Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The metabolism of serotonin was studied in cancer patients of their first day of their first course of chemotherapeutic drugs either with strongly or moderately emetogenic regimens. It was observed that strongly emetogenic treatments induce greater increases in serotonin release than moderately emetogenic regimens. High-dose cisplatinum (75 +/- 5 or 83.8 +/- 5 mg m-2) produced a marked increase in the plasma levels and in the urinary excretion of 5-hydroxyindole acetic acid (5-HIAA). Neither platelet nor plasma (platelet-free plasma) serotonin were significantly modified by high-dose cisplatinum. Dacarbazine (283 +/- 22 mg m-2), another strongly emetogenic agent, induced acute nausea and emesis paralleled by marked increases in the urinary excretion of 5-HIAA. Both for high-dose cisplatinum and dacarbazine, the increases in serotonin metabolism occurred with a similar time-course than those of vomiting, and lasted for a period of 4 to 8 h. Low-dose cisplatinum (30.8 +/- 3 mg m-2) as well as cyclophosphamide-based chemotherapies (520 +/- 30 mg m-2) produced very small increases in the urinary excretion of 5-HIAA. Platelet and plasma serotonin levels failed to increase in cyclophosphamide-treated patients. Octreotide, a long-acting somatostatin analog, did not inhibit the increase in urinary 5-HIAA and the nausea and vomiting produced by high-dose cisplatinum. These results suggest that for treatments that induce marked increases in serotonin release such as high-dose cisplatinum or dacarbazine: (a) the amount and time course of serotonin release induced by chemotherapeutic drugs determines the severity, time of onset and pattern of emesis observed; (b) platelet serotonin play no role in chemotherapy-induced emesis; (c) strongly emetogenic regimens release serotonin from enterochromaffin cells; and (d) intestinal release of serotonin is the consequence of the damage induced by the chemotherapeutic drugs on the gut mucosa.
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PMID:Changes in serotonin metabolism in cancer patients: its relationship to nausea and vomiting induced by chemotherapeutic drugs. 137 60

Progress in antiemetic research dictates that clinical trials of antiemetic agents be conducted according to guidelines for Good Clinical Practice, as follows. Studies must be of a prospective, parallel-group design in which the new treatment is compared with the existing best available treatment, after optimal dosage schedules for each have been established. Ethically, placebo-controlled trials can only be justified when chemotherapy with a low emetogenic potential is used. All end-points (nausea, vomiting, adverse events and quality of life parameters) must be specified in detail before the trial is begun. Patient populations must be homogenous with respect to prior chemotherapy and other confounding variables. Finally, patients must actively participate in the evaluation of antiemetic therapy, since only they can provide reliable information regarding the impact of nausea and vomiting on their quality of life.
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PMID:Methodology of antiemetic trials. 138 Apr 27

The efficacy of tropisetron in the prevention of nausea and vomiting induced by chemotherapy of varying emetogenic potential was evaluated in 545 patients with a variety of malignancies who had either proved refractory to antiemetic treatment during previous chemotherapy courses or who were considered to be at high risk of nausea and vomiting. Tropisetron 5 or 10mg was administered intravenously just before chemotherapy, with the possibility of additional oral or intravenous doses on the day before chemotherapy and on 1 or more subsequent days. On day 1 of the first course of chemotherapy, a complete response (no nausea and no vomiting) was achieved in 62% of patients and a partial response (1 to 4 vomits and/or episodes of nausea) in 29%. Among the 325 patients who received a second course of chemotherapy, more than 80% of those with a complete response on day 1 of course 1 also had a complete response on day 1 of course 2; 37% and 26%, respectively, of patients with a partial response or failure (1 or more vomits and/or episodes of nausea) on day 1 of course 1 then had a complete response on day 1 of course 2.
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PMID:Compassionate use of a 5-HT3-receptor antagonist, tropisetron, in patients refractory to standard antiemetic treatment. 138 Apr 30

The efficacy of ondansetron, a selective 5-HT3 receptor antagonist, in preventing postoperative nausea and vomiting in surgical patients was studied. Fifty women were randomized in a double-blind manner to receive either two 8 mg doses of intravenous ondansetron or two doses of placebo vehicle: the first given just before general anesthesia induction and the second 8 hours later. During the first 24 postoperative hours, the number of emetic episodes was recorded and the subjects rated their nausea on a scale from 0 to 10. Ondansetron-treated subjects had fewer emetic episodes (p less than 0.001) and lower subjective nausea scores (p less than 0.001). The number of complete responders (no emetic episodes and no rescue therapy) was 1 of 24 (4%) and 15 of 26 (58%) in the placebo and ondansetron groups, respectively (p less than 0.001). Ondansetron is clearly more effective than placebo in the prophylaxis of postoperative nausea and vomiting. The adverse event profile for ondansetron was similar to that of placebo.
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PMID:Ondansetron is effective in decreasing postoperative nausea and vomiting. 138 67

In a placebo-controlled, double-blind study, we have compared the efficacy of ondansetron 16 mg, 8 mg and 1 mg administered 8-hourly for prevention of postoperative nausea and vomiting. We studied 995 patients undergoing major gynaecological surgery; 982 were included in the analysis. Study medication was administered 1 h before induction of anaesthesia and second and third doses were given 8 and 16 h after the first. The treatment groups were similar for patient characteristics, surgical procedures, anaesthetics administered and opioids given. The frequency of nausea was 75%, 70%, 56% and 55% after placebo and ondansetron 1 mg, 8 mg and 16 mg, respectively; the corresponding frequencies of vomiting were 60%, 55%, 37% and 37%. Ondansetron 8 mg was as effective as 16 mg and both resulted in significant reductions in nausea and vomiting compared with placebo and ondansetron 1 mg (P less than 0.001).
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PMID:Efficacy of orally administered ondansetron in the prevention of postoperative nausea and vomiting: a dose ranging study. 138 23

The anti-emetic effect, safety and clinical usefulness of ondansetron for the treatment of nausea and vomiting caused by anticancer drugs including cisplatin, was evaluated by a multi-institutional study in patients with various malignancies. In this study, ondansetron was given intravenously with mainly a single dose of 4 mg to intervene nausea and vomiting. 1. Efficacy ratio of overall effects on nausea and emesis observed for 24 hours after treatment was 69.8%. 2. No side effect was observed. Laboratory tests showed temporary elevation of serum uric acid level in 1 patient in the group given 4 mg. 3. From these results, it seems that ondansetron, given intravenously after initial vomiting, was highly safe and clinically useful anti-emetic for the treatment of nausea and vomiting associated with anti-cancer drugs.
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PMID:[Evaluation of SN-307 (ondansetron), given intravenously for the treatment of nausea and vomiting caused by anticancer drugs including cisplatin-open study]. 138 76

Following a single intravenous dose given pre-chemotherapy, the efficacy and tolerability of oral ondansetron treatment given twice daily was compared with the established three times daily oral supplementary regimen in the prophylaxis of nausea and vomiting induced by cyclophosphamide (greater than or equal to 500 mg/m2) in combination with doxorubicin (greater than or equal to 40 mg/m2) or epirubicin (greater than or equal to 40 mg/m2). Oral ondansetron given twice daily or three times daily was equally effective in controlling nausea and emesis. The twice daily oral treatment prevented emesis in 73% of patients in the first 24 hours and in 65% of patients over 3 days. Both dose schedules were safe and were tolerated well. Twice daily oral ondansetron showed good efficacy for controlling emesis and nausea in oncology outpatients.
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PMID:Efficacy of twice daily versus three times daily oral ondansetron in the prevention of chemotherapy induced emesis: a randomized, single-blind, multicentre study. The Ondansetron International Emesis Study Group. 139 Mar 40

Adequate control of side effects during medical treatment of cancer increases patient compliance and quality of life. Antiemetic drugs are not an effective treatment for the one in three cancer patients on chemotherapy who experience anticipatory nausea and vomiting (ANV); the behavioral treatment of systematic desensitization has been found effective for ANV when delivered by clinical psychologists. This study examined the effectiveness of systematic desensitization when delivered by medical personnel versus clinical psychologists. Seventy-two consecutive cancer patients with ANV were randomly assigned to no-treatment control or to systematic desensitization from 5 behaviorally trained clinical psychologists, 6 clinical oncologists, or 10 oncology nurses. The treatment was found effective in reducing anticipatory nausea, anticipatory vomiting, posttreatment nausea, and posttreatment vomiting compared to control patients, with no significant differences in effectiveness found between clinical psychologists and oncology staff. Although medical personnel should not engage patients in psychotherapy or other interventions that cannot be completed successfully, they can treat patients effectively with systematic desensitization and should be encouraged to learn and use this and other behavioral intervention techniques to benefit total patient care.
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PMID:Comparing the effectiveness of behavioral treatment for chemotherapy-induced nausea and vomiting when administered by oncologists, oncology nurses, and clinical psychologists. 139 93

It is unclear whether behavioral depression and suppression of food intake by cholecystokinin (CCK) is contributed to by aversive gastrointestinal effects such as nausea. In the present study we examined the effect of a new antiemetic agent, ondansetron, a specific antagonist of 5-HT3 receptors, on suppression of variable-interval self-stimulation by the CCK analogue caerulein. Responding by rats for brain-stimulation reward is especially sensitive to CCK, and provides a convenient means of investigating this question. Caerulein (30 micrograms/kg, s.c.), injected alone, was followed by a profound (ca. 80%) reduction in the rate of self-stimulation, lasting about 30 min. Ondansetron (1.0-1000 micrograms/kg, s.c.) injected on its own had no effect on self-stimulation rate, and a 100-micrograms/kg dose did not lessen the depressant action of caerulein. The behavioural depressant effects of CCK are thus unlikely to depend on brain mechanisms for nausea and vomiting involving 5-HT3 receptors.
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PMID:Effect of the 5-HT3 receptor antagonist ondansetron on hypothalamic self-stimulation in rats and its interaction with the CCK analogue caerulein. 140 94

In order to make an objective evaluation of anti-emetic effect, safety and usefulness of ondansetron injection in nausea and vomiting associated with cancer chemotherapy, we carried out a double-blind placebo controlled comparative study in patients receiving high-single dose (50 mg/m2 or more) of cisplatin. Either 4 mg of ondansetron or saline injection was given intravenously at 15 min. before administration of cisplatin. If anti-emetic effect of the test drug was insufficient, an additional dose of 4mg of ondansetron was given intravenously, as the rescue medication. Ondansetron was significantly superior to placebo in anti-emetic effect (p < 0.001). Efficacy rates were 66.7% (22/33 cases) in ondansetron and 20.0% (6/30 cases) in placebo groups. Seven and 21 cases required rescue medication with 4 mg single intravenous dose of ondansetron due to insufficiency of anti-emetic effect, in ondansetron group and placebo group, respectively. Thus the number of patients who required rescue medication was obviously greater in placebo group than that in ondansetron group. The rates of inhibitory effect of rescue medication on nausea and emesis were 14.3% (1/7 cases) in ondansetron group and 61.9% (13/21 cases) in placebo group. Side effects were observed in 1 case (eruption) in ondansetron group and in 2 cases (headache, diarrhoea; 1 case each) in placebo group. Furthermore, fever developed in 1 case in placebo group after the rescue medication. Elevation of total bilirubin value was observed in 2 cases in ondansetron group and 1 case in placebo group, however, these changes were mild and did not pose noteworthy clinical problem. From these results, ondansetron was shown to possess an excellent anti-emetic effect on nausea and emesis induced by highly emetogenic anti-cancer drugs, such as cisplatin, and to have no problem in safety, and thus it was considered to be a useful anti-emetic agent.
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PMID:[Anti-emetic effect and safety of single dose of ondansetron injection in double-blind comparison study with placebo]. 141 13


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