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PubMedDate not supplied

[Mechanism of emetic action of adrenaline and histamine in the dog].

It has been established in dog experiments that phentolamine prevents the emetic action of adrenaline whereas diphenhydramine the emetic effect of histamine. Both the drugs in the doses studied do not produce any effect on vomiting induced by L-DOPA. The dopamine blockers, etaperazine, haloperidol and metoclopramide given in the doses suppressing the emetic action of L-DOPA do not prevent the adrenaline- and histamine-induced vomiting. It is assumed that the emetic action of adrenaline is effected in dogs via alpha-adrenoreceptors, whereas the histamine-induced vomiting via H1-histamine receptors of the trigger zone of the vomiting center.

Animals↗
PubMed2006

Prescribing patterns of anti-emetic drugs during pregnancy in Germany.

OBJECTIVES: The purpose of this study was to examine the prescribing patterns of anti-emetics for pregnant women in Germany. METHOD: A large, nation-wide German statutory sickness fund provided data of reimbursed prescriptions and personal data for all insured women giving birth between June 2000 and May 2001 (n = 41,293). The prescribed drugs were classified according to the Anatomical Therapeutic Chemical code. RESULT: About 13.9% (n = 5,746) of all pregnant women received an anti-emetic prescription. Over 98.5% of these women were treated with anti-emetics that are considered safe. But only 27.8% received the recommended anti-histamine meclozine and 2.1% the safest drug pyridoxine. CONCLUSION: As there are no official guidelines for the treatment of nausea and vomiting during pregnancy in Germany, many different drugs are used, sometimes ignoring effectiveness and even safety. Therefore, evidence-based guidelines for anti-emetic therapy are needed.

Adolescent↗
PubMed1996

GR205171: a novel antagonist with high affinity for the tachykinin NK1 receptor, and potent broad-spectrum anti-emetic activity.

It has been demonstrated recently that antagonists of the tachykinin NK1 receptor, specifically CP-99,994 and GR203040, possess anti-emetic activity in a range of species. To optimise this activity, a series of analogues based around the structure of GR203040 have been synthesised and their affinity at the human tachykinin NK1 receptor determined. In addition, the potency of these analogues to inhibit emesis induced in the ferret by whole-body X-irradiation has been examined. A range of substitution at the C-1 position of the tetrazole moiety in GR203040 were explored in vitro and in vivo. The trifluoromethyl compound, GR205171, was the most potent antagonist with regard to the ability to inhibit emesis induced by X-irradiation. This compound was demonstrated to have a broad spectrum of anti-emetic activity, inhibiting emesis in the ferret induced by cisplatin, cyclophosphamide, morphine, ipecacuanha and copper sulphate. Furthermore, emesis was also inhibited in the house-musk shrew, Suncus murinus, when induced by either motion or cisplatin, and in the dog when induced by ipecacuanha. GR205171 has the most potent anti-emetic activity of any tachykinin NK1 receptor antagonist described to date. The compound is orally active in the ferret and dog, long-lasting, and warrants further investigation as a potential broad-spectrum anti-emetic agent.

Administration, Oral↗
PubMed2005

Interaction between tramadol and two anti-emetics on nociception and gastrointestinal transit in mice.

BACKGROUND: Clinical studies suggest that tramadol-induced analgesia is partially antagonized by ondansetron. AIMS: To investigate the type of interaction between tramadol and two anti-emetics on antinociception and gastrointestinal transit in mice. METHODS: We assessed the antinociceptive (acetic acid writhing test, plantar test) and antitransit (charcoal meal) effects of tramadol individually, and combined with ondansetron or droperidol in female Swiss CD-1 mice. Isobolograms and analysis of variance were used to determine the type of interaction. RESULTS: In the writhing test, tramadol, ondansetron and droperidol, each induced dose-related inhibition of nociception. The ED(50)'s were: tramadol 4.2+/-0.33 mg kg(-1); ondansetron 1.03+/-0.05 mg kg(-1), and droperidol 1.00+/-0.14 mg kg(-1). Dose-response curves were also obtained with tramadol combined with ondansetron or droperidol at 1:1 fixed ratios. The isobolographic analysis demonstrated antagonism for both combinations. In the plantar test, the ED(50) for tramadol was 51.4+/-2.3 mg kg(-1), but no dose-response curves could be obtained with ondansetron or droperidol individually. The interaction was assessed from dose-response curves to tramadol in the presence of a fixed dose of ondansetron (0.1 mg kg(-1)) or droperidol (0.05 mg kg(-1)). The results show antagonism between tramadol-ondansetron (p<0.05) and no interaction for the tramadol-droperidol combination. Both anti-emetics antagonized the antitransit effects of tramadol. CONCLUSIONS: The interaction of tramadol with ondansetron or droperidol on antinociception can be antagonistic or additive, depending on the type of stimuli. Both anti-emetics antagonize the anti-transit effects of tramadol. The results demonstrate antagonism between tramadol and the two anti-emetics for analgesia and inhibition of gastrointestinal transit, supporting previous clinical studies.

Analgesics, Opioid↗
PubMed2005

Anti-emetic activity of ghrelin in ferrets exposed to the cytotoxic anti-cancer agent cisplatin.

Emesis may be modulated via multiple mechanisms. The actions of ghrelin suggest an ability to couple an induction of hunger with preparation of the stomach for ingestion of food. Such a process might reduce any tendency to vomit, so an anti-emetic activity of ghrelin was investigated in the ferret cisplatin-induced emesis model. In controls, intra-peritoneal cisplatin (10 mg/kg) induced 41.4+/-8.4 episodes of emesis comprising 310.4+/-55.3 retches and 28.8+/-6.9 vomits during the 6h observation; the latency to onset of the first emetic episode was 108.9+/-4.8 min. Intra-peritoneal ghrelin (1mg/kg, split as a 30 min pre- and 30 min-post dose) did not induce a change in behaviour or modify cisplatin-induced emesis (p>0.05). Intracerebroventricular (i.c.v.) administration (third ventricle) was achieved via a pre-implanted cannula. At the first emetic episode following cisplatin, ghrelin or vehicle (20 microl saline) was administered i.c.v. During the 30 min following the initial episode of emesis, control animals exhibited 18.0+/-2.6 emetic episodes comprising 160.3+/-24.1 retches and 13.8+/-2.7 vomits. Ghrelin 10 microg i.c.v. reduced the number of retches by 61.5% (p<0.05) and at a dose of 30 microg i.c.v. ghrelin reduced the number of episodes, individual retches and vomits by 74.4 (p<0.05), 80.4 (p<0.01), and 72.5% (p<0.05), respectively. At subsequent time periods there were no differences between ghrelin- or saline-treated animals (p>0.05). An ability of ghrelin to reduce emesis is consistent with a role in modulating gastro-intestinal functions and identifies a novel approach to the treatment of emesis.

Animals↗
PubMed2002

Dose-range effects of propofol for reducing emetic symptoms during cesarean delivery.

OBJECTIVE: To evaluate the efficacy and safety of propofol at subhypnotic doses for reducing emetic symptoms in parturients undergoing cesarean delivery under spinal anesthesia. METHODS: In a randomized, double-masked trial, 80 patients received lidocaine intravenously 0.1 mg/kg (for injection pain relief) followed by either placebo or propofol at three different doses (0.5 mg/kg per hour, 1.0 mg/kg per hour, 2.0 mg/kg per hour) (n = 20 in each group) immediately after clamping of the umbilical cord. Emetic episodes and safety assessments were performed during spinal anesthesia for cesarean delivery. To estimate a sufficient sample size, it was calculated that 20 patients per group would be required with alpha =.05 and beta =.2. RESULTS: The rate of patients experiencing no emetic symptoms in an intraoperative, postdelivery period was 45% with propofol 0.5 mg/kg per hour (P =.5), 80% with propofol 1.0 mg/kg per hour (P =.011), and 80% with propofol 2.0 mg/kg per hour (P =.011), compared with placebo (40%). No clinically serious adverse events caused by the study drugs were observed. CONCLUSION: Propofol 1.0 mg/kg per hour is the minimum effective subhypnotic dose for reducing emetic symptoms during cesarean delivery. Increasing the dose to 2.0 mg/kg per hour provides no further benefit.

Adult↗
PubMed2004

Identification of emetic toxin producing Bacillus cereus strains by a novel molecular assay.

Bacillus cereus causes two types of gastrointestinal diseases: emesis and diarrhea. The emetic type of the disease is attributed to the heat-stable depsipeptide cereulide and symptoms resemble Staphylococcus aureus intoxication, but there is no rapid method available to detect B. cereus strains causing this type of disease. In this study, a polymerase chain reaction (PCR) fragment of unknown function was identified, which was shown to be specific for emetic toxin producing strains of B. cereus. The sequence of this amplicon was determined and a PCR assay was developed on this basis. One hundred B. cereus isolates obtained from different food poisoning outbreaks and diverse food sources from various geographical locations and 29 strains from other species belonging to the B. cereus group were tested by this assay. In addition, 49 non-B. cereus group strains, with special emphasis on food pathogens, were used to show that the assay is specific for emetic toxin producing B. cereus strains. The presented PCR assay is the first molecular tool for the rapid detection of emetic toxin producing B. cereus strains.

Bacillus cereus↗
PubMed1999

A prospective randomized trial of the anti-emetic efficacy of ondansetron and granisetron during bone marrow transplantation.

To determine the comparative anti-emetic efficacy of ondansetron and granisetron in patients undergoing bone marrow transplantation, we performed a double-blind, randomized trial in pediatric and adult patients receiving transplants at the University of Minnesota. The results in 187 patients stratified by age (<18 years, n = 51; > or =18 years, n = 136) were analyzed. The average number of emetic episodes in the entire group from day -7 to 2 was 0.86/day for patients receiving ondansetron and 0.73/day for those receiving granisetron (p = 0.32). No differences were noted between the two drugs in total days of complete or major control of emesis or in the number of requests for additional drugs to alleviate symptoms of nausea. The use of total-body irradiation-containing conditioning regimens was associated with a decreased number of emetic episodes compared with regimens of chemotherapy alone. Perceived nausea was evaluated using a nausea scoring system, and no differences were apparent between the granisetron and ondansetron groups; however, reported nausea was significantly higher in females (p<0.01) and in the adult population (p = 0.05). We conclude that both ondansetron and granisetron provide good control of nausea and vomiting experienced with conditioning regimens for bone marrow transplantation. The relative cost of the drugs within an institution must be considered in developing standard anti-emetic regimens for bone marrow transplantation.

Adolescent↗
PubMed1997

Ondansetron suppository: an effective treatment for the prevention of emetic disorders induced by cisplatin-based chemotherapy. French Ondansetron Study Group.

This multicentre, randomised, double-blind, double-dummy, parallel group study was investigated in order to compare on 3 days the efficacy and the safety of the 16 mg once a day (od) ondansetron suppository (suppository group) with the recommended ondansetron treatment, i.e. 8 mg intravenous (i.v.) ondansetron on day 1 followed by 8 mg tablet (p.o.) twice daily (i.v. + p.o. group) on days 2 and 3 in patients receiving cisplatin (> or = 50 mg/m2) containing chemotherapy. In the 420 patients included in the intent-to-treat population, 209 received the 16 mg suppository and 211 the i.v. + p.o. treatment. The number of emetic episodes and the nausea score were recorded each day. Concerning the primary criterion, both treatments provided good anti-emetic control with 87% of all patients having a complete or major response (0-2 emetic episodes) on day 1 in the suppository group and 92% in the i.v. + p.o. group (P = 0.058). The 90% confidence interval for the difference between the two treatments for complete or major control was included in the interval (-15%, 15%) and showed that the treatment groups could be regarded as equivalent. Small differences in favour of the i.v. + p.o. group were observed concerning the secondary parameters. Both treatments were well tolerated. The results of this study show that both treatments are equivalent in the prevention of cisplatin-containing chemotherapy induced emesis for the primary efficacy criteria and that the ondansetron suppository is efficient and well tolerated and is a suitable alternative to the anti-emetic treatment combining the intravenous and oral routes.

Administration, Oral↗
PubMed2000

Nissen-type fundoplication and its effects on the emetic reflex and gastric motility in the ferret.

Recurrent vomiting with failure to thrive is a common problem in neurologically impaired children. Many undergo fundoplication to control the underlying gastro-oesophageal reflux. The results of surgery are not always satisfactory and post-operative retching may be a major problem - a symptom indicative of activation of the emetic reflex. An animal model of antireflux surgery has been developed and used to investigate the effects of such surgery upon the emetic reflex and vagal influences on gastric motility. Following surgery, animals responded to a previously subemetic dose of a centrally acting opiate receptor agonist (loperamide), suggesting that fundoplication may sensitize the emetic reflex. A gastric vago-vagal reflex (tonic inhibition of corpus tone) and responses to direct stimulation of vagal motor efferents (both cholinergic and nonadrenergic noncholinergic responses) were not significantly affected by antireflux surgery. Mechanisms by which neural damage may sensitize the emetic reflex are discussed, together with the possible clinical implications for the management of post-operative symptoms in neurologically impaired children.

Animals↗
PubMed1994

Fos expression in ferret dorsal vagal complex after peripheral emetic stimuli.

The aim of this study was to investigate neuronal activation in the dorsal vagal complex of the halothane-anesthetized ferret after peripheral emetic stimuli. Neuronal activity was studied by examining the distribution of the nuclear phosphoprotein Fos using immunohistochemistry. The emetic stimuli used were electrical stimulation of the supradiaphragmatic vagal communicating branch (SVCB) or intraduodenal injection of hypertonic saline. Electrical stimulation of the SVCB induced the densest Fos expression within the medial subnucleus of the nucleus of the solitary tract. After hypertonic saline injection, the greatest density of Fos-positive nuclei was observed within the area postrema and also in the medial subnucleus of the nucleus of the solitary tract. It was concluded that the emetic response to hypertonic saline involves neurons in both the area postrema and the nucleus of the solitary tract, especially the medial subnucleus, and that the medial subnucleus is important in the emetic response to SVCB stimulation.

Animals↗
PubMed2006

Cereulide synthetase gene cluster from emetic Bacillus cereus: structure and location on a mega virulence plasmid related to Bacillus anthracis toxin plasmid pXO1.

BACKGROUND: Cereulide, a depsipeptide structurally related to valinomycin, is responsible for the emetic type of gastrointestinal disease caused by Bacillus cereus. Recently, it has been shown that this toxin is produced by a nonribosomal peptide synthetase (NRPS), but its exact genetic organization and biochemical synthesis is unknown. RESULTS: The complete sequence of the cereulide synthetase (ces) gene cluster, which encodes the enzymatic machinery required for the biosynthesis of cereulide, was dissected. The 24 kb ces gene cluster comprises 7 CDSs and includes, besides the typical NRPS genes like a phosphopantetheinyl transferase and two CDSs encoding enzyme modules for the activation and incorporation of monomers in the growing peptide chain, a CDS encoding a putative hydrolase in the upstream region and an ABC transporter in the downstream part. The enzyme modules responsible for incorporation of the hydroxyl acids showed an unusual structure while the modules responsible for the activation of the amino acids Ala and Val showed the typical domain organization of NRPS. The ces gene locus is flanked by genetic regions with high homology to virulence plasmids of B. cereus, Bacillus thuringiensis and Bacillus anthracis. PFGE and Southern hybridization showed that the ces genes are restricted to emetic B. cereus and indeed located on a 208 kb megaplasmid, which has high similarities to pXO1-like plasmids. CONCLUSION: The ces gene cluster that is located on a pXO1-like virulence plasmid represents, beside the insecticidal and the anthrax toxins, a third type of B. cereus group toxins encoded on megaplasmids. The ces genes are restricted to emetic toxin producers, but pXO1-like plasmids are also present in emetic-like strains. These data might indicate the presence of an ancient plasmid in B. cereus which has acquired different virulence genes over time. Due to the unusual structure of the hydroxyl acid incorporating enzyme modules of Ces, substantial biochemical efforts will be required to dissect the complete biochemical pathway of cereulide synthesis.

Antigens, Bacterial↗
PubMed2000

Psychosocial morbidity among women with nausea and vomiting of pregnancy: prevalence and association with anti-emetic therapy.

Unlike severe nausea and vomiting of pregnancy (NVP), it is not known whether milder forms of NVP have been associated with psychosocial morbidity. We undertook the study to explore the prevalence of psychosocial morbidity by severity of NVP, and determine whether, after correction for severity of nausea/vomiting, there is a relationship between psychosocial morbidity and women's decisions to take anti-emetics as a reflection of their distress due to NVP. From 1996-97, an NVP Healthline was advertised. Callers underwent semi-structured interviews about both their NVP and associated psychosocial morbidity in a previous pregnancy. Most of the 3201 callers resided in Canada, worked outside the home, reported on planned pregnancy (a median of) 4 years before, and described severe (> 5 episodes/day of) nausea and vomiting. More severe nausea/vomiting was associated with more frequent feelings of depression, consideration of termination of pregnancy, adverse effects on women's relationships with their partners or their partners' everyday lives, and the perceived likelihood that NVP would harm their baby (p < 0.0001). However, all psychosocial factors were reported by a clinically important proportion of women with mild nausea/vomiting (0-1 episodes/day). The severity of vomiting was most closely related to women's decisions to take anti-emetics, but other psychosocial factors were also independently associated with anti-emetic therapy. We conclude that psychosocial morbidity is evident across the spectrum of severity of nausea and vomiting among women with NVP. The severity of nausea or vomiting does not appear adequately to reflect the distress caused by NVP, as reflected by women's decisions to take anti-emetic therapy.

Adult↗
PubMed1986

Preserving the emetic effect of syrup of ipecac with concurrent activated charcoal administration: a preliminary study.

Activated charcoal is reported to block the emetic effect of syrup of ipecac. Therefore, activated charcoal administration is commonly delayed until syrup of ipecac induced emesis is complete. The advantages of early administration of activated charcoal have been well documented. Preservation of the emetic effect of syrup of ipecac in the presence of activated charcoal may produce a synergistic effect by enhancing toxin elimination. A study was conducted in ten human volunteers to determine if activated charcoal prevents the emetic effect of syrup of ipecac when a temporal separation exists between administration of the two substances. Syrup of ipecac 60 ml plus water 480 ml was administered via an 18 French nasogastric tube followed by an aqueous slurry of activated charcoal 50 g five minutes later. Eight (80%) of the subjects had emesis in a mean time of 20.25 minutes (range 16-26 min). The total dose of activated charcoal was retained for a mean time of 6.75 minutes (range 0-17 min). Two subjects (20%) failed to have emesis. This study illustrates that activated charcoal may not completely block the emetic effect of syrup of ipecac.

Adult↗
PubMed1992

[Anti-emetic effect and safety of ondansetron tablet in double-blind comparison with placebo].

Ondansetron, a selective 5-HT3 receptor antagonist, has already been reported to have a marked effect to alleviate or prevent nausea and vomiting associated with cancer chemotherapy, after its intravenous administration. The present study was planned to examine the usefulness of its tablet form, which was prepared for the convenient use in outpatients receiving chemotherapy. In order to make an objective evaluation of anti-emetic effect and safety of ondansetron 4 mg tablet, this study was conducted in double-blind comparison versus placebo in patients receiving cisplatin at a single dose of 50mg/m2 or higher. Either 4 mg of ondansetron or placebo (lactose tablet) was administered orally once at 2 hrs prior to administration of cisplatin. If any satisfactory anti-emetic effects were not obtained, 4 mg of ondansetron injection was given once intravenously as a rescue medication. The inhibitory effect on nausea and vomiting was assessed in 4 grades as "excellent", "good", "fair" and "poor" based on severity of nausea and number of vomiting that occurred during the first 24hrs after administration of cisplatin. When rescue medication was conducted, the case was assessed as "poor". Ondansetron was significantly superior to placebo in inhibition of nausea and vomiting, in which efficacy rates (excellent+good) of ondansetron and placebo groups were 58.1% (25/43 cases) and 16.7% (7/42 cases), respectively. Number of cases requiring rescue medication with ondansetron injection was obviously greater in placebo group (31 cases) than that in ondansetron group (12 cases). In those patients given ondansetron injection as the rescue medication, satisfactory effects were obtained in 5 cases in ondansetron group and in 18 cases in placebo group. Although side effects including chest itching (ondansetron group), headache and dull headache (placebo group) were observed after the rescue medication with ondansetron injection, these symptoms were not severe and disappeared after 1-2 days. As mentioned above, ondansetron tablet was shown to possess excellent anti-emetic effect on nausea and emesis induced by high dose of cisplatin and to have no problem in safety. Hence ondansetron was proven to be clinically very useful anti-emetic.

Administration, Oral↗
PubMed1990

A comparative study of the use of granisetron, a selective 5-HT3 antagonist, versus a standard anti-emetic regimen of chlorpromazine plus dexamethasone in the treatment of cytostatic-induced emesis. The Granisetron Study Group.

Patients with cancer were randomized in single-blind fashion to receive either granisetron (n = 114) or a conventional anti-emetic combination of chlorpromazine and dexamethasone (n = 113) as prophylactic agents against the nausea and vomiting induced by a number of designated cytostatic drugs. In the first 24 h, 70% of patients in the granisetron group remained free from vomiting and had no, or only mild nausea compared with 49% of patients in the comparator group, a significant improvement over the conventional anti-emetic (P = 0.0013). Significantly fewer adverse events were reported in the granisetron group (P less than 0.05) and treatment did not result in the somnolence reported by patients receiving chlorpromazine plus dexamethasone (P less than 0.05). In the conventional treatment group, initial infusions were maintained with oral chlorpromazine at 4-6 h intervals in the first 24 h. Ten per cent of these patients received alternative, rescue anti-emetics during this period. In the granisetron group, 70% of patients received only a single prophylactic dose of 40 micrograms/kg granisetron throughout the 7-day period. During the first 24 h, 20% of patients in the granisetron group received up to two additional 40 micrograms/kg doses of granisetron and 6% received rescue anti-emetics.

Adolescent↗
PubMed1989

An outline of anti-emetic treatment.

With the advent of new chemotherapeutic agents, and their well-known side effect of emesis, the need for a greater facility with anti-emetics has emerged. As well as the common problem of chemotherapy-induced emesis, other problems have become apparent such as delayed emesis and anticipatory emesis. The control of such emetic problems may be affected by certain patient characteristics, such as a history of chronic high alcohol intake, and age. Blockade of the different types of neuroreceptors can lead to effective emetic control. Dopamine receptor blockers such as the phenothiazines, butyrophenones and substituted benzamides have been among the most effective agents. However, newer agents, such as ondansetron, which specifically bind to serotonin receptors, may preserve the anti-emetic efficacy of the dopamine-blockers, but without the associated extrapyramidal side effects of these agents.

Antiemetics↗
PubMed1978

Metabolic effects of some antibilharzial drugs. Comparative study on the effect of tartar-emetic and piperazine hexahydrate on the activity of some oxidoreductase enzymes of the rat livers.

IN THIS INVESTIGATION, the effects of the examined antibilharzial agents are as follows: Bilharcid and tartar-emetic similarly affected succinate oxidation. 50% inhibition could be obtained at a concentration of 10(-3) of both drugs. Malate oxidation was differently affected by the drugs. Bilharcid and tartar-emetic at a concentration of 10(-3) M induced 50% and 70% inhibition respectively, while tartar-emetic stimulated malate oxidation if added in a concentration of 10(-5) M. Pyruvate oxidation was affected in the same manner and to the same extent as malate oxidation. Citrate oxidation was slightly inhibited by Bilharcid and tartar-emetic. 10% and 30% inhibition could be obtained if the concentration was 10(-3) M of both drugs respectively. Bilharcid had a biphasic effect on citrate oxidation. Stimulation could be observed at low concentrations (up to 10(-8) M and inhibition at higher ones (up to 10(-3) M. Piperazine hexahydrate was nearly without effect on the rate of oxidation of the four mentioned substrates.

Animals↗