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

As part of an open dose-ranging study, the pharmacokinetics of granisetron (BRL 43694A), a selective 5-HT3 receptor antagonist given by the i.v. route, was studied in 18 patients receiving highly emetogenic cytotoxic drugs, predominantly cisplatin, either alone or in combination with other cytostatic agents. All patients received 30-min infusions of granisetron at a dose of 40 micrograms/kg. Nine showed complete absence of the gastrointestinal side effects normally associated with cisplatin, and in the majority of the remaining patients, the onset and severity of nausea was significantly modified. No acute side effects were observed at this dose and the drug was well tolerated in all cases. Peak plasma concentrations and area under the curve (AUC) values for granisetron showed considerable inter-patient variation. Higher plasma levels of granisetron were observed at 5 h in responding patients compared with those in whom the drug was ineffective in controlling emesis (P less than 0.05). AUC values were higher in responding patients, but this difference was not statistically significant. There was apparently no defined plasma concentration threshold for the drug's anti-emetic effect in these patients. Granisetron seems to be an effective and safe anti-emetic in patients receiving cytotoxic chemotherapy. Further exploration of its dose scheduling and pharmacokinetic profile is warranted.
 ...
PMID:A pharmacokinetic study of granisetron (BRL 43694A), a selective 5-HT3 receptor antagonist: correlation with anti-emetic response. 254 37

In a phase I study of BRL43694A, a 5HT3-receptor antagonist, a single dose of 40 micrograms/kg was given to 24 patients. All patients received cytostatic treatment expected to cause nausea and vomiting. During the first 24 h, 12 patients were completely protected from nausea and vomiting, 4 experienced nausea and 8 had moderate vomiting; mild headache occurred in 10 patients. No cardiovascular (including ECG) changes took place. Apart from headache, no neurological side effects occurred.
 ...
PMID:A phase I study of a new 5HT3-receptor antagonist, BRL43694A, an agent for the prevention of chemotherapy-induced nausea and vomiting. 254 9

In ferrets, the selective 5-hydroxytryptamine (5-HT) 5-HT3 receptor antagonist BRL 43694 given as a single injection (0.05-0.5 mg kg-1 i.v.) before cisplatin, or by divided dose (2 x 0.005-2 x 0.5 mg kg-1 i.v.) before and after cisplatin dramatically reduced or abolished the severe cisplatin-induced vomiting. BRL 43694 also substantially reduced the vomiting induced by cyclophosphamide:doxorubicin, and prevented the trimelamol-induced emesis. The severe emesis caused by whole body exposure to X-irradiation was prevented by intravenous or oral BRL 43694. A single i.v. dose of BRL 43694 given during an emetic episode or within the peak emetic period, abolished the vomiting induced by the cytotoxic drugs and by X-irradiation, usually within 30 s. Where the induction of emesis was prevented or subsequently abolished by BRL 43694, the associated behaviour (subjectively assessed as nausea) was also absent or greatly attenuated. BRL 43694 (0.1 mg kg-1 i.v.) did not affect the emesis evoked in dogs by the dopamine agonist apomorphine. The potent anti-emetic activity of BRL 43694 is discussed in terms of potential clinical use, and of the fundamental role that 5-HT3 receptors may play in the mechanisms of nausea and vomiting.
 ...
PMID:The anti-emetic potential of the 5-hydroxytryptamine3 receptor antagonist BRL 43694. 285 11

15 patients receiving cytotoxic drugs (other than cisplatin) that had previously produced nausea and vomiting refractory to first-line antiemetics were given a selective 5-HT3 receptor antagonist (GR38032F), 4 mg intravenously and 4 mg orally, immediately before chemotherapy, the oral dose being repeated 5 and 10 h later. Nausea, vomiting, and side-effects were recorded for the ensuing 24 h. The 15 patients received a total of thirty-one courses of chemotherapy. Only 1 patient vomited. The only adverse events were dryness of the mouth in 1 patient, mild sedation in 1, and diarrhoea in 1, and these were not clearly drug related.
 ...
PMID:Prevention of emesis in patients receiving cytotoxic drugs by GR38032F, a selective 5-HT3 receptor antagonist. 288 54

The serotonin (5HT3) antagonist ondansetron was compared in a randomised study with metoclopramide and dexamethasone for the prevention of chemotherapy induced emesis. Thirty children aged 1-15 years with acute lymphoblastic leukaemia received 'intensification modules' according to the MRC United Kingdom acute lymphoblastic leukaemia regimen UKALL XI. This contains the moderately emetogenic drugs daunorubicin, etoposide, and cytarabine. Fifteen children received an intravenous loading dose of ondansetron followed by intravenous or oral doses 12 hourly for five days. Fifteen children received intravenous metoclopramide every six hours for three days with a loading dose of dexamethasone, repeated every eight hours for three days intravenously or orally. Efficacy was assessed by a diary card documenting the incidence of nausea, retching, or vomiting. In the 24 hour period after starting chemotherapy, ondansetron was more effective, with a complete or major response rate of 93%, compared with 33% using metoclopramide/dexamethasone.
 ...
PMID:Randomised comparison of ondansetron and metoclopramide plus dexamethasone for chemotherapy induced emesis. 749 64

The safety and tolerability of dolasetron mesylate, a potent and selective 5-HT3 receptor antagonist, were evaluated after single intravenous doses in healthy male volunteers. In this double-blind, placebo-controlled, randomized, phase I study, 80 subjects received either placebo or dolasetron in escalating doses (0.6 to 5.0 mg/k). Subjects were monitored for adverse events, vital sign and laboratory alterations, and changes in electrocardiographic (ECG) intervals and electroencephalographic (EEG) patterns. Overall, the percentage of subjects reporting adverse events was similar in those receiving dolasetron (44/64; 68.8%) or placebo (10/16; 62.5%); most adverse events were mild in severity. Subjects receiving dolasetron reported a higher incidence of central nervous system (headache and dizziness/lightheadedness), gastrointestinal (increased appetite and nausea), and visual adverse events and taste alterations. No clinically significant changes in laboratory variables were observed. Transient and asymptomatic ECG changes (small mean increases in PR interval and QRS complex duration versus baseline) were noted in several subjects at 1 to 2 hours after infusion at doses > or = 3.0 mg/kg. Transient, mild blood pressure decreases were observed in five subjects, including one on placebo. Dolastron mesylate was well tolerated in single intravenous doses up to 5.0 mg/kg in healthy male volunteers. Clinical studies of the drug are ongoing for antiemetic indications.
 ...
PMID:A double-blind, placebo-controlled, dose-ranging safety evaluation of single-dose intravenous dolasetron in healthy male volunteers. 756 Feb 51

A prospective trial was performed to better assess the risk of nausea and vomiting and the rescue value of tropisetron (TRO), a 5-HT3 receptor antagonist, in 88 patients undergoing fractionated radiotherapy to the abdomen or to large supradiaphragmatic fields and failing a first anti-emetic trial with metoclopramide (MET). Nausea was graded 0 (absent), 1 (mild), 2 (moderate) and 3 (severe). Nausea requiring anti-emetics (> or = grade 2) was present in 64% of the patients. MET was able to control nausea (< or = grade 1) in 26 of 58 patients (45%) who developed > or = grade 2 nausea during radiation treatment (2 patients vomiting without nausea included). 34 patients required TRO, and 31 experienced immediate relief. However, nausea (> or = grade 2) recurred in 7 patients from 1 to 3 weeks after starting TRO. Sex, age, field type and field size (cm2) did not influence the incidence and severity of nausea and vomiting. Only 24/88 patients vomited after starting radiotherapy. MET helped to eliminate emesis in one third of these patients. TRO helped to control vomiting in 73% of the salvaged patients. Constipation was observed in 8 patients on TRO and was a reason to stop the medication in 4 cases.
 ...
PMID:Nausea and vomiting in fractionated radiotherapy: a prospective on-demand trial of tropisetron rescue for non-responders to metoclopramide. 757 72

As clinical and economic analyses to date have shown clear benefits of using the new 5-hydroxytryptamine3 receptor antagonists (5-HT3RAs) over traditional antiemetics, the choice between them may necessitate the assessment of comparative cost-effectiveness. This paper presents the results of an assessment of the relative cost-effectiveness of two current 5-HT3RAs: ondansetron and granisetron. The analysis was based on a retrospective assessment of the cost and effectiveness (defined as no vomiting and no worse than mild nausea) of these new antiemetics. Efficacy data were based on the results of two recently published directly comparative clinical studies of ondansetron versus granisetron in the treatment of chemotherapy-induced emesis following both single-dose and fractionated chemotherapy. The cost of treatment was derived by combining clinical data from these studies with manufacturers' drug prices, and published costs of drug administration and emetic episodes. Costs for inpatient stay and side-effects were assumed to be equal across both treatment alternatives. The results were expressed in terms of the total cost per patient of emetic treatment and the cost per well-controlled patient. On this basis, granisetron was found to be more than 50% more cost-effective than ondansetron. This result was robust to variation in key assumptions concerning efficacy and cost, although ondansetron would become the more cost-effective if the dose was reduced to one 8 mg i.v., with no concomitant loss of efficacy.
 ...
PMID:Cost effectiveness of 5-hydroxytryptamine3 receptor antagonists: a retrospective comparison of ondansetron and granisetron. 874 10

Chemotherapy-induced nausea and emesis are frequent and patients fearful. Emesis caused by cytotoxic agents can be related to their effects on central chemoreceptor or on the gut chemoreceptor by serotonin. 5HT3 receptor antagonists produce a major improvement in the control of cisplatin induced-emesis (70 to 80% of patients). The 5HT3-antagonist efficacy is significantly better than metoclopramide alone, or antimemetic combinations in highly emetogenic chemotherapy regimens but less good in moderately emetogenic chemotherapy. Studies with 5HT3 receptor antagonist plus corticosteroids show advantage over 5HT3 antagonist alone. Comparison studies between the different setrons didn't show any significant difference. Anticipary emesis are treated with anxiolytic drugs. The prevention of delayed emesis, not yet well controlled by 5HT3 antagonist, is a great therapeutic deal. Finally, some therapeutic problems are not resolved: minimal dose, use of oral route, efficacy in fractionated chemotherapy, treatment after loss of efficacy of 5HT3 antagonist.
 ...
PMID:[Antiemetic treatment and chemotherapy: general review]. 784 92

The selective 5HT3 antagonist tropisetron was studied in 91 outpatients meeting DSM-III criteria for Generalized Anxiety Disorder. Following a placebo washout period of up to 1 week, one of three active treatments (tropisetron 0.5 mg, 5 mg, or 25 mg daily) or placebo was given for a further 3 weeks. After 7 days treatment termination rates due to inefficacy showed a statistically significant dose-related therapeutic effect of tropisetron. Similar effects were seen on the Hopkins Symptom Check List total score and the Global Impression Scale. The Hamilton Anxiety Scale showed a similar trend which, however, failed to reach statistical significance. At day 21 tropisetron showed significant dose-dependent effects on all anxiety-related outcome measures. The incidence of adverse events was low and the severity generally mild. Most frequent complaints were headache, nausea, constipation and nervousness. Laboratory tests and physical examination performed at baseline and study end showed no significant treatment effects.
 ...
PMID:A randomized double-blind placebo-controlled study of tropisetron in the treatment of outpatients with generalized anxiety disorder. 787 Oct 1


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>