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PubMed1993

Randomized double-blind comparison of three dose levels of intravenous ondansetron in the prevention of cisplatin-induced emesis.

The selective 5-hydroxytryptamine3 (5HT3) antagonist ondansetron has been shown to be an effective antiemetic in patients receiving cisplatin chemotherapy. This double-blind study compared the efficacy and safety of three doses of intravenous ondansetron in the prevention of nausea and vomiting associated with high-dose (> or = 100 mg/m2) cisplatin chemotherapy. A total of 125 patients were randomized (1:1:1) to receive 0.015, 0.15, or 0.30 mg/kg every 4 h for a total of 3 doses. All patients were monitored for emetic episodes, adverse events, and laboratory safety parameters for 24 h following cisplatin administration. The 0.15-mg/kg dose was superior to the 0.015-mg/kg dose with respect to the median number of emetic episodes (P = 0.033) and complete response (no emetic episodes, P = 0.005). No statistically significant difference was found between the 0.15 and the 0.30-mg/kg groups. The most common adverse event was headache. Three 0.15-mg/kg doses of intravenous ondansetron are safe, effective, and adequate for the control of cisplatin-induced emesis.

Adult↗
PubMed1996

A double-blind, placebo-controlled trial of i.v. dolasetron mesilate in the prevention of radiotherapy-induced nausea and vomiting in cancer patients.

The aim of this work was to measure the safety and efficacy of single i.v. doses of dolasetron mesilate for the control of emesis caused by single high-dose (at least 6 Gy) radiotherapy to the upper abdomen. The double-blind, placebo-controlled, multicenter study stratified patients on the basis of being naive or nonnaive to radiotherapy. Patients with or without a history of previous chemotherapy were enrolled. Patients were randomized to receive placebo or 0.3, 0.6, or 1.2 mg/kg dolasetron mesilate 30 min before radiotherapy, then monitored for 24 h. Antiemetic efficacy was assessed from the time to the first emetic episode or rescue, from whether there was a complete response (0 emetic episodes /no rescue medication) or a complete-plus-major response (0-2 emetic episodes/no rescue medication), from the severity of nausea (rated by patients and the investigator), and from the investigator's assessment of efficacy. Fifty patients completed the study (owing to changing medical practice, enrollment objectives were not met; consequently, no significant linear dose trend was expected). Pooled dolasetron was superior to the placebo in its effect on the time to first emesis or rescue in radiotherapy-nonnaive patients (P = 0.015). Dolasetron was statistically superior to the placebo in the overall population on the basis of a complete plus major response: 54%, 100%, 93%, and 83% for the placebo and 0.3-, 0.6-, and 1.2-mg/kg doses respectively (P = 0.002). The low response in the highest dose group may be due to an imbalance in the number of chemotherapy-nonnaive patients in that group. Dolasetron was superior to the placebo on the basis of nausea assessed by the investigator (P = 0.024) and administration of rescue medication (P = 0.006). Complete response at the 0.3-mg/ kg dose was superior to results with the placebo (P = 0.050). Treatment-related adverse events were rare, mild to moderate in intensity, and evenly distributed across the four groups. Overall, dolasetron mesilate was effective and well-tolerated in the control of single, high-dose radiotherapy-induced emesis.

Adult↗
PubMed1996

Marked depression of radiation-induced emesis by olfactory bulbectomy or pre-exposure using low doses.

Acute emetic response to relatively low-doses of X-irradiation on suncus (Suncus murinus) was examined. The behaviors recorded for each subject, using a video-cassette recorder system, were (1) the number of emesis, during exposure to a dose of 3.0 Gy; (2) emesis threshold. Results showed that the emetic threshold was observed at 0.85 Gy, and the number of radioemesis during exposure was 29. However, the observed threshold dose became 2.22 Gy following olfactory bulbectomy. The emetic number decreased significantly (p <0.01), and reached a value one-fourth of the sham-control. The bulbectomized suncus showed a resistance to X-irradiation. Furthermore, I examined whether the animals could also acquire radio-resistance when they were subjected to a brief of dose X-rays (0.3 Gy) prior to a exposure to 3.0 Gy. Results showed that brief pre-exposure increased the observed threshold, a pattern that was exactly the same as shown in the bulbectomized animals. Increasing the pre-exposure dose further to 0.45-0.60 Gy, however, resulted in the complete disappearance of the effect. These results suggest that only the mice pre-irradiated with 0.30 Gy acquired resistance to radiation-induced emesis.

Animals↗
PubMed2005

Effects of Korean red ginseng extract on cisplatin-induced nausea and vomiting.

Ginseng, the root of Panax ginseng C.A. Meyer, is well known as a tonic medicine for restoring and enhancing human health. In traditional medicine, ginseng is utilized for the alleviation of emesis, which includes nausea and vomiting. However, it has not yet been demonstrated whether ginseng exhibits in vivo anti-nausea and anti-vomiting properties. In this study, we examined the anti-emetic effect of Korean red ginseng total extract (KRGE) on cisplatin-induced nausea and vomiting using ferrets. Intraperitoneal administration (i.p.) of cisplatin (7.5 mg/kg) induced both nausea and vomiting with one-hour latency. The episodes of nausea and vomiting reached a peak after 1.5 h and persisted for 3 h. Treatment with KRGE via oral route significantly reduced the cisplatin-induced nausea and vomiting in a dose-dependent manner. The anti-emetic effect was 12.7 +/- 8.6, 31.8 +/- 6.9, and 67.6 +/- 4.0% with doses of 0.3, 1.0, and 3.0 g/kg of KRGE, respectively. Pretreatment with KRGE via oral route 1 and 2 h before cisplatin administration also significantly attenuated the cisplatin-induced nausea and vomiting. However this did not occur with a pretreatment 4 h before cisplatin administration. These results are supportive of KRGE being utilized as an anti-emetic agent against nausea and vomiting caused by chemotherapy (i.e. cisplatin).

Animals↗
PubMed2003

Granisetron plus dexamethasone versus granisetron alone in the prevention of vomiting induced by conditioning for stem cell transplantation: a prospective randomized study.

This prospective randomized study compared the efficacy and toxicity of granisetron and dexamethasone to those of granisetron alone for antiemetic control in patients receiving high-dose chemotherapy with or without total body irradiation (TBI) for stem cell transplantation. Patients were divided randomly into 2 groups. Groups received granisetron twice daily at a dose of 40 microg/kg with or without 4 mg dexamethasone (GS group and G group, respectively), starting 30 minutes before each dose of chemotherapeutic agent or TBI, or 12 hours after the first dose if TBI or a drug was given once a day. Fifty patients were evaluated for the analysis. During the first 24 hours of conditioning, 23 of 25 patients (92.0%) in the GS group achieved complete control of emesis (no emetic episodes over the course of a day), compared with 72.0% in the G group (P = .06). For patients receiving TBI on the first day of conditioning, complete emetic control was achieved in all patients (100.0%) in the GS group, compared with 63.2% in the G group (P = .02). The same degree of emetic control was maintained throughout the conditioning period in 38.8% of the GS group and 29.9% of the G group (P = .10). Adverse reactions were observed more frequently in the GS group (68.0% versus 5.0% in the G group). These reactions included insomnia, headache, flushing, and hyperglycemia. None of the events were serious. We conclude that granisetron with dexamethasone seems superior to granisetron alone for the prevention of emesis resulting from the conditioning regimen; however, the more frequent side effects may limit the wide use of this combination.

Adolescent↗
PubMed1991

Metoclopramide does not decrease the incidence of nausea and vomiting after alfentanil for outpatient anaesthesia.

Sixty patients were studied in a randomized, double-blind manner to determine whether metoclopramide added to droperidol decreased further the incidence of emetic symptoms (nausea, retching, vomiting) in outpatients receiving alfentanil anaesthesia for nasal surgery. Group 1 (n = 30) received metoclopramide 0.15 mg.kg-1 and Group 2 (n = 30) received placebo. In addition, both groups received droperidol 0.02 mg.kg-1 immediately before anaesthesia which was supplemented by alfentanil 20 micrograms.kg-1 at induction followed by an infusion of 0.25-1 micrograms.kg-1.min-1. Emetic symptoms were assessed 0-3 hr, 3-6 hr and 6-24 hr after surgery. Both groups received similar doses of alfentanil (mean +/- SD; Group 1 4641 +/- 1894 micrograms, Group 2 4714 +/- 1640 micrograms). The percentage of patients who had either nausea or vomiting at 0-3, 3-6 or 6-24 hr was 23%, 14% and 13% in Group 1; and 20%, 17% and 10% in Group 2. The overall incidence for each group was 8/30 (27%). There was no difference in the incidence of emetic symptoms between the groups at any time interval or throughout the study. Metoclopramide did not improve upon the antiemesis of droperidol during alfentanil anaesthesia for outpatient nasal surgery.

Adult↗
PubMed1992

Total intravenous anaesthesia with propofol and alfentanil protects against postoperative nausea and vomiting.

The incidence of postoperative nausea and vomiting and requirements for anti-emetic medication were assessed in 80 female patients undergoing day-case anaesthesia during assisted conception therapy. Anaesthesia was induced with alfentanil 50 micrograms.kg-1 and propofol 1 mg.kg-1; atracurium 0.5 mg.kg-1 was given to facilitate tracheal intubation. The patients were allocated to receive either total intravenous maintenance of anaesthesia with an infusion of propofol and increments of alfentanil (Group P) or inhalational maintenance of anaesthesia with nitrous oxide and enflurane (Group E). Postoperative nausea, retching, vomiting, requirements for anti-emetic therapy, and unplanned admission for overnight stay in hospital were recorded. Overall incidence of nausea was 64% in group E and 39% in Group P (P less than 0.05). Incidence of vomiting was 67% in Group E and 34% in Group P (P less than 0.05). Metoclopramide was requested by 62% of patients in Group E, and 32% of those in Group P (P less than 0.05); 21% of the patients in Group E were admitted to hospital overnight, while only 5% of the patients in Group P required unscheduled admission to hospital (P less than 0.05). We conclude that total intravenous anaesthesia with propofol and alfentanil is superior to inhalational maintenance with nitrous oxide and enflurane in that it is associated with less nausea and vomiting, less requirement for anti-emetic medication, and a lower probability of unplanned admission to hospital after day-care gynaecological surgery.

Adult↗
PubMed1996

A comparison of ranitidine, droperidol or placebo in the prevention of nausea and vomiting after hysterectomy.

PURPOSE: The effect of ranitidine on postoperative nausea and vomiting (PONV) was assessed when compared with droperidol and with placebo. METHODS: Three groups of sixty patients were studied in a double-blind randomized manner. The first group received ranitidine tablets 300 mg on the night before and on the following morning, one hour before induction of anaesthesia. Thirty minutes before surgery ended they were given isotonic saline 0.3 ml iv. The second group had placebo in place of ranitidine while before the operation ended, droperidol 0.75 mg (0.3 ml) was injected. The third group received placebos rather than the study drugs. The immediate two-hour postoperative recovery room period and that on the ward were evaluated until the next morning. PONV information was gathered from complaints by the patients and from direct questioning by the nursing staff. Droperidol 0.75 mg iv served as the "rescue drug." RESULTS: Less PONV occurred in patients who received anti-emetics than those given placebo: recovery room, P = 0.0109; ward, P = 0.007. Droperidol better suppressed PONV in the recovery room (P = 0.005) with no statistical significance seen between ranitidine and placebo. On the ward, both anti-emetics were more effective than placebo (ranitidine, P = 0.01; droperidol, P = 0.003). "Rescue drug" requirements throughout the study periods were not statistically significant. CONCLUSION: Although both anti-emetics were associated with a smaller incidence of PONV than was placebo, droperidol was superior to ranitidine in preventing sickness during the immediate postoperative period. The need for the "rescue drug" was similar in all groups.

Adult↗
PubMed1998

Comparison of the efficacy and side-effects of ondansetron and metoclopramide-diphenhydramine administered to control nausea and vomiting in children treated with antineoplastic chemotherapy: a prospective randomized study.

UNLABELLED: Nausea and vomiting following antineoplastic therapy in patients receiving chemotherapy remains a problem. To prevent nausea and vomiting due to antineoplastic therapy, many types of drugs have been used. Ondansetron and the combination metoclopramide-diphenhydramine have been widely used in children. In this prospective randomized study these drugs were compared both for their efficacy and side-effects in children treated with antineoplastic chemotherapy (with and without cisplatin) the number of chemotherapy courses being equal in both groups. Ondansetron gave complete anti-emetic cover in five of nine courses in patients treated with cisplatin. Metoclopramide-diphenhydramine gave complete anti-emetic cover in one out of nine courses, and 17 out of 23 courses in patients treated without cisplatin. Metoclopramide-diphenhydramine produced side effects in nine courses whereas ondansetron produced side-effects in three courses. CONCLUSION: Ondansetron appeared to be superior to metoclopramide-diphenhydramine in the control of emesis induced by chemotherapy regimens containing cisplatin. The results of the present prospective randomized study indicate that ondansetron is a useful anti-emetic in the treatment of chemotherapy-induced emesis.

Antiemetics↗
PubMed1998

Continuous-infusion granisetron compared to ondansetron for the prevention of nausea and vomiting after high-dose chemotherapy.

PURPOSE: The serotonin receptor antagonists effectively prevent emesis with little toxicity when employed with standard doses of emetogenic chemotherapy. The optimal approach to the prevention of the emesis associated with the high doses of chemotherapy used for autologous stem cell transplantation is not known. A randomized controlled trial was designed to assess the relative efficacy and toxicity of granisetron compared to ondansetron in the setting of autologous stem cell transplantation. METHODS: A group of 48 patients with breast cancer were randomized in a double-blind fashion to receive either (1) granisetron as a 0.5-mg i.v. bolus 30 min. before chemotherapy followed by a continuous infusion of 0.04 mg/h (1 mg/day) for 7 days or (2) ondansetron as an 8-mg i.v. bolus 30 min before chemotherapy followed by a continuous infusion of 1 mg/h (24 mg/day) for 7 days. All patients also received 10 mg dexamethasone/day i.v. for 7 days. Chemotherapy consisted of 1500 mg cyclophosphamide per m2/day, 125 mg thiotepa m(-2) day(-1), and 200 mg carboplatin per m2/day all as a continuous infusion for 4 consecutive days. The two study arms were then compared for the incidence and severity of nausea, incidence of emesis, number of salvage anti-emetics required, cost, and toxicity. RESULTS: A total of 46 patients were evaluable. The treatment arms were well-balanced for known risk factors for chemotherapy-induced nausea and vomiting. Compliance with self-reporting of nausea and vomiting was poor but indicated no difference between the two treatment arms. The average number of anti-emetics required was 15.8 in both treatment arms and the average time to the first dose of a salvage anti-emetic was 2.8 days in the granisetron arm and 2.9 days in the ondansetron arm. The incidence of headache was 36 % in the granisetron arm and 39 % in the ondansetron arm. None of these differences was statistically significant. The use of granisetron resulted in a cost saving of 6.5 %. CONCLUSION: There was no significant difference between granisetron and ondansetron in either efficacy or toxicity. At our institution, the use of granisetron resulted in a moderate cost saving.

Adult↗
PubMed2002

A double-blind, randomised, parallel group, multinational, multicentre study comparing a single dose of ondansetron 24 mg p.o. with placebo and metoclopramide 10 mg t.d.s. p.o. in the treatment of opioid-induced nausea and emesis in cancer patients.

Nausea and emesis are common side effects of opioid drugs administered for pain relief in cancer patients. The aim of this study was to compare the anti-emetic efficacy and safety of ondansetron, placebo and metoclopramide in the treatment of opioid-induced nausea and emesis (OIE) in cancer patients. This was a multinational, multicentre, double-blind, parallel group study in which cancer patients who were receiving a full opioid agonist for cancer pain were randomised to receive one of oral ondansetron 24 mg once daily, metoclopramide 10 mg three times daily, or placebo. Study medication was started only if the patient experienced nausea and/or emesis following opioid administration. Efficacy and safety assessments were made over a study period of 24 h from the time of the first dose of anti-emetics/placebo. The study was terminated prematurely because of the difficulties in recruiting patients satisfying the stringent entry criteria. Ninety-two patients were included in the intent-to-treat population: 30 patients received placebo, 29 patients ondansetron and 33 patients metoclopramide. There was no statistically significant difference between the groups in the proportion achieving complete control of emesis (33% of patients on placebo, 48% on ondansetron and 52% on metoclopramide) or complete control of nausea (23% of patients on placebo, 17% on ondansetron and 36% on metoclopramide). Rescue anti-emetics were required in 8 of 33 patients on metoclopramide, 4 of 29 on ondansetron, and 3 of 30 on placebo. The incidence of adverse events was very low and similar in all treatment groups. Neither ondansetron 24 mg once daily nor metoclopromide 10 mg t.d.s. given orally was significantly more effective than placebo in the control of OIE in cancer patients.

Adult↗
PubMed2005

A pilot study of ondansetron plus metopimazine vs. ondansetron monotherapy in children receiving highly emetogenic chemotherapy: a Bayesian randomized serial N-of-1 trials design.

GOALS OF WORK: Chemotherapy-induced nausea and vomiting is problematic in paediatric brain tumour treatment protocols which often discourage the use of corticosteroids as anti-emetics. The dopamine receptor antagonist, metopimazine, is an effective anti-emetic in combination with ondansetron in adults. The present study was designed to assess its efficacy in children with cancer, a group in which it has not been studied previously. PATIENTS AND METHODS: We conducted a series of randomized, multiple-crossover, double-blind, placebo-controlled N-of-1 trials comparing ondansetron/metopimazine with ondansetron monotherapy in children with brain tumours receiving highly emetogenic therapy and combined the individual results using Bayesian statistical modeling. MAIN RESULTS: Ten of twelve enrolled patients completed at least one chemotherapy cycle on study (median=2.5 cycles, range 1-11). Two patients were unable to complete any cycles, and a further three patients withdrew from the study prior to completing all cycles because of an inability to tolerate the taste of the study drug. Combination therapy increased the proportion of days during which patients had no emesis (overall odds ratio=1.52, 95% credible region=0.32-6.40, probability of odds ratio>1=72%), decreased the number of emetic episodes per day (overall rate ratio=0.67, 95% credible region=0.15-3.14, probability of rate ratio<1=75%) and decreased parents' ratings of their child's distress. The drug was more effective during the delayed chemotherapy phase than the acute phase. No adverse events were attributed to metopimazine. CONCLUSIONS: Based on this pilot study, we believe that the high likelihood that metopimazine is an effective adjunct to ondansetron monotherapy suggests that this combination therapy is worthy of further study in children receiving emetogenic chemotherapy.

Antiemetics↗
PubMed1998

An open-label dose comparison study of ondansetron for the prevention of emesis associated with chemotherapy prior to bone marrow transplantation.

Nausea and vomiting are significant side effects in bone marrow transplant (BMT) patients who receive high-dose preparative regimens. Higher than conventional ondansetron doses and continuous infusion might improve emetic control, because of the high doses and combinations of chemotherapy (CT) used in this setting. Our objective was to conduct a prospective, randomized study comparing two different administration methods of high-dose ondansetron during a BMT preparative regimen in breast cancer patients. Patients were eligible if they were nonpregnant women over 18 but under 65 years of age, undergoing highly emetogenic CT in preparation for autologous BMT. All patients received ondansetron as an intermittent (INT = 24 mg i.v. q 12 h/day) or continuous intravenous infusion (CIV = 8 mg i.v. loading dose followed by a continuous infusion of 2 mg/h per day). A total of 66 patients were enrolled in the study (n = 34, INT; n = 32, CIV). There was no statistical difference between treatment groups in the worst grade of emesis for the entire study period (P = 0.49). Greater than 90% of all patients were graded as failures (> or = 5 emetic episodes or need for rescue antiemetics). Complete control (no vomiting episodes) and complete plus major control (1-2 emetic episodes) per day ranged from 8% to 85% and 11% to 91%, respectively. There was no significant difference between the treatment arms in: grade of emesis, episodes of vomiting and retching, nausea scores, and mean number of rescue medications administered. There were no differences in efficacy when high-dose ondansetron was given as CIV or INT for the control of nausea and vomiting in breast cancer patients undergoing high-dose CT for autologous BMT. Ondansetron alone was not adequate to provide sustained control of CT-induced nausea and vomiting over the entire 5-day study period. A combination of antiemetics targeting various mechanisms of CT-induced nausea and vomiting may be necessary to improve response rates.

Adult↗
PubMed1993

Litoxetine: a selective 5-HT uptake inhibitor with concomitant 5-HT3 receptor antagonist and antiemetic properties.

The selective 5HT uptake inhibitor, litoxetine (SL 81.0385), currently under development as an antidepressant was shown to have antiemetic properties in the ferret. Litoxetine (at 1 and 10 mg/kg i.v.) dose dependently reduced the number of retches and vomiting as well as the number of emetic episodes induced by cisplatin (10 mg/kg i.v.) and delayed the onset of emesis. Fluoxetine (at 1 or 10 mg/kg i.v.) failed to inhibit cisplatin-induced emetic responses and, in contrast, significantly increased the number of retches and vomiting and accelerated the onset of emesis. The possibility that the antiemetic effects of litoxetine may be mediated through an interaction with 5HT3 receptors was studied using [3H]quipazine or [3H]BRL 43694 to label the 5HT3 receptor. Litoxetine has moderate affinity for cerebral 5HT3 receptors (Ki = 85 nM), while fluoxetine, similar to other 5HT uptake inhibitors, has only negligible affinity for this receptor (Ki = 6.5 microM). It is proposed that litoxetine inhibits cisplatin-induced emetic responses due to its moderate 5HT3 antagonist properties. The clinical use of the majority of serotonergic antidepressants (e.g. fluoxetine, fluvoxamine etc.) is associated with gastrointestinal discomfort (particularly nausea and vomiting) as a major side-effect. If nausea and vomiting associated with the use of 5 HT uptake inhibitors are due to stimulation of 5HT3 receptors, the concomitant 5HT3 antagonism of litoxetine may limit the gastrointestinal side-effects of this novel antidepressant and thus offer an important advantage.

Animals↗
PubMed1987

Noradrenaline-induced emesis. Alpha-2 adrenoceptor mediation in the area postrema.

The emetic action of noradrenaline was investigated in unanesthetized cats, after it was injected into the cerebral ventricles through chronically implanted cannulae. Intracerebroventricular injection of noradrenaline produced dose-dependent and shortlasting emesis, which was abolished after ablation of the area postrema. However, copper sulphate, given orally, evoked emesis in cats with an ablated area postrema. The selective alpha-2 adrenoceptor antagonist, yohimbine, as well as the mixed alpha-1 and alpha-2 adrenoceptor blocking drugs, phentolamine, tolazoline, phenoxybenzamine and dihydroergotamine, but not the selective alpha-1 adrenoceptor antagonist, prazosin, all injected into the cerebral ventricles, attenuated or blocked the emesis evoked by intracerebroventricular injection of noradrenaline. Of the alpha-adrenoceptor antagonist, only yohimbine produced dose-dependent inhibition of the emesis induced by noradrenaline. On the contrary, selected beta-adrenoceptor blocking agents, an antimuscarinic drug, a ganglionic blocking agent, an antihistamine, dopamine antagonists and a 5-hydroxytryptamine antagonist, all injected into the cerebral ventricles, had no significant effect on the emesis induced by noradrenaline, similarly injected. The emetic response to intracerebroventricular injection of noradrenaline, as well as to intragastric administration of copper sulphate was not altered in cats pretreated with intracerebroventricular injections of alpha-methyl-p-tyrosine and bretylium. On the other hand, the emetic response to intracerebroventricular injection of noradrenaline and to intragastric administration of copper sulphate was attentuated or blocked in cats pretreated with reserpine intracerebroventricularly. Moreover, in cats pretreated with intracerebroventricular injection of 6-hydroxydopamine and hemicholinium, the emesis induced by intracerebroventricular administration of noradrenaline but not that produced by intragastric injection of copper sulphate, was depressed.(ABSTRACT TRUNCATED AT 250 WORDS)

5,6-Dihydroxytryptamine↗
PubMed1987

Further studies on nicotine-induced emesis: nicotinic mediation in area postrema.

In unanesthetized cats the emetic action of an injection of nicotine into the cerebral ventricle through chronically implanted cannulae was investigated. Nicotine injected in doses of 0.02-1.0 mg produced dose-dependent vomiting, which was abolished after ablation of the area postrema. However, copper sulfate given intragastrically evoked vomiting in cats with an ablated area postrema. The emetic response to intracerebroventricular (ICV) nicotine as well as the vomiting produced by intragastric copper sulfate was depressed or abolished in cats pretreated with ICV reserpine. On the other hand, the emetic response to ICV nicotine and to intragastric copper sulfate was virtually unchanged in cats pretreated with ICV 6-hydroxydopamine and 5,6-dihydroxytryptamine. The duration of vomiting produced by intragastric copper sulfate, but not that of ICV nicotine, was potentiated in cats pretreated with hemicholinium-3. Ganglionic blocking agents, mecamylamine and hexamethonium, injected ICV prevented the vomiting elicited by ICV nicotine. On the other hand, selected anti-muscarinic drugs, alpha and beta adrenergic receptor antagonists, dopamine antagonists, antihistamines and a 5-hydroxytryptamine antagonist all injected into the cerebral ventricle had virtually no effect on the vomiting induced by ICV nicotine. It is postulated that nicotine evokes vomiting by its action on nicotinic receptors within the area postrema but not on catecholaminergic or serotonergic neurones. Finally, acetylcholine could also be involved in the inhibition of the complex mechanisms underlying the central regulation of vomiting.

Acetylcholine↗
PubMed1992

Sigma ligand-induced emesis in the pigeon.

Pigeons were fed a fixed amount of grain-based feed and behavior was observed after administration of doses of ditolyguanidine (DTG), (+)-3-(3-hydroxyphenyl)-N-(1-propyl)-piperidine [(+)-3-PPP], dextromethorphan, haloperidol, (+)-N-allylnormetazocine (NANM), alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine-butanol (BMY-14802) apomorphine, pentobarbital, propranolol, and MK-801. Of the drugs tested, DTG, dextromethorphan, and (+)-3-PPP each produced dose-related increases in the percentage of pigeons exhibiting an emetic response. The emetic response produced by DTG was antagonized by haloperidol and BMY-14802 but not by propranolol. These observations suggest that the emetic response in the pigeon may be mediated by sigma sites and is unlikely to be mediated by phencyclidine receptors.

Animals↗
PubMedDate not supplied

Ondansetron for nausea and vomiting associated with moderately emetogenic cancer chemotherapy.

This multicenter, randomized, double-blind study compared the efficacy and tolerability of ondansetron 8 mg twice daily for 3 days with placebo in preventing nausea and vomiting in 81 patients receiving cyclophosphamide-doxorubicin-based chemotherapy. The first dose of study drug was administered 30 minutes before the initiation of chemotherapy. Patients received a rescue antiemetic if the investigator deemed it necessary or if the patient experienced more than two emetic episodes during the 3-day study. Sixty-one percent of patients treated with ondansetron compared with 6% of patients receiving placebo (P < 0.001) had no emetic episodes during the 3-day study. Among patients with at least one emetic episode, the mean time to emesis was 24 hours 18 minutes in the ondansetron group compared with 8 hours 1 minute in the placebo group (P < 0.001). In the intent-to-treat analysis, 78% of patients in the ondansetron group and 29% of patients in the placebo group completed the study with no need for rescue therapy. Clinical laboratory and adverse-event profiles were similar between groups. The most common adverse event was headache, occurring in 23% of ondansetron patients and 24% of placebo patients. This study is the first double-blind, placebo-controlled trial to demonstrate that ondansetron 8 mg twice daily is effective in the prevention of nausea and vomiting associated with cyclophosphamide-doxorubicin-based chemotherapy. The twice-daily regimen may encourage patient compliance and may be more cost-effective than regimens that need to be given three times daily.

Antibiotics, Antineoplastic↗