considerably longer. Total body irradiation and irradiation of the upper part of the abdomen or whole abdomen are considered the most emetogenic regimens in radiotherapy. Instead, the emetogenic potential is considered moderate in radiotherapy of the thorax, pelvis and lower half-body irradiation, and low in radiotherapy of head and neck, extremities, brain and skin. In contrast to the very extensive literature on the prevention of chemotherapy-induced emesis, relatively few studies have been published on patients submitted to radiotherapy. Metoclopramide, prochlorperazine and cannabinoids offer only limited symptom control in patients undergoing radiotherapy of moderate to severe emetogenic potential. Double-blind randomized studies showed the superior antiemetic efficacy of the 5-HT3 antagonists with respect to placebo and to the older antiemetic drugs in patients submitted to single dose or fractionated doses of radiotherapy to the upper abdomen, to lower hemibody radiotherapy and to total body irradiation. In all these cases the 5-HT3 antagonists should be considered the antiemetic treatment of choice and should be administered as prophylactic agents. The optimal duration of antiemetic therapy with the 5-HT3 antagonists is unknown. Whether corticosteroids added to the 5-HT3 antagonists will increase their antiemetic efficacy, as in chemotherapy-treated patients, remains to be demonstrated in double-blind controlled trials. Patients submitted to radiotherapy of low emetogenic risk do not require any antiemetic prophylaxis. In this case a rescue antiemetic treatment can be administered if patients present vomiting or moderate to severe nausea.
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PMID:Prevention of radiotherapy-induced emesis. 962 Feb 57

Metoclopramide, a benzamide substitute, is used frequently as an antiemetic drug. Sulpiride, another benzamide substitute, was investigated and found to be safe and effective in a handful of studies involving only oncologic or other severely symptomatic patients. In this investigation the authors compared prospectively the antiemetic efficacy of sulpiride versus metoclopramide in a double-blind, randomized study involving 36 nononcologic patients with transient vomiting or nausea of various etiologies. Each group of 18 patients received oral metoclopramide or sulpiride (10 mg or 50 mg respectively) every 8 hours for a total of three doses each (24 hours of treatment). A 5-point score was used to evaluate symptomatic relief. Efficacy of the two drugs proved similar, and at the end of the study, 14 and 13 of 18 patients on sulpiride or metoclopramide respectively were asymptomatic. Only transient, minor side effects were reported in one patient in each group. The authors conclude that sulpiride is an effective and safe antiemetic drug that can be adopted legitimately in such cases as a first choice, or serve as an equipotent alternative to metoclopramide in patients sensitive to the latter.
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PMID:Sulpiride versus metoclopramide in nononcologic patients with vomiting or nausea. 1040 34

Metoclopramide has been used for almost 40 yr to prevent postoperative nausea and vomiting (PONV). We have reviewed the efficacy and safety of metoclopramide for the prevention of PONV. A systematic search (MEDLINE, EMBASE, manufacturers' databases, hand searching, bibliographies, all languages, up to June 1998) was performed for full reports of randomized comparisons of metoclopramide with placebo in surgical patients. Relevant end-points were prevention of early PONV (within 6 h after operation), late PONV (48 h) and adverse effects. Combined data were analysed using relative benefit/risk and number-needed-to-treat/harm. In 66 studies, 3260 patients received 18 different regimens of metoclopramide, and 3006 controls received placebo or no treatment. There was no evidence of dose-responsiveness with oral, i.m., intranasal or i.v. metoclopramide in children and adults. In adults, the best documented regimen was 10 mg i.v. There was no significant anti-nausea effect. The numbers-needed-to-treat to prevent early and late vomiting were 9.1 (95% confidence intervals 5.5-27) and 10 (6-41), respectively. In children, the best documented regimen was 0.25 mg kg-1 i.v. The number-needed-to-treat to prevent early vomiting was 5.8 (3.9-11). There was no significant late anti-vomiting effect. Minor drug-related adverse effects (sedation, dizziness, drowsiness) were not significantly associated with metoclopramide. There was one adult who experienced extrapyramidal symptoms with metoclopramide.
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PMID:Metoclopramide in the prevention of postoperative nausea and vomiting: a quantitative systematic review of randomized, placebo-controlled studies. 1069 Jan 40


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