苯妥英钠和丙戊酸钠预防术后癫痫的对照研究

目的　对比苯妥英钠和丙戊酸钠预防术后癫痫的作用、毒副反应以及和血药浓度的关系。方法　采用随机前瞻对照性研究 ,选择幕上开颅手术病人 ,苯妥英纳组 72例 ,丙戊酸钠组 80例 ,术前术后分别规则服用苯妥英钠和丙戊酸钠 ,监测抗癫痫药物的血药浓度和术后癫痫及毒副反应发生情况。结果　两组共 15例术后发生早期癫痫 ,10例 (10 /15 )达到有效血浓度 ;其中 ,苯妥英钠组 6例 (8 3 % )发生早期癫痫 ,2例达到有效血浓度 ,丙戊酸钠组 9例 (11 3 % )发生早期癫痫 ,8例达到有效血浓度 ;远期癫痫发作 7例中丙戊酸钠组 5例 ,苯妥英钠组 2例。苯妥英钠组 11例 (15 3 % )及丙戊酸钠组2例 (2 5 % )出现了毒副反应。经χ2 检验 ,两组术后癫痫发生率无显著性差异 ,术后未发癫痫组和癫痫发作组间药物血浓度无显著性差异 (P >0 0 5 ) ,苯妥英钠组毒副反应发生率高于丙戊酸钠组。结论　苯妥英钠和丙戊酸钠预防控制术后癫痫无差别 ,苯妥英钠毒副反应较丙戊酸钠严重。     

丙戊酸钠对苯妥英血浆浓度的影响

本文观察15例癫痫患者丙戊酸钠对苯妥英钠血浆浓度的影响。服用苯妥英钠2周后加服丙戊酸钠3周,于每周末用高压液相色谱法测定苯妥英钠血浆浓度。结果表明,在加用丙戊酸钠后1周苯妥英钠血浆浓度均值从18.74μg/ml降至12.86μg/ml,虽有下降,但仍在有效范围内。第二周又逐步回升,直至第三周接近单用苯妥英钠的水平,停用丙戊酸钠后无变化。     

丙戊酸钠相关性高血氨脑病1例报告并文献复习

目的 报告1例罕见的丙戊酸钠相关性高血氨脑病患者,探讨颅脑术后患者血丙戊酸钠药物浓度监测的价值。方法 回顾性分析1例左侧颞叶肿瘤切除术后预防性应用丙戊酸钠致高血氨脑病患者的临床资料,包括临床表现、实验室检查、影像学检查,分析意识障碍原因。结果 患者为31岁女性,体重偏轻,以发作性四肢抽搐起病,行左侧颞叶肿瘤切除术后,患者1周内逐渐出现谵妄及意识障碍,并伴肢体抽动、肢体偏瘫,加量丙戊酸钠及脱水剂甘露醇不缓解,复查头颅CT及MRI 未见明显脑干病变、大面积脑梗死、脑内弥漫性病变及再出血,检测血氨及血丙戊酸钠浓度示轻中度增高,明确病因后,停用丙戊酸钠,患者意识逐渐恢复,肢体瘫痪逐渐恢复,预后良好。结论 对应用丙戊酸钠术后预防癫痫的病人,在用药过程中注意监测血丙戊酸钠与血氨浓度,减少不良反应发生。     

53种抗癫癎中成药的成分分析

目的：检测部分抗癫痫中成药中是否含有西药抗癫痫药物的成分。方法：用高效液相色谱法测定53种抗癫痫中成药中是否含有苯巴比妥、苯妥英钠、卡马西平和丙戊酸钠。结果：83.01%中成药中测出含有苯巴比妥、苯妥英钠、卡马西平和丙戊酸。结论：市场上大量未标明含有抗癫痫西药成分的中成药,严重影响癫痫用药安全。     

卡马西平联合丙戊酸钠治疗早期癫痫的效果观察

目的观察卡马西平联合丙戊酸钠治疗早期癫痫的临床效果。方法选取我院神经内科2010-01—2012-06收治的早期癫痫患者90例,随机分成3组,每组30例,分别采取卡马西平单药治疗,丙戊酸钠单药治疗以及卡马西平联合丙戊酸钠治疗;对所有患者在治疗开始后随访半年,比较3组有效率及不良反应。结果卡马西平组总有效率66.67%,丙戊酸钠组60.67%,联合用药组93.33%,联合用药组较其他2组整体有效率均明显增高(P0.05)。3组并发症发生率比较差异无统计学意义(P0.05)。结论与单药卡马西平或者丙戊酸钠用药治疗相比,卡马西平联合丙戊酸钠治疗癫痫具有很好的效果,且不良反应发生率与单药治疗无明显差别,可作为癫痫临床治疗的常规方案。     

丙戊酸钠的应用进展

本文对丙戊酸钠的抗痫机制及用量进行了综述,详述了丙戊酸钠的临床应用,与卡马西平、苯妥英钠的相互作用及不良反应。     

丙戊酸钠直肠给药治疗儿童癲痫持续状态

本文报告丙戊酸钠直肠给药治疗7例儿童癫痫持续状态并讨论了其疗效及安全性。所有患儿对苯巴比妥、苯妥英钠和安定均无效。丙戊酸钠有效指持续性癫痫放电消失或无癫痫发作。患儿,男4例,女3例,平均年龄7.7岁(1.7～16岁),4例为全身性抽搐,2例为局限性运动性发作,1例为持续性痫性放电,丙戊酸钠剂量为9.7～20mg/kg(平均17.5mg/kg)。其最高血浓度为41～55mg/L(平均为46.4mg/L),其中有5例经丙戊酸钠直肠给药后24小时内(平均11.4小时)发作缓解。同时脑电图结果也有所改善。仅为持续性发作性放电的例6,在开始用药的头12小时内持续性痫性放电缓解。但有间歇痫性放电。3例SGOT明显增高,停药后恢复正常,疗程为1～8天(平均4.1天)。有3例患儿在持续状态控制后口服丙戊酸钠维持。     

癫痫病人丙戊酸钠血浓度监测及其临床应用

本文报告丙戊酸钠治疗各型癫痫122例,丙戊酸钠治疗各型癫痫的有效率为83％。多数患者的有效血浓度范围为30～120μg/ml,有效剂量为10～60mg/kg·d,对癫痫患者,应据其临床发作情况,有无药物不良反应,参考丙戊酸钠血浓度调整剂量。     

丙戊酸钠致高氨血症脑病性意识障碍(附5例报告)

目的 报告神经外科患者使用丙戊酸钠(sodium valproate,VPA)预防癫痫致高氨血症脑病(hyperammonemia encephalopathy,VHE)性意识障碍的临床表现、治疗.方法 回顾性分析我科丙戊酸钠致VHE出现意识障碍5例患者的临床资料,分析VHE性意识障碍患者的肝功能、血氨浓度、药物浓度、脑电图等特征性变化.结果 本组患者出现专科难以解释的急性亚急性意识障碍,血氨浓度升高,丙戊酸药物浓度及肝功能均在正常范围之内,脑电图广泛慢波增多、δ波θ波活跃、出现三相波,予以停用丙戊酸钠,同时予以精氨酸降血氨处理,血氨浓度下降,患者意识同时出现好转.结论 临床使用丙戊酸钠期间,应定期复查丙戊酸药物浓度、血氨浓度、肝功能,脑电图出现特征性变化时,要高度重视高氨血症脑病性意识障碍的存在,以免耽误病情,造成不必要的损害.     

丙戊酸钠所致夜尿症

本文报告2例癫痫儿童因丙戊酸钠治疗引起的夜尿症。例1:女孩6岁,发育正常。3岁时即能自控小便。因癫痫小发作一日10～20次,并伴有阵挛动作和自动症,给予丙戊酸钠200mg一日三次,症状明显控制,但用药第二天后每天出现夜尿,清晨血浆丙戊酸钠浓度为52.2μg/ml。将丙戊酸钠减为200mg一日二次(血浆丙戊酸钠浓度33μg/ml)后夜尿消失。例2:女孩,出生3月后即有痉挛发作。有癫痫家族遗传史。曾给予苯巴比妥5mg/kg无明显疗效。患儿3岁半时开始给予丙戊酸钠100mg一日三次,20mg/kg治疗,因用药后第三天出现夜尿而自行停药。患儿3岁时能自控小便。6岁时因服苯巴比妥每日80mg仍癫痫大发作一月1～2次,而再次给予丙戊酸钠一日三次150mg(19mg/kg)。用药后第三天夜尿复发。清晨血浆丙戊酸钠浓度为     

A comparative study of serum F protein and other liver function tests as an index of hepatocellular damage in epileptic patients

Gamma glutamyl transferase (GGT) and alkaline phosphatase (ALP) may not be sensitive indicators of hepatocellular damage in patients taking anticonvulsant drugs as raised levels may only reflect enzyme induction. Aspartate aminotransferase (AST) is a specific, but relatively insensitive marker of liver damage and has a poor correlation with liver histology. Serum F protein is found in high concentration in the liver and levels are not influenced by enzyme induction. We measured serum F protein levels in patients taking carbamazepine (CBZ) and phenytoin (PHT) as monotherapy and in patients receiving multiple drugs. We compared the results with patients taking sodium valproate (VPA). Serum F protein levels were elevated in 6%, 22% and 13% of patients receiving CBZ, PHT and VPA, respectively. Raised GGT levels were reported for both the CBZ (26%) and PHT (78%) groups. Raised ALP levels were observed in 16%, 25% and 4% of the CBZ, PHT and VPA groups, respectively. Raised levels of serum F protein in the VPA group and the absence of any associated increases in either GGT or AST may further support the suggestion that serum F protein is an indicator of hepatocellular dysfunction associated with anticonvulsant therapy. However, further correlation with liver histology is required.     

Lack of Interaction of Gabapentin with Carbamazepine or Valproate

Summary: Gabapentin (GBP) studies were conducted in patients with epilepsy receiving carbamazepine (CBZ, n= 12) or valproate (VPA, n = 14) monotherapy. The effects of GBP coadministration on steady-state CBZ or VPA concentrations and of these antiepileptic drugs (AEDs) on GBP pharmacokinetics were investigated. GBP (400 mg) was coadministered every 8 h for 3% days with CBZ or for 5 1/3 days with VPA. GBP was well tolerated. Mean steady-state plasma CBZ/CBZ-10, ll-epoxide (CBZ-E) and serum VPA concentrations before, during, and after GBP administration were not significantly different. Mean steady-state GBP pharmacokinetic parameters during CBZ or VPA coadministration were similar to steady-state parameters reported in healthy subjects. Thus, no pharmacokinetic interaction exists between CBZ or VPA and GBP. No dosage adjustment is necessary when GBP and CBZ or VPA are coadministered.     

Evaluation of the relationship between C677T variants of methylenetetrahydrofolate reductase gene and hyperhomocysteinemia in children receiving antiepileptic drug therapy

Homocysteine (Hcy) is a sulfur-containing amino acid involved in methionine metabolism. Elevated plasma Hcy concentration is a possible risk factor for vascular disease. Folate and vitamin B-12 are vitamins that are necessary for remethylization of Hcy to methionine. The methylenetetrahydrofolate reductase (MTHFR) is the key enzyme in remethylation of Hcy to methionine and supplies the required 5-methyltetrahydrofolate as the methyl donor for this reaction. It is well known that some antiepileptic drugs (AED) can lead to hyperhomocysteinemia by affecting the levels of folate and vitamin B-12. The C677T variant of MTHFR gene can also lead to hyperhomocysteinemia particularly when serum folate level is decreased. In this study, we investigated the levels of serum folate, vitamin B-12 and Hcy in epileptic patients receiving carbamazepine (CBZ) or valproic acid (VPA) as monotherapy, and we also evaluated the probable contribution of the C677T variant of MTHFR gene in hyperhomocysteinemia. A total of 93 patients with idiopathic epilepsy receiving CBZ or VPA as monotherapy were included in this study. CBZ and VPA groups consisted of 29 and 64 patients, respectively. The control group comprised 62 healthy children. We measured serum folate, vitamin B-12 and Hcy levels in each group. We found that mean serum folate level was statistically lower and mean Hcy level was higher in epileptic patients receiving CBZ or VPA when compared with those of controls'. We also determined the C677T variants of MTHFR gene (as normal, heterozygote or homozygote) in epileptic patients. We compared the variant groups for serum folate, vitamin B-12 and Hcy levels and found no significant differences among them. In conclusion, C677T variants of MTHFR gene have no contribution in hyperhomocysteinemia in epileptic patients receiving CBZ or VPA.     

抗癫痫药物四种对中青年绝经前女性骨代谢的影响

目的研究不同的常用抗癫痫药物对中青年女性骨代谢的影响。方法通过测量各组受试者的血清钙、25-羟基维生素D、碱性磷酸酶、甲状旁腺激素、胰岛素生长因子-1、胰岛素结合蛋白-3、骨密度等,分析长期单药服用不同抗癫痫药物如苯妥英钠(PHT)、卡马西平(CBZ)、丙戊酸钠(VPA)、左乙拉西坦(LEV)等对受试者骨代谢的影响。结果服用CBZ、PHT和VPA的受试者血清钙浓度低于服用LEV的受试者(P=0.002);服用PHT的受试者的ALP浓度显著高于服用CBZ、LEV和VPA的受试者(P=0.000);与LEV组相比,PHT组血清IGF-1水平降低(P=0.03);与LEV组相比,PHT组血清的IGFBP-3浓度显著降低(P=0.000)。结论抗癫痫药物会影响骨代谢,导致患者血清钙下降、骨量减低。LEV较其他抗癫痫药物对骨代谢的影响较小,但仍能造成患者碱性磷酸酶含量下降等。抗癫痫药物对中青年女性的骨代谢会产生一定影响,在临床用药过程中需监测相关指标。     

Effectiveness and tolerance of adjunctive treatment of lamotrigine and conversion to monotherapy in pediatric patients with epilepsy. Preliminary studies

The examination concerned patients with intractable epilepsy aged 9-19 years with partial seizures simple or complex, developing into generalized ones years, treated with VPA (valproate) or CBZ (carbamazepine). They received VPA or CBZ for at least 4 weeks and even with the therapeutic concentration of these drugs in blood serum in the month preceding the examination they demonstrated seizures at least twice. For a period of 8 weeks lamotrigine (LTG) was progressively added to the therapy. Both drugs were administered for at least 8 weeks in a full dose. In case of achieving a good therapeutic effect assessed on the basis of at least 50% seizure reduction the use of VPA or CBZ was gradually discontinued. In the period of 12-week observation an application of LTG monotherapy 2/3 of patients achieved 50-100% reduction of seizures. These patients improved reasoning dynamics and memorizing ability. After LTG administration EEG showed normalization of background activity and reduction of number and time of epileptic discharges.     

Reproductive effects of valproate, carbamazepine, and oxcarbazepine in men with epilepsy

BACKGROUND: Recent observations have indicated that reproductive endocrine disorders are common among women taking valproate (VPA) for epilepsy, but it is not known whether respective abnormalities develop in men taking VPA for epilepsy. Carbamazepine (CBZ) may induce endocrine disorders in men with epilepsy, but the endocrine effects of oxcarbazepine (OXC) are not known. METHODS: Reproductive endocrine function was evaluated in 90 men taking VPA (n = 21), CBZ (n = 40), or OXC (n = 29) as monotherapy for epilepsy and in 25 healthy control men. RESULTS: Twelve men (57%) taking VPA had increased serum androgen levels. The mean serum level of androstenedione was high in patients taking VPA. Serum levels of dehydroepiandrosterone sulfate were low, and serum concentrations of sex hormone-binding globulin (SHBG) were high in men taking CBZ. The endocrine effects of OXC seemed to be dose-dependent, because serum hormone levels were normal in patients with low OXC doses (< 900 mg/day), but serum concentrations of testosterone, gonadotropins, and SHBG were high in patients with a daily OXC dose > or = 900 mg. CONCLUSIONS: VPA increases serum androgen concentrations in men with epilepsy. The endocrine effects of CBZ and OXC were different, because CBZ appears to decrease the bioactivity of androgens, whereas OXC does not.     

Early and persistent increase in serum lipoprotein (a) concentrations in epileptic children treated with carbamazepine and sodium valproate monotherapy

PURPOSE: The aim of this study was to investigate by a prospective, self-controlled method, whether treatment with carbamazepine (CBZ) and sodium valproate (VPA) monotherapy may alter serum lipoprotein (a) [Lp(a)] concentrations in epileptic children. METHODS: Serum Lp(a) concentrations have been determined in 18 epileptic children before and at 6, 12 and 24 months of treatment with CBZ monotherapy and in 30 epileptic children before and at 6, 12 and 24 months of treatment with VPA monotherapy. Serum total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoproteins A-I and B concentrations and serum concentrations of biochemical markers of liver and renal function were also measured in the study participants. RESULTS: Serum Lp(a) concentrations were significantly increased at 6, 12 and 24 months of CBZ and VPA monotherapy. There were no significant correlations between serum Lp(a) and serum lipids, lipoproteins, apolipoproteins, concentrations of biochemical markers of liver and renal function or antiepileptic-drugs concentrations. CONCLUSIONS: Children who receive CBZ or VPA monotherapy may have significant and persistent increase in serum lipoprotein (a) concentrations, occuring early in the course of therapy. It may be useful to measure serum Lp(a) concentrations routinely in epileptic children taking these antiepileptic drugs, especially in those that are already at higher atherosclerotic risk.     

Studies on the pharmacokinetics of total and free valproate in mono- and bitherapy with carbamazepine in epileptic children and adolescents

The aim of this study was to obtain a pharmacokinetic calculation for valproic acid (VPA) and its free fraction in 50 children and adolescents (4-18 years) treated for epilepsy in VPA monotherapy and bitherapy with carbamazepine (CBZ). The diurnal fluctuation of serum concentration of total and free VPA during monotherapy was observed. The additional antiepileptic medication of VPA and CBZ was connected with prominent diurnal free VPA serum fluctuations. Pharmacokinetic parameters of total and free VPA in monotherapy were significantly different. The change of free and total VPA pharmacokinetics during bitherapy with CBZ was observed, too. No changes in half-life time of VPA in mono- and bitherapy were noticed. The variability of pharmacokinetic parameters of free VPA suggests the need for monitoring unbound VPA plasma concentrations during bitherapy with CBZ.     

Thyroid function in men taking carbamazepine, oxcarbazepine, or valproate for epilepsy

PURPOSE: Antiepileptic drugs (AEDs) may affect serum thyroid hormone concentrations. This study aimed to evaluate thyroid function in men taking carbamazepine (CBZ), oxcarbazepine (OCBZ), or valproate (VPA) for epilepsy. METHODS: Ninety men with epilepsy (40 taking CBZ, 29 taking OCBZ, and 21 taking VPA monotherapy) and 25 control subjects participated in the study. After clinical examination, a blood sample for hormone, gamma-glutamyl-transferase (GGT) and antibody (ab) assays was obtained. RESULTS: Serum thyroxine (T4) and free thyroxine (FT4) concentrations were low in men taking CBZ or OCBZ. Forty-five percent of men taking CBZ and 24% of men taking OCBZ had serum T4 and/or FT4 levels below the reference range. However, no correlations were found between T4 or FT4 and GGT concentrations in men taking CBZ or OCBZ. Thirteen percent of men taking CBZ, 17% of men taking OCBZ, and 6% of control men had increased levels of thyroid peroxidase (TPO)-ab and/or thyroglobulin (TG)-ab, but these were not associated with altered serum thyroid hormone concentrations. Serum triiodothyronine and thyrotropin levels in men taking CBZ or OCBZ were normal. In men taking VPA, the concentrations of thyroid hormones, thyrotropin, and antithyroid ab were normal. CONCLUSIONS: Serum thyroid hormone concentrations are low in CBZ- or OCBZ-treated men. However, these low levels do not seem to be due to liver enzyme induction or activation of immunologic mechanisms. Therefore, interference with hypothalamic regulation of thyroid function by CBZ and OCBZ seems possible. VPA does not have any significant effects on thyroid function.     

UrinaryN-acetyl-β-glucosaminidase and guanidinoacetic acid levels in epileptic patients treated with anti-epileptic drugs

We investigated potential renal functional impairment induced by chronic use of anti-epileptic drugs (AEDs) in 79 epileptic children. They were divided into five groups: valproic acid (VPA) monotherapy where the serum concentration (SC) of VPA was no less than 60 μg/ml (VPA [SC≥ 60]) (15 cases), VPA monotherapy where the SC VPA was less than 60 μg/ml (VPA [SC< 60]) (29 cases), phenobarbital monotherapy (PB) (7 cases), carbamazepine monotherapy (CBZ) (16 cases), and polytherapy containing VPA (12 cases). Urinalysis (proteinuria and hematuria) and serum creatinine were normal except for two cases of proteinuria and two cases of hematuria. The level of urinary excretion of N-acetyl-β-glucosaminidase (u-NAG) was high in 29% of all patients, and 47% of VPA (SC≥ 60), 38% of CBZ, 25% of polytherapy, and 24% of VPA (SC< 60) groups. There was a significant positive correlation between serum concentration of VPA and u-NAG/urinary creatinine (u-Cr). The level of guanidinoacetic acid (u-GAA) excreted in the urine was normal except in one patient. U-NAG/u-Cr may be a more sensitive marker than u-GAA/u-Cr for renal functional impairment in AED therapy.