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)

Ondansetron (OND) is a new 5-HT3 receptor antagonist that give complete protection from emesis/nausea in approximately 50% of cisplatin (CDDP)-treated patients. To evaluate if dexamethasone (DEX) added to OND increases antiemetic efficacy, we carried out a double-blind randomized crossover study to compare the antiemetic activity of OND with OND plus DEX. One hundred two chemotherapy-naive patients (44 women and 58 men) scheduled to receive CDDP chemotherapy at doses greater than or equal to 50 mg/m2 entered the study. Eighty-nine patients completed both cycles with the following results: complete protection from emesis/nausea was obtained in 57/59 patients (64.0%/66.3%) with OND and in 81/79 (91.0%/88.8%) with OND plus DEX (P = .0005/P = .0021). At the end of the study, 53% of the patients expressed a treatment preference, and of these, 74% chose OND plus DEX compared with 26% who preferred OND alone, a statistically significant difference (P less than .003). Side effects were very mild and not significantly different between the two treatments. We conclude that OND plus DEX is more efficacious than OND in protecting patients from CDDP-induced emesis and nausea.
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PMID:Prevention of cisplatin-induced emesis: a double-blind multicenter randomized crossover study comparing ondansetron and ondansetron plus dexamethasone. 182 57

Ondansetron, a new 5-HT3 receptor antagonist, has been compared with high-dose metoclopramide in the control of acute emesis (24 h) induced by cisplatin (greater than or equal to 100 mg/m2). Ondansetron, given as three intravenous doses (0.15 mg/kg) 4-hourly, was superior to six intravenous doses of metoclopramide (2.0 mg/kg) in the control of acute emesis. Complete control of emesis was achieved in 40% of patients receiving ondansetron compared to 30% of patients receiving metoclopramide (P = 0.07); complete or major control (0-2 emetic episodes) was achieved in 65% and 51% of the patients receiving the two treatments respectively (P = 0.016). Patients entered in the acute emesis study who experienced no emesis or up to two episodes were randomised between placebo and ondansetron on day 2 to evaluate the control of delayed emesis up to day 5. Complete control of persistent or delayed emesis over days 2-5 was achieved in 59-78% of patients with oral ondansetron (16 mg t.d.s.) compared to 39-50% of patients receiving oral placebo. These differences failed to reach statistical significance except on day 4. Some patients with complete or major control of emesis on their first course of chemotherapy subsequently received further courses of ondansetron (median 3 courses; range 2-10) on a non-comparative basis. Similar control was achieved in 85% of courses. There may be some reduction in the degree of control with subsequent courses. Of 44 patients with complete control at cycle 1, 19 (44%) were emesis free and 3 (7%) experienced 1-2 episodes with cycle 3, though patients were sometimes withdrawn before cycle 3 for reasons other than inadequate anti-emetic control. Efficacy with successive courses can only be established in a prospective comparative trial. Both treatments were well tolerated but ondansetron caused significantly greater transient asymptomatic elevations in ALT/AST (P = 0.003/0.005). Acute dystonic reactions (2 patients) and akathisia (10 patients) occurred with metoclopramide only (P = 0.002). The role of ondansetron in the control of delayed emesis requires further study.
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PMID:Progress in the control of acute and delayed emesis induced by cisplatin. 183 33

The racemic 5-HT3 receptor antagonist, zacopride (10-100 micrograms kg-1, i.m.) evoked an emetic response in ferrets. This property appeared to reside totally in the S-enantiomer which also produced emesis over the same dose range. This emesis could be prevented by pretreatment with ondansetron (1 mg kg-1, i.m.) or by R-zacopride (100 micrograms kg-1, i.m.). In urethane-anaesthetized ferrets, S-zacopride (0.3 micrograms kg-1, i.v.) evoked a profound Bezold-Jarisch reflex which was blocked by both ondansetron (30 micrograms kg-1, i.v.) and by R-zacopride (100 micrograms kg-1, i.v.). These results suggest that, in the ferret, S-zacopride possesses 5-HT3 receptor agonist properties which may be responsible for the emetic effect. In contrast R-zacopride does not appear to possess 5-HT3 receptor agonist properties in this species.
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PMID:5-HT3 receptor agonism may be responsible for the emetic effects of zacopride in the ferret. 183 84

Twenty-four patients with severe post-chemotherapy emesis (greater than 15 emetic episodes) refractory to prior combination antiemetic therapy were treated with a selective 5-HT3 receptor antagonist ondansetron (GR38032F). Ondansetron was given as 8 mg three times daily orally for 5 days with the first dose given 1 h prior to chemotherapy. Control of emesis was evaluated over the 5-day period. All chemotherapy was administered on an outpatient basis. Worst day analysis of antiemetic response was 87.5%: complete protection in 9/24 patients (37.5%) and major protection (1-2 emetic episodes) in 12/24 patients (50%). No protection from emesis was observed in 3 patients (12.5%). No side effects and no alterations in liver function tests were observed. Ondansetron is a safe and highly effective antiemetic agent.
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PMID:Control of refractory, chemotherapy-induced emesis with the serotonin antagonist ondansetron (GR38032F). 183 58

Ondansetron is a 5-hydroxytryptamine3 receptor antagonist for the treatment of chemotherapy- and radiotherapy-induced nausea and emesis. A sensitive, accurate, and precise HPLC method for the determination of ondansetron in plasma is described. Samples are prepared by solid-phase extraction and, after chromatography of the extracts on a silica analytical column, ondansetron is detected by UV absorbance at 305 nm. The method is sensitive down to 1 ng/mL, at which concentration the coefficient of variation was 6.2% in a single assay run. Repeated analyses of quality control samples, nominally at 2 ng/mL, were carried out over a number of assay runs with a coefficient of variation of 5.5%. The method is specific for ondansetron with respect to endogenous plasma components, identified phase I metabolites, and some co-administered chemotherapeutic drugs. In sustained use over several months, and in support of the clinical development of ondansetron, the method has been shown to be robust. An application of the assay in the investigation of the pharmacokinetics of ondansetron in the young and elderly is described.
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PMID:Determination of ondansetron in plasma and its pharmacokinetics in the young and elderly. 183 13

Several binding sites for serotonin or 5-hydroxytryptamine (5-HT) were identified by using selective agonists and antagonists. Today, 5-HT3 receptor types are considered to occupy a critical position in the emetic pathway. The discovery of 5-HT3 receptor antagonists originated from metoclopramide, an antidopaminergic drug introduced in France 25 years before as a modifier of digestive motricity; it represents a therapeutic advance, since it led to the first class of antiemetic drugs specifically designed to prevent severe cytotoxic drugs-evoked emesis and devoid of noticeable side-effects. It must be emphasized upon the necessity of developing new experimental tests in living animals and performing controlled trials on patients under chemotherapy to achieve this progress.
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PMID:[Value of 5-HT3 receptor antagonists, particularly as anti-emetic drugs]. 184 69

Despite a number of significant advances over the past decade, prevention and treatment of chemotherapy-induced emesis remain formidable problems, particularly with cisplatin-containing regimens. Nearly one third of patients receiving high-dose cisplatin still experience substantial emesis despite the best available conventional antiemetics, and the toxic effects of these agents remain quite troublesome. In recent years, a new class of agents, the serotonin antagonists, has been identified. These agents hold promise for clinical utility in a wide range of areas. Selective antagonists of the serotonin (5-hydroxytryptamine) type 3 (5-HT3) receptor have proven in early clinical trials to be potent antiemetic agents in patients receiving cytotoxic chemotherapy, with efficacy comparable to or superior to that of conventional antiemetics. Toxic effects to date with the 5-HT3 receptor antagonists have been modest. The current state of knowledge with respect to these agents as antiemetics for patients receiving cytotoxic chemotherapy is summarized.
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PMID:Serotonin antagonists: a new class of antiemetic agents. 185 Aug 6

We conducted a double-blind, randomized crossover study to compare the toxicity and antiemetic efficacy of the 5-hydroxytryptamine3 receptor antagonist batanopride with that of metoclopramide in 21 chemotherapy-naive patients receiving at least 70 mg/m2 cisplatin. The study was terminated when hypotension was observed following the infusion of batanopride at other institutions testing similar drug schedules. Although we observed no hypotension following treatment with batanopride in this trial, we did note asymptomatic prolongation of the corrected QT interval (QTc), PR interval, and QRS complex on the EKG in the batanopride arm. Of 15 evaluable patients, 8 experienced less than or equal to 2 episodes of emesis within 24 h of the first batanopride infusion, whereas 9/15 subjects experienced less than or equal to 2 emetic episodes following the administration of metoclopramide. Overall, the evidence suggests that this dosing schedule for batanopride may be too toxic for clinical use.
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PMID:Double-blind, randomized crossover study of metoclopramide and batanopride for prevention of cisplatin-induced emesis. 185 80

The racemate and (+)- and (-)-isomers of fenfluramine (5 mg kg-1 i.p., 1 h pretreatment) antagonized cisplatin-induced retching and vomiting in the ferret. The intravenous injection of (+/-)-fenfluramine administered on an established cisplatin-induced emesis antagonized the response within minutes of injection. The administration of a lower dose of (+/-)-fenfluramine (1.0 mg kg-1 i.p., 1 h pretreatment) failed to antagonize cisplatin-induced emesis when administered alone but enhanced the antiemetic effects of metoclopramide and ICS 205-930. This pretreatment with (+/-)-fenfluramine failed to enhance the antiemetic effects of zacopride. It is considered that an action of the racemate on presynaptic 5-HT/catecholaminergic systems to reduce neurotransmitter release may enhance the action of certain 5-HT3 receptor antagonists in controlling emesis induced by cisplatin.
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PMID:The actions of fenfluramine and interaction with 5-HT3 receptor-antagonists to inhibit emesis in the ferret. 197 9

The intravenous injection of cisplatin (10 mg/kg), the subcutaneous injection of apomorphine (0.125-1 mg/kg) and lisuride (0.001-0.1 mg/kg), the oral administration of ipecacuanha (0.3-2.4 mg/kg) and the intragastric administration of copper sulphate (25-100 mg/kg), induced a vomiting and retching response in the ferret. Pretreatment with dl-fenfluramine (5 mg/kg i.p.) prevented or reduced the emesis induced by cisplatin, apomorphine, ipecacuanha and lisuride but failed to significantly antagonise copper sulphate-induced emesis. The 5-HT3 receptor antagonist ICS 205-930 (0.1 mg/kg i.p.) prevented emesis induced by cisplatin and ipecacuanha but failed to prevent or significantly reduce the emesis induced by apomorphine, lisuride or copper sulphate. Dopamine receptor antagonists, including fluphenazine (0.1-1.0 mg/kg i.p.) prevented apomorphine- and lisuride-induced emesis but were less potent or had inconsistent actions to antagonise cisplatin- or ipecacuanha-induced emesis and failed to inhibit the emesis induced by copper sulphate. The data indicate that dopamine and/or 5-HT3 receptor systems are involved in drug-induced emesis but that emesis caused by gastric irritation induced by copper sulphate is mediated by different receptor mechanisms.
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PMID:Fluphenazine, ICS 205-930 and dl-fenfluramine differentially antagonise drug-induced emesis in the ferret. 197 49


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