抗癫癎药物对内分泌系统及妊娠的影响

疾病状态的药物干预是内科治疗的重要方法之一，药物疗效和安全性在疾病治疗中具有同等重要的作用。对于癫癎这一慢性脑疾病而言，由于患者需要接受长期的药物治疗，故其安全性显得尤为重要。自Isojarvi报告丙戊酸（VPA）可引起女性癫癎患者生殖内分泌系统功能失调后，有关抗癫癎药物（AEDs）对内分泌系统的影响即成为癫癎药物治疗研究的焦点。     

抗癫药物对血液系统的影响

抗癫痫药物(AEDs)对血液系统中的各种成分几乎均有影响,包括白细胞、血小板计数减少,以及血小板黏附或聚集障碍、淋巴细胞增多或减少、淋巴瘤样改变、短暂性纯红细胞发育障碍、再生障碍性贫血、类白血病反应、平均红细胞压积(HCT)增加、大红细胞症、溶血性贫血、凝血因子减少、出凝血时间延长等。这些患者治疗前实验室检查各项血清学指标均于正常值范围,且停药后可恢复至正     

新型抗癫药物在我国的应用

癫痫的治疗目前仍以药物治疗为主。在过去的10余年中,有许多新药在中国上市并应用于临床,逐渐成为国内治疗癫痫的重要手段,尤其是耐药性癫痫的治疗。理想的抗癫痫药物(AEDs)一般应该具备以下条件:(1)比一线传统抗癫痫药物疗效更佳。(2)无严重不良反应。(3)无明显耐药性。(4)呈线性药代动力学,吸收迅速,清除完全,血浆蛋白结合率低。(5)能够迅速透过血-脑脊液屏障进入中枢神经系统,半衰期长。(6)使用简单,可以口     

抗癫药物的皮肤不良反应

癫痫(epilepsy)是中枢神经系统常见病和多发病,流行病学调查显示,其患病率约为0.70%,全球范围内约有5000万例癫痫患者。目前,抗癫痫药物(AEDs)仍是有效控制癫痫发作的主要手段,临床常用抗癫痫药物主要包括丙戊酸(VPA)、苯巴比妥(PB)、地西泮(DZP)、托吡酯(TPM)、拉莫三嗪(LTG)、左乙拉西坦(LEV)、苯妥英(PHT)、卡马西平(CBZ)、加巴喷丁(GBP)、乙琥胺(ESX)、奥卡西平(OXC)、噻加宾(TGB)和普瑞巴林(PGB)等。皮     

抗癫药物性脑病

许多抗癫痫药物(AEDs)在治疗过程中均可诱发与治疗药物相关的脑病,此为中枢神经系统毒性作用,甚者可导致死亡。各种抗癫痫药物导致脑病的机制和临床表现各异,但其共同的特点表现为:(1)反应迟钝。(2)精神迟滞甚至恍惚。(3)意识障碍。(4)无诱发因素的癫痫发作显著增加。(5)脑电图背景活动变慢,棘波发放增多。(6)减药或停药后     

抗癫药物的心血管系统不良反应

几乎所有抗癫痫药物(AEDs)都是针对细胞膜或突触膜上钠、钾、钙离子通道,以及参与信号转导的神经递质或调质如γ-氨基丁酸(GABA)等而发挥抗癫痫作用。细胞膜是人体基本功能单位,抗癫痫药物在通过细胞膜离子通道发挥抗癫痫作用的同时,也可能影响细胞膜的生理功能,从而出现药物不良反应,而对心血管系统的影响,则是抗癫痫药物最为重要的不良反应之一。     

抗癫药物不良反应:一个值得关注的问题

抗癫痫药物的不良反应是与其抗癫痫发作效应共存而有害的药理反应。一般发生于剂量过大、血药浓度超过治疗范围时,亦可出现于任何剂量范围内。急性不良反应多系与药物剂量无关的特异性体质所致,慢性不良反应则与药物蓄积有关;轻微不良反应对人体无明显不良影响,严重者则可危及生命。一、抗癫痫药物的不良反应与疗效抗癫痫药物不良反应的发生率与药物治疗的目的不同有关。完全控制癫痫发作是抗癫痫药物     

抗癫癎药物对血液系统的影响

抗癫癎药物（AEDs）对血液系统中的各种成分几乎均有影响，包括白细胞、血小板计数减少，以及血小板黏附或聚集障碍、淋巴细胞增多或减少、淋巴瘤样改变、短暂性纯红细胞发育障碍、再生障碍性贫血、类白血病反应、平均红细胞压积（HCT）增加、大红细胞症、溶血性贫血、凝血因子减少、血凝血时间延长等。     

新型抗癫癎药物在我国的应用

癫癎的治疗目前仍以药物治疗为主。在过去的10余年中,有许多新药在中国上市并应用于临床,逐渐成为国内治疗癫癎的重要手段,尤其是耐药性癫癎的治疗。理想的抗癫癎药物（AEDs）一般应该具备以下条件：（1）比一线传统抗癫癎药物疗效更佳。（2）无严重不良反应。（3）无明显耐药性。     

抗癫癎药物的皮肤不良反应

癫癎（epilepsv）是中枢神经系统常见病和多发病,流行病学调查显示,其患病率约为0．70％,全球范围内约有5000万例癫癎患者。目前,抗癫癎药物（AEDs）仍是有效控制癫癎发作的主要手段,临床常用抗癫癎药物主要包括丙戊酸（VPA）、苯巴比妥fPB）、地西泮（DZP）、托毗酯（TPM）、拉莫三嗪（LTG）、左乙拉西坦（LEV）、苯妥英（PHT）、卡马西平（CBZ）、加巴喷丁（GBP）、乙琥胺（ESX）、奥卡西平（OXC）、噻加宾（TGB）和普瑞巴林（PGB）等。     

Effects of antiepileptic drugs on reproductive endocrine function,sexual function and sperm parameters in Chinese Han men with epilepsy

The effects of the antiepileptic drugs sodium valproate (VPA) and levetiracetam (LEV) on reproductive endocrine function, sexual function, and spermatozoa were explored, together with their possible etiological mechanisms, in Chinese Han men with epilepsy. Following VPA treatment (n = 32), luteinizing hormone and follicle-stimulating hormone levels were significantly lower than in controls (n = 30). The bioactive testosterone/luteinizing hormone ratio and the prolactin level were significantly elevated in the VPA treatment group. There were no significant differences in these hormones between the LEV treatment (n = 20) and control groups. The rates of sperm morphologic abnormality (head, body, and tail) were significantly higher in the VPA treatment group than the control group but did not differ significantly between the LEV treatment and control groups. The sperm motility rate was significantly lower in the VPA treatment group (grade A sperm motility rate <25%, grade A + B sperm motility rate <50%) than in controls, as well as in the LEV treatment group (grade A sperm motility rate <25%). Patients in the VPA and LEV treatment groups had lower scores on questions 1, 2 and 3 of a simplified International Index of Erectile Function Scale than controls, but no significant difference on questions 4 or 5. The total International Index of Erectile Function Scale scores were significantly lower in the VPA and LEV treatment groups. We conclude that treatment with VPA adversely affects reproductive endocrine function, sperm parameters and sexual function to varying degrees in Chinese men with epilepsy.     

Effects of the antiepileptic drugs on peripheral nerve function

Objective –  We aimed to compare the effects of antiepileptic drugs and provide findings of peripheral nerve impairment using standard electrophysiological techniques.
Materials and methods –  Young adult outpatients with epilepsy on monotherapy for no less than 6 months with carbamazepine (CBZ), valproic acid (VPA), oxcarbazepine (OXC) and topiramate (TPM) were examined. Patients who had any other disease that could effect nerve conduction studies and who had neuropathic symptoms were excluded.
Results –  Each group contained 15 patients and 20 healthy subjects were examined as the control group. Prolonged latency of median sensory nerve ( P  =   0.004), ulnar sensory nerve ( P  =   0.01) and sural nerve ( P  =   0.003) with a diminished nerve conduction velocity was observed in the CBZ group ( P  =   0.014, P  =   0.002, P  =   0.025, respectively). No correlation was found between VPA, OXC and TPM and the nerve conduction studies ( P  >   0.05).
Conclusions –  Valproic acid, oxcarbazepine and topiramate don't have effects on nerve conduction studies. Mild electrophysiological changes contribute to carbamazepine therapy.     

Effect of antiepileptic drugs on thyroid function

Abstract Chronic treatment with antiepileptic drugs (AED) is known to reduce serum thyroid hormone levels. Serum thyrotropin (TSH) level is unchanged despite low thyroxine (T₄) level. We studied serum tri-iodothyronine (T₃), T₄ and TSH in 30 epileptic patients prior to discontinuation and 2, 4, 8 and 16 weeks after AED discontinuation. One AED was discontinued in each patient. Serum T₃ levels were reduced consistently after AED discontinuation. Serum T₄ and rT₃ levels were increased, but not persistently. Serum TSH levels were unchanged. Our results suggest that during AED treatment serum T₃ level was increased. This could be an increased conversion of T₄ to T₃. An acceleration of thyroid hormones degradation by enzyme induction is physiologically balanced by an increased conversion of T₄ to T₃.     

抗癫痫药物对脑胶质瘤患者手术后认知功能的影响

目的 分析抗癫痫药物对脑胶质瘤患者手术后认知功能的影响。方法 选取2018年1月—2021年1月在攀枝花市攀钢集团总医院显微镜下手术治疗的94例脑胶质瘤患者的临床资料。依据患者的癫痫病史及治疗情况分组,A组（n=37）为有癫痫发作病史且使用抗癫痫药物治疗≥3个月者,B组（n=57）为无癫痫发作病史且仅术后预防性使用抗癫痫药物者。比较两组治疗前后脑电图各频段功率、P300、认知功能和韦氏成人智力量表等数据。结果 两组治疗前后不同时间点及组间脑电图各频段功率比较,差异有统计学意义（P<0.05）,与B组相比,A组脑电图θ、δ、θ+δ功率较高,相对认知功能较差。两组治疗前后不同时间点及组间P300比较,差异有统计学意义（P<0.05）,与B组相比,A组P300较长,相对认知功能较差。两组治疗前后不同时间点及组间各项认知功能评分比较,差异有统计学意义（P<0.05）,与B组相比,A组各项认知功能评分较低,相对认知功能较差。两组治疗前后不同时间点及组间各项韦氏成人智力量表评分比较,差异有统计学意义（P<0.05）,与B组相比,A组各项韦氏成人智力量表评分较低,相对认知功能较差。结论 有癫痫发作病史且使用抗癫痫药物治疗的脑胶质瘤患者手术后相对认知功能较差,术前应用抗癫痫药物是否会损伤术后认知功能尚不能确定。 [国际神经病学神经外科学杂志, 2022, 49(3): 36-40.]     

Effects of antiepileptic drugs on thalamocortical excitability.

Comparative effects of anticonvulsant drugs on the thalamocortical system were analyzed quantitatively. Paired stimuli were delivered to the ventrolateral thalamus with evoked responses recorded from the ipsilateral sensorimotor cortex in the cat. Threshold and excitability profiles were developed with an on-line computer. Effects of phenytoin and diazepam were generally similar, with depression of excitability and slight elevation of thresholds. Ethosuximide produced a pronounced pair-interval dependent effect of unchanged or increased excitability and lowered threshold at shorter intervals, with depressed excitability and raised threshold at longer intervals. These data demonstrate a marked difference in effect of the petit mal and grand mal agents tested and suggest a basis for the effectiveness of ethosuximide in controlling 3-per-second repetitive activity.     

Reversible effects of antiepileptic drugs on reproductive endocrine function in men and women with epilepsy--a prospective randomized double-blind withdrawal study

PURPOSE: Epilepsy, antiepileptic drugs (AEDs), and reproductive endocrine function have complex interactions. In this study, we wanted to investigate the effects of AEDs on reproductive endocrine function after withdrawal of AEDs and look for reversible endocrine effects. METHODS: The study was prospective, randomized, and double-blinded. A total of 160 patients were included and randomized to withdrawal or not and 150 (80 females, 53%) patients went through the intervention and was included in the study for 12 months. Complete serum samples from before and 4 months after completed withdrawal/no withdrawal were obtained from 130 patients (63 females, 48%). RESULTS: The main finding was that reversible endocrine changes in sex steroid hormone levels could be observed in both sexes after withdrawal of AEDs. For CBZ, which was the drug used by the majority of the patients, withdrawal led to significant increases in serum testosterone concentrations and free androgen index (FAI) in both men (n = 19) and women (n = 19). Mean differences in change in FAI between the withdrawal group and nonwithdrawal group were in men 17.49 (CI 10.16-24.81, p 相似文献   

Effects of topiramate versus other antiepileptic drugs on the cognitive function of patients with epilepsy

BACKGROUND: Only very large dose of topiramate has neurotoxicity, indicating that topiramate has low neurotoxicity and high safety. The residual rate of topiramate is affected by many cognitive-related adverse effects. Patients who take topiramate often accompany with thought slowness, difficulty in finding words, dyscalculia, blunt reaction, attention decreasing, memory deterioration, etc. OBJECTIVE: To compare the effects of topiramate with traditional anti-epileptic drugs (including carbamazepine and Valproic acid (VPA) on cognitive function of patients with epilepsy. DESIGN: Observational experiment, self-control and intergroup comparison. SETTING: Sichuan Academy of Medical Science. PARTICIPANTS: Eighty-seven inpatients and outpatients with newly diagnosed epilepsy who received preliminary diagnosis and follow-up in the Department of Neurology, Sichuan People's Hospital between January 2004 and June 2006 were involved in this survey. They were diagnosed according to disease history and electroencephalogram (EEG). The onset type was diagnosed following the definition of epilepsy and epileptic syndrome in 1989 International Anti-epileptic League. The involved patients and their relatives were informed of detection and therapeutic regimen. The patients were assigned into two groups according to table of random digit: traditional antiepileptic drugs group (AEDs group, n =44) and topiramate (TPM) group (n =43). METHODS: ①Among the patients in AEDs group, carbamazepine was the first choice for 21 patients with partial seizures or partial secondarily generalized seizures, and VPA for 23 patients with generalized seizures. The initial dose of carbamazepine was 300 mg/d, and that of VPA was 500 mg/d. Patients in the TPM group took TPM with the initial dose of 25 mg/d, increased by 25 mg/d each week to target dose 150 mg/d within 8 weeks. ② Curative effect was graded into 4 degrees: markedly effective, effective, ineffective and aggravated. Total effective rate was calculated. ③ Cognitive function of patients was tested before and 6 months after administration by using Wechsler Adult Intelligence Scale(WAIS) or Wechsler Intelligence Scale for Children (WISC, Chinese edition), (Higher scores indicated better cognitive function), Stroop color word interference, test of memory of past numbers, test of telling the names of fruits and vegetables within 1 minute (Shorter time for reading word, telling color and memory of past numbers demonstrated better cognitive function. Less errors in reading words, telling colors and memory of past numbers, numbering and telling the names of fruits and vegetables within 1 minute indicated better cognitive function), etc. totally 22 items. ④ t test and paired t test were used for measurement data. MAIN OUTCOME MEASURES: Clinical curative effects and adverse reactions as well as neurological tests. RESULTS: Eighty-four pationts praticipated final analysis and 3 dropped out. ① Inthe AEDS group and TPM group, total effective rate was 86% and 99%, respectively. ② In the AEDs group, there were no significant changes in the scores of each test of WIS before and after treatment (P > 0.05). In the TPM group, total IQ, word scores, verbal IQ and digit span scores were significantly decreased （t =2.097–4.423，P < 0.05–0.01）.Following treatment, the time for reading word and telling color for patients in the AEDs group was prolonged in Stroop color interference test（t =–2.304，–2.454，P < 0.05）, and time for reading word and memory of past numbers for patients in the topiramate group was significantly prolonged （t =–3.054，2.272，P < 0.01，0.05）. ③There were no significant differences in scores of WIS before and after treatment in AEDs group and TPM group (P > 0.05). Following treatment, verbal IQ, word scores, total IQ, digit span of patients in the TPM group were significantly lower than those in the AEDs group（t =2.052–3.297，P < 0.05–0.01）.There were no significant differences in Stroop color word interference, memory of past numbers and telling the names of fruits and vegetables within 1 minute before and after treatment in AEDs group and TPM group (P > 0.05). CONCLUSION: ① Moderate and small doses of both TPM and AEDs may lead to mild cognitive function impairment of patients, mainly presenting delayed reaction and decreased sensitivity. ②TPM mainly influences attention, language comprehension ability and fluency, while AEDs cause delayed reaction easily, but influence executive function mainly.     

Effects of topiramate versus other antiepileptic drugs on the cognitive function of patients With epilepsy

BACKGROUND： Only very large dose of topiramate has neurotoxicity, indicating that topiramate has low neurotoxicity and high safety. The residual rate of topiramate is affected by many cognitive-related adverse effects. Patients who take topiramate often accompany with thought slowness, difficulty in finding words, dyscalculia, blunt reaction, attention decreasing, memory deterioration, etc. OBJECTIVE： To compare the effects of topiramate with traditional anti-epileptic drugs （including carbamazepine and Valproic acid （VPA） on cognitive function of patients with epilepsy. DESIGN： Observational experiment, self-control and intergroup comparison. SETTING： Sichuan Academy of Medical Science. PARTICIPANTS： Eighty-seven inpatients and outpatients with newly diagnosed epilepsy who received preliminary diagnosis and follow-up in the Department of Neurology, Sichuan People＇s Hospital between January 2004 and June 2006 were involved in this survey. They were diagnosed according to disease history and electroencephalogram （EEG）. The onset type was diagnosed following the definition of epilepsy and epileptic syndrome in 1989 International Anti-epileptic League. The involved patients and their relatives were informed of detection and therapeutic regimen. The patients were assigned into two groups according to table of random digit： traditional antiepileptic drugs group （AEDs group, n =44） and topiramate （TPM） group （n =43）. METHODS： （1）Among the patients in AEDs group, carbamazepine was the first choice for 21 patients with partial seizures or partial secondarily generalized seizures, and VPA for 23 patients with generalized seizures. The initial dose of carbamazepine was 300 mg/d, and that of VPA was 500 mg/d. Patients in the TPM group took TPM with the initial dose of 25 mg/d, increased by 25 mg/d each week to target dose 150 mg/d within 8 weeks. （2） Curative effect was graded into 4 degrees： markedly effective, effective, ineffective and aggravated. Total effective rate was calculated. （3） Cognitive function of patients was tested before and 6 months after administration by using Wechsler Adult Intelligence Scale（WAIS） or Wechsler Intelligence Scale for Children （WISC, Chinese edition）, （Higher scores indicated better cognitive function）, Stroop color word interference, test of memory of past numbers, test of telling the names of fruits and vegetables within 1 minute （Shorter time for reading word, telling color and memory of past numbers demonstrated better cognitive function. Less errors in reading words, telling colors and memory of past numbers, numbering and telling the names of fruits and vegetables within 1 minute indicated better cognitive function）, etc. totally 22 items. （4） t test and paired t test were used for measurement data. MAIN OUTCOME MEASURES： Clinical curative effects and adverse reactions as well as neurological tests. RESULTS： Eighty-four pationts praticipated final analysis and 3 dropped out. （1） Inthe AEDS group and TPM group, total effective rate was 86% and 99%, respectively. （2） In the AEDs group, there were no significant changes in the scores of each test of WIS before and after treatment （P 〉 0.05）. In the TPM group, total IQ, word scores, verbal IQ and digit span scores were significantly decreased （ t =2.097 - 4.423, P 〈 0.05 - 0.01 ） .Following treatment, the time for reading word and telling color for patients in the AEDs group was prolonged in Stroop color interference test （ t = - 2.304, - 2.454, P 〈 0.05 ）, and time for reading word and memory of past numbers for patients in the topiramate group was significantly prolonged （ t = - 3.054, 2.272, P 〈 0.01, 0.05 ）. （3）There were no significant differences in scores of WIS before and after treatment in AEDs group and TPM group （P 〉 0.05）. Following treatment, verbal IQ, word scores, total IQ, digit span of patients in the TPM group were significantly lower than those in the AEDs group （t =2.052 - 3.297, P 〈 0.05- 0.01 ） .There were no significant differences in Stroop color word interference, memory of past numbers and telling the names of fruits and vegetables within 1 minute before and after treatment in AEDs group and TPM group （P 〉 0.05）. CONCLUSION： （1） Moderate and small doses of both TPM and AEDs may lead to mild cognitive function impairment of patients, mainly presenting delayed reaction and decreased sensitivity. （2）TPM mainly influences attention, language comprehension ability and fluency, while AEDs cause delayed reaction easily, but influence executive function mainly.     

The effect of antiepileptic drugs on thyroid function in children

BackgroundLimited and conflicting data exist for the influence of antiepileptic drugs on thyroid function in children.ObjectiveThe aim of this study was to investigate the effects of phenobarbital, valproate, carbamazepine, oxcarbazepine, and levetiracetam monotherapy on thyroid function in daily clinical practice during a 12-month treatment period.MethodA total of 223 children (103 females and 120 males) with new onset and controlled epilepsy treated with valproate (n = 129), phenobarbital (n = 33), carbamazepine (n = 36), oxcarbazepine (n = 14), levetiracetam (n = 11) were enrolled in the study. Serum free thyroxine (fT4) and thyroid-stimulating hormone (TSH) levels were measured before and at first, sixth and twelfth months of therapy.ResultsAt baseline, average fT4 and TSH concentrations were not different between the drug groups. Valproate-treated patients had decreased fT4 and increased TSH levels at months 1, 6, and 12. Carbamazepine-treated patients had decreased fT4 levels at months 1, 6, and 12 and increased TSH levels at months 1, and 6. Phenobarbital-treated patients had decreased fT4 levels at months 1, and 6, and increased TSH levels at months 6 and 12. Oxcarbazepine-treated patients had decreased fT4 levels at month 1. Levetiracetam-treated patients showed no significant change of fT4 and TSH at any times. The frequency of subclinical hypothyroidism at month 12 was 28% in valproate, 21.4% in oxcarbazepine, 18.2% in phenobarbital, 13.9% in carbamazepine, and 0% in levetiracetam groups.ConclusionOur data suggest that all antiepileptic drugs studied except levetiracetam had varying degrees of deleterious effects on thyroid function.     

Interactions between antiepileptic drugs,and between antiepileptic drugs and other drugs

Interactions between antiepileptic drugs, or between antiepileptic drugs and other drugs, can be pharmacokinetic or pharmacodynamic in nature. Pharmacokinetic interactions involve changes in absorption, distribution or elimination, whereas pharmacodynamic interactions involve synergism and antagonism at the site of action. Most clinically important interactions of antiepileptic drugs result from induction or inhibition of drug metabolism. Carbamazepine, phenytoin, phenobarbital and primidone are strong inducers of cytochrome P450 and glucuronizing enzymes (as well as P‐glycoprotein) and can reduce the efficacy of co‐administered medications such as oral anticoagulants, calcium antagonists, steroids, antimicrobial and antineoplastic drugs through this mechanism. Oxcarbazepine, eslicarbazepine acetate, felbamate, rufinamide, topiramate (at doses ≥200 mg/day) and perampanel (at doses ≥8 mg/day) have weaker inducing properties, and a lower propensity to cause interactions mediated by enzyme induction. Unlike enzyme induction, enzyme inhibition results in decreased metabolic clearance of the affected drug, the serum concentration of which may increase leading to toxic effects. Examples of important interactions mediated by enzyme inhibition include the increase in the serum concentration of phenobarbital and lamotrigine caused by valproic acid. There are also interactions whereby other drugs induce or inhibit the metabolism of antiepileptic drugs, examples being the increase in serum carbamazepine concentration by erythromycin, and the decrease in serum lamotrigine concentration by oestrogen‐containing contraceptives. Pharmacodynamic interactions between antiepileptic drugs may also be clinically important. These interactions can have potentially beneficial effects, such as the therapeutic synergism of valproic acid combined with lamotrigine, or adverse effects, such as the reciprocal potentiation of neurotoxicity observed in patients treated with a combination of sodium channel blocking antiepileptic drugs.