• 【大鼠的周围皮层: 微输注抗惊厥药以对抗梭曼诱发的癫痫发作的复杂区域。】 复制标题 收藏 收藏
    DOI:10.1016/j.neuro.2012.10.019 复制DOI
    作者列表:Myhrer T,Enger S,Aas P
    BACKGROUND & AIMS: :Microinfusion of anticonvulsants into the perirhinal cortex through 1 guide cannula in each hemisphere only invades a small area of this seizure controlling site in rats exposed to soman. The purpose of the present study was to examine whether infusions made through 2 cannulas in each perirhinal cortex may produce more efficacious anticonvulsant action against soman intoxication than the use of 1 cannula only in rats infused with the ionotropic antagonists procyclidine and caramiphen or the metabotropic glutamate modulators DCG-IV and MPEP. The results showed that the mere presence of indwelling double cannulas caused proconvulsant effect in response to subsequent systemic administration of soman. Both the control and caramiphen groups with double cannulas had significantly shorter latencies to seizure onset than the corresponding groups with single cannula. Procyclidine resulted in anticonvulsant efficacy, even in rats with double cannulas. In rats that received twin infusions of DCG-IV or MPEP, the anticonvulsant impact was very high, inasmuch as a majority of the rats in each group was protected against seizure activity. Drugs possessing powerful anticonvulsant potency can apparently counteract the proconvulsant effect of double cannulas, and some can even gain enhanced anticonvulsant capacity when invading a larger area of the perirhinal cortex. Perirhinal EEG recordings (electrodes in indwelling cannulas) in a separate set of rats not exposed to soman or drugs showed no differences in basal electrical activity (total power 0.5-25Hz or the theta band 4-12Hz) between groups with single or double cannulas. The intrinsic excitability and synaptic connectivity of the perirhinal cortex may be associated with the proconvulsant impact observed in rats with double cannulas when exposed to soman.
    背景与目标: : 在暴露于梭曼的大鼠中,通过每个半球的1个引导套管将抗惊厥药微注入到周围皮层中,仅侵入该癫痫发作控制部位的一小部分。本研究的目的是检查通过每个周围皮层中的2根套管输注是否比仅在注入离子型拮抗剂procyclidine和caramiphen的大鼠中使用1根套管对梭曼中毒产生更有效的抗惊厥作用或代谢型谷氨酸调节剂dcg-iv和MPEP。结果表明,仅留置双套管的存在会对随后的梭曼全身给药产生惊厥作用。具有双插管的对照组和卡拉米芬组的癫痫发作发作的潜伏期均明显短于具有单插管的相应组。即使在双插管的大鼠中,Procyclidine也具有抗惊厥的功效。在接受两次dcg-iv或MPEP输注的大鼠中,抗惊厥作用非常高,因为每组中的大多数大鼠都受到了癫痫发作的保护。具有强大抗惊厥效力的药物显然可以抵消双插管的促惊厥作用,有些甚至可以在侵入较大区域的周围皮层时获得增强的抗惊厥能力。在未暴露于梭曼或药物的另一组大鼠中,脊髓周围脑电图记录 (留置插管中的电极) 显示,具有单或双插管的组之间的基础电活动 (总功率0.5-25Hz或 θ 带4-12Hz) 没有差异。暴露于梭曼时,双套管大鼠的固有兴奋性和突触连通性可能与观察到的惊厥冲击有关。
  • 【抗惊厥药在强迫症和相关疾病治疗中的潜在作用。】 复制标题 收藏 收藏
    DOI:10.1111/pcn.12186 复制DOI
    作者列表:Wang HR,Woo YS,Bahk WM
    BACKGROUND & AIMS: :We reviewed the extant literature to evaluate the current evidence regarding the efficacy and safety of anticonvulsants in the treatment of obsessive-compulsive and related disorders. Relevant literature was accessed using the Cochrane database, embase and PubMed on 29 October 2013. Prospective studies examining the efficacy of anticonvulsants in obsessive-compulsive and related disorders were included. Case reports, case series, and retrospective studies were excluded. A total of 10 studies were included in this review. The studies of obsessive-compulsive disorder, except for two negative studies, showed favorable efficacy results of anticonvulsants. In one study on body dysmorphic disorder, levetiracetam showed favorable efficacy. In two lamotrigine studies for pathologic skin-picking, the efficacy findings were inconsistent. In one trichotillomania study, topiramate had reduced hair-pulling symptoms. Despite limited evidence, our review suggests that anticonvulsants have a potential role in the treatment of obsessive-compulsive and related disorders.
    背景与目标: : 我们回顾了现有文献,以评估有关抗惊厥药治疗强迫症和相关疾病的疗效和安全性的最新证据。使用Cochrane数据库,embase和PubMed on 2013年10月29日访问了相关文献。包括前瞻性研究,以检查抗惊厥药对强迫症和相关疾病的疗效。排除病例报告、病例系列和回顾性研究。本综述共纳入10项研究。除两项阴性研究外,对强迫症的研究显示了抗惊厥药的良好疗效。在一项关于身体畸形疾病的研究中,左乙拉西坦显示出良好的疗效。在两项针对病理性皮肤采摘的拉莫三嗪研究中,疗效结果不一致。在一项毛滴虫病研究中,托吡酯减轻了拉毛症状。尽管证据有限,但我们的评论表明,抗惊厥药在强迫症和相关疾病的治疗中具有潜在作用。
  • 【概述用于治疗酒精戒断和酒精依赖的药物,重点是使用较旧和较新的抗惊厥药。】 复制标题 收藏 收藏
    DOI:10.1016/j.addbeh.2005.12.029 复制DOI
    作者列表:Ait-Daoud N,Malcolm RJ Jr,Johnson BA
    BACKGROUND & AIMS: :There is a growing interest in the development of new pharmacological tools for treating alcohol withdrawal and dependence. A number of anticonvulsants including valproate and carbamazepine have been shown to be safe and effective alternatives to benzodiazepines for treating alcohol withdrawal. These agents are relatively safe, are free from demonstrated abuse liability, and do not usually potentiate the psychomotor and cognitive effects of alcohol. For the treatment of alcohol dependence, there is a growing literature on the utility of medications that have neurochemical effects at opioid, serotonergic, GABAergic, and glutamate receptors. Furthermore, as a class of medication, there appears to be a growing interest in investigating the utility of novel anticonvulsants such as topiramate for the treatment of alcohol dependence.
    背景与目标: : 人们对开发用于治疗酒精戒断和依赖的新药理学工具的兴趣日益浓厚。许多抗惊厥药 (包括丙戊酸盐和卡马西平) 已被证明是治疗酒精戒断的苯二氮卓类药物的安全有效替代品。这些药物相对安全,没有明显的滥用责任,通常不会增强酒精的精神运动和认知作用。对于酒精依赖的治疗,越来越多的文献报道了对阿片类药物,5-羟色胺能,gaba能和谷氨酸受体具有神经化学作用的药物的效用。此外,作为一类药物,人们似乎越来越有兴趣研究新型抗惊厥药 (例如托吡酯) 用于治疗酒精依赖。
  • 【孕妇叶酸缺乏和妊娠浪费。四.叶酸补充剂,抗惊厥药和口服避孕药的作用。】 复制标题 收藏 收藏
    DOI:10.1016/0002-9378(71)90326-7 复制DOI
    作者列表:Pritchard JA,Scott DE,Whalley PJ
    BACKGROUND & AIMS: A group of studies on indigent hospital patients were conducted on the role of folate supplements, pregnancy and oral contraceptives in megaloblastic anemia. First 25 pregnant women, given 500 mg iron dextran and 30 mg folic acid for 2-3 months, had 12.4% hemoglogin at delivery, compared with 49 women given only iron who had 12.5% hemoglobin, and 49 untreated women who had 11.3% hemoglobin. Second, plasma folate levels in groups of pregnant women were comparedmean folate was 4.7 ng/ml in 82 normal women, 3.1 in 21 treated epileptics, and about 1.2 in 31 women with megaloblastic anemia. In 77 pregnancies in 43 epileptic women there were no reasons to blame low folate levels for pregnancy wastage since no abruptio placentae or bleeding occurred; and incidence of low birth weight, perinatal death, and prematurity was lower than in the general population. Third, the effect of oral contraceptives on folate levels was observed. Mean plasma folate levels were 8.1 ng/ml in 55 control women, 8.0 in 57 women using the pill, 4.7 in normal women in late pregnancy, and about 1.1 in pregnant women with megaloblastic anemia. Fourth, mean hemoglobin levels rose from 7.6 to 13.4 9m/100 ml within a few weeks in 5 women with gestational megaloblastic anemia after treatment with normal diet, without supplement, and oral contraceptives. One woman with puerperal megaloblastic anemia failed to respond to a regular diet while taking Ovulen, 6 tablets daily. The results suggest that plasma folate levels were neither lower in oral contracepting women nor did the pill prevent the increase in folate in megaloblastic anemia patients treated with diet. Thus the authors concluded that folate supplement is not needed for pill users.

    背景与目标: 对贫困的医院患者进行了一组研究,研究叶酸补充剂,怀孕和口服避孕药在巨幼细胞性贫血中的作用。前25名孕妇,给予500毫克右旋糖酐铁和30毫克叶酸2-3个月,在分娩时12.4% 血红素,而49名仅给予铁的妇女12.5% 血红蛋白,49名未经治疗的妇女11.3% 血红蛋白。第二,比较孕妇组的血浆叶酸水平,82名正常妇女的平均叶酸为4.7 ng/ml,21名癫痫患者的3.1,31名巨幼细胞性贫血妇女的约1.2。在43名癫痫妇女的77例妊娠中,没有理由将低叶酸水平归咎于妊娠浪费,因为没有发生胎盘早剥或出血; 低出生体重,围产期死亡和早产的发生率低于一般人群。第三,观察口服避孕药对叶酸水平的影响。55名对照妇女的平均血浆叶酸水平为8.1 ng/ml,使用该药丸的57名妇女为8.0,怀孕后期正常妇女为4.7,患有巨幼细胞性贫血的孕妇为约1.1。第四,5名患有妊娠期巨幼细胞性贫血的妇女在正常饮食,无补充和口服避孕药的治疗后,平均血红蛋白水平在几周内从7.6 m/100毫升上升到13.4 9m/2。一名患有产褥期巨幼细胞性贫血的妇女在每天服用6片Ovulen时对常规饮食无反应。结果表明,口服避孕药妇女的血浆叶酸水平既没有降低,也没有阻止饮食治疗的巨幼细胞性贫血患者叶酸的增加。因此,作者得出结论,避孕药使用者不需要补充叶酸。
  • 【在未经治疗和地西epa治疗的猴子中,阳性GABAA调节剂和其他抗焦虑药,镇静剂和抗惊厥药的歧视性刺激作用。】 复制标题 收藏 收藏
    DOI:10.1124/jpet.102.040931 复制DOI
    作者列表:McMahon LR,France CP
    BACKGROUND & AIMS: :Positive GABAA modulators and other sedatives, anxiolytics, and anticonvulsants were used to evaluate mechanisms underlying the discriminative stimulus effects of midazolam in untreated monkeys and of flumazenil in monkeys treated with diazepam (5.6 mg/kg/day). Positive GABAA modulators at benzodiazepine (e.g., flunitrazepam and abecarnil) and neuroactive steroid sites (e.g., androsterone) substituted for midazolam in all monkeys; the neuroactive steroids dihydroandrosterone and epipregnanolone substituted for midazolam in two of three monkeys. All positive GABAA modulators attenuated flumazenil in diazepam-treated monkeys; doses of flunitrazepam and abecarnil larger than doses substituting for midazolam were required to attenuate flumazenil, whereas doses of neuroactive steroids smaller than doses substituting for midazolam attenuated flumazenil. Drugs with mechanisms that do not predominantly involve allosteric modulation of GABA (e.g., buspirone, ketamine, valproic acid, and diphenhydramine) did not substitute for midazolam or flumazenil. However, valproic acid enhanced the midazolam discriminative stimulus and attenuated the flumazenil discriminative stimulus; diphenhydramine attenuated the midazolam discriminative stimulus. These results suggest that drugs not sharing a mechanism of action with benzodiazepines can modulate the behavioral effects of benzodiazepines. In addition, this study demonstrates that endogenous ligands, presumably by acting at neuroactive steroid sites on the GABAA receptor complex, share discriminative stimulus effects with benzodiazepines. This study also suggests that positive GABAA-modulating neuroactive steroids are especially potent in attenuating behavioral effects that are related to diazepam withdrawal.
    背景与目标: : 使用阳性GABAA调节剂和其他镇静剂,抗焦虑药和抗惊厥药来评估未治疗的猴子中的咪达唑仑和用地西epa (5.6 mg/kg/天) 治疗的猴子中的氟马西尼的鉴别性刺激作用的潜在机制。在所有猴子中,苯二氮卓 (例如氟硝西泮和阿贝卡尼尔) 和神经活性类固醇位点 (例如雄酮) 的GABAA调节剂阳性取代了咪达唑仑; 在三只猴子中的两只猴子中,神经活性类固醇二氢雄酮和表pregnanolone取代了咪达唑仑。在地西epa治疗的猴子中,所有阳性的GABAA调节剂均减弱了氟马西尼; 氟硝西泮和阿贝卡尼的剂量大于替代咪达唑仑的剂量,以减弱氟马西尼,而神经活性类固醇的剂量小于替代咪达唑仑的剂量则减弱了氟马西尼。具有主要不涉及GABA变构调节机制的药物 (例如丁螺环酮,氯胺酮,丙戊酸和苯海拉明) 不能替代咪达唑仑或氟马西尼。但是,丙戊酸增强了咪达唑仑的判别性刺激并减弱了氟马西尼判别性刺激; 苯海拉明减弱了咪达唑仑判别性刺激。这些结果表明,与苯二氮卓类药物不具有作用机制的药物可以调节苯二氮卓类药物的行为作用。此外,这项研究表明,内源性配体可能通过在GABAA受体复合物上的神经活性类固醇位点起作用,与苯二氮卓类药物具有歧视性刺激作用。这项研究还表明,积极的GABAA调节神经活性类固醇在减轻与地西epa戒断相关的行为作用方面尤其有效。
  • 【抗精神病药,抗抑郁药,抗惊厥药和安慰剂对边缘性人格障碍的症状维度: 随机对照和开放标签试验的荟萃分析。】 复制标题 收藏 收藏
    DOI:10.1097/JCP.0b013e31822c1636 复制DOI
    作者列表:Vita A,De Peri L,Sacchetti E
    BACKGROUND & AIMS: :The aim of this study was to quantitatively review randomized controlled trials (RCTs) and open-label trials analyzing the efficacy of antidepressants, mood stabilizers, and antipsychotics for the treatment of the core symptoms of borderline personality disorder (BPD). Using a similar meta-analytic approach, the efficacy of placebo on the same core symptoms of BPD was evaluated. The risk of discontinuation of each of the medication classes reported in the studies was also analyzed to establish the major causes of discontinuation. MEDLINE (1966 to June 2010) and EMBASE (1980 to June 2010) databases were systematically searched to identify relevant RCTs and open studies. The primary outcome was improvement in the specific core symptoms of the disorder: affective dysregulation, impulsive-behavioral dyscontrol, and cognitive-perceptual symptoms. Evidence from RCTs and open studies suggests that drug treatment, especially with mood stabilizers and antipsychotics, may be effective for treating affective dysregulation and impulsive-behavioral dyscontrol. Antipsychotics were also effective in reducing cognitive-perceptual symptoms. Antidepressants failed to show efficacy in treating BPD symptom dimensions other than affective dysregulation. Our analyses of the placebo arm of RCTs showed a significant improvement of symptomatology in these patients also. There were no significant differences in overall dropout rates between patients on medications and those on placebo. In conclusion, the efficacy of pharmacological treatment on the symptom dimensions of BPD has been shown by various independent meta-analyses, with a positive effect of drug treatment on the core symptoms of BPD and some documentable differences in terms of efficacy between different drug classes in each of the symptom domains.
    背景与目标: : 本研究的目的是定量回顾随机对照试验 (RCTs) 和开放标签试验,分析抗抑郁药,情绪稳定剂和抗精神病药治疗边缘性人格障碍 (BPD) 核心症状的疗效。使用类似的荟萃分析方法,评估了安慰剂对BPD相同核心症状的疗效。还分析了研究中报告的每种药物类别的停药风险,以确定停药的主要原因。系统地搜索MEDLINE (1966至2010年6月) 和EMBASE (1980至2010年6月) 数据库,以识别相关的rct和开放研究。主要结果是改善该疾病的特定核心症状: 情感障碍,冲动行为控制障碍和认知知觉症状。RCTs和开放研究的证据表明,药物治疗,尤其是使用情绪稳定剂和抗精神病药,可能对治疗情感失调和冲动行为控制障碍有效。抗精神病药在减轻认知知觉症状方面也有效。抗抑郁药在治疗BPD症状方面没有表现出除情感失调以外的功效。我们对rct安慰剂组的分析表明,这些患者的症状学也有显着改善。服用药物的患者和服用安慰剂的患者的总体辍学率没有显着差异。总之,通过各种独立的荟萃分析显示了药物治疗对BPD症状维度的疗效,药物治疗对BPD核心症状的积极作用以及在每个症状领域中不同药物类别之间的疗效方面的一些可证明的差异。
  • 【使用抗惊厥药治疗神经性疼痛。】 复制标题 收藏 收藏
    DOI:10.1212/wnl.59.5_suppl_2.s14 复制DOI
    作者列表:Backonja MM
    BACKGROUND & AIMS: :Emerging evidence from animal models of neuropathic pain suggests that many pathophysiologic and biochemical changes occur in the peripheral and central nervous system. Similarities between the pathophysiologic phenomena observed in some epilepsy models and in neuropathic pain models justify the use of anticonvulsants in the symptomatic management of neuropathic pain. Positive results from laboratory and clinical trials further support such use. Carbamazepine was the first of this class of drugs to be studied in clinical trials and has been longest in use for treatment of neuropathic pain. Clinical trial data support its use in treating trigeminal neuralgia, but data for treatment of painful diabetic neuropathy are less convincing. Use of newer anticonvulsants has marked a new era in the treatment of neuropathic pain. Gabapentin has demonstrated efficacy, specifically in painful diabetic neuropathy and postherpetic neuralgia. Lamotrigine has been reported to be effective in relieving pain from trigeminal neuralgia refractory to other treatments, HIV neuropathy, and central post-stroke pain. Results from clinical trials of phenytoin are equivocal. Zonisamide's mechanisms of action suggest that it would be effective in controlling neuropathic pain symptoms. Other anticonvulsants, including lorazepam, valproate, topiramate, and tiagabine, have also been under investigation. Anecdotal experience provides support for studies with oxcarbazepine and levetiracetam for treating neuropathic pain. Evidence supporting the efficacy of anticonvulsants in treatment of such pain is evolving. Additional clinical trials should provide information that will better define their role in neuropathic pain.
    背景与目标: : 来自神经性疼痛动物模型的新证据表明,周围和中枢神经系统发生了许多病理生理和生化变化。在某些癫痫模型和神经性疼痛模型中观察到的病理生理现象之间的相似性证明在神经性疼痛的症状治疗中使用抗惊厥药是合理的。实验室和临床试验的积极结果进一步支持了这种使用。卡马西平是在临床试验中研究的此类药物中的第一种,并且在治疗神经性疼痛方面使用时间最长。临床试验数据支持其用于治疗三叉神经痛,但治疗糖尿病性神经病的数据令人信服。新型抗惊厥药的使用标志着神经性疼痛治疗的新纪元。加巴喷丁已证明有效,特别是在痛苦的糖尿病性神经病和带状疱疹后神经痛中。据报道,拉莫三嗪可有效缓解其他治疗方法难治的三叉神经痛,HIV神经病和中风后疼痛。苯妥英临床试验的结果是模棱两可的。Zonisamide的作用机制表明,它将有效控制神经性疼痛症状。其他抗惊厥药,包括劳拉西泮,丙戊酸,托吡酯和替加滨,也正在研究中。轶事经验为奥卡西平和左乙拉西坦治疗神经性疼痛的研究提供了支持。支持抗惊厥药治疗此类疼痛疗效的证据正在不断发展。其他临床试验应提供信息,以更好地定义其在神经性疼痛中的作用。
  • 【小抗惊厥药和惊厥药对丘脑神经元的不同作用: 钙电流减少。】 复制标题 收藏 收藏
    DOI:10.1111/j.1476-5381.1990.tb14095.x 复制DOI
    作者列表:Coulter DA,Huguenard JR,Prince DA
    BACKGROUND & AIMS: :1. Succinimide derivatives can be either convulsant (tetramethylsuccinimide (TMS)), or anticonvulsant (ethosuximide (ES); alpha-methyl-alpha-phenylsuccinimide (MPS)). ES, an anticonvulsant succinimide, has previously been shown to block calcium currents of thalamic neurones, while the convulsant succinimide TMS blocks gamma-aminobutyric acid (GABA) responses in a similar fashion to the convulsant pentylenetetrazol (PTZ). 2. Using voltage-clamp techniques, we analysed the effects of the anticonvulsant succinimides ES and MPS and the convulsants TMS and PTZ on calcium currents of acutely isolated thalamic relay neurones of the rat. 3. MPS and ES reduced low-threshold calcium current (LTCC) in a voltage-dependent manner, without affecting steady-state inactivation. MPS was less potent than ES (IC50 of 1100 vs 200 microM) but greater in efficacy (100% maximal reduction vs 40% for ES). 4. PTZ had no effect on calcium currents, and TMS only reduced LTCC at very high concentrations, and did not occlude MPS effects when applied concurrently. 5. These results, which demonstrate that anticonvulsant, but not convulsant, succinimides block LTCC, provide additional support for the hypothesis that LTCC reduction is a mechanism of action of the anticonvulsant succinimides related to their effects in petit mal epilepsy.
    背景与目标: : 1。琥珀酰亚胺衍生物可以是惊厥剂 (四甲基琥珀酰亚胺 (TMS)),也可以是抗惊厥剂 (ethosuximide (ES); Α-甲基-α-苯基琥珀酰亚胺 (MPS))。ES是一种抗惊厥药琥珀酰亚胺,以前已被证明可以阻断丘脑神经元的钙电流,而惊厥药琥珀酰亚胺TMS则以与惊厥药戊四氮 (PTZ) 相似的方式阻断 γ-氨基丁酸 (GABA) 反应。2.使用电压钳技术,我们分析了抗惊厥药琥珀酰亚胺ES和MPS以及惊厥药TMS和PTZ对大鼠急性分离的丘脑中继神经元钙电流的影响。3. MPS和ES以电压依赖性方式降低了低阈值钙电流 (LTCC),而不影响稳态失活。MPS的效力低于ES (1100的IC50与200的microM),但效力更高 (100% 的最大降低与ES的40%)。4. PTZ对钙电流没有影响,TMS仅在非常高的浓度下降低LTCC,同时使用时不会抑制MPS效应。5.这些结果表明抗惊厥药而非惊厥药琥珀酰亚胺阻断LTCC,为LTCC减少是抗惊厥药琥珀酰亚胺的作用机制与它们在小癫痫中的作用有关的假说提供了额外的支持。
  • 【抗惊厥药治疗特发性不宁腿综合征: 系统评价。】 复制标题 收藏 收藏
    DOI:10.1590/s0004-282x2008000300034 复制DOI
    作者列表:Conti CF,Oliveira MM,Valbuza JS,Prado LB,Carvalho LB,Prado GF
    BACKGROUND & AIMS: BACKGROUND:Restless legs syndrome (RLS) is a sensory motor disorder characterized by a distressing urge to move the legs and sometimes also other parts of the body usually accompanied by a marked sense of discomfort or pain in the leg or other affected body part. Many treatments have been used to minimize the discomfort of the disease, among them the anticonvulsant therapy. AIM:This review aims to evaluate the efficacy and safety of anticonvulsant treatment for idiopathic RLS. METHOD:Systematic review of randomized or quasi-randomized, double blind trials on anticonvulsant treatment for RLS. OUTCOMES:relief of RLS symptoms, subjective and objective sleep quality, quality of life, and adverse events associated with the treatments. RESULTS:A total of 231 patients were randomized in three cross over studies and one parallel study. Three studies with carbamazepine, one with sodium valproate, and one with gabapentin, and they were very heterogeneous so we could not perform a meta-analysis. CONCLUSIONS:There is no scientific evidence on RLS treatment with anticonvulsants for clinical practice.
    背景与目标:
  • 10 Maternal anticonvulsants and perinatal risk. 复制标题 收藏 收藏

    【孕产妇抗惊厥药和围产期风险。】 复制标题 收藏 收藏
    DOI:10.1016/0028-2243(75)90037-4 复制DOI
    作者列表:Ramaekers LH,The TS
    BACKGROUND & AIMS: :According to data found in the literature, children born to epileptic mothers on anticonvulsant therapy have an increased perinatal mortality rate, namely 2-3 times the average. The congenital malformations attributed to anticonvulsant drugs cannot fully account for this high mortality rate. A case is described in which a severe bleeding disorder manifested itself in successive offspring. A discussion follows in which this defect in blood coagulation in the newborn and the role played by vitamin K is considered as representing an important and preventable cause of neonatal death and morbidity. Other features of the postnatal syndrome (CNS depression, congenital heart disease, withdrawal symptoms, anemia) are mentioned in the case report. Suggested preventative measures employing vitamin K, folic acid and vitamin D are briefly discussed.
    背景与目标: : 根据文献中发现的数据,抗惊厥疗法的癫痫母亲所生的孩子围产期死亡率增加,是平均水平的2-3倍。归因于抗惊厥药物的先天性畸形不能完全解释这种高死亡率。描述了一个案例,其中严重的出血性疾病在连续的后代中表现出来。随后进行了讨论,其中新生儿的凝血缺陷和维生素k的作用被认为是新生儿死亡和发病率的重要且可预防的原因。病例报告中提到了产后综合征的其他特征 (中枢神经系统抑郁症,先天性心脏病,戒断症状,贫血)。简要讨论了使用维生素k,叶酸和维生素d的建议预防措施。
  • 【特定的小抗惊厥药可降低丘脑神经元的钙电流。】 复制标题 收藏 收藏
    DOI:10.1016/0304-3940(89)90376-5 复制DOI
    作者列表:Coulter DA,Huguenard JR,Prince DA
    BACKGROUND & AIMS: :Low-threshold calcium current (LTCC) in thalamic neurons is important in generation of normal thalamocortical rhythms, and may be involved in the genesis of abnormal activities such as spike-wave discharges that characterize petit mal epilepsy. Ethosuximide and dimethadione, anticonvulsants effective in petit mal, reduced the LTCC when applied to thalamic neurons at clinically relevant concentrations. Therapeutic concentrations of phenytoin and carbamazepine, drugs ineffective in the control of petit mal, had minimal effects on calcium conductances. Reduction in LTCC may be an important mechanism of action by which specific petit mal anticonvulsants depress spike-wave activity.
    背景与目标: : 丘脑神经元中的低阈值钙电流 (LTCC) 在正常丘脑皮质节律的产生中很重要,并且可能参与异常活动的发生,例如表征小癫痫的尖峰波放电。Ethosuximide和dimethadione,对小动物有效的抗惊厥药,当以临床相关浓度应用于丘脑神经元时,会降低LTCC。苯妥英和卡马西平的治疗浓度对控制小剂量无效的药物对钙电导的影响很小。减少LTCC可能是一种重要的作用机制,通过这种作用,特定的小抗惊厥药可抑制尖峰波活性。
  • 【脑出血的预防性抗惊厥药。】 复制标题 收藏 收藏
    DOI:10.1007/s12028-017-0385-8 复制DOI
    作者列表:Mackey J,Blatsioris AD,Moser EAS,Carter RJL,Saha C,Stevenson A,Hulin AL,O'Neill DP,Cohen-Gadol AA,Leipzig TJ,Williams LS
    BACKGROUND & AIMS: BACKGROUND AND PURPOSE:Prophylactic anticonvulsants are routinely prescribed in the acute setting for intracerebral hemorrhage (ICH) patients, but some studies have reported an association with worse outcomes. We sought to characterize the prevalence and predictors of prophylactic anticonvulsant administration after ICH as well as guideline adherence. We also sought to determine whether prophylactic anticonvulsants were independently associated with poor outcome. METHODS:We performed a retrospective study of primary ICH in our two academic centers. We used a propensity matching approach to make treated and non-treated groups comparable. We conducted multiple logistic regression analysis to identify independent predictors of prophylactic anticonvulsant initiation and its association with poor outcome as measured by modified Rankin score. RESULTS:We identified 610 patients with primary ICH, of whom 98 were started on prophylactic anticonvulsants. Levetiracetam (97%) was most commonly prescribed. Age (OR 0.97, 95% CI 0.95-0.99, p < .001), lobar location (OR 2.94, 95% CI 1.76-4.91, p < .001), higher initial National Institutes of Health Stroke Scale (NIHSS) score (OR 2.31, 95% CI 1.40-3.79, p = .001), craniotomy (OR 3.06, 95% CI 1.51-6.20, p = .002), and prior ICH (OR 2.36, 95% CI 1.10-5.07, p = .028) were independently associated with prophylactic anticonvulsant initiation. Prophylactic anticonvulsant use was not associated with worse functional outcome [modified Rankin score (mRS) 4-6] at hospital discharge or with increased case-fatality. There was no difference in prescribing patterns after 2010 guideline publication. DISCUSSION:Levetiracetam was routinely prescribed following ICH and was not associated with worse outcomes. Future investigations should examine the effect of prophylactic levetiracetam on cost and neuropsychological outcomes as well as the role of continuous EEG in identifying subclinical seizures.
    背景与目标:
  • 【接受抗惊厥药的儿童的抗核抗体和狼疮样综合征。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Singsen BH,Fishman L,Hanson V
    BACKGROUND & AIMS: Drug-induced systemic lupus erythematosus (SLE)-like syndromes in children are most commonly associated with the administration of ethosuximide, diphenylhydantoin, and trimethadione. Five children receiving ethosuximide who presented with syndromes suggestive of SLE were studied. Each and fever, malar rash, arthritis, and lymphadenopathy. Two children had pleural effusions and another developed myocarditis and pericarditis. Three patients had anti-DNA antibodies associated with low serum C3. In four of five children symptoms disappeared with the discontinuation of ethosuximide; two of these continue to have antinuclear antibodies (ANA). One child continues to have active SLE with nephritis. A group of 101 children from a seizure clinic were tested for the presence of ANA. ANA were found in 14 of 70 children receiving ethosuximide and/or diphenylhydantoin; 2 of 14 had anti-DNA antibodies. Serum ANA titers in the drug-induced SLE group did not differ significantly from those of the asymptomatic seizure patients. ANA were also present in 5 of 23 children receiving phenobarbital only. The induction of ANA by phenobarbital is a possible hypothesis. Quantitative immunoglobulins and C3 were not significantly altered in the asymptomatic children with ANA. Follow-up studies at ten months showed no asymptomatic child with ANA to have developed clinical with ANA to have developed clinical evidence of SLE. This study suggests that asymptomatic children who develop ANA should have careful observation, but need not have their anticonvulsants discontinued.

    背景与目标: 儿童药物诱导的系统性红斑狼疮 (SLE) 样综合征最常见的是使用乙硫胺,二苯乙内酰脲和三美甲二酮。研究了五名接受ethosuximide的儿童,他们出现了提示SLE的综合征。每个发热,斑疹,关节炎和淋巴结肿大。两个孩子有胸腔积液,另一个则发展为心肌炎和心包炎。三名患者的抗DNA抗体与低血清c3相关。在五名儿童中,有四名症状随着ethosuximide的停用而消失; 其中两个继续具有抗核抗体 (ANA)。一名儿童继续患有活动性系统性红斑狼疮并肾炎。对来自癫痫发作诊所的101名儿童进行了ANA的测试。在接受乙硫胺和/或二苯乙内酰脲的70名儿童中,有14名发现了ANA; 14个中有2个具有抗DNA抗体。药物诱导的SLE组的血清ANA滴度与无症状癫痫患者的血清ANA滴度无显着差异。仅接受苯巴比妥治疗的23名儿童中有5名也存在ANA。苯巴比妥诱导ANA是一个可能的假设。在无症状的ANA儿童中,定量免疫球蛋白和C3没有显着改变。10个月的随访研究显示,没有无症状的ANA患儿发展为临床的ANA并发展为SLE的临床证据。这项研究表明,患有ANA的无症状儿童应仔细观察,但不必停用抗惊厥药。
  • 【抗惊厥药而不是全身麻醉药对不同的T型电流变体具有不同的阻断作用。】 复制标题 收藏 收藏
    DOI:10.1124/mol.58.1.98 复制DOI
    作者列表:Todorovic SM,Perez-Reyes E,Lingle CJ
    BACKGROUND & AIMS: :The sensitivity to anticonvulsants and anesthetics of Ca(2+) currents arising from alpha1G and alpha1H subunits was examined in stably transfected HEK293 cells. For comparison, in some cases blocking effects on dorsal root ganglion (DRG) T currents were also examined under identical ionic conditions. The anticonvulsant, phenytoin, which partially blocks DRG T current, blocked alpha1G current completely but with weaker affinity ( approximately 140 microM). Among different cells, alpha1H current exhibited either of two responses to phenytoin. In one subpopulation of cells, phenytoin produced a partial, higher affinity block (IC(50) approximately 7.2 microM, maximum block approximately 43%) similar to that in DRG neurons. In other cells, phenytoin produced complete, but lower affinity, blockade (IC(50) approximately 138 microM, maximum block approximately 89%). Another anticonvulsant, alpha-methyl-alpha-phenylsuccinimide (MPS), blocked DRG current partially, but blocked both alpha1G and alpha1H currents completely with weaker affinity ( approximately 1.7 mM). These data suggest that higher affinity blockade of T-type currents by phenytoin and MPS may require additional regulatory factors that can contribute to native T-type channels. In contrast, anesthetics blocked all T current variants similarly and completely. Block of alpha1G current by anesthetics had the following order of potency: propofol (IC(50) approximately 20.5 microM) > etomidate ( approximately 161 microM) = octanol ( approximately 160 microM) > isoflurane ( approximately 277 microM) > ketamine ( approximately 1.2 mM), comparable with results on DRG T currents. Barbiturates completly blocked alpha1G currents with potency [thiopental ( approximately 280 microM), pentobarbital ( approximately 310 microM), phenobarbital ( approximately 1.54 mM)] similar to that in DRG cells. The effects of propofol, octanol, and pentobarbital on alpha1H currents were indistinguishable from effects on alpha1G currents.
    背景与目标: : 在稳定转染的HEK293细胞中检查了对 α1g和 α1h亚基引起的Ca(2) 电流的抗惊厥药和麻醉药的敏感性。为了进行比较,在某些情况下,还在相同的离子条件下检查了对背根神经节 (DRG) T电流的阻断作用。部分阻断DRG T电流的抗惊厥剂苯妥英完全阻断 α1g电流,但亲和力较弱 (约140微米)。在不同的细胞中,α1h电流表现出对苯妥英的两种反应之一。在一个细胞亚群中,苯妥英产生与DRG神经元相似的部分较高亲和力阻滞 (IC(50) 约7.2微米,最大阻滞约43%)。在其他细胞中,苯妥英产生完全但较低的亲和力阻断 (IC(50) 约138微米,最大阻断约89%)。另一种抗惊厥药 α-甲基-α-苯基琥珀酰亚胺 (MPS) 部分阻断DRG电流,但以较弱的亲和力 (约1.7 mM) 完全阻断 α1g和 α1h电流。这些数据表明,苯妥英和MPS对T型电流的更高亲和力阻断可能需要其他可能有助于天然T型通道的调节因素。相反,麻醉药相似且完全地阻断了所有T电流变体。麻醉剂阻断 α1g电流具有以下效力顺序: 丙泊酚 (IC(50) 约20.5微米)> 依托咪酯 (约161微米) = 辛醇 (约160微米)> 异氟烷 (约277微米)> 氯胺酮 (约1.2毫米),与DRG T电流的结果相当。巴比妥酸盐完全阻断 α1g电流,其效力 [硫喷妥钠 (约280微米),戊巴比妥 (约310微米),苯巴比妥 (约1.54毫米)] 类似于DRG细胞。异丙酚,辛醇和戊巴比妥对 α1h电流的影响与对 α1g电流的影响没有区别。
  • 【使用Technicon “FAST-LC” 系统对血清中的药物进行在线液相色谱分析: 茶碱和四种常用的抗惊厥药及其代谢产物的性能数据。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Dolan JW,van der Wal S,Bannister SJ,Snyder LR
    BACKGROUND & AIMS: We describe a new instrument for use in assay of therpeutic drugs in serum by "high-performance" liquid chromatography, the "FAST-LC" system (Technicon). Serum samples are aspirated directly into the unit, extracted with solvent, and the evaporated and redissolved extract is injected onto a chromatographic column. We illustrate the performance of the system by assays in serum for theophylline and four anticonvulsants (primidone, phenobarbital, phenytoin, and carbamazepine) plus two of their active metabolites (phenylethylmalonamide and carbamazepine epoxide). For theophylline, final chromatograms are monitored at 270 nm, at analysis rates of 10/h. Concentration and absorbance are linearly related from 0 to 130 mg of theophylline per liter. For the anticonvulsants, chromatograms are monitored at 200 nm, at analysis rates of 7.5/h. The six individual determinations are each linear beyond the therapeutic range. For both drug panels, day-to-day CV's were 4 to 6%. Results correlate well with those by enzyme immunoassay. A total sample volume of 150 microL is required.

    背景与目标: 我们描述了一种用于通过 “高效” 液相色谱法测定血清中治疗药物的新仪器,即 “FAST-LC” 系统 (Technicon)。将血清样品直接吸入装置,用溶剂提取,然后将蒸发和再溶解的提取物注入色谱柱。我们通过测定血清中的茶碱和四种抗惊厥药 (扑米酮,苯巴比妥,苯妥英钠和卡马西平) 及其两种活性代谢物 (苯乙基丙隆酰胺和卡马西平环氧化物) 来说明系统的性能。对于茶碱,在270 nm下以10/h的分析速率监测最终色谱图。浓度和吸光度从0至130毫克茶碱每升线性相关。对于抗惊厥药,在200 nm下以7.5/h的分析速率监测色谱图。六个单独的测定都是超出治疗范围的线性。对于两个药物小组,日常CV为4到6%。结果与酶免疫分析结果具有良好的相关性。需要150 microL的总样品量。

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