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71.
The discriminative attributes of drugs were used to assess the degree to which several anticonvulsants have behavioral effects resembling those of pentobarbital. Rats were trained to make alternative responses to obtain water, depending on whether they had been injected IP with pentobarbital (10 mg/kg) or saline 10 min before the session. The pentobarbital response was chosen in tests with phenobarbital, dimethylphenobarbital, or methsuximide in the anticonvulsant dosage range. Increasing doses increased the percentage pentobarbital choice. Response rate was generally increased by doses that increased percentage of pentobarbital choice. The rats predominantly chose the saline response when administered phenytoin, primidone, or phenylethylmalondiamide, even at doses that were sufficiently high to reduce the response rate. The results suggest that different types of depressant effects are associated with the anticonvulsants tested. 相似文献
72.
Summary Pretreatment of rats and rabbits with Phenobarbital (80 mg/kg and 60 mg/kg respectively) caused a 30% increase in the liver weight relative to body weight. There was a smaller increase in the kidney weight (7% in rats and 10% in rabbits) which was not statistically significant. The yields of microsomes per gram of liver was also increased by about 90% and 60% in rats and rabbits respectively, but only a slight increase was observed for kidneys (12% and 18% respectively).Pretreatment with Phenobarbital, 3,4-Benzpyrene or Chlorophenothane neither significantly increased the cytochromes of rat kidney microsomes, nor the oxidative drug metabolism. However, in the kidneys of rabbits the cytochrome-b5-and P450-concentrations and drug metbolism were 2–3 fold higher after Phenobarbital. The correlation between P450 content and drug oxidase activity in the kidney microsomes of untreated and Phenobarbital treated rabbits was low.Suspensions of rabbit kidney microsomes revealed the same spectral changes after addition of Hexobarbital or Aniline as those reported for liver microsomes.
Teilweise vorgetragen bei der Tagung der Britischen und Deutschen Pharmakologischen Gesellschaften in Cambridge, 6.–8. Sept. 1967 (Abstr. Uehleke u. Greim, 1968). 相似文献
73.
Donald A. Overton 《Psychopharmacology》1977,53(2):195-199
Rats learned drug vs. drug (D vs. D) or drug vs. no drug (D vs. N) discriminations in a T-maze shock-escape task with various doses of pentobarbital, phenobarbital, or ethanol. Dose-effect curves were obtained for each drug using D vs. N training. After D vs. N training with any one of these drugs, rats made D choices during substitution tests with the other two drugs, suggesting drug interchangeability. D vs. D training also showed that pentobarbital and phenobarbital were virtually indistinguishable from one another. However, ethanol was readily discriminated from pentobarbital, showing that the two drugs differed. The results show the utility of D vs. D training as a method for studying drug differences that may be too small to detect with substitution tests. 相似文献
74.
目的:建立同时测定人血清中氨茶碱(APL)、苯巴比妥(PB)、苯妥英钠(DPH)和卡马西平(CBZ)的高效液相色谱(HPLC)法。方法:以Agilent TC-C18(250 mm×4.6 mm,5μm)为分析柱,甲醇-水(60∶40)为流动相,检测波长230 nm,流速1.0 ml/min,柱温35℃。结果:APL、PB、DPH、CBZ均能达到良好的分离,与相邻峰的分离度(R)均〉1.5;线性范围分别为1.01~40.34 mg/L(r=0.999 5)、1.24~59.52 mg/L(r=0.999 1)、2.60~31.20 mg/L(r=0.998 6)、1.09~32.61 mg/L(r=0.999 2);平均回收率分别为98.15%、99.25%、98.86%、100.3%;日内和日间精密度的RSD均〈4.3%。结论:本法灵敏、准确、简便、快速,适用于临床血药浓度的检测。 相似文献
75.
《Clinical toxicology (Philadelphia, Pa.)》2013,51(1):1-6
Background: Cocaine is often associated with trauma; however, little is known about how its use alters the response to blood loss. The effect of cocaine on hemodynamics following acute hemorrhage was studied in a rat model. Methods: Following baseline measurements, rats were administered either intravenous cocaine, or saline as a control. Both groups then underwent arterial catheter hemorrhage of 30% of total blood volume. Outcome variables include blood pressure, heart rate, hematocrit, pH, Pco2, Po2, and serum bicarbonate. Results: Following hemorrhage, blood pressure decreased in both groups but the hypotension was significantly greater in the saline group than the intravenous cocaine group at 0 and 5 minutes posthemorrhage. Heart rate was increased significantly for the intravenous cocaine group compared to the saline group starting at 15 minutes postcocaine and lasting for the next 25 minutes. No difference was noted for hematocrit, pH, Po2, or serum bicarbonate. Conclusion: Although transient, cocaine blunted the hypotensive response to acute controlled hemorrhage and resulted in tachycardia. 相似文献
76.
《Clinical toxicology (Philadelphia, Pa.)》2013,51(8):800-805
Introduction. Seizures are a common sequela of self-poisoning. However, their mechanism differs from seizures of other etiologies. Toxicological seizures result from alterations in the excitatory and inhibitory balance of otherwise normal neurons. In contrast, idiopathic or trauma related seizures usually start with a focus of abnormal neurons. For both forms of seizures, benzodiazepines are recommended as first-line therapy; however, there is debate about the use of phenytoin or barbiturates for second-line therapy. Methods and Results. In this article, we systematically review the evidence for the use of these drugs as second-line therapy for toxicological seizures. Barbiturates complement the anticonvulsant effect of benzodiazepines at the GABAA receptor by increasing the duration of chloride channel opening; phenytoin blocks voltage-dependent sodium channels to inhibit propagation from active electrical foci, an effect more useful for nontoxicological seizures. We found no randomized controlled trial comparing phenytoin and barbiturates in toxicological seizures refractory to benzodiazepines; similarly no trial was found comparing the use of these drugs in nonpoisoned patients. Animal studies indicate that phenobarbital has greater effectiveness than phenytoin for many poisons; a few case reports suggest a better response in patients. Conclusion. Despite the lack of high-quality clinical trial data, pharmacological knowledge and animal studies suggest that phenobarbital or thiopentone should be second-line agents for controlling toxicological seizures. The role of newer agents such as propofol and levetiracetam in toxicological seizures is currently unclear because of a lack of clinical or animal studies. 相似文献
77.
目的了解全球抗癫痫运动中国农村抗癫痫示范项目终止后4年曾接受苯巴比妥治疗的癫痫患者的远期治疗效果及转归,以为我国农村癫痫患者的防治和管理提供参考依据。方法2008年7—12月由经过培训的乡卫生院医师采用问卷与访谈相结合的形式入户调查,对原示范项目6省(市)共8个县经苯巴比妥治疗管理的2455例惊厥型癫痫患者进行随访。结果接受苯巴比妥治疗的2455例患者中共随访到1780例,其中939例(52.75%)继续服药,无发作和发作减少超过50%(有效)的患者于项目终止后的12、24、36和48个月时所占比例分别为66.77%(627/939)、68.37%(642/939)、71.35%(670/939)和73.06%(686/939);841例(47.25%)停药患者中244例(29.01%)无发作、320例(38.05%)仍然发作但已停药、277例(32.94%)改用其他类型抗癫痫药物。对939例继续服用苯巴比妥与841例停药的癫痫患者进行疗效比较,继续服药者的远期疗效优于停药者(x2=12.423,P=0.002)。停药原因分别为发作停止(244例,29.01%)、改用其他抗癫痫药物(277例,32.94%)、未提供免费药物或无钱买药(93例,11.06%)、治疗效果欠佳(92例,10.94%)、当地买不到苯巴比妥(54例,6.42%)等。至2008年随访结束时共有206例患者死亡,标化死亡比达19.10;其中意外事故死亡为59例(28.64%),其次为脑血管病30例(14.56%)、癫痫持续状态窒息死亡28例(13.59%)。结论“全球抗癫痫运动”中国农村癫痫示范项目开展成功,远期治疗效果良好,值得进一步推广。癫痫人群死亡率高,尤其是意外事故死亡率高,值得引起注意。 相似文献
78.
The purpose of this study was to test the hypothesis that latency of REM onset is a negative function of drug-induced precentral fast (18 to 26 cps) activity in the EEG. Chlorpromazine increased this activity during sleep and wakefulness and decreased latency of REM sleep, whereas α-chloralose, pentothal, and phenobarbital were associated with a decrease of this activity during sleep, increased slow wave sleep, and increased latency of REM sleep. Phenobarbital and pentothal increased this fast activity during wakefulness and drowsiness, respectively. However, 18 to 26 cps precentral activity was reduced during sleep with α-chloralose and pentothal. A supporting study in cats demonstrates apparent synchrony of fast activity in the limbic system and cortex during wakefulness, and chlorpromazine increases fast activity in the limbic system. It is speculated that chlorpromazine enhances the effect of the limbic system on cortical (primarily precentral) activity. The sedatives are thought to potentiate the spontaneous slow wave sleep pattern. 相似文献
79.
摘 要 目的:分析我院2013~2015年抗癫痫药物血药浓度监测(TDM)结果, 为临床合理用药提供参考。方法:采用回顾性研究方法,收集1 098例次患者使用丙戊酸钠、卡马西平、苯巴比妥的TDM数据并进行统计分析。 结果:1 098例次TDM结果中丙戊酸钠1 009例次,卡马西平65例次,苯巴比妥24例次,3种药品血药浓度在推荐范围内的比例分别为42.6%,64.6%,37.6%。联合用药共31例次,药物浓度均在推荐浓度范围内的8例次(25.8%)。末次给药和采血时间对TDM结果有明显影响。结论:抗癫痫药物血药浓度个体差异大,影响因素多,临床用药应综合考虑各方面因素,实施个体化给药方案, 确保用药安全有效。 相似文献
80.
Queiroz RH Bertucci C Malfará WR Dreossi SA Chaves AR Valério DA Queiroz ME 《Journal of pharmaceutical and biomedical analysis》2008,48(2):428-434
A sensitive and reproducible stir bar-sorptive extraction and high-performance liquid chromatography-UV detection (SBSE/HPLC-UV) method for therapeutic drug monitoring of carbamazepine, carbamazepine-10,11-epoxide, phenytoin and phenobarbital in plasma samples is described and compared with a liquid:liquid extraction (LLE/HPLC-UV) method. Important factors in the optimization of SBSE efficiency such as pH, extraction time and desorption conditions (solvents, mode magnetic stir, mode ultrasonic stir, time and number of steps) assured recoveries ranging from 72 to 86%, except for phenytoin (62%). Separation was obtained using a reverse phase C(18) column with UV detection (210nm). The mobile phase consisted of water:acetonitrile (78:22, v/v). The SBSE/HPLC-UV method was linear over a working range of 0.08-40.0mugmL(-1) for carbamazepine, carbamazepine-10,11-epoxide and phenobarbital and 0.125-40.0mugmL(-1) for phenytoin, The intra-assay and inter-assay precision and accuracy were studied at three concentrations (1.0, 4.0 and 20.0mugmL(-1)). The intra-assay coefficients of variation (CVs) for all compounds were less than 8.8% and all inter-CVs were less than 10%. Limits of quantification were 0.08mugmL(-1) for carbamazepine, carbamazepine-10,11-epoxide and phenobarbital and 0.125mugmL(-1) for phenytoin. No interference of the drugs normally associated with antiepileptic drugs was observed. Based on figures of merit results, the SBSE/HPLC-UV proved adequate for antiepileptic drugs analyses from therapeutic levels. This method was successfully applied to the analysis of real samples and was as effective as the LLE/HPLC-UV method. 相似文献