抗癫痫药和抗惊厥药课件

1、抗癫痫药和抗惊厥药 16药理学教研室王俊平2009.9.26抗癫痫药和抗惊厥药 16药理学教研室异常电流：Na+, K+, Ca2+脑部病灶神经阵发性异常放电，并向周围扩散，导致短暂的大脑功能障碍的一种慢性疾病。 第1节 抗癫痫药1.异常运动2.异常感觉 如何治疗？异常电流：Na+, K+, Ca2+脑部病灶神经阵发性异常放癫痫的分型癫痫分型1. 局限性 单纯局限性发作神经运动性发作2. 全身性 强直-阵挛性发作（大发作） 肌肉阵挛性发作癫痫持续状态 失神性发作（小发作）癫痫的分型癫痫分型1. 局限性抗癫痫药物的分类老药: Phenytoin Ethosuximide Carbamazepin

2、e Valproate Benzodiazepine Barbiturates 2. 新药: Topiramate Lamotrigine et al1.疗程长（数年）， 不良反应重要。2.对症选药，合理用药。抗癫痫药物的分类老药: 1.疗程长（数年），重 点：代表药物：苯妥英钠其它药物的适应征和 主要不良反应3. 各种癫痫的首选药物重 点：第2节 常用抗癫痫药物 Antiepilepsy DrugsGABANa+,K+,Ca2+ ChannelCurrent is too weak, how to do？To block them第2节 常用抗癫痫药物GABACurrent is too P

3、henytoin Sodium (Dilantin)苯妥英钠 PD 1. Na+, Ca2+ channel blocker Use-dependence （对高频放电的癫痫病灶有选择性?） 2. Inhibition of posttentanic potentiation and calmodulin神经递质的释放是否也会被抑制？Phenytoin Sodium (Dilantin) PPosttetanic potentiation(PTP):In many cells activity can affect synaptic effectiveness. In particular,

4、a train of high-frequency action potentials will be followed by a period during which each subsequent spike will produce a larger EPSP (excitatory postsynaptic potential ) than normal. This enhancement usually lasts several minutes but it can persit for 1 hr or more in some cells.Posttetanic potenti

5、ation(PTP):Phenytoin (Dilantin)Phenytoin (Dilantin)1.A: slow, F(79%), great individual differences.2.D: 0.6L/kg, whole body.3.M: Liver, Hepatoenteral Circulation T1/2=20h, Css: how many days?4.Therapeutic level: 1020g/ml Toxic level: 20 g/ml TI is samll. 5.Therapeutic drug monitoring: at least 5-7 h

6、alf-lives. PK of Dilantine1.A: slow, F(79%), great indiINDICATIONS1. Control of generalized tonic-clonic epilepsy2. Complex / Simple partial epilepsy(Tab.11?) 3. Prevention and treatment of seizures during or following neurosurgery. Absence epilepsy?INDICATIONSAbsence epilepsy?Adverse Reactions1. Do

7、se-related: IV too fast - Cardiac Arrhythmia P.O.-over dose, nystagmus, ataxia 40 g/ml mental confusion. 50 g/ml Dizziness, insomnia.2. Gingival hyperplasia (AD, 20%)3. Vitamin D deficiency rickets? 4. Hypersensitivity syndrome5. Liver Damage6. Fetal Hydantion SyndromeHow to stop?Adverse Reactions1.

8、 Dose-relatWithdral effect:Small doseIncreaseEpilepsy is controlledIf untolerableChange to another drug问题：如何停药？如何换药？Withdral effect:Small doseIncrCarbamazepine卡马西平Mechanism:Similar with DilantinGABA response increaseAll types of epilepsy including Absence epilepsyAplastic Anemia再生障碍性贫血CarbamazepineM

9、echanism:SimilarDrug InteractionPhenytoin: Plasma protein binding rate（PPBR）: 90% Liver Drug Enzyme InducerPhenylbutazone保泰松To decrease PPBR of Phenytoin对血药浓度监测有何影响？2. Carbamazepine and Phenobarbital： Liver Drug Enzyme InducerDrug InteractionPhenytoin:PhGABA-RCa2+ uptake inhibition in presynaptic me

10、mebraneAt high dose, Na+ and Ca2+ channels blockerPhenobarbital and Primidone苯巴比妥&扑米酮INDICATIONS1. Control of generalized tonic-clonic epilepsy2. Simple partial epilepsy 困倦，记忆力下降！GABA-RPhenobarbital and Primid扑痫酮为什么与苯妥英钠或卡马西平有协同作用？与苯巴比妥也协同？扑痫酮为什么与苯妥英钠或卡马西平有协同作用？Ethosuximide 乙虎胺Ca2+ channel blockThe

11、first choice forGeneralized Absence Seizures Mental DisorderClonazepam,氯硝西泮？Sodium Valproate 丙戊酸钠？Ethosuximide 乙虎胺Ca2+ channel Sodium Valproate丙戊酸钠Inhibition of GABA metabolism2. Accelerate GABA synthesis3. Increase response to GABA4. Block Na+, Ca2+ channelsAll types of epilepsyLiver ToxicitySodium ValproateInhibition of DiazepamInjection for Status EpilepticusNitrozepam硝西泮ClonicDiazepamInjection for Status ENew Agents: Lamotrigine, 拉莫三秦Topiramate， 托吡