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At least 19 recordsLinked to original sources
PubMed1986

Steroid hormones in emetic and non-emetic pregnancy.

Nausea and/or vomiting in early pregnancy is common enough to be generally accepted as normal or 'physiological'. The specific etiology of these complaints is still obscure. One possibility is that endocrine factors may play some part. In this study, 102 healthy pregnant women, of whom 62 complained of nausea, were followed throughout pregnancy and the circulating levels of cortisol, testosterone, dehydroepiandrosterone sulphate (DHEA-S), progesterone, oestradiol and total and free oestriol were measured. In early pregnancy, serum levels of cortisol and progesterone were significantly lower in emetic subjects. In the last trimester, significantly higher DHEA-S concentrations and lower testosterone values were found in women who had suffered from nausea and vomiting in early pregnancy compared to asymptomatic subjects. Overt differences were found between emetic and non-emetic pregnancy and it is concluded that endocrine factors are of etiological importance in emesis gravidarum.

Dehydroepiandrosterone↗
PubMed1991

Does propofol have an anti-emetic effect? A prospective study of the anti-emetic effect of propofol following laparoscopy.

In order to investigate the putative anti-emetic effect of propofol, 53 patients undergoing gynaecological laparoscopy were given a standard anaesthetic including induction with thiopentone. At the end of surgery, the patients received either a sub-anaesthetic does of propofol or an equivalent volume of normal saline. There was no difference in the incidence of nausea and vomiting between the propofol and control group. It is concluded that low-dose propofol does not have an anti-emetic effect.

Adult↗
PubMed1992

Neurons in the nucleus of the solitary tract mediating inputs from emetic vagal afferents and the area postrema to the pattern generator for the emetic act in dogs.

Roles of neurons in the nucleus of the solitary tract corresponding to the area subpostrema (mNST) for the retching reflex were investigated in decerebrate, paralyzed dogs. Retching was defined as rhythmic coactivation of the phrenic and abdominal muscle nerves. Retching which had been induced by stimulation of the left and right abdominal vagus nerves was impaired by cooling the left and right mNSTs, respectively. This result indicates that the mNST neurons mediate activities of emetic vagal afferents. All 40 non-respiratory neurons in the mNST, which had excitatory response to pulse train stimulation of the vagus nerve, were also activated by continuous stimulation of the vagus nerve to provoke retching. During provoked retching, however, these neurons did not exhibit any activities modulated in association with retching. The average latency of responses of these neurons to the pulse train stimulation (306.5 ms) was significantly shorter than that of the inspiratory neurons in the lateral NST and the adjacent reticular formation. Discharge frequencies of these neurons in the mNST gradually increased after administration of apomorphine (6/10) and glutamate (14/14) to the 4th ventricle. Antidromic responses to stimulation of the Bötzinger complex were observed in some (20/289) of the mNST neurons. These findings suggest that neurons in the mNST mediate the information from both the abdominal vagal afferents and the area postrema and drive the pattern generator for retching and vomiting, which is assumed to be located in the Bötzinger complex.

Animals↗
PubMed1990

The inhibitory effect of halothane on the emetic response in the ferret.

Emesis and nausea are often associated with anaesthesia and continue to be a common clinical problem. Past clinical studies have demonstrated that halothane produces a higher incidence of vomiting compared with other anaesthetics, but some investigators have described an antiemetic effect. The purpose of this study was to investigate the effects of various doses of halothane on the emetic response in the decerebrate ferret. Following a control emetic response, a maximum of six increasing cumulative concentrations of halothane were delivered. At the end of each delivery period, the supradiaphragmatic vagal communicating branch, which has been shown to reproducibly elicit vomiting, was electrically stimulated and the emetic response was monitored. An increase in halothane concentration produced a marked depression of tongue, abdominal muscle, and diaphragm EMG activity as well as a decrease in central venous pressure. Licking, a prodromal response comparable to nausea in the human, appeared to be most sensitive. An increase in latency of the emetic response occurred as the concentration of halothane was increased. All phases of the response were observed at concentrations below 0.6 vol% halothane. At 0.6 vol% halothane, 75% of the animals vomited. At higher concentrations, the emetic response was completely abolished. One hour post-halothane, all latencies had returned to near control values. The methods utilized in this study provided a model that was not complicated by a large number of variables usually present in clinical studies. These data demonstrate that halothane exerts an inhibitory, concentration-dependent, and reversible effect on the emetic response in the ferret and provide further support that halothane alone does not possess emetic properties at clinical properties at clinical concentrations.

Animals↗
PubMed1991

An appraisal of chemical aversion (emetic therapy) approaches to alcoholism treatment.

More than 35,000 alcoholics have received chemical aversion (emetic therapy) in at least 75 settings worldwide since the 1930s. This consummatory aversion (CA) treatment, which pairs ethanol ingestion with emetically induced nausea, incorporates the highly efficient variety of learning known as taste aversion (TA) conditioning. The CA literature indicates that emetic therapy should induce conditioned alcohol aversions in many alcoholics. Such aversions have been widely reported by clinicians and have been confirmed by recent psychophysiological evidence. Long standing evidence of treatment effectiveness is found in the results of private hospitals which have consistently produced 1-yr abstinence rates approximating 60%. Diminished alcohol craving is a frequently reported benefit. Few experimental evaluations have been completed, as is generally the case for all alcoholism treatments, but those which used methodologically sound temporal parameters during conditioning have supported the clinical efficacy of emetic therapy. The clear need for more definitive research notwithstanding, there are compelling indications that emetic therapy is a useful component of multimodal treatment within certain alcoholic populations. However, its availability is severely limited. Many alcoholics could probably benefit from expanded treatment availability. The time is ripe for a reevaluation of resistances to the clinical use of emetic therapy alcoholism treatment.

Alcoholism↗
PubMed1975

A comparison of the efficacy of cyclizine and perhenazine in reducing the emetic effects of morphine and pethidine.

1 The ability of cyclizine (50 mg) and perphenazine (2.5 and 5.0 mg) to counteract the emetic effects of pethidine (100 mg) and morphine (10 and 15 mg) was compared in women undergoing a standard minor operation with a standard anaesthetic. 2 Perphenazine (5.0 mg) was as effective an anti-emetic as cyclizine (50 mg) and both were more effective than perphenazine (2.5 mg). 3 The reduction in vomiting and nausea by cyclizine (50 mg) and perphenazine (5 mg) was approximately the same following pethidine (100 mg) and morphine (10 mg) but much less against the larger dose of morphine. 4 Both anti-emetics had a rapid onset of action but their anti-emetic activity did not last as long as the emetic effect of morphine. 5 Perphenazine (5 mg) was accompanied by an unacceptably high incidence of restlessness. 6 In clinical practice cyclizine (50 mg) is preferred to perphenazine (5 mg) as an anti-emetic.

Antiemetics↗
PubMed1992

[Anti-emetic effect and safety of single dose of ondansetron injection in double-blind comparison study with placebo].

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.

Adult↗
PubMed1992

Methodology and assessment in clinical anti-emetic research: a meta-analysis of outcome parameters.

There have been major clinical advances in the control of chemotherapy-induced nausea and emesis. These advances were achieved partly by the introduction of new anti-emetic agents but important improvement came from the use of existing agents in ways developed from the results of studies based on new approaches and methods in anti-emetic research. By developing basic research tools, improving methodology and applying psychometrically sound assessments better management or chemotherapy-induced nausea and vomiting has been achieved. The goals of anti-emetic assessment are discussed here along with data and examples of assessment techniques for emesis and nausea. Examination of 153 separate anti-emetic studies between the years of 1975 and 1988 showed that emesis was the most common outcome measure used and that approximately 1 out of five studies measured some other type of outcome usually in the context of nausea and emesis. The frequency of outcome events was most commonly the dimension assessed. Examination of size of the effect of an anti-emetic regimen for these anti-emetic studies showed it to be independent of the type of outcome measured, but to be quite dependent on how the outcome was quantified. For instance, differences in the frequency or incidence of either nausea or emesis were generally larger than measurements made of the duration of either of these.

Antiemetics↗
PubMed1986

Emetic and antiemetic effects of opioids in the dog.

The emetic and antiemetic effects of opioid agonists were studied in awake dogs. The mu-agonists morphine, fentanyl and methadone, in sedative doses, prevented the emetic response to apomorphine and copper sulphate; only morphine induced emesis, at doses lower than those required to prevent emesis. The delta-agonist [D-Ala2,Met5]enkephalinamide (DALA) and [Leu5]enkephalin induced emesis in some of the dogs studied but had no antiemetic activity. The kappa-agonists bremazocine and ethylketocyclazocine (EKC) did not induce emesis but, at sedative doses, prevented the emetic response to apomorphine. The emetic effect of DALA was antagonized by naloxone in some dogs; the antiemetic effect of morphine, bremazocine and EKC was blocked by both naloxone and MR 2266. The non-opioid sedatives diazepam, phenobarbital and xylazine, administered in sedative doses, did not prevent apomorphine-induced emesis. Our results suggest that a delta-receptor is involved in the emetic effect and a mu- and/or or kappa-receptor in the antiemetic effect of opioids.

Animals↗
PubMed1990

Dexamethasone can potentiate the anti-emetic action of a 5HT3 receptor antagonist on cyclophosphamide induced vomiting in the ferret.

A new group of selective 5HT3 antagonists are proving to be effective anti-emetics for cytotoxic and radiation induced vomiting in both animal models and man. Current anti-emetic regimens often benefit from combination therapy, in particular the efficacy of metoclopramide (which can be a weak 5HT3 antagonist), can be improved by combination with dexamethasone, another anti-emetic. Hence it was of interest to evaluate whether a 5HT3 receptor antagonist GR38032F could be improved by combination with dexamethasone. Vomiting induced by cyclophosphamide in the ferret was observed after pre-treatment with dexamethasone alone or in combination with GR38032F. Animals were also observed for signs of 'nausea'. Dexamethasone alone proved a weak anti-emetic in this system but did have significant effects on 'nausea'. GR38032F has previously been shown to be capable of totally controlling emesis due to cyclophosphamide in the ferret. Here a dose of GR38032F that is not 100% effective was employed; this was shown to have effects on 'nausea' but most interestingly its anti-emetic action was increased by combination with dexamethasone. This may be important for the minority of patients whose vomiting is not completely controlled by GR38032F alone.

Animals↗
PubMed1992

Methodology in anti-emetic trials.

The most promising anti-emetic drugs are identified during preclinical testing. Phase I and II clinical studies are used to optimize doses and schedules for the various routes of administration. Most methodological issues arise in relation to phase III studies. A prospective, randomised, double-blind, parallel-subjects design is recommended. Stratification helps balance the factors influencing emesis between the 2 arms of a randomised study. The most important of these are the strength of the emetic stimulus, prior exposure to chemotherapy, age, sex and a history of chronic alcohol consumption. The evaluation of efficacy of an anti-emetic should include its efficacy in controlling acute post-chemotherapy nausea and vomiting as well as anticipatory and delayed emesis. The side effects of an anti-emetic must also be considered since they may negate any anti-emetic advantage. Patients and observers have reported successfully evaluating these parameters using both categorical and linear-analogue scales.

Antiemetics↗
PubMed1992

[Anti-emetic effect of ondansetron in cisplatin induced nausea and vomiting--a randomized clinical trial].

The anti-emetic effect of ondansetron in cisplatin induced nausea and vomiting was studied in a randomized cross-over trial in 52 patients. The dose of cisplatin was 80-120 mg/M2 iv drip given in 1-3 days. The patients randomly received ondansetron or our routine anti-emetic regimen in the first cycle of chemotherapy. All the patients were crossed-over to the other anti-emetic regimen on the second cycle of the same cisplatin containing regimen. The results showed that ondansetron was superior to our routine anti-emetic regimen in controlling acute nausea and vomiting. 86% of patients treated with ondansetron and 20.4% treated with the routine regimen had a complete or marked response (O-2 emetic episodes). The mean frequency of vomiting were 1.3 times in ondansetron and 8.0 times in the routine regimen (P less than 0.01). Control of delayed emesis was comparable in the two arms. No patient had neurological symptoms in the ondansetron group whereas 4 patients in the routine group had extrapyramidal symptoms.

Adult↗
PubMed1991

Effective emetic control during conditioning of children for bone marrow transplantation using ondansetron, a 5-HT3 antagonist.

Preparation for bone marrow transplantation (BMT) uses the extremely emetogenic combination of chemotherapy and total body irradiation (TBI). Ondansetron is a selective 5-HT3 antagonist and has clear anti-emetic capabilities. The efficacy of the drug was assessed in 15 children (aged 2-17 years) who received high dose cyclophosphamide (on days -6 and -5) and TBI (days -3 to 0 inclusive). During days -6 to -4 when the emetic effect of cyclophosphamide would be most pronounced, 12 of the 15 patients (80%) had fewer than five emetic episodes during their worst 24-h period, 11 (73%) had fewer than three vomits whilst nine (60%) experienced no vomiting or retching. Eleven patients progressed to TBI and 10 (91%) had fewer than five emetic events in the worst 24-h period (days -3 to +2), six (55%) had no vomiting at all. Of 100 evaluable 'patient-days' 83 (83%) were without any vomiting or retching and a further 10 'patient-days' had only one or two emetic episodes. There were no significant side-effects noted and in particular no extrapyramidal reactions. Headaches and constipation, which have been seen in adult studies, were not reported by patient or parent on any of the study days and transient elevation of liver enzymes were noted in only two patients. Ondansetron has a major role in preparing patients for BMT.

Adolescent↗
PubMed1986

The influence of cyclizine and perphenazine on the emetic effect of meptazinol.

The effectiveness of 50 mg cyclizine and 2.5 mg perphenazine against the emetic sequelae of 100 mg meptazinol were studied in a randomized double-blind placebo-controlled trial. Three groups of 40 women received the opioid, together with an anti-emetic by i.m. injection, as premedication prior to minor gynaecological surgery. Beneficial or noxious effects were noted at standard time intervals and anaesthesia standardized as incremental methohexitone with nitrous oxide/oxygen. In the placebo group, 33 out of 40 subjects experienced either nausea or vomiting at some time after the opioid. Cyclizine, 50 mg, provided significant reduction of emetic tendency in both pre-operative and post-operative phases of the study with 22 out of 40 subjects experiencing nausea or vomiting overall. Perphenazine, 2.5 mg, showed no useful anti-emetic effect. Both anti-emetics increased the soporific effect of premedication at the 90-min interval. Subjects receiving perphenazine experienced significantly more dizziness than those of other groups.

Azepines↗
PubMed1991

Studies on the emetic and antiemetic properties of zacopride and its enantiomers.

In ferrets, the oral emetic activity of zacopride was compared with its R- and S-enantiomers. Increasing doses of 0.01, 0.1, 1.0, 10.0 and 31.6 mg/kg of zacopride or its 2 enantiomers were each administered at hourly intervals to separate groups of animals until emesis occurred. The emetic (100%) dose for zacopride and its S-enantiomer was 0.11 mg/kg p.o. (cumulative dose). The R-enantiomer at a cumulative dose of 42.71 mg/kg p.o. produced emesis in 25% of the animals. By the i.p. route zacopride and its S-enantiomer were more potent than the R-enantiomer in blocking the emetic activity of 0.1 mg/kg p.o. of zacopride. The involvement of 5-HT3 mechanisms is indicated by a correlation between zacopride and its enantiomers to cause and prevent emesis and their affinity at 5-HT3 binding sites. Further, the putative 5-HT3 agonists, 2-methyserotonin and phenylbiguanide, at 10 mg/kg p.o., produced emesis that was blocked by zacopride (0.1 mg/kg i.p.) or ICS 205-930 (1 mg/kg i.p.). The results suggest that in the ferret the S-enantiomer is predominantly responsible for both the emetic and antiemetic properties of zacopride and that 5-HT3 agonism and antagonism are involved in these actions.

Administration, Oral↗
PubMed1986

The emetic effect of B-HT 920 and apomorphine in the dog: antagonism by haloperidol.

Recent investigations have suggested that the alpha 2-adrenoreceptor agonist B-HT 920 is also a dopamine (DA) agonist with a selectivity for presynaptic receptors. In the present study, the emetic effect of B-HT 920 was investigated. Intravenous injections of B-HT 920 (0.32-10.0 micrograms/kg) and a DA2-agonist apomorphine (3.2-100.0 micrograms/kg) caused dose-dependent emesis. The ED50 of B-HT 920 and apomorphine were 3.2 and 12.3 micrograms/kg, respectively. When haloperidol (10.0-24.5 micrograms/kg i.v.), a DA2-antagonist, was given 5 minutes before B-HT 920 (10 micrograms/kg) or apomorphine (32 micrograms/kg), it caused a dose-dependent prevention of B-HT 920- and apomorphine-induced emesis. The ED50 of haloperidol in preventing the emetic effect of both drugs was identical (13.5 micrograms/kg). In contrast, haloperidol (32 micrograms/kg i.v.) did not prevent the emetic effect of ouabain (40 micrograms/kg i.v.). Neither did yohimbine (0.1 mg/kg i.v.), an alpha 2-adrenoreceptor antagonist, prevent the emetic effect of B-HT 920 (10 micrograms/kg). These results suggest that B-HT 920, acting like apomorphine, induces emesis by activating DA2-receptors probably in the chemoreceptor trigger zone of the area postrema.

Adrenergic alpha-Agonists↗
PubMed1990

The abdominal visceral innervation and the emetic reflex: pathways, pharmacology, and plasticity.

In recent years the role of the area postrema in the emetic reflex has been predominant and the involvement of the abdominal visceral innervation has tended to be overlooked. This paper attempts to redress the balance reflex by reviewing aspects of the existing literature and complementing this with original studies from the ferret. In view of the widespread use of the ferret in studies of emesis and particularly in the characterization of the antiemetic actions of 5-HT3 receptor antagonist, the opportunity is taken to assess the suitability of this species for studies of emesis. It is concluded that the ferret is sensitive to a wide range of emetic stimuli including intragastric irritants, opiate and dopamine receptor agonists, many cytotoxic drugs, and radiation. For several stimuli it is more sensitive than other species and for radiation on the basis of its ED100 it appears to be the most sensitive of the laboratory animals studied. Using electrical stimulation of the central end of the dorsal vagal trunk in the abdomen in conscious and anaesthetized animals, the vagal afferents were shown to be capable of eliciting emesis. Using lesioning studies an involvement of the vagus in the emetic response to a number of cytotoxic drugs (e.g., cisplatinum, cyclophosphamide, mustine) and radiation was demonstrated, although the magnitude of the effect varied with the different stimuli. An attempt is made to reconcile these observations with previous studies of area postrema ablation. The problems of interpreting the effects of nerve lesions are critically discussed in light of preliminary evidence presented here that there may be a degree of plasticity in the emetic pathway following such lesions. The range of antiemetic effects of 5-HT3 receptor antagonists is reviewed and an attempt is made to identify the site(s) at which these agents act. Results are presented that suggest a link between the vagus and 5-HT3 receptor antagonism. These studies are discussed together with others and lead us to propose that (in the ferret) 5-HT3 receptor antagonists have their main antiemetic effect by acting on vagal afferent terminals in the wall of the upper gut with an additional minor site either in the nucleus tractus solitarius or presynaptically on the vagal afferent terminals in the medulla where binding sites for 5-HT3 receptor ligands have recently been demonstrated in this species.

Abdomen↗