A COMPARISON OF ORAL ONDANSETRON SYRUP OR INTRAVENOUS ONDANSETRON LOADING DOSE REGIMENS GIVEN IN COMBINATION WITH DEXAMETHASONE FOR THE PREVENTION OF NAUSEA AND EMESIS IN PEDIATRIC AND ADOLESCENT PATIENTS RECEIVING MODERATELY/HIGHLY EMETOGENIC CHEMOTHERAPY

This double-blind, parallel-group, multicenter study compared the efficacy and safety of intravenous (IV) ondansetron with oral syrup ondansetron plus oral dexamethasone in the prevention of nausea and emesis in pediatric patients receiving moderately/highly emetogenic chemotherapy. On each day of chemotherapy, patients were administered on dansetron 5 mg/m2 IV and placebo syrup orally ( n = 215) orondansetron 8 mg syrup orally and placebo IV ( n = 223) plus dexamethasone 2-4 mg PO. Ondansetron 4 mg syrup PO was administered twice daily for 2 days following the cessation of chemotherapy. Complete or major control of emesis was obtained in 89% patients in the IV group and 88% patients in the oral syrup group during the worst day of chemotherapy treatment (90% CI: 6, 4) and in 85% and 82% patients, respectively, during the worst day of the study period (90% CI: 8, 3). Intravenous ororal syrup ondansetron plus dexamethasone was well tolerated and effective in preventing chemotherapy-induced emesis in pediatric patients.     

Penetration-enhancing effect of ethanolic solution of menthol on transdermal permeation of ondansetron hydrochloride across rat epidermis

The aim of this investigation was to study the effect of an ethanol-water solvent system and ehtanolic solution of menthol on the permeation of ondansetron hydrochloride across the rat epidermis in order to select a suitable ethanol-water vehicle and optimal concentration of menthol for the development of a transdermal therapeutic system. The solubility of ondansetron hydrochloride in ethanol, water and selected concenetrtaion of ethanol-water vehicles (20:80 v/v, 40:60 v/v and 60:40 v/v) was determined. The effect of these solvent vehicles, containing 1.5% w/v of ondansetron hydrochloride, on the in vitro permeation of the drug was studied across the rat epidermis. The highest permeation was observed from 60% v/v of ethanol-water vehicle that showed highest solubilty. Hence, the hydroxypropyl cellulose (HPC) (2% w/w) gel formulations containing 1.5% w/w of ondansetron hydrochloride and selected concentrations of menthol (0, 2, 4, 8 and 10% w/w) were prepared using 60% v/v of ethanol-water vehicle, and subjected to in vitro permeation of the drug across rat epidermis. The transdermal permeation of ondansetron hydrochloride was enhanced markedly by the addition of menthol to HPC gel drug reservoir formulations. A maximum flux of ondansetron hydrochloride (77.85 ± 2.85 μ g/cm^2.h) was observed with a mean enhancement ratio of 13.06 when menthol was incorporated at a concentration of 8% w/w in HPC gels. However, there was no significant increase in the drug flux with 10% w/w menthol when compared to that obtained with 8% w/w of menthol in HPC gel formulations. The results suggest that 2% w/w HPC gel drug reservoir formulation, prepared with 60% v/v ethanol-water, containing 8% w/w of menthol provides an optimal transdermal permeation of ondansetron hydrochloride.     

Update on neuropharmacological treatments for alcoholism: scientific basis and clinical findings

The past decade has seen an expansion of research and knowledge on pharmacotherapy for the treatment of alcohol dependence. The Food and Drug Administration (FDA)-approved medications naltrexone and acamprosate have shown mixed results in clinical trials. Oral naltrexone and naltrexone depot formulations have generally demonstrated efficacy at treating alcohol dependence, but their treatment effect size is small, and more research is needed to compare the effects of different doses on drinking outcome. Acamprosate has demonstrated efficacy for treating alcohol dependence in European trials, but with a small effect size. In U.S. trials, acamprosate has not proved to be efficacious. Research continues to explore which types of alcohol-dependent individual would benefit the most from treatment with naltrexone or acamprosate. The combination of the two medications demonstrated efficacy for treating alcohol dependence in one European study but not in a multi-site U.S. study. Another FDA-approved medication, disulfiram, is an aversive agent that does not diminish craving for alcohol. Disulfiram is most effective when given to those who are highly compliant or who are receiving their medication under supervision. Of the non-approved medications, topiramate is among the most promising, with a medium effect size in clinical trials. Another promising medication, baclofen, has shown efficacy in small trials. Serotonergic agents such as selective serotonin reuptake inhibitors and the serotonin-3 receptor antagonist, ondansetron, appear to be efficacious only among certain genetic subtypes of alcoholic. As neuroscientific research progresses, other promising medications, as well as medication combinations, for treating alcohol dependence continue to be explored.     

Delayed emesis following anticancer chemotherapy

As the control of acute chemotherapy-induced emesis has improved, delayed emesis (occurring 24 h or more after treatment) has become the most bothersome vomiting problem. Delayed vomiting occurs after treatment with many anticancer drugs, but has been most often studied following cisplatin or combinations of cyclophosphamide and anthracyclines. The mechanism of this phenomenon is unknown. Empirical trials of antiemetic agents effective in controlling acute emesis identified the combination of metoclopramide and dexamethasone as useful in lessening delayed emesis after displatin in a randomized, placebocontrolled study. The specific serotonin receptor (5-HT₃) antagonist ondansetron yielded results equivalent to the prior placebo results in a phase II trial using identical methodology in similar patients given cisplatin. Following anthracycline and cyclophosphamide combination chemotherapy, the delayed vomiting prevention observed with dexamethasone alone exceeds that of ondansetron. These observations suggest that delayed emesis is primarily mediated by neurotransmitters other than serotonin. Since delayed emesis occurs more frequently in patients who experience nausea and vomiting on the day they receive chemotherapy, tested combination antiemetic regimens, employing a 5-HT₃ antagonist (either granisetron, metoclopramide, ondansetron or tropisetron), dexamethasone, and a benzodiazepine (lorazepam and alprazolam) should be routinely employed. This approach provides the best protection for acute and delayed emesis. Further research, looking beyond the specific 5-HT₃ antagonists, provides the best strategy to improve the control of delayed symptoms.Presented as an invited lecture at the 6th International Symposium: Supportive Care in Cancer, New Orleans, La., USA, 2–5 March 1994     

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 (≥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.     

Dexamethasone versus a combination of dexamethasone and ondansetron as prophylactic antiemetic in patients receiving intrathecal morphine for caesarean section

Background

Intrathecal morphine for caesarean delivery provides excellent postoperative analgesia but it is commonly associated with nausea and vomiting. This prospective, randomized, double blind study was carried out to compare the effectiveness of a combination of dexamethasone and ondansetron with dexamethasone alone for prevention of postoperative nausea and vomiting (PONV) following intrathecal morphine injection for caesarean section.

Methods

A total of 108 parturients aged 18–40 years for elective caesarean section were randomized into 2 groups (n=54) to receive either intravenous dexamethasone 8mg (Group A) or a combination of intravenous dexamethasone 8mg and ondansetron 4mg (group B). The study drug for each group consisted of 0.5% hyperbaric bupivacaine and 0.2mg morphine. The primary outcome variables were postoperative nausea and vomiting (PONV) which were assessed for a period of 24 hours. The patient''s vital signs were monitored and documented.

Results

The incidence of nausea and vomiting was significantly reduced in patients who received a combination of dexamethasone and ondansetron compared with dexamethasone alone (9.3% Vs 37%, respectively, P = 0.003).

Conclusion

This study showed that a combination of dexamethasone and ondansetron administered prophylactically significantly reduced the incidence of PONV in pregnant women on intrathecal morphine for caesarean section.     

耳穴贴压对化疗后呕吐的作用观察(英文)

目的:探究耳穴贴压对化疗后患者呕吐的缓解作用,同时观察对昂丹司琼使用剂量的影响。方法:将50例患者随机分为对照组和观察组,对照组进行常规化疗,化疗前静脉注射昂丹司琼;观察组化疗药物使用与对照组相同,但从化疗前 1 日起配合耳穴贴压,直至化疗结束。结果:观察组使用昂丹司琼剂量低于对照组,两组差异有统计学意义(P<0.05)。结论:耳穴贴压可降低化疗后呕吐患者的昂丹司琼使用剂量,有效缓解患者的呕吐症状。     

联合用药对全麻术后自控镇痛患者恶心呕吐的随机对照研究

目的探讨联合用药对术后自控镇痛患者恶心呕吐的疗效。方法 176例手术后应用患者自控镇痛(patient controlled analgesia,PCA)随机分为4组:A组,分别在术中、PCA泵中给予昂丹司琼8mg;B组,在PCA泵中给予地塞米松5mg、氟哌利多2.5mg;C组,在术中给予昂丹司琼8mg、PCA泵中给予地塞米松5mg、氟哌利多2.5mg及昂丹司琼8mg;D组,分别在术中给予昂丹司琼8mg、在PCA泵中给予地塞米松5mg及氟哌利多2.5mg。术后48h回访患者术后恶心呕吐(postoperative nausea and vomiting,PONV)的发生情况。结果 4组PONV发生率分别为A组29.5%(13/44)、B组34.1%(15/44)、C组7.0%(3/43),D组11.4%(5/44),联合用药组即C组和D组PONV发生率明显低于单一用药组A组和B组(P0.05);A、B2组PONV发生率差异无显著性(χ2=0.210,P=0.647),C组PONV发生率与D组间差异无显著性(χ2=0.114,P=0.736)。结论联合应用昂丹司琼、地塞米松及氟哌利多3种止吐药可以显著减少术后自控镇痛患者的恶心呕吐的发生率。     

昂丹司琼复合丁丙诺啡预防阑尾牵拉反应的临床观察

目的比较阑尾切除手术过程中,运用昂丹司琼复合布托啡诺和氟芬合剂对阑尾牵拉反应的抑制效果。方法选择连续硬膜外麻醉下行阑尾切除手术的患者80例,随机分为布托啡诺组(n=40)、氟芬合剂组(n=40)。两组均在切皮时静脉给药,观察并记录各组阑尾牵拉时的不良反应及镇静评分,并进行组间比较分析。结果昂丹司琼复合布托啡诺组抑制阑尾牵拉反应的有效性明显优于氟芬合剂组(P<0.05)。结论阑尾切除术中运用昂丹司琼复合布托啡诺,可以明显减轻手术中牵拉反应。     

Delta-9-tetrahydrocannabinol and cannabidiol, but not ondansetron, interfere with conditioned retching reactions elicited by a lithium-paired context in Suncus murinus: An animal model of anticipatory nausea and vomiting

Chemotherapy patients report not only acute nausea and vomiting during the treatment itself, but also report anticipatory nausea and vomiting upon re-exposure to the cues associated with the treatment. We present a model of anticipatory nausea based on the emetic reactions of the Suncus murinus (musk shrew). Following three pairings of a novel distinctive contextual cue with the emetic effects of an injection of lithium chloride, the context acquired the potential to elicit conditioned retching in the absence of the toxin. The expression of this conditioned retching reaction was completely suppressed by pretreatment with each of the principal cannabinoids found in marijuana, Delta(9)-tetrahydrocannabinol or cannabidiol, at a dose that did not suppress general activity. On the other hand, pretreatment with a dose of ondansetron (a 5-HT(3) antagonist) that interferes with acute vomiting in this species, did not suppress the expression of conditioned retching during re-exposure to the lithium-paired context. These results support anecdotal claims that marijuana, but not ondansetron, may suppress the expression of anticipatory nausea.