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。     

抗癫痫药的诱变性与叶酸

本文就主要抗癫痫药物:苯妥英钠,丙戊酸钠、卡马西平的诱变性与叶酸的关系作一综述。     

癫痫治疗中丙戊酸钠与苯妥英钠或卡马西平的相互作用

丙戊酸钠与苯妥英钠或卡马西平合用治疗各型癫痫90例,丙戊酸钠使苯妥英钠和卡马西平血浓度下降;丙戊酸钠和卡马西平是强有力的肝酶诱导剂,使丙戊酸钠血浓度降低。抗痫药之间的相互作用错综复杂,临床上选择单一用药,尽量避免联合用药。     

儿童癫痫及抗癫痫治疗对血脂水平影响的研究

对１１４例儿童癫痫患者的血脂水平进行监测。结果发现癫痫本身对血脂水平无影响，抗癫痫药物治疗后总胆固醇和甘油三产高，且随治疗时间的延长差异更为明显，高密度脂蛋白无变化。丙戊酸钠对血脂无影响，而苯舀英钠，苯巴比舀，卡马西平可使ＴＣ，ＴＧ明显升高。     

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。     

儿童癫痫及抗癫痫治疗对甲状腺功能影响的前瞻性研究

采用放射免疫分析法动态观察４０例儿童癫痫的甲状腺功能，结果发现癫痫本身对甲状腺功能无影响，而诱导肝酶类抗癫痫药如苯妥英钠、卡马西平、苯巴比妥可使Ｔ４降低。且随治疗时间的增长降低更明显，Ｔ３、ＴＳＨ无明显改变。丙戊酸钠对甲状腺功能无影响。提示对癫痫患儿要常规监测甲状腺功能，对同时有甲状腺疾病病史及其他可引起甲状腺功能改变的情况者，丙戊酸钠优于诱导肝酶类的抗癫痫药。     

三种主要抗癫痫药物对癫痫患儿记忆的影响

为了解抗癫痫药物对癫痫患儿记忆的影响，对４６例全面性强直一阵挛发作患儿服药前后的记忆改变进行了观察。结果表明：服药３－４个月后，在血药浓度达治疗范围的情况下，苯妥英钠组患儿记忆商较对照组低，而丙戊酸钠组和卡马西平组记忆商的相互比较及 对照组比较则无显著差异，通过分析记忆测验中不同的分测验，提示苯妥英钠影响患儿记忆，且以短时     

卡马西平联合丙戊酸钠治疗额叶癫痫的疗效研究

目的 研究丙戊酸钠和卡马西平联合治疗对额叶癫痫的临床疗效和安全性.方法 将额叶癫痫患者随机分为联合用药组(86例)和对照组(83例),联合用药组给予丙戊酸钠和卡马西平联合治疗,剂量分别为20mg(kg·d)-1、10 mg(kg·d)-1;对照组给予卡马西平治疗,随访半年.结果 联合用药组的疗效为:显效率54.7%、有效率30.2%、无效率15.1%;对照组的疗效为:显效率42.2%、有效率14.5%、无效率43.3%.两组的疗效有统计学差异.结论 丙戊酸钠和卡马西平联合治疗额叶癫痫能够明显地提高疗效,并且不良反应无明显增加,值得临床作为首选治疗方案推广应用.     

卡马西平联合丙戊酸钠与单用卡马西平治疗癫痫的疗效及不良反应对比

目的比较卡马西平联合丙戊酸钠与单用卡马西平治疗癫痫的临床疗效及不良反应。方法选择2013-01—2014-01我院收治的癫痫患者90例,随机分为观察组和对照组各45例。对照组给予单纯卡马西平治疗,观察组给予卡马西平联合丙戊酸钠治疗。对比2组患者的临床疗效及不良反应发生率。结果 (1)观察组总有效率(95.6%)明显高于对照组(82.2%),差异有统计学意义(P0.05)。(2)观察组头晕、皮疹及白细胞减少的发生率均明显低于对照组,差异有统计学意义(P0.05);而2组患者的纳差、嗜睡、脱发及耳鸣的发生率差异无统计学意义(P0.05)。结论卡马西平联合丙戊酸钠治疗癫痫,可明显提高临床疗效,减轻不良反应,值得临床推广应用。     

奥卡西平和丙戊酸钠对癫痫患者血浆同型半胱氨酸和不对称二甲基精氨酸水平的影响

目的探讨奥卡西平和丙戊酸钠对癫痫患者血浆同型半胱氨酸(Hcy)和不对称二甲基精氨酸(ADMA)水平的影响。方法选取2010—2014年我院收治的癫痫患者84例,随机分为2组,分别应用奥卡西平与丙戊酸钠单药治疗,测定患者血浆Hcy和ADMA水平并与健康人群比较。结果两种药物单药治疗的临床疗效无明显差异(P0.05),而血浆Hcy与ADMA水平明显高于健康对照组(P0.05);治疗时间与血浆Hcy与ADMA水平呈正相关(P0.05)。结论奥卡西平与丙戊酸钠均能有效治疗癫痫,缓解症状,但药物治疗会导致患者体内Hcy与ADMA水平升高,长期服用应当监测血清Hcy、ADMA指标,及时采取有效措施预防脑血管事件的发生。     

Thyroid Function with Antiepileptic Drugs

Serum thyroid hormone balance was assessed in 108 patients receiving chronic antiepileptic drug (AED) therapy. Forty-five patients were receiving carbamazepine (CBZ), 26 phenytoin (PHT), 16 CBZ-PHT, 11 valproate (VPA), and 10 CBZ-VPA. Serum thyroxine (T4) and free thyroxine (FT4) concentrations were low in patient groups receiving CBZ and/or PHT. Serum T4 concentrations were below the normal range in 24 (53.3%) CBZ patients, 11 (42.3%) PHT patients, 12 (75%) CBZ-PHT patients, and in all 10 patients (100%) receiving CBZ-VPA. Furthermore, serum levels of FT4 were below the normal range in 13 (28.9%) CBZ patients, 6 PHT (23.1%) patients, 5 (31.3%) CBZ-PHT patients, and 5 (50%) CBZ-VPA patients. Despite the decreased serum T4 and FT4 levels in these patients, serum basal and stimulated thyrotropin (TSH) concentrations were normal, except for the slightly increased basal TSH in the CBZ-VPA group. In the VPA group, the findings were different from those in other patients: T4 serum levels were unchanged and FT4, T3, and basal TSH levels increased, but stimulated TSH levels did not differ from those of the control group. The decrease in serum thyroid hormone levels during CBZ and/or PHT medication probably is caused by an accelerated hepatic plasma clearance of these hormones due to induction of hepatic microsomal enzyme systems by these AEDs. VPA, an AED with no liver enzyme-inducing properties, does not cause similar changes. The feedback mechanism is not activated, possibly because of a hypothalamic interference by CBZ and PHT.(ABSTRACT TRUNCATED AT 250 WORDS)     

托吡酯与卡马西平对成年癫痫患者甲状腺激素的影响

目的探讨托吡酯（TPM）及卡马西平（CBZ）对成年癫痫患者甲状腺激素水平的影响。方法选择新确诊的100例成年癫痫患者（50例服用TPM、50例服用CBZ）为试验组,用化学发光法测定用药前甲状腺激素水平并与40例成年健康对照进行比较；再经TPM、CBZ单药治疗3、6个月及1年后检测血中甲状腺激素水平,并与治疗前比较。结果未经治疗的癫痫患者甲状腺激素水平与正常对照组比较无显著性差异（P＞0．05）；与治疗前相比,CBZ治疗3个月、6个月及1年后的游离T4（FT4）、三碘甲状腺原氨酸（TT3）及CBZ治疗6个月及1年后的甲状腺素（TT4）显著降低（P＜0．05）,而CBZ治疗3个月的TT4与服用CBZ后各时点的游离T3（FT3）、促甲状腺素（TSH）无显著性变化（P＞0．05）；经TPM治疗后的不同时段的甲状腺激素水平与治疗前比较均无显著性差异（P＞0．05）。结论CBZ治疗可造成成年癫痫患者甲状腺激素水平的降低。癫痫本身及TPM治疗并不引起成年患者甲状腺激素水平的改变,表明TPM治疗对成年癫痫患者的甲状腺功能更安全。     

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.     

男性癫痫患者服用抗痫药物后血清性激素水平改变及其临床意义

目的 研究抗痫药物对男性癫痫患者性激素水平的影响。方法 应用放射免疫分析法和免疫放射测定分析法测定应用多种ＡＥＤｓ治疗和未经治疗的男性癫痫患者及健康对照组血清睾酮,游离睾酮,性激素结合球蛋白,雌二醇,间质细胞刺激素,滤泡刺激素的水平。结果未治疗组与正常对照组相比,各项指标均无显著差异。各治疗组与对照组相比,ＦＴ水平均显著降低,ＳＨＢＧ水平显著升高;苯妥英钠治疗组的Ｅ２水平升高;而ＴＴ,ＬＨ,ＦＳ     

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.     

Antiepileptic drugs alter reproductive endocrine hormones in men with epilepsy

Disturbances of reproductive endocrine hormones are more often found in men with epilepsy than in the general population. There is an ongoing debate whether this can be attributed to chronic use of antiepileptic drugs or to the epilepsy itself. The aim of the present study was to evaluate the degree of endocrine disturbances in men with epilepsy compared with healthy controls, and to investigate whether there was a drug-specific effect of valproate (VPA) or carbamazepine (CBZ). Men with epilepsy, 20-40 years old, having used either VPA (n = 16) or CBZ (n = 19) as monotherapy for >2 years were included and compared with age-matched controls. Men with epilepsy (VPA + CBZ) had significantly lower FSH values and higher C-peptide values compared with controls. Regarding possible drug-specific effects, the VPA treated patients had significantly higher dehydroepiandrosterone (DHEAS) levels and lower FSH and LH concentrations compared with the controls, whereas there were no differences in testosterone, testosterone/sexhormone-binding globulin (SHBG) ratio or androstenedione levels. Men on VPA also had significantly lower free carnitine/total carnitine, which may have implications for sperm motility, and also higher insulin and C-peptide concentrations. The CBZ treated patients had significantly lower testosterone/SHBG ratio than the controls. Compared with the CBZ treated patients, men on VPA had significantly higher DHEAS concentrations and lower levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) as well as a lower free carnitine/total carnitine ratio. A marked age dependency was found in all three groups regarding several of the endocrine hormones. In conclusion, drug-specific endocrine effects of VPA and CBZ were found in men with epilepsy. Long-term VPA treatment leads to significant changes in DHEAS, FSH, LH, insulin, C-peptide and carnitine ratio. Long-term CBZ treatment leads to significant lower testosterone/SHBG ratio. A strict age matching were found to be of importance in the evaluation of endocrine function in men.     

Effects of antiepileptic drugs on delivery and early childhood--comparison among mono-therapies of valproic acid, phenytoin, carbamazepine and phenobarbital

The effects of antiepileptic drugs (AED) on infants during pregnancy and delivery were studied in a total of 82 epileptic mothers on various monotherapies; 29 cases receiving valproic acid (VPA), 20 receiving phenytoin (PHT), 18 on carbamazepine (CBZ) and 15 on phenobarbital (PB). While AED serum concentrations were low in most cases of VPA, PHT and PB except for one case of VPA which exceeded therapeutic limits, concentrations were within therapeutic levels in many cases of CBZ. Conclusion: When compared with normal controls, abnormal deliveries such as caesarian section were seen more frequently in epileptic mothers under AED treatment. In addition, infants in PB cases were shown to have significantly lower mean birth length, weight and head circumference, suggesting that PB may retard fetal growth. The incidence of malformation in cases of VPA, PHT, CBZ and PB, was 10.3%, 5.0%, 0% and 6.7%, respectively. There were five types of malformation: in VPA cases, spina bifida, Siamese twins and ventricular septal defect tended to be severe, while in PHT and PB cases, cor biloculare and hypospadias respectively were observed. In cases of VPA, serum levels in the umbilical cord were found to be 150% higher than those in the mother.     

Influence of carbamazepine on serum thyroxine and triiodothyronine in patients with epilepsy

Hypothyroidism induced by anti-epileptic drug treatment gave rise to thyroid function test studies in patients treated with carbamazepine (CBZ) only. In 42 patients on long-term CBZ treatment thyroxine (T4), free T4-index (FT4I), and triiodothyronine (T3) concentrations in serum were significantly lower than in controls, while triiodothyronine uptake (T3U) and thyrotropin (TSH) concentrations did not differ between patients and controls. In 12 patients starting on CBZ, means T4, calculated FT4 and thyroxine binding globulin (TBG) were 1-5 months later reduced compared to the initial levels. Thus, CBZ reduced thyroid hormones, TBG and FT4I. A CBZ-induced increase in conversion and metabolism of the thyroid hormones could explain this effect. The normal T3U values and decreased concentrations of TBG make a competitive CBZ binding to TBG less probable. Although the thyroid hormones levels were found lowered in the patients, all remained clinically euthyroid during the study.     

Effects of Discontinuation of Phenytoin, Carbamazepine, and Valproate on Concomitant Antiepileptic Medication

We report a prospective, controlled study of the effects of the reduction and discontinuation of phenytoin (PHT) (22 patients), carbamazepine (CBZ) (23 patients), and valproate (VPA) (25 patients) with concomitant antiepileptic drugs (AEDs). The principal changes in the serum concentrations of concomitant AEDs were (a) phenobarbital (PB) concentrations decreased by a mean of 30% on discontinuation of PHT; (b) total CBZ concentrations increased by a mean of 48% and free CBZ concentrations increased by a mean of 30% on discontinuation of PHT, with no change in CBZ-10, 11-epoxide (CBZ-E) concentrations; (c) VPA concentrations increased by a mean of 19% on discontinuation of PHT; (d) VPA concentrations increased by a mean of 42% on discontinuation of CBZ; (e) ethosuximide (ESM) concentrations increased by a mean of 48% on discontinuation of CBZ; (f) PHT concentrations decreased by a mean of 26% on discontinuation of CBZ; (g) PHT free fraction decreased from a mean of 0.11 to 0.07 on discontinuation of VPA; and (h) the mean concentrations of total and free CBZ increased by a mean of 10 and 16%, respectively, on VPA discontinuation, with a concomitant mean 24% decrease in total CBZ-E and a 22% decrease in free CBZ-E. Apart from the decrease in PB concentrations on PHT discontinuation, all significant changes had occurred by 1 week after the end of AED discontinuation. The implication for clinical practice is that a serum AED concentration at this time reflects the new steady state. Free concentrations did not add any clinically useful information to that gained from analysis of total serum concentrations.     

Thyroid hormones in children on antiepileptic therapy

The aim of this study was to evaluate the thyroid function alterations in a group of epileptic children taking antiepileptic drugs (AEDs). Patients demographic data and the free throxine (fT4) and thyroid-stimulating hormone (TSH) levels at the beginning of the treatment and at the third, sixth and ninth months of AED treatment were recorded retrospectively. A total of 106 children, 59 males and 47 females, were enrolled in the study. Mean patient age was 3.7 years, ranging between 3 months and 14 years. In total, 54% of patients were on valproic acid (VPA), 16% phenobarbital (PB), 14% were on carbamazepine (CBZ), 6% were on oxcarbazepine (OXC), 5% were on levetiracetam, and 5% were on topiramate therapy. There were no significant differences in average fT4 values between the drug groups. But the mean fT4 levels of the patients on VPA therapy showed a clear decrease within the observation period. No significant difference in average TSH values between the groups was detected in the beginning and in the third and sixth month. However, in the ninth month, a significant increase in TSH values was found in the VPA group (p = 0.007). In the patients taking VPA, average TSH values rose progressively while staying within normal limits. During follow-up, thyroid dysfunction were found in 21 patients (19.6%). A statistically significant relationship was found between severe electroencephalography (EEG) findings and thyroid dysfunction (p = 0.041). It was concluded that epileptic children with severe EEG findings and using VPA could have thyroid dysfunction. These patients should be followed up closely by thyroid function tests during treatment.