Treatment of Status Epilepticus

Summary: Status epilepticus, particularly the convulsive form, is a medical emergency, warranting prompt and aggressive treatment. To do this, one must have a thorough understanding of the pharmacology of the anticonvulsant agents. Therapy should be directed toward rapid termination of the status epilepticus, prevention of seizure recurrence, and treatment of any underlying cause. Most importantly, one should establish and adhere to a standard treatment protocol for best results.     

Changes in the inducibility of a hepatic aldehyde dehydrogenase by various effectors

A hepatic soluble aldehyde dehydrogenase (ALDH), inducible by polycyclic aromatic hydrocarbons, was studied in Wistar rats in connection with substances known to affect drug metabolism or aldehyde dehydrogenase activity, such as phenobarbital (PB), disulfiram (DS), -diethylaminoethyl diphenylpropylacetate (SKF 525A) and calcium cyanamide (CC). 3-Methylcholanthrene (MC) was given as a model inducer of ALDH (100 mg/kg, i.p., as a single dose) and the animals were killed after 3 days. Pretreatment with PB (1 g/l drinking water, for 2 weeks) enhanced the inducing effect of MC. On the contrary, pretreatment with DS (100 mg/kg, i.p., daily x4) reduced by 70% the expected increase in ALDH activity. Neither SKF 525A (25 mg/kg, i.p., daily x4), nor CC (5 mg/kg, i.p., daily x4) could affect the action of the inducer. At the above doses, basal ALDH activity was inhibited by DS (30%) and CC (70%), but was not affected at all by PB or SKF 525A. The results were somewhat different when the various effectors tested were administered to animals already treated with MC (20 mg/kg, i.p., daily x6). In this case, DS did not affect the already induced ALDH activity. On the contrary, CC was still an effective inhibitor. Unexpectedly, post-treatment with SKF 525A further enhanced the initial induction brought about by MC. Our findings show that substances affecting microsomal drug metabolism can interfere with the process of ALDH induction by MC. The additive result of PB pretreatment is probably due to the enhanced accumulation of an active metabolite of MC. The opposite effect of DS on drug metabolism could explain the decreased ability of MC to induce ALDH activity. The MC-inducible ALDH isozyme can be effectively inhibited with CC, but not with DS.     

Microarray analysis on Phase II drug metabolizing enzymes expression in pregnant rats after treatment with pregnenolone-16alpha-carbonitrile or phenobarbital

We previously reported the expression profiles of 9 cytochrome P450 isozymes (CYPs) proteins and those of 40 CYPs genes in pregnant rat's liver, placenta and fetal liver after treatment with pregnenolone-16alpha-carbonitrile (PCN) or phenobarbital (PB). This study was carried out focusing on the gene expression profiles of Phase II drug metabolizing enzymes, Glutathione S-transferase isozymes (GSTs) and UDP-glycosyltransferase isozymes (UDPGTs). Fischer 344 (F344) pregnant rats were daily treated intraperitoneally with 50 mg/kg of PCN or 80 mg/kg of PB from 13 to 16 days of gestation (DG). They were sacrificed on 17 DG, and microarray analysis using Affymetrix Rat Expression Array 230 A was performed. Among 16 GSTs genes examined in this study, 7 genes were significantly induced in dam's liver and 3 genes in fetal liver, respectively, in the PCN-group, while 8 genes were significantly induced in dam's liver and 1 gene in fetal liver, respectively, in the PB-group. On the other hand, among 11 UDPGTs genes examined, 5 genes were significantly induced in dam's liver and 3 genes in fetal liver, respectively, in the PCN-group, while 5 genes were significantly induced in dam's liver and 1 gene in fetal liver, respectively, in the PB-group. There were no significant changes in the placenta of all groups. This is the first report of the gene expression profiles of Phase II drug metabolizing enzymes in pregnant rat and fetal livers and placenta after treatment with typical inducers of drug metabolizing enzymes.     

Acute effect of phenobarbital on escape behavior

Rats were trained to run in a straight alley to escape shock. Subsequently, phenobarbital was administered and more trials given. Phenobarbital retards running at all doses tested in a curve that is positively accelerating as a function of dose on the first trial. The first trial is markedly slower than later trials with the greatest effect occurring at the higher dosages.     

负荷量苯巴比妥预防新生儿缺氧缺血性脑病及颅内出血

观察重度窒息儿静注苯巴比妥预防新生儿缺氧缺血性脑病及颅内出血的效果。方法：选择本院产科出生的重度窦息儿６０例为观察对象,随机分为用药组和对照组各３０例。用药组转入我科后即给予苯巴比妥钠荷量２０ｍｇ／ｋｇ,１２小时后给予维持量５ｍｇ／ｋｇ．ｄ,共７天。     

Depletion of brain norepinephrine: differential influence on anxiolyic treatment effects

Rationale: Previous studies have demonstrated that anxiolytic-like anticonflict effects can be produced by either (1) acute administration of traditional anti-anxiety compounds (benzodiazepines or barbiturates) or (2) chronic administration of tricyclic (TCA) or monoamine oxidase inhibitor (MAOI) antidepressants. Objective: The present study determined the effects of noradrenergic neuronal depletion on these distinct anticonflict treatments. Methods: After 3 weeks of training in a repeated measures drink suppression conflict paradigm, water-restricted rats consumed 11–14 ml water/session (unpunished responding) and accepted 25–40 shocks/session (punished responding) during control (i.e., non-drug) 10-min test sessions. The noradrenergic neurotoxin DSP4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride; 65 mg/kg, IP] or its vehicle (saline; 1 ml/kg) was administered after 3 weeks of conflict testing. Conflict behavior was then evaluated for 8 weeks post-treatment. In separate groups of DSP4- and vehicle-pretreated subjects, the effects of acute administration (10-min pretreatment) of phenobarbital (5–40 mg/kg) or alprazolam (0.3–2.5 mg/kg) were determined. In a third experiment, the effects of chronic treatment with the TCA desipramine (DMI; 5 mg/kg, twice daily for 8 weeks) or the non-selective MAOI phenelzine (4.0 mg/kg, twice daily for 8 weeks) on conflict behavior were determined in additional groups of DSP4- or vehicle-pretreated subjects. Results: DSP4 treatment produced a modest yet statistically significant decrease in punished responding (i.e., anxiogenic-like effect) relative to vehicle controls. DSP4 pretreatment did not alter the anticonflict effects of acute alprazolam or phenobarbital treatment. In contrast, DSP4 treatment completely abolished the anticonflict effects produced by chronic DMI or chronic phenelzine treatment. Conclusions: Thus, noradrenergic neuronal integrity appears to be required for the anxiolytic-like effects of chronic antidepressant treatment, but not for the anxiolytic-like effects of acute treatment with barbiturates and benzodiazepines. Received: 6 August 1998/Final version: 16 October 1998     

WHO“癫痫社会控制”方案的扩展性试验研究

本研究对WHO“癫痫的社会控制”提案在山西和宁夏回族自治区农村进行了为期一年的扩展性观察试验。共选定癫痫大发作患者120例作为样本。两地各随机分为二组,一组由经过短期培训的乡村医生治疗,另一组由神经科医生治疗。规定使用同一种药物苯巴比妥。结果表明两组都取得了令人满意的疗效,乡村医生可以按规定方案担当起治疗和管理多数癫痫太发作病人的任务。从而再次证实此方案在我国大部分农村地区是可行的、适用的,值得逐步推广。     

Dibromoethane effects on the induction of γ-glutamyl-transpeptidase positive foci in rat liver

The initiating and promoting activities of 1,2-dibromoethane in rat liver were investigated using the enzyme-altered foci bioassay. The incidence of -glutamyl-transpeptidase (GGT)-positive foci was used as an early histochemical marker for hepatocarcinogenesis. To determine the initiating activity of 1,2-dibromoethane, the halogenated hydrocarbon was administered orally in corn oil as single or multiple doses (60 or 120 mg/kg) either before or after partial hepatectomy. The animals were then given a promoting regimen of 500 ppm phenobarbital in their drinking water. No increase in the incidence of GGT-positive foci was observed in any of the 1,2-dibromoethane initiation groups. The tumor promoting activity of 1,2-dibromoethane was determined in partially hepatectomized rats which were initiated with N-nitrosodiethylamine (30 mg/kg; po), and one week later were administered 1,2-dibromoethane (10 or 30 mg/kg) orally in corn oil five times weekly for 8 weeks. Control groups receiving sham hepatectomy or no initiator were also treated with the halogenated hydrocarbon five times weekly. Only in those animals which received partial hepatectomy, N-nitrosodiethylamine initiation, and 1,2-dibromoethane was the incidence of GGT-positive foci significantly increased. These results do not support significant initiator activity of 1,2-dibromoethane in rat liver, but do indicate that 1,2-dibromoethane possesses promoter activity which may contribute to its carcinogenic activity.     

苯巴比妥预防热性惊厥再发80例分析

目的:探讨苯巴比妥对热性惊厥再发的预防作用。方法:对已发1次热性惊厥患儿,在体温再次达37.5℃以上时,治疗组给予苯巴比妥4 mg/(kg·次)预防热性惊厥,对照组未作预防热性惊厥处理。结果:随访2-5年,治疗组1例(1.25％)热性惊厥复发.对照组27例(33.75％)复发。结论:苯巴比妥对预防热性惊厥复发有显著疗效。     

苯巴比妥在患儿血清样品中的稳定性

目的:探讨患儿苯巴比妥(PB)血清样品在冷处储存的稳定性.方法:荧光偏振免疫法(FPIA)测定30例患儿应用PB治疗时的血药浓度,比较其血清样品当天测定浓度(C1)与其在冷处储存7 d后测定浓度(C7).结果:PB血药浓度C1与C7呈正相关(P＜0.01),其回归方程:C7＝1.054 5C1－1.275 8,r＝0.983 1.平均Re(C7/C1,相当于PB在患儿血清中的平均回收率)为(100.4±4.8)%,RSD为4.70%(n＝30),且两者的各组偏差［(C7－C1)/C1］均小于10%.结论:患儿血清样品在冷处储存7 d,其PB能保持稳定,有利于常规治疗药物监测(TDM)时的样品储存.