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。     

抗癫痫药对脑发育影响的实验研究

抗癫痫药物在产生抗癫痫作用的同时,通过多种机制影响脑发育过程中神经细胞的迁移和分化、突触形成与可塑性及神经纤维髓鞘形成,增加神经细胞的凋亡,阐明AEDs对正常脑发育的影响及其机制,对于临床合理使用抗癫痫药物,促进脑功能恢复具有重要意义.     

抗癫痫药物及其对认知功能影响的研究进展

癫痫是以脑部神经元超同步化放电导致突然、反复和短暂的中枢神经系统功能失常为特征的复杂神经科临床综合征。目前临床治疗以抗癫痫药物为主,常用的抗癫痫药物分为传统的和新型的两大类,均可引起患者的认知功能障碍,并且近年来很受广大医务人员、患者及其家属的关注。本文就传统的、新型的抗癫痫药物及其对认知功能的影响、可能的机制与预防措施进行综述。     

左乙拉西坦在癫痫治疗中的作用

详细总结新型抗癫痫药物左乙拉西坦的药物代谢动力学特点、药物相互作用、抗癫痫作用机制、对成人及儿童各种不同发作类型癫痫的添加治疗及单药治疗研究进展、安全性评价及常见不良反应、特异质性不良事件、认知功能及生活质量影响。结论该药具有理想的药动学特性、较高的安全性及抗癫痫效能,对认知功能无明显损害,适应证扩大后已经可用于16岁以上人群部分性发作癫痫的单药治疗、全面性发作癫痫中某些特定发作类型的添加治疗。     

丙戊酸抗癫痫机制

丙戊酸(VPA)起初被用来治疗失神发作,近年来已经发展成为一广谱抗癫痫药(AED_(?))而广泛应用于临床。其抗癫痫机制仍在探索中,迄今为止的研究主要集中在三个方面:①增加脑部抑制性神经递质r-氨基丁酸(GABA)浓度;②加强突触后神经元对GABA的反应性;③推测VPA有直接的膜作用以降低神经元的兴奋性。 一、VPA增高脑组织GABA水平 Godln于1969年首先提出这一假说,并推测GABA的增加是GABA转氨酶(GABA-T)受抑制的结果,但     

抗癫痫药物对认知功能的影响

随着抗癫痫药物在临床上的大量应用,它所造成的认知功能的损害及损害程度是癫痫治疗中值得关注的问题。抗癫痫药物的多药联合治疗及血药浓度高增加了对认知功能的损害。并且对特殊人群的认知功能损害更明显。本文针对这些问题,综述了传统抗癫痫药物与新型抗癫痫药物在这一领域的研究进展及干预措施。     

癫痫合并认知功能障碍研究进展

认知功能障碍是癫痫常见共病,严重影响患者生活质量。近年来日益受到重视,其机制及影响因素复杂,目前尚缺乏特异有效的治疗手段,且治疗效果欠佳。因此阐明癫痫认知功能障碍的发病机制对于开发新的治疗药物具有重要意义。癫痫合并认知功能障碍的原因可能是癫痫病因、发作本身、间期放电、神经网络异常、抗癫痫药物、手术等多种因素共同作用的结果,现将对癫痫合并认知功能障碍的机制及影响因素做一综述。     

拉莫三嗪对癫痫患者认知功能影响的研究

癫痫是神经系统常见病之一,口服抗癫痫药是癫痫治疗的首选方法,药物在控制痫性发作的同时其对认知功能的影响愈来愈受到人们的关注,选择既能够控制癫痫发作又不影响患者认知功能的抗癫痫药物成为提高癫痫患者生活质量的关键所在。     

抗癫痫药物对高级神经机能的毒副作用

采用神经心理学测验方法测试抗癫痫药物对病人高级神经机能的毒副作用,近年来在国外开展较多,发现不同的抗癫痫药物对病人认知功能、情绪及行为的影响是不同的。苯妥英钠毒性最大,其次是苯巴比妥、苯并二氮(艹卓)类,而丙戊酸钠、卡马西平则相对较轻。     

传统抗癫痫药物对认知功能影响的研究进展

<正>药物是癫痫治疗的主要手段,抗癫痫药物对认知(coni- tion)功能的损害愈来愈受到临床的重视。目前约75％的癫痫患者需要抗癫痫药(antiepileptic drugs,EDs)来控制痫性发作,而AEDs对认知功能的损害不同程度地影响了患者的生存质量及其对药物的依从性。     

The effect of antiepileptic drugs on visual performance.

Visual disturbances are a common side-effect of many antiepileptic drugs. Non-specific retino- and neurotoxic visual abnormalities, that are often reported with over-dosage and prolonged AED use, include diplopia, blurred vision and nystagmus. Some anticonvulsants are associated with specific visual problems that may be related to the mechanistic properties of the drug, and occur even when the drugs are administered within the recommended daily dose. Vigabatrin, a GABA-transaminase inhibitor, has been associated with bilateral concentric visual field loss, electrophysiological changes, central visual function deficits including reduced contrast sensitivity and abnormal colour perception, and morphological alterations of the fundus and retina. Topiramate, a drug that enhances GABAergic transmission, has been associated with cases of acute closed angle glaucoma, while tiagabine, a GABA uptake inhibitor, has been investigated for a potential GABAergic effect on the visual field. Only mild neurotoxic effects have been identified for patients treated with gabapentin, a drug designed as a cyclic analogue of GABA but exhibiting an unknown mechanism while carbamazepine, an inhibitor of voltage-dependent sodium channels, has been linked with abnormal colour perception and reduced contrast sensitivity. The following review outlines the visual disturbances associated with some of the most commonly prescribed anticonvulsants. For each drug, the ocular site of potential damage and the likely mechanism responsible for the adverse visual effects is described.     

Ocular Manifestations of Crystal Methamphetamine Use

Numerous medical sequelae associated with illicit drug use have been reported. Nevertheless, there has been scarce documentation of the effects of these drugs on the eyes. Drug-induced ocular symptoms include decreased visual acuity, disturbances in perception, and even flashbacks. Methamphetamine (METH) is a highly addictive drug whose abuse has spread worldwide during the past two decades. METH abuse is associated with many adverse psychiatric and medical consequences including strokes and psychosis. METH-induced ophthalmic complications are rarely discussed but include retinal vasculitis, episcleritis, panophthalmitis, endophthalmitis, scleritis, retinopathy, corneal ulceration, and transient visual losses. Because the drug has shown a marked increase in the prevalence of its use amongst pregnant women, there has also been an increase of drug-induced complications in fetuses and newborn babies. These complications need to be further detailed and studied. Herein, the authors report on the ocular complications associated with METH abuse. They also discuss some potential mechanisms for the toxic effects of the drug on that system.     

Neuropsychological performance in HIV/AIDS intravenous drug users

It is known that HIV can directly infect the CNS and, as a result of such infection, neuropsychological alterations with cognitive, behavioural and motor manifestations can be developed. In this study we seek to determine whether seropositivity is associated with a poor neuropsychological performance in patients with a history of intravenous drug consumption (n=90). For this purpose we carried out an extensive neuropsychological evaluation and compared their performance with that of two seronegative control groups, one comprised of subjects with no history of drug abuse (n=22), which allowed us to obtain a reference of normal neuropsychological performance, and the other of seronegative subjects with a history of drug abuse (n=48), which allowed us to differentiate whether the performance of the seropositive subjects derives from their history of drug abuse. The results reveal that HIV infection in drug users is associated with deficits in attention, verbal and visual memory, verbal skills, concept formation and reasoning, visual-constructive skills, manual dexterity, and perceptive-motor speed, which cannot be attributed to a history of drug abuse. However, the seronegative drug users also showed some of these alterations, which suggests that seropositivity is not only associated with a decrease in performance in these tasks, but also adds to the alterations seen in seronegative subjects as a consequence of drug abuse.     

Palinopsia from posterior visual pathway lesions without visual field defects.

Palinopsia, or perseveration of a previously viewed image, may be caused by drug use or by posterior visual pathway lesions. Most cases of palinopsia due to visual pathway lesions have an associated homonymous hemianopic visual field defect. We report two patients with palinopsia caused by structural lesions of the posterior visual pathway in the absence of visual field defects. Patients with palinopsia should undergo neuroimaging even in the presence of normal visual fields.     

Reversed visual field constrictions in children after vigabatrin withdrawal--true retinal recovery or improved test performance only?

While vigabatrin-associated visual field constrictions have been generally considered irreversible, some case reports have raised the hope of partial improvement after drug withdrawal in occasional patients. Here we describe seven children with epilepsy, whose visual field constrictions, as demonstrated by the kinetic perimetry (Goldmann), attenuated or recovered after discontinuation of vigabatrin therapy. While this improvement may be largely due to better performance in later test sessions, we want to raise the possibility that some visual field recovery may be possible at least in young patients.     

Pharmacologic Treatment of the Catastrophic Epilepsies

Summary:  Treatment of the catastrophic epilepsies [infantile spasms (IS), Lennox-Gastaut syndrome (LGS), and progressive myoclonic epilepsy (PME)] remains a challenge to clinicians. For IS, adrenocorticotropic hormone has traditionally been the drug of choice in the United States but may be associated with serious side effects in some patients. Vigabatrin has shown promise in treating IS patients, particularly those with tuberous sclerosis. However, the drug is associated with visual field loss and is not commercially available in the United States. Newer antiepilepsy drugs (AEDs), such as zonisamide, topiramate (TPM), and lamotrigine (LTG), may be useful in patients with IS. Although LTG, TPM, and felbamate are approved in the United States for the treatment of LGS, the overall effectiveness of therapy in patients with LGS is poor. For PME, valproate is a first-line treatment. Zonisamide and levetiracetam also show promise. Supplementation with certain cofactors to correct deficiencies and increase mitochondrial function may be useful in some patients with PME, but response to such therapy is not well documented. Advances in our understanding of the etiologies, mechanisms, and genetics underlying the catastrophic epilepsies may facilitate more effective pharmacologic interventions.     

Increased visual cortical excitability in ecstasy users: a transcranial magnetic stimulation study

OBJECTIVES: To test the presence of abnormalities of visual cortical excitability in people using ecstasy as a recreational drug. METHODS: Ecstasy users and control subjects underwent single pulse transcranial magnetic stimulation (TMS) of the occipital cortex. The phosphene threshold was analysed and compared in the two groups. RESULTS: Phosphene thresholds were significantly lower in ecstasy users compared with control subjects, and were correlated negatively with frequency of ecstasy use. Frequency of use was positively correlated with the presence of visual hallucinations. The phosphene threshold of subjects with hallucinations was significantly lower than that of subjects without hallucinations. CONCLUSIONS: The use of ecstasy as a recreational drug is associated with an increased excitability of the visual cortex, possibly linked with massive serotonin release, followed by serotonin depletion, in this cortical area.     

Childhood traumas and hallucinations: an analysis of the National Comorbidity Survey

Data from the National Comorbidity Survey were used to estimate the relationship between occurrences of childhood trauma and self-reported experiences of hallucinations. Variables representing (1) childhood neglect, (2) childhood physical abuse, (3) rape under the age of 16, and (4) molestation under the age of 16 were used to predict experiences of visual, auditory and tactile hallucinations. After controlling for background variables (sex, age, depression, family history of depression, urbanicity, income, drug, and alcohol dependence), a history of childhood rape and molestation were significantly associated with visual, auditory and tactile hallucinations. Additionally, neglect was associated with visual hallucinations and physical abuse with tactile hallucinations. Experiencing multiple types of trauma was associated with increases in the likelihood of reporting each of the three types of hallucinations. Hallucinatory experiences are possible indicators of a traumatic childhood history.     

Visual field defects associated with vigabatrin therapy

OBJECTIVE: To estimate the prevalence of visual field defects in patients taking the anticonvulsant drug vigabatrin and to characterise the features of visual dysfunction found. METHODS: Thirty three unselected patients attending neurology and epilepsy clinics were identified as taking vigabatrin and asked to attend for neuro-ophthalmic evaluation. A control group of 16 patients with epilepsy unexposed to vigabatrin was also evaluated. Visual fields were examined by static perimetry using a Humphrey field analyser. Patients underwent detailed ophthalmic examination, various blood tests, and brain MRI where necessary. Visual evoked responses (VERs), electro-oculograms (EOGs), and electroretinograms (ERGs) were recorded. RESULTS: Of 31 assessable patients treated with vigabatrin, 16 (52%) had definitely abnormal visual fields, nine (29%) had fields that were inconclusive, four (13%) had normal fields, and two (6%) proved unable to cooperate with testing. In four patients some plausible cause was found for the field abnormality leaving 12 patients (39%) in whom a definite bilateral field defect was found, possibly caused by vigabatrin treatment. Of 16 control patients none had definitely abnormal fields, 12 (75%) had normal fields, and four (25%) had fields that were inconclusive. The field defects associated with vigabatrin treatment showed a characteristic pattern of concentric peripheral field loss with temporal and macular sparing. The VERs and ERGs were normal. The EOG Arden Index was reduced in patients taking vigabatrin, although this returned towards normal when vigabatrin was stopped, even in the presence of persistent field defects. Multifocal ERGs recorded in two patients were abnormal, showing marked reduction in amplitude of the peripheral focal ERG. CONCLUSIONS: Treatment with vigabatrin was associated with a high prevalence of peripheral visual field defects. This seemed to be the result of a toxic effect of vigabatrin on the retina and seemed to persist if the drug was withdrawn.     

Electro-oculography, electroretinography, visual evoked potentials, and multifocal electroretinography in patients with vigabatrin-attributed visual field constriction

PURPOSE: Symptomatic visual field constriction thought to be associated with vigabatrin has been reported. The current study investigated the visual fields and visual electrophysiology of eight patients with known vigabatrin-attributed visual field loss, three of whom were reported previously. Six of the patients were no longer receiving vigabatrin. METHODS: The central and peripheral fields were examined with the Humphrey Visual Field Analyzer. Full visual electrophysiology, including flash electroretinography (ERG), pattern electroretinography, multifocal ERG using the VERIS system, electro-oculography, and flash and pattern visual evoked potentials, was undertaken. RESULTS: Seven patients showed marked visual field constriction with some sparing of the temporal visual field. The eighth exhibited concentric constriction. Most electrophysiological responses were usually just within normal limits; two patients had subnormal Arden electro-oculography indices; and one patient showed an abnormally delayed photopic b wave. However, five patients showed delayed 30-Hz flicker b waves, and seven patients showed delayed oscillatory potentials. Multifocal ERG showed abnormalities that sometimes correlated with the visual field appearance and confirmed that the deficit occurs at the retinal level. CONCLUSION: Marked visual field constriction appears to be associated with vigabatrin therapy. The field defects and some electrophysiological abnormalities persist when vigabatrin therapy is withdrawn.