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)

During the past decade the demand for outpatient surgery has grown rapidly. Postoperative nausea and vomiting is one of the more common undesirable consequences of surgery, which may significantly delay the patient's discharge from the ambulatory surgery center. None of the currently used antiemetic drugs is considered totally effective in abolishing nausea or vomiting. The purpose of this study was to compare the efficacy of ondansetron, a highly selective 5-hydroxytryptamine subtype-3 receptor antagonist, with that of metoclopramide for the prevention of postoperative emesis in patients undergoing cataract surgery. The incidence of postoperative nausea was significantly less in the ondansetron group than that in the metoclopramide group (p = 0.046). Although the incidence of vomiting was clinically less frequent in the ondansetron group, there were no significant differences between both treatment groups. To our knowledge, this is the first study to demonstrate that ondansetron is effective to prevent postoperative emesis after extracapsular cataract extraction.
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PMID:Prophylactic intravenous ondansetron in patients undergoing cataract extraction under general anesthesia. 928 4

We recently reported that chronic administration of cyclophosphamide significantly increased urinary 5-hydroxyindole acetic acid (5-HIAA) excretion in rats indicative of a release of 5-hydroxytryptamine (5-HT) from intestinal enterochromaffin (EC) cells. Cyclophosphamide is considered to be an inactive prodrug and require conversion to active emetic metabolities (e.g. phosphoramide mustard) by hepatic metabolism. However the presence of cytochrome P450 in the intestine raises the possibility of cyclophosphamide metabolism in the wall of the intestine, a site which would have considerable significance for 5-HT release and the emetic effects of cyclophosphamide. The aim of this study was to investigate whether cyclophosphamide could induce the release of 5-HT from the isolated ileum and to examine its mechanism of action. Cyclophosphamide (10(-6)M and 10(-7)M) induced a concentration dependent increase of 5-HT from rat isolated ileum. This cyclophosphamide-induced 5-HT release was significantly reduced by granisetron (10(-6)M and 10(-7)M) or atropine (10(-7)M and 10(-6)M). Tetrodotoxin (10(-6)M completely inhibited the increased 5-HT release induced by cyclophosphamide. These results suggest that cyclophosphamide has the capacity to induce 5-HT release via activation of enteric cholinergic neurons. In addition the in vitro study demonstrate for the first time that cyclophosphamide may be activated to emetic metabolites at extra-hepatic sites (e.g. intestine) and that conversion at these sites could contribute to the mechanism of cyclophosphamide induced emesis.
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PMID:Cyclophosphamide increases 5-hydroxytryptamine release from the isolated ileum of the rat. 950 64

Recently, the availability of 5-hydroxytryptamine-3 antagonists has provided better protection from chemotherapy-induced emesis. These drugs, in combination with dexamethasone, are more expensive but more cost-effective than the alternative antiemetic regimens in the prevention of acute emesis induced by high single dose and low and repeated doses of cisplatin and, probably, of acute emesis induced by moderately emetogenic chemotherapy. In the prevention of emesis induced by oral cyclophosphamide-methotrexate-fluorouracil and in the prevention of delayed emesis induced by cisplatin and moderately emetogenic chemotherapy, the most cost-effective choices are represented, respectively, by a combination of intravenous dexamethasone on day 1 and 8 plus 14-day oral metoclopramide (a combination of oral dexamethasone plus metoclopramide and oral dexamethasone alone). In all cases, the 5-hydroxytryptamine-3 antagonists should be used only in patients in whom the most cost-effective antiemetic regimens either fail or are not tolerated.
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PMID:The efficacy and cost-effectiveness of various antiemetic regimens. 970 98

We have used the rat to examine the involvement of the 5-HT3 receptor in the mechanism(s) of conditioned taste aversion induced by 5-hydroxytryptamine (5-HT) and selected emetic drugs. 5-HT, ipecacuanha and cisplatin all induced conditioned taste aversion at doses known to induce emesis in other species but the responses were resistant to treatment with the 5-HT3 receptor antagonists ondansetron and granisetron. Further, m-chlorophenylbiguanide, a selective and potent 5-HT3 receptor agonist, failed to induce a conditioned taste aversion. The data provide strong evidence that the 5-HT3 receptor is not involved in conditioned taste aversion mechanisms in the rat. Results are discussed in terms of the usefulness of the rat conditioned taste aversion paradigm to anti-emetic research.
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PMID:5-HT3 receptors are not involved in conditioned taste aversions induced by 5-hydroxytryptamine, ipecacuanha or cisplatin. 971 48

We have studied the efficacy of granisetron, a selective 5-hydroxytryptamine type 3 receptor antagonist, administered orally for the prevention of postoperative vomiting after tonsillectomy in children. In a randomized, double-blind, placebo-controlled study, 160 paediatric patients, ASA 1, aged 4-10 yr, received placebo or granisetron (20, 40 or 80 micrograms kg-1) (n = 40 each) orally, 1 h before surgery. A standard general anaesthetic technique was used throughout. A complete response, defined as no emesis and no need for another rescue antiemetic during the first 24 h after anaesthesia, occurred in 40%, 48%, 85% and 90% of patients who had received placebo, or granisetron 20, 40 or 80 micrograms kg-1, respectively (P < 0.05; overall Fisher's exact probability test). There were no clinically important adverse events. We conclude that preoperative oral granisetron, in doses more than 40 micrograms kg-1, was effective for the prevention of postoperative vomiting in children.
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PMID:Oral granisetron prevents postoperative vomiting in children. 2350 3

para-Chlorophenylalanine (PCPA, 100-200 mg/kg) was used as a pharmacological tool to characterize the 5-hydroxytryptamine (5-HT) involvement in the emesis occurring 24 hr after the administration of cisplatin (10 mg/kg) in the ferret. PCPA was effective to antagonize the initial 8 hr period of retching and vomiting, but potentiated the emesis that occurred during the remaining 8- to 24-hr observation period. Tissue samples removed from the brainstem at 24 hr post injection of cisplatin alone revealed an elevation of 5-HT, dopamine and homovanillic acid that was antagonized by the injection of PCPA. Cisplatin also induced increases in the urinary levels of 5-hydroxyindoleacetic acid that was similarly antagonized by PCPA. Results are discussed in terms of the relevance of 5-HT to the model of cisplatin (10 mg/kg)-induced emesis in the ferret compared to the problem of acute and delayed emesis in man. The residual or delayed phase of cisplatin-induced emesis may involve a 5-HT-independent mechanism.
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PMID:Serotonin-independent model of cisplatin-induced emesis in the ferret. 986 58

The antiemetic activity of sendide, a new peptide tachykinin NK1 receptor antagonist, against cisplatin-induced emesis was investigated using ferrets. The frequency of cisplatin (10 mg/kg, i.p.)-induced retching (104.6 +/- 14.3/6 h) and vomiting (19.0 +/- 3.0/6 h) was significantly reduced by pretreatment with sendide (3.0 mg/kg, s.c.) (14.0 +/- 8.1/6 h and 1.8 +/- 1.2/6 h, respectively). Intravenous bolus injection of substance P (1-10 microg/kg) or 5-hydroxytryptamine (5-HT) (10-50 microg/kg) produced a dose-dependent increase in the abdominal afferent vagus nerve activity. The change from pre-injection level in the afferent nerve activity induced by substance P (1 microg/kg, i.v.) (453.7 +/- 51.5%) was significantly reduced by pretreatment with either sendide (100 microg/kg, i.v.) (276.1 +/- 50.1%, P < 0.05) or granisetron, a 5-HT3 receptor antagonist (1 mg/kg, i.v.) (146.3 +/- 14.0%, P < 0.01). The amount of 5-HT released into the solution during a 1-h exposure to 2-methyl-5-HT (10(-6) M), a 5-HT3 receptor agonist, was significantly increased (317.9 +/- 46.7%, P < 0.05) compared with that of the control tissues (160.4 +/- 8.1%). The 2-methyl-5-HT-induced 5-HT release was significantly inhibited by administration of sendide (10(-6) M) (174.0 +/- 21.6%, P < 0.05) or granisetron (10(-6) M) (186.6 +/- 27.3%, P < 0.05). Since sendide does not penetrate the central nervous system, these results suggest that the antiemetic effects of sendide are due to the inhibition of NK1 and 5-HT3 receptors on the emetic peripheral detector sites.
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PMID:Antiemetic effects of sendide, a peptide tachykinin NK1 receptor antagonist, in the ferret. 987 81

This study was undertaken to determine the minimum effective dose of granisetron, 5-hydroxytryptamine type 3 receptor antagonist, for the prevention of post-operative vomiting in children undergoing general inhalational anaesthesia for surgery (inguinal hernia and phimosis). In a randomized, double-blind manner, 120 children, ASA physical status I, aged 4-10 years, were assigned to receive placebo (saline) or granisetron at three different doses (20 micrograms kg-1, 40 micrograms kg-1, 100 micrograms kg-1) intravenously immediately after inhalation induction of anaesthesia (n = 30 of each). A complete response, defined as no emesis and no need for another rescue antiemetic during the first 24 h after anaesthesia, occurred in 57% with placebo, 67% with granisetron 20 micrograms kg-1, 90% with granisetron 40 micrograms kg-1 and 90% with granisetron 100 micrograms kg-1 respectively (P < 0.05; overall Fisher's exact probability test). No clinically important adverse events were observed in any of the groups. Our results suggest that granisetron 40 micrograms kg-1 is the minimum effective dose for the prevention of emesis after paediatric surgery, and that increasing its dose to 100 micrograms kg-1 provides no demonstrable benefit.
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PMID:Granisetron reduces post-operative vomiting in children: a dose-ranging study. 2357 44

This study was undertaken to compare the efficacy and safety of granisetron, a 5-hydroxytryptamine type 3 receptor antagonist, and dexamethasone and each drug alone for the prevention of post-operative vomiting by children, with no history of motion sickness and/or previous post-operative vomiting, undergoing general inhalational anaesthesia for surgery (inguinal hernia and phimosis). In a randomized, double-blind manner, 150 children, ASA physical status 1, aged 4-10 years, were assigned to receive granisetron 40 mg kg-1, dexamethasone 150 mg kg-1, or granisetron 40 mg kg-1 plus dexamethasone 150 mg kg-1 intravenously immediately after inhalation induction of anaesthesia (n = 50 of each). A complete response, defined as no emesis and no need for another rescue anti-emetic during the first 24 h after anaesthesia, was 86% with granisetron, 68% with dexamethasone and 98% with granisetron plus dexamethasone, respectively (P < 0.05; overall Fisher's exact probability test). No clinically serious adverse events were observed in any of the groups. In conclusion, prophylactic therapy with combined granisetron and dexamethasone was more effective than was each anti-emetic alone for the prevention of vomiting after paediatric surgery.
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PMID:Prophylactic therapy with combined granisetron and dexamethasone for the prevention of post-operative vomiting in children. 2357 42

Serotonin [5-hydroxytryptamine (5-HT)] is involved in the production of emesis associated with cisplatin treatment. Serotonin released from intestinal enterochromaffin cells may act either directly on vagal afferents and/or pass to the circulation and stimulate central emetic centers. However, the role for circulating 5-HT has not been determined. In this study, i.v. microdialysis probes were used to investigate 1) cisplatin-induced changes in 5-HT release and metabolism assessed through changes in blood dialysate levels of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA), 2) whether free 5-HT in blood increases after cisplatin, and 3) whether granisetron and ondansetron exert different effects on cisplatin-induced 5-HT release and metabolism. Control experiments conducted in 10 healthy volunteers revealed stable 5-HT and 5-HIAA dialysate levels for a period of 6 h. In patients with cancer (n = 16), baseline blood dialysate 5-HIAA concentrations averaged 2.98 +/- 0.38 ng/ml, which were equivalent to a total of 94 +/- 10 pg in the 30-min collection period at a flow rate of 1 microl/min. Cisplatin (89 +/- 2.9 mg of cisplatin/m(2)) produced a gradual increase in blood dialysate 5-HIAA levels (104 +/- 4% increase at 4 h). Increases in dialysate 5-HIAA were associated with increases in the urinary excretion of this metabolite. After cisplatin, dialysate 5-HIAA levels increased to 5.89 +/- 0.5 ng/ml in granisetron and to 5.27 +/- 0.9 ng/ml in ondansetron-treated patients (P >.1). Similar time courses and percentages of increase in blood dialysate and urinary 5-HIAA levels were observed in ondansetron- and granisetron-treated patients. Contrary to 5-HIAA, no significant increases in dialysate 5-HT were observed from 2 to 8 h after cisplatin either for the total group or for each of the groups separately. In conclusion, i.v. microdialysis probes coupled to HPLC-EC allowed the continuous monitoring of free-5-HT and 5-HIAA in blood. Cisplatin-induced increases in blood 5-HIAA were not associated with increases in 5-HT blood dialysates. These results argue against a possible action of free 5-HT in plasma on the chemoreceptor trigger zone (unprotected from the blood brain barrier) but support the view that 5-HT released within the intestinal wall triggers emesis after cisplatin. Our results argue against the view that at clinically effective doses, granisetron and ondansetron exert different actions on cisplatin-induced 5-HT release and metabolism.
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PMID:Use of intravenous microdialysis to monitor changes in serotonin release and metabolism induced by cisplatin in cancer patients: comparative effects of granisetron and ondansetron. 1056 11


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