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PubMed2004

[Effectiveness of anti-emetics for the prophylaxis of cisplatin-induced delayed emesis: a systematic review].

We performed a systematic review of the effectiveness of anti-emetics for prophylaxis of cisplatin-induced delayed emesis using meta-analysis. We selected 12 reports of randomized controlled trials from MEDLINE (1966-2003. 4) and The Cochrane Library Issue 1, 2003. Nine of these reports were evaluated as high quality and the others as low quality according to the evaluation criteria of Jadad et al., and only the high-quality reports were subjected to meta-analysis. The statistical results obtained from all 12 reports were also compared with those obtained from the 9 reports of high quality. Corticosteroids significantly reduced the occurrence of delayed emesis. Metoclopramide tended to reduce the occurrence of delayed emesis, although not to a significant extent. In contrast, 5-HT3 receptor antagonists did not show a significant prophylactic effect on delayed emesis. Combination treatments using corticosteroids with metoclopramide or 5-HT3 receptor antagonists did not show significant additional benefits over corticosteroids alone. In conclusion, treatment with corticosteroids without additional metoclopramide or 5-HT3 receptor antagonists appears to be preferable for the prevention of delayed emesis induced by cisplatin.

Adrenal Cortex Hormones↗
PubMed2002

Anti-emetics in development.

Despite important advances in pharmacotherapeutic options for the prevention and treatment of nausea and vomiting during the 1990s, a significant proportion of patients still suffer debilitating nausea and vomiting symptoms. The most problematic areas are chemotherapy-induced nausea and vomiting particularly delayed emesis, postoperative nausea and vomiting, opioid-induced nausea and vomiting and motion sickness. The most vigorous research into new anti-emetics has focused on the neurokinin-1 (substance P) antagonists. Clinical trials conducted to date indicate that these agents have similar efficacy to 5-HT(3) antagonists in acute chemotherapy-induced nausea and vomiting, superior efficacy to available agents in delayed emesis, possibly superior efficacy against emesis in postoperative nausea and vomiting and no evidence of efficacy versus opioid or motion-induced nausea and vomiting. Other pharmacological strategies in development include agonising CB1 (cannabinoid) receptors, "broad spectrum" receptor antagonists and 5-HT(1A) receptor agonists, although clinical trials of these types of agents are not yet available. The neurokinin-1 antagonists appear to be promising agents for some nausea and vomiting states, although further clarification of their role is required.

Animals↗
PubMed2006

Value of mink vomit model in study of anti-emetic drugs.

AIM: To establish a new, reliable vomit model of minks. METHODS: Adult male minks were randomly divided into 8 groups (n=6): cisplatin (7.5 mg/kg) intraperitoneal injection (i.p.) group, copper sulfate (40 mg/kg) intragastric injection (i.g.) group, apomorphine (1.6 mg/kg) subcutaneous injection (s.c.) group, and 18 Gy whole-body X-irradiation group, ondansetron injection group (2 mg/kg i.p.) 30 min later followed by cisplatin (7.5 mg/kg) i.p., normal saline (NS) i.p. injection control group, metoclopramide injection group (4 mg/kg i.p.) 30 min later followed by apomorphine (1.6 mg/kg) s.c., NS i.g. control group. The frequency of retching and vomiting was calculated. After behavioral experiment, distribution of 5-HT in the ileum was detected by immunohistologic method. RESULTS: Cisplatin, apomorphine, copper sulfate and X-irradiation administered to minks evoked a profound emetic response in the animals. However, retching and vomiting were significantly inhibited by pretreatment with ondansetron and metoclopramide in cisplatin and copper sulfate groups (P=0.018). Immunohistologic result showed that 5-HT released from enterochromaffin cells (EC cells) was involved in vomiting mechanism. CONCLUSION: Mink vomit model has a great value in studying the vomiting mechanism and screening new antiemetic drugs.

Animals↗
PubMed2000

[Improvement in the control of chemotherapy induced emesis with ondansetron, methylprednisolone and lorazepam combination in patients treated by a moderate emetic treatment and uncontrolled by a previous antiemetic combination].

The objective of this double blind parallel-group multicentre study was to compare the efficacy and safety of the combination ondansetron + methylprednisolone + lorazepam (O + M + L) in the prevention of emesis induced by chemotherapy with cyclophosphamide or adriamycin . This tritherapy was compared to a bitherapy O + M. Patients included were suffering from severe haemopathy or breast cancer. They had to have an incomplete response to a previous antiemetic association of 5HT3 serotoninergic receptor antagonist and corticoid. One hundred and thirty-five adult patients were included and were randomised to receive : O + M + L or O + M for 3 days. The emesis control during the 3 days of treatment (no emetic episode during the complete course) was significantly superior in the group O + M + L than in the group O + M (69% versus 46%, p = 0. 042); nausea control on the worst day of the cure was significantly superior in the group O + M + L than in the group O + M (p = 0.04) with 76% of patients in the group O + M + L having complete or major nausea control compared to 51% in the group O + M. The stability of quality of life during the days following chemotherapy measured by one questionnaire, including two scales, one cancer specific (FLIC) and one emesis specific (FLIE), appeared significantly better in group O + M + L (p = 0.04 and p = 0.019). Safety of both antiemetic regimens was good and similar between the two treatment groups. This trial shows that the adjunction of lorazepam to ondansetron and corticoid in combination increases the antiemetic control for patients with an incomplete response to a previous regimen containing a 5HT3 serotoninergic receptor antagonist and a corticosteroid in the prevention of chemotherapy-induced emesis.

Adult↗
PubMed2001

[Does the addition of an anxiolytic drug improve the anti-emetic effectiveness of the steroid and granisetron combination in the prophylaxis of cisplatin-induced vomiting?].

Authors evaluated two forms of antiemetic therapy in 129 courses of 51 gynecological cancer patients treated with cisplatin chemotherapy of moderately or highly emetic dose (50-100 mg/m2) in a prospective, non randomized study. The patients received granisetron (3 mg, intravenously) and methylprednisolone (100 mg, orally) in the group A. An additional anxiolytic drug (alprazolam or meprobamate or diazepam) or droperidol with known sedative characteristics (1 ml, intravenously) was given in the combination of the group B. 80.3% and 73.5% complete responses were achieved in groups A and B, respectively (p = 0.4084). No differences were found in the side effects of the two antiemetic combinations. Authors conclude the addition of an anxiolytic drug does not improve the antiemetic effectivity of the granisetron-methylprednisolone combination in the first 24 hours of cisplatin chemotherapy.

Alprazolam↗
PubMed1992

[Examination of anti-emetic effect, safety and usefulness of single oral dose of ondansetron tablet in nausea and emesis induced by anti-cancer drugs--dose-finding study of ondansetron tablet in patients receiving non-platinum anti-cancer drugs].

Inhibitory effects on acute nausea and emesis, safety and usefulness of a single oral dose of Ondansetron tablet were evaluated in 3 different dose levels for comparison by telephone registration system, in patients receiving non-platinum anti-cancer drugs. A single dose of ondansetron at 4 mg, 8 mg or 12 mg was given orally at 2 hrs before the initial administration of anti-cancer drugs. The patients were observed for 24 hours after administration of anti-cancer drugs, for occurrence of nausea and emesis. Efficacy rates of inhibitory effects on nausea and emesis were 83.3% (10/12 cases) in 4 mg dose group, 78.6% (11/14 cases) in 8 mg dose group and 84.6% (11/13 cases) in 12 mg dose group, without statistically significant difference. Side effects were observed in 3 cases (headache, cold feeling and trembling in limbs, sleepiness) in 12 mg dose group, but these symptoms were not severe and disappeared after several hours or several days. No abnormality in clinical laboratory findings attributable to Ondansetron was observed. From the above, it was considered that Ondansetron was a clinically useful anti-emetic for nausea and emesis induced by non-platinum anti-cancer drugs and that 4 mg once daily was the optimal dose.

Administration, Oral↗
PubMed1992

Selectivity of 5-HT3 receptor antagonists and anti-emetic mechanisms of action.

5-HT3 receptor antagonists, ondansetron, granisetron and tropisetron are highly specific for the 5-HT3 receptor and have a selectivity ratio of approximately 1000:1 compared with affinities for other receptors. Other 5-HT3 receptor antagonists, largely those having a benzamide structure, are non-selective. These include metoclopramide, renzapride and zacopride which stimulate gastric motility via activation of 5-HT4 receptors; metoclopramide is also a potent dopamine receptor antagonist. Selective 5-HT3 receptor antagonists are a major advance in the treatment of chemotherapy- and radiotherapy-induced emesis in cancer patients. These agents inhibit emesis by blocking 5-HT3 receptors on vagal afferent nerve terminals in the gastrointestinal mucosa and on terminals on the same vagal nerves in the vomiting system. Inhibition of acute emesis appears to be produced by blocking the initiation of the emetic reflex induced via 5-HT3 receptors and by 5-HT released from enterochromaffin cells in the small intestine, as well as by blocking 5-HT3 receptors in the hindbrain vomiting system.

Animals↗
PubMed2003

In vitro propagation of emetic nut Randia dumetorum (Lamb.).

An efficient protocol for in vitro shoot multiplication of Randia dumetorum (Emetic nut) has been developed. The seeds of R. dumetorum were germinated in vitro in MS medium in 5 weeks. Subsequent propagation using shoot tip as an explant was carried out in MS medium along with different concentrations and combinations of BAP (0.5-2.0) and NAA (0.0-2.0). Maximum shoot multiplication was obtained (12.7 shoots per shoot tip) in MS medium containing 1 mg/L BAP and 1 mg/L NAA. Micropropagated shoots were rooted in 1/2 MS medium supplemented with 1 mg/l IBA. This is the first report of in vitro plant propagation of R. dumetorum. In vitro grown plantlets showed a survival rate of 70% after 2 months of transplantation to natural environment.

Culture Media↗
PubMed1991

[Value of 5-HT3 receptor antagonists, particularly as anti-emetic drugs].

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.

Antiemetics↗
PubMed1990

The efficacy of granisetron as a prophylactic anti-emetic and intervention agent in high-dose cisplatin-induced emesis.

A single-centre, double-blind, placebo-controlled study was carried out in 28 patients with malignant disease, naive to chemotherapy, receiving cisplatin at a mean dose in excess of 80 mg/m2. Patients were randomized into two groups, receiving either granisetron (40 micrograms/kg) or placebo. Patients in both groups who experienced symptoms of vomiting and nausea were given up to a further three 40 micrograms/kg doses of granisetron on an open-label basis, allowing the assessment of granisetron as an intervention anti-emetic in the placebo group. Following granisetron administration, 13 (93%) patients had no vomiting or nausea in the first 24 h, a significant difference compared with the one patient in the placebo group who remained free from vomiting and had only mild nausea in the same period (P less than 0.001). As a single intervention agent, granisetron achieved control or improvement of existing symptoms in the remaining members of the placebo group.

Adult↗
PubMed1989

Evidence for the involvement of alpha 2-adrenoceptors in the emetic action of xylazine in cats.

Intramuscular injection of xylazine induced dose-dependent vomiting in cats (ED50 = 0.277 mg/kg); administration of standard dose of xylazine (2 mg/kg, 2 times the 100% emetic dose) induced vomiting in 100% of the cats studied. The xylazine-induced vomiting was antagonized by adrenoceptor antagonists possessing alpha 2-blocking activity, which were yohimbine, tolazoline, and phentolamine. Of these antagonists, yohimbine was the most effective; the maximal antagonistic effect was seen at 1 mg of yohimbine/kg, a dose at which the other drugs had little or no effect. At the doses studied, prazosin and phenoxybenzamine, adrenoceptor antagonists with alpha 1-blocking activity, did not prevent vomiting induced by xylazine. Beta-Adrenoceptor (propranolol), dopamine receptor (domperidone and chlorpromazine), a cholinoceptor (atropine), an opiate receptor (naloxone), and a histamine-receptor (diphenhydramine) antagonists, at the doses studied, did not prevent xylazine-induced vomiting. Pretreatment with 6-hydroxydopamine failed to prevent xylazine-induced vomiting. These results indicated that xylazine-induced vomiting in cats is mediated by alpha 2-adrenoceptors and suggested that the alpha 2-adrenoceptors mediating the vomiting attributable to xylazine may not be presynaptic alpha 2-receptors located on noradrenergic nerve terminals.

Adrenergic alpha-Antagonists↗
PubMed1989

[Comparative influence of nootropic preparations on the emetic effect of morphine].

The effect of electroshock (ECS) and piracetam, oxiracetam or N-acetylglycinamide on the passive avoidance conditioned response in rats was studied. The antiemetic effect of the compounds was examined in cats as well. The results obtained allowed us to distinct the nootropic and antiemetic action of the drugs. The substances possessed a similar ability to prevent ECS-induced amnesia. On the contrary, oxiracetam completely prevented the emetic response to morphine at doses 100 times lower and piracetam at doses 10 times higher then those of the opioid. N-Acetylglycinamide had no antiemetic activity. The results obtained show that oxiracetam is 100 times more active in antiemetic test than piracetam. These data comprise the novel properties of nootropic drugs.

Amnesia, Retrograde↗
PubMed1988

Dehydrobenzperidol as peroperative anti-emetic: most effective administration time.

206 female patients undergoing curettage or laparoscopy were randomized in 4 comparable groups. Group 1 did not receive dehydrobenzperidol (DHBP), group 2 was given DHBP during premedication, group 3 during induction of anesthesia and group 4 when patients presented symptoms of nausea and/or vomiting. Again, the statistical results confirm the strongly anti-emetic effects of DHBP. Because of the existing trend towards a more beneficial effect of DHBP if given during induction and the avoidance of a possible adverse reaction, administration during induction is to be preferred, at least in non-ambulatory patients.

Antiemetics↗
PubMed1987

[Anti-emetic treatment with metoclopramide and other drugs during CDDP therapy].

The present trial was designed to compare the effect of metoclopramide(MCP) + dexamethasone(DM) (Method A) with that of MCP + DM + lorazepam(Lor) (Method B) in the treatment of CDDP (cis-diamminedichloroplatinum)-induced nausea and vomiting in a randomized fashion. The results were collected by questionnaire given to 50 patients. The dosage of CDDP was 80-100 mg/m2. In addition, MMC and VDS, or VP-16 were used concurrently. Within 24 hours after the administration of CDDP, vomiting was not observed in 72% and 88% of the patients treated with Method A and Method B, respectively, and nausea was not noted in 48% and 68%, respectively. Marked malaise was observed in 36% of patients in the Method A group and in 12% in the Method B group. With respect to the extent of comfort, 16% of patients in the Method A group and 56% in the Method B group felt good. Sixteen percent in the Method A group and 56% in the Method B group were satisfied with the anti-emetic treatment. Thus, Method B was significantly superior to Method A with regard to the degree of comfort and treatment satisfaction.

Aged↗
PubMed1985

[Effect of combined use of adrenocortical hormones and domperidone as anti-emetics during cisplatin therapy].

Eighteen patients received repeated administrations of cisplatin in relatively large amounts (55-75-100 mg/m2) given systemically by drop infusion. As antiemetic treatments, the following were scheduled: on the day before; prednisolone 30mg (3 X p.o.), immediately before; methylprednisolone 500mg (i.v.), and 3 hours after administration of cisplatin ; methylprednisolone 500mg (i.v.) and domperidone 60 mg (suppo.). Domperidone was given twice a day for one week. Nausea, vomiting and anorexia were studied objectively for two weeks. At a dose of 75 mg/m2 of cisplatin, the occurrence and the duration of nausea and vomiting were effectively reduced by the regimen; nausea was observed in 67% of all cases (average duration: 3.3 days) and vomiting was experienced in 40% (1.2 days). Anorexia was observed in 67% of cases and lasted longer (5.2 days). The severity and duration of these side effects of nausea, vomiting and anorexia seemed to appear in a manner related to the dose of cisplatin given, but even at a dose of 100 mg/m2, the regimen described above reduced the patients' discomfort to acceptable levels. No remarkable side effect of this anti-emetic regimen was evident.

Adult↗
PubMed1967

The use of penicillamine as an adjuvant to tartar emetic in the treatment of experimental schistosomiasis.

One of the principal drawbacks of antimonial therapy in schistosomiasis has been the prevalence of annoying, and sometimes dangerous, side-effects. The adjuvant administration of chelating agents offers a possible solution to this problem, providing this can be achieved without appreciably decreasing the therapeutic effect of the drug.The authors found that the chelating agent penicillamine lowered the toxicity of tartar emetic for mice and hamsters without affecting the tissue uptake of antimony. When administered in a similar manner to hamsters infected with Schistosoma mansoni there was no effect on the uptake of antimony by the parasites, or on the cure rate. This suggests a potential usefulness of penicillamine in antimony therapy.

Animals↗
PubMed1978

Left ventricular dysfunction after intravenous tartar emetic.

Left ventricular dysfunction had been reported in many patients suffering from schistosomal cor pulmonale. The nocuous agents affecting the left ventricle have not been defined. Antischistosomal therapy is suspected to contribute in the adverse effects on the myocardium, particularly antimonials and niridazole. In this study, the left ventricular performance was studied in 29 patients suffering from schistosomiasis before and 30 min after i.v. therapeutic dose of a tartar emetic. After the injection, the PEPI and PEPI/LVETI were increased, the LVETI was abbreviated, EF. was reduced, the LVEDP was raised, the peak dp/dt and the Vmax were reduced. Toxic effects of the T.E. on the myocardium and diminished contractility of the left ventricle were presumed to be caused by T.E. Other factors adversely affecting the myocardium in patients suffering from schistosomiasis cannot be excluded.

Adolescent↗
PubMed1981

Emetic food poisoning caused by Bacillus cereus.

Symptoms of acute food poisoning developed in eight members of a group who ate lunch at a cafeteria. After brief incubation periods, all affected individuals complained of nausea and abdominal cramps. Four persons promptly experienced vomiting. None of those affected was found to have fever and all recovered with 48 hours. Epidemiologic investigation incriminated macaroni and cheese as a cause of the illness and samples of this food contained large numbers of Bacillus cereus. Previous outbreaks of B cereus emetic food poisoning have been associated with consumption of contaminated fried rice and may occur after ingestion of other foods.

Adult↗