抗癫痫药和抗惊厥药专业知识专家讲座.pptx

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,The characteristic event of epilepsy is the,seizure(often associated with a convulsion),which is caused by abnormal high-frequency discharge of some group of neurons,starting locally and spreading to a varying extent to affect other part of the brain.Current drug therapy is effective in 70%80%of patients.,第一节,抗癫药,Epilepsy,抗癫痫药和抗惊厥药专业知识专家讲座,第1页,各种病因引发,长久重复发作性大脑功效失调。,其,特征,为发作时大脑局部病灶神经元突发性异常高频放电并向周围组织扩散，出现短暂大脑功效失调,。,表现,为突然发作,性短暂运动、感觉、意识和植物神经功效异常,可伴有脑电图改变。癫,治疗,应长久用药，以降低或预防发作，但不能根治。,癫,抗癫痫药和抗惊厥药专业知识专家讲座,第2页,Table 16-1(1),Types of Epilepsy and,Anti-epileptic Drugs,types of epilepsy,clinical features,anti-epileptic drugs(*preferred),partial seizures,1.simple partial seizures,involuntary muscle contraction and abnormal sensory experience without loss of consciousness,seizures lasting for 2060 sec;,carbamazepine*,valproate,clonazepam,phenytoin,phenobarbital,primidone,antiepilepsirine,lamotrigine;,plex partial seizures(,psychomotor epilepsy),conscious disturbance and psychiatric symptom,with often involuntary movement,such as shake head,lasting for 0.52min;,t,he same drugs mentioned above;,抗癫痫药和抗惊厥药专业知识专家讲座,第3页,Table 16-1 (2),Types of Epilepsy and,Anti-epileptic Drugs,types of epilepsy,clinical features,anti-epileptic drugs(*preferred),3.partial seizures with,following tonic-clonic seizures,partial seizures is,followed by tonic-clonic seizures without loss of consciousness,lasting for 12min;,t,he same drugs mentioned above;,generalized seizures,1.tonic-clonic seizures(,grandmal)and status epilepticus,immediate loss of consciousness with generalized tonic-clonic convulsion,lasting for a few minutes.Seizures lasting for longer time is termed as status epilepticus;,carbamazepine*,phenytoin,valproate,phenobarbital,primidone,vigabatrin,lamotrigine,antiepilepsirine;,status epilepticus:diazepam*(i.v.);,抗癫痫药和抗惊厥药专业知识专家讲座,第4页,Table 16-1 (3),Types of Epilepsy and,Anti-epileptic Drugs,types of epilepsy,clinical features,anti-epileptic drugs(*preferred),2.,absence seizures,(petit mal),patient abruptly ceases whatever he or she is doing,and stares vacantly for a few seconds,with unaware of surroundings;,ethosuximide*,clonazepam,valproate,nitrazepam,clobazam;,3.atypical,absence seizures,This seizures occurs and recovers more slowly than absence seizures;,ethosuximide*,clonazepam,valproate,nitrazepam,clobazam;,抗癫痫药和抗惊厥药专业知识专家讲座,第5页,Table 16-1 (4),Types of Epilepsy and,Anti-epileptic Drugs,types of epilepsy,clinical features,anti-epileptic drugs(*preferred),4.myoclonic seizures,local myoclonia lasts for a few seconds;,valproate,clonazepam,clobazam;,5.infant myoclonic seizures,generalized rhythmic myoclonia with unconsciousness in infant.clonazepam,valproate,clobazam,glucocorticoid,抗癫痫药和抗惊厥药专业知识专家讲座,第6页,ethosuximide,carbamazepine valproate sodium,phenytoin phenobarbital primidone,Fig.16-1 Molecular structures of antiepileptic drugs,抗癫痫药和抗惊厥药专业知识专家讲座,第7页,抑制癫病灶神经元过分放电，或作用于病灶周围正常神经元，抑制异常放电扩散。这些作用基础与其增强GABA介导突触抑制作用相关，如:1.,苯二氮类,(benzodiazepines,)和苯巴比妥,(phenobarbital,),激动GABA,A,受体、促进GABA介导氯,通道开放。2.,噻加宾(tiagabine,),抑制GABA摄取、增加突触后膜GABA浓度。,3.,氨己烯酸,(vigabatrin,),抑制GABA转氨酶活性、降低GABA灭活。,【抗癫药品作用机制】,抗癫痫药和抗惊厥药专业知识专家讲座,第8页,4.一些药品作用与阻滞离子通道相关，如,phenytoin，carbamazepine，valproate,和,lamotrigine,可经过阻滞细胞膜电压依赖性钠通道,(,valtage-dependent Na,+,channels)，抑制Na,+,内流而降低膜兴奋性。5.一些药品如,氟桂利嗪,(flunarizine,)，phenytoin,和,ethosuximide,效应可能还与阻滞T型钙通道相关,6.,抗痫灵,(antiepilepsirine,),与增加脑内5-HT含量相关,(表16-2)。,【抗癫药品作用机制】,抗癫痫药和抗惊厥药专业知识专家讲座,第9页,【体内过程】,1.口服吸收慢而不规则，连续服用治疗量需经610天才能到达有效血药浓度。所以，常先用phenobarbital等作用较快药品控制发作，在改用,phenytoin同时，普通将本药与前用药适用710天。,2.治疗癫连续状态时宜静脉注射。其血浆蛋白结合率约为90，大部分经肝药酶代谢为无活性羟基苯妥英。3.血药浓度个体差异较大，因而临床用量应注意个体化。,苯妥英钠,(Phenytoin,大仑丁dilantin),抗癫痫药和抗惊厥药专业知识专家讲座,第10页,1.,对,高频异常放电神经元钠通道含有显著阻滞作用，降低细胞膜兴奋性，从而能抑制癫病灶神经元高频异常放电及其放电扩散。另外，还与阻滞神经元T型钙通道,抑制,Ca,2+,内流相关,。2.高浓度时也能抑制神经末梢对,GABA,摄取和诱导,GABA,A,受体增多，从而增强,GABA,介导突触后抑制作用。这些作用与其抑制癫病灶神经元高频放电产生及其扩散相关。,【药理作用】,抗癫痫药和抗惊厥药专业知识专家讲座,第11页,1.抗癫,是惯用抗癫药，对癫大发作、单纯部分性发作和对精神运动性发作疗效很好，但对小发作无效或甚至加重。,2.治疗外周神经痛,用于治疗三叉神经、舌咽神经和坐骨神经等神经性疼痛。其中对三叉神经痛疗效很好，使疼痛显著减轻，发作次数降低。,3.抗心律失常。,【临床应用】,抗癫痫药和抗惊厥药专业知识专家讲座,第12页,1局部刺激,口服可引发厌食、恶心、呕吐和腹痛等症状,；静脉注射可发生静脉炎。,2齿龈增生,多见于儿童和青少年，发生率约20，普通停药36个月后可自行消退。,3神经系统反应：,量中毒出现为眩晕、共济失调、精神错乱或昏迷等。,【不良反应】,抗癫痫药和抗惊厥药专业知识专家讲座第13页,4血液系统反应,抑制folinic acid吸收并加速其代谢，以及抑制二氢叶酸还原酶活性，长久用药可致巨幼红细胞性贫血。,5骨骼系统反应,诱导肝药酶而加速,Vit.D代谢，可致低钙血症、佝偻病样改变和骨软化症。,6过敏反应,可发生皮疹、血小板降低、粒细胞缺乏、再生障碍性贫血。,7其它反应,偶见男性乳房增大、女性多毛症等。偶致畸胎，故孕妇慎用。久服骤停可使癫发作加剧，甚至诱发癫连续状态。,【不良反应】,抗癫痫药和抗惊厥药专业知识专家讲座,第14页,Butazolidin、Sulfanilamide,s,和,salicylates,可与,phenytoin,竞争血浆蛋白结合部位。,Phenytoin,诱导肝药酶而加速各种药品如避孕药代谢和降低其药效。,Chloromycetin,等经过抑制肝药酶而提升,phenytoin,血药浓度,。,Phenobarbital,诱导肝药酶而加速,phenytoin,代谢。,【药品相互作用】,抗癫痫药和抗惊厥药专业知识专家讲座,第15页,药品,应用,不良反应,Phenobarbital,大发作、癫连续状态、单纯部分性发作、精神运动性发作,见镇静催眠药,Primidone,对大发作疗效优于phenobarbital，但对部分性发作疗效不及phenytoin和carbamazepine,嗜睡、共济失调、巨幼红细胞性贫血、白细胞和血小板降低,Mephenytoin,主要用于癫大发作，因为不良反应较重，仅用于其它药品不能控制患者,多形性红斑、高热、黄疸、中毒性肝炎、精神症状,Ethotoin,对大发作和复杂部分性发作有效。因为作用弱，只作辅助药品与其它药适用,不良反应少见,惯用抗癫药比较,(1),抗癫痫药和抗惊厥药专业知识专家讲座,第16页,惯用抗癫药比较,(2),药品,应用,不良反应,Ethosuximide,对小发作不及氯硝西泮(clonazepam)，但副作用及耐受性较少，故仍为防治小发作首选药,常见为胃肠道反应，其次为中枢神经系统症状如头痛，偶见粒细胞缺乏症和再障,Benzodiaze-pine,diazepam是癫连续状态首选药，nitrazepam主要用于小发作和非经典失神性发作，clonazepam和clobazam对各型癫有效,diazepam静过快可致呼吸抑制，故应迟缓静脉注射。其它见镇静催眠药,Valproate,对各型癫都有效。对大发作不及phenytoin和phenobarbital；对小发作疗效优于ethosuximide,常见有恶心、呕吐等，CNS反应少，约25%患者有肝毒性,Carbamaze-pine,对各类型癫有效，其中对精神运动性发作和大发作疗效很好,眩晕、恶心、呕吐，少数可有粒细胞和血小板降低。,抗癫痫药和抗惊厥药专业知识专家讲座,第17页,1.合理选择药品和剂量,单纯型癫普通选取一个有效药品，先从小剂量开始，逐量增加至取得理想疗效而不产生严重不良反应有效剂量。若一个药难以奏效或治疗混合型患者，常需联适用药。,2.合理疗程,在治疗过程中不宜随便更换药品，必要时采取过渡用药方法，即在原药基础上加用新药，待新药发挥疗效后再逐步停用原药。症状完全控制后，还要维持治疗23年再逐步停药，以防复发。,3.注意不良反应,因为癫需长久甚至终生用药。,抗癫药合理应用,抗癫痫药和抗惊厥药专业知识专家讲座,第18页,Table 16-2 (1),Summary of Charateristics of Some Newly Developed Anti-epileptic Drugs,drugs,cellular mechanisms,main uses,mainly unwanted effects,antiepilepsirine,i,ncrease in content of 5-serotonin;,broad therapeutic profile;,relatively free of side-effects,drowsiness etc.,vigabatrin,inhibition of GABA transaminase;,effective in patients unresponsive to conventional drugs;,drowsiness,behaviour and mood changes,lamotrigine,inhibition of Na,+,channels;,broad therapeutic profile;,hypersensitivity reactions(especially skin rashes),抗癫痫药和抗惊厥药专业知识专家讲座,第19页,Table 16-2 (2),Summary of Charateristics of Some Newly Developed Anti-epileptic Drugs,drugs,cellular mechanisms,main uses,mainly unwanted effects,felbamate,unknown;,broad therapeutic profile;,use limited to intractable disease,owing to risk of hypersensitivity reactions resulting in aplastic anemia,gabapentin,unknown;,partial seizures;,safe in overdose.relatively free of side-effects,抗癫痫药和抗惊厥药专业知识专家讲座,第20页,Table 16-2 (3),Summary of Charateristics of Some Newly Developed Anti-epileptic Drugs,drugs,cellular mechanisms,main uses,mainly unwanted effects,tiagabine,GABA uptake inhibitor;,partial seizures in adults;,dizziness and confusion,flunarizine,block of Ca,2+,and Na,+,channels;,broad therapeutic profile;,relatively free of side-effects,drowsiness,increase in body weight,抗癫痫药和抗惊厥药专业知识专家讲座,第21页,惊厥,是因为中枢神经系统过分兴奋而引发全身骨骼肌呈强直性或阵挛性抽搐，常见于高热、破伤风、子痫和中枢兴奋药中毒等引发惊厥。惯用抗惊厥,药有,苯二氮类,如,diazepam、巴比妥类,如,phenobarbital、magnesium sulfate,和,水合氯醛,(chloral hydrate,)。,第二节 抗惊厥药,抗癫痫药和抗惊厥药专业知识专家讲座,第22页,【,药理作用】,给药路径不一样而产生不一样药理效应。口服有泻下和利胆作用，注射给药含有抗惊厥和降压作用。,1.抗惊厥,阻断神经肌肉接头传递,。因为,Mg,2+,与,Ca,2+,化学性质相同，它竞争性地与,Ca,2+,受点结合，抑制,Ca,2+,内流，从而使运动神经末梢ACh释放降低，产生肌肉松弛作用。当,Mg,2+,过量中毒时同理可用,Ca,2+,来解救。,2.降压,可使血管扩张和血压下降。,3.中枢抑制,大剂量时因为中枢神经系统抑制而出现感觉和意识障碍。,硫酸镁,(,Magnesium sulfate),抗癫痫药和抗惊厥药专业知识专家讲座,第23页,【临床应用】,本药,主要用于治疗子痫、破伤风等惊厥，也用于高血压危象救治。常以肌内注射、静脉注射或滴注给药。,【不良反应】,本药过量中毒可引发呼吸抑制、血压剧降和心脏骤停。肌腱反射消失是中毒先兆表现，所以在用药过程中应注意检验腱反射，且宜迟缓静脉注射给药。中毒时马上进行人工呼吸，并迟缓静脉注射氯化钙或葡萄糖酸钙抢救。,抗癫痫药和抗惊厥药专业知识专家讲座,第24页,第 16 章学习结束,END！,下一章,主菜单,前一章,抗癫痫药和抗惊厥药专业知识专家讲座,第25页,