The use of ondansetron to treat pruritus associated with intrathecal morphine in two paediatric patients

Intrathecal morphine is an effective technique for providing postoperative analgesia after major surgical procedures in children. Pruritus is a common side effect associated with intrathecal morphine. We report two patients who experienced significant pruritus associated with intrathecal morphine administration and were successfully treated with ondansetron. Ondansetron appears to be a beneficial and safe method of relieving pruritus associated with intrathecal morphine.     

Ondansetron in Radiation Therapy of Brain Tumor in Children

Ten children receiving 5 to 6 week courses of radiotherapy after brain tumor surgery were given ondansetron treatment for persistent nausea and emesis. All patients continued the ondansetron treatment until the end of their radiotherapy course. Nausea, emesis, appetite, and adverse events were scored throughout the ondansetron treatment period. Ondansetron was well tolerated by all patients and was effective at reducing symptoms in 60% of the children.     

A Randomized Study of Ondansetron Syrup in Children: Evaluation of Taste Acceptability and Tolerance

Ondansetron, a highly selective 5-HT3 receptor antagonist, is available in an intravenous (IV) formulation and tablets, but syrup would be particularly useful in children. As chemotherapy can affect taste perceptions, this study was undertaken to determine the preference between two flavors of ondansetron syrup in children undergoing chemotherapy. Fifty-nine children, randomized into a multicenter, double-blind, crossover study, each received 5 mg/² of IV ondansetron daily before chemotherapy. The syrup was then randomly given in two doses, one of each flavor, strawberry and grape, 30 minutes apart. The preference was assessed 30 minutes after the second dose of syrup had been administered. Taste was assessed by the child against a panel of five faces. Of those children expressing any preference, 70% preferred the strawberry flavor. Overall, 59% of children preferred the strawberry flavor, whilst 25% preferred grape (P = 0.005) and 15% expressed no preference. The only adverse event assessed as drug related by the investigator was constipation, which occurred in one patient. In conclusion, a strong preference was found for the strawberry formulation. The ondansetron syrup was safe and well tolerated.     

Nasal administration of ondansetron using a novel microspheres delivery system

Gellan gum microspheres of ondansetron hydrochloride, for intranasal delivery, were prepared to avoid the first pass metabolism as an alternative therapy to parentral, and to improve therapeutic efficiency in treatment of nausea and vomiting. The microspheres were prepared using conventional spray-drying method. The microspheres were evaluated for characteristics like particle size, incorporation efficiency, swelling ability, zeta potential, in-vitro mucoadhesion, thermal analysis, XRD study and in-vitro drug release. Treatment of in-vitro data to different kinetic equations indicated diffusion controlled drug delivery from gellan gum microspheres. The results of DSC and XRD studies revealed molecular amorphous dispersion of ondansetron into the gellan gum microspheres.     

Development of HPTLC method for the estimation of ondansetron hydrochloride in bulk drug and sublingual tablets

A new, simple, rapid, accurate and precise high performance thin layer chromatography (HPTLC) method has been developed for the estimation of ondansetron hydrochloride in bulk and sublingual tablets. The mobile phase composition was chloroform : ethyl acetate : methanol : ammonia (9:5:4:0.1 v/v). Spectrodensitometric analysis of ondansetron was carried out at 254 nm and a symmetrical, well‐resolved, well‐defined peak was obtained at mean retardation factor (R_f) 0.52 ± 0.02. The calibration plot was linear in the range 200‐1200 ng/spot and showed good linear relationship with coefficient of regression, R² = 0.9952 with respect to peak area. The method was validated according to the guidelines of the International Conference on Harmonization (ICH Q2(R1). The limit of detection and quantitation were 14.83 and 44.92 ng per spot, respectively. The recovery study was carried out by standard addition method and the percentage recovery was found to be 99.34 ± 1.08. Therefore it was concluded that the proposed developed HPTLC method can be applied for identification and quantitative determination of ondansetron in bulk drug and dosage forms. Copyright © 2011 John Wiley & Sons, Ltd.     

昂丹司琼预防和治疗腹腔镜胆囊切除术后恶心呕吐的疗效观察

目的：观察并分析昂丹司琼预防和治疗腹腔镜胆囊切除术后恶心、呕吐反应的临床效果。方法86例慢性结石性胆囊炎患者在全麻下接受常规腹腔镜胆囊切除术。将其分为术前用药组36例、术后用药组25例和对照组25例。术前用药组于麻醉前30分钟通过静脉注射盐酸昂丹司琼8 mg、术后用药组麻醉清醒后立即给予静脉注射盐酸昂丹司琼8 mg,对照组不给予任何止吐药物。观察至术后48小时,统计各组中恶心、呕吐反应的发生例数和药物不良反应情况。结果86例患者共有25例发生恶心、呕吐反应。术前用药组、术后用药组和对照组的恶心、呕吐发生率分别为27.8%、12.0%和48.0%。术后用药组与对照组相比有统计学意义（χ^2=7.71,P＜0.05）,说明术后用药可减少术后恶心、呕吐的发生;术前用药组与对照组比较无统计学意义（χ^2=2.61,P＞0.05）,说明术前用药不能预防术后恶心、呕吐的发生。25例患者术后发生恶心、呕吐,给予经静脉注射盐酸昂丹司琼8 mg,有21例患者缓解,缓解率为84.0%,用药过程中未发生药物不良反应。结论盐酸昂丹司琼预防和治疗LC术后恶心、呕吐是安全、有效的,预防性用药最佳时机应该为麻醉清醒时。     

E MERGENCY P REPAREDNESS FOR C HILDREN WITH S PECIAL H EALTH C ARE N EEDS

Objective. To evaluate the change in nausea scales andincidence of vomiting with the use of ondansetron in the treatment of nausea andvomiting in the prehospital setting. Methods. Data were prospectively collected on all emergency medical service patients who received ondansetron for undifferentiated nausea andvomiting during a 6-month study period. Added outcome measures for this study were verbal quantitative (scale of 1–10) andqualitative “nausea scales,” incidence of vomiting prior to andafter administration of ondansetron, andadverse events. Patients who had this additional data collected andones who did not were compared. Changes in the “nausea scales” andincidence of vomiting before andafter administration andcorrelation among these measures were also compared. There was no control or placebo group. Results. Ondansetron was administered to 952 patients of 20,054 patients transported during this time period (5%); of these 472 had at least some of the outcome measures documented. There were minimal differences in the two cohorts; 198 patients had paired before andafter quantitative “nausea scales” documented: 7.6 ± 2.4 and4.6 ± 3.1, respectively (Δ = 2.9, 95% CI: 2.5–3.4); 447 patients had a qualitative change in nausea level documented: 0.4% “a lot worse,” 1.3% “a little worse,” 34% “unchanged,” 40% “a little better,” and25% “a lot better”; 187 patients had all three measures documented with a Pearson correlation coefficient of 0.63 between the change in the quantitative scale andthe qualitative scale (95% CI: 0.14–0.20, R 0.39). In 462 patients, vomiting decreased from 60% to 30% (Wilcoxon signed ranks test p < 0.001). The Pearson correlation coefficients for the change in vomiting incidence with the qualitative andquantitative “nausea scales” were poor: 0.012 (95% CI: ?0.015 to 0.039, R 0.00014) and0.051 (95% CI: ?0.032 to 0.118, R 0.00026), respectively. There were no reported adverse events. Conclusions. Ondansetron appears to be moderately effective in decreasing nausea andvomiting in undifferentiated prehospital patients. Additional controlled trials may be needed to compare it with other antiemetics.     

Pharmacological characterization of a rat 5-hydroxytryptamine type3 receptor subunit (r5-HT3A(b)) expressed in Xenopus laevis oocytes

1. The present study has utilized the two electrode voltage-clamp technique to examine the pharmacological profile of a splice variant of the rat orthologue of the 5-hydroxytryptamine type 3A subunit (5-HT_3A(b)) heterologously expressed in Xenopus laevis oocytes.
2. At negative holding potentials, bath applied 5-HT (300 nM–10 μM) evoked a transient, concentration-dependent (EC₅₀=1.1±0.1 μM), inward current. The response reversed in sign at a holding potential of −2.1±1.6 mV.
3. The response to 5-HT was mimicked by the 5-HT₃ receptor selective agonists 2-methyl-5-HT (EC₅₀=4.1±0.2 μM), 1-phenylbiguanide (EC₅₀=3.0±0.1 μM), 3-chlorophenylbiguanide (EC₅₀=140± 10 nM), 3,5-dichlorophenylbiguanide (EC₅₀=14.5±0.4 nM) and 2,5-dichlorophenylbiguanide (EC₅₀= 10.2±0.6 nM). With the exception of 2-methyl-5-HT, all of the agonists tested elicited maximal current responses comparable to those produced by a saturating concentration (10 μM) of 5-HT.
4. Responses evoked by 5-HT at EC₅₀ were blocked by the 5-HT₃ receptor selective antagonist ondansetron (IC₅₀=231±22 pM) and by the less selective agents (+)-tubocurarine (IC₅₀=31.9± 0.01 nM) and cocaine (IC₅₀=2.1±0.2 μM).
5. The data are discussed in the context of results previously obtained with the human and mouse orthologues of the 5-HT_3A subunit. Overall, the study reinforces the conclusion that species differences detected for native 5-HT₃ receptors extend to, and appear largely explained by, differences in the properties of homo-oligomeric receptors formed from 5-HT_3A subunit orthologues.

     

Prophylactic anti-emetic efficacy of ondansetron in laparoscopic cholecystectomy under total intravenous anaesthesiaA randomised, double-blind comparison with droperidol, metoclopramide and placebo

The prophylactic anti-emetic efficacy and safety of pre-operative intravenous ondansetron was evaluated in a randomised, double-blind, comparison with droperidol, metoclopramide and placebo in 160 ASA grade 1 and 2 patients undergoing laparoscopic cholecystectomy under total intravenous anaesthesia. The patients were randomly allocated to receive ondansetron (4 mg), droperidol (1.25 mg), metoclopramide (10 mg) or placebo given as a single intravenous dose immediately before induction of a standardised general anaesthetic. There were no significant differences between the four study groups with regard to the demographic and anaesthetic data, postoperative analgesia, postoperative sedation scores, duration of postoperative hospital stay and incidence of adverse events. The incidence of nausea and vomiting was significantly lower (p < 0.05) between 1 h and 4 h after surgery in the ondansetron group compared with the droperidol, metoclopramide and placebo groups. The incidence of nausea was similar in the four groups in the other study periods: 0-1 h and 4-24 h. The incidence of vomiting was lower in the ondansetron, droperidol and metoclopramide groups than in the placebo group between 1 and 4 h but was the same between 4 and 24 h. As a result of the lower incidence of nausea and vomiting between 1 h and 4 h in the ondansetron group, the overall incidence of nausea and vomiting was lower during the first 24 h after surgery in this group than in the other three groups.