神经系统药理—魏尔清-抗癫痫药.ppt

Part 9 Antiepileptic and Anticonvulsant Drugs Psychomotor seizures Petit mal(absence)Grand mal(tonic-clonic)Epilepsy is not a single entity;it is a family of different recurrent seizure disorders that have in common the sudden,excessive and disorderly discharge of central neurons.This results in abnormal movement or perceptions that are of short duration but that tend to recur.Classification of epilepsy(older)Generalized seizures(全身发作全身发作）Grand mal（大发作大发作）：）：tonic-clonic seizures（强直阵挛强直阵挛）Petit mal（小发作小发作）：absence seizures（失神发作失神发作）Partial seizures(部分性发作部分性发作)Pshychomotor（精神运动性精神运动性）：）：temporal lobe seizures（颞叶癫痫颞叶癫痫）Partial（部分发作部分发作）：）：motor,sensory,ANS,etc.（局限性发作局限性发作）Classification of epilepsy Normal EEG Absence EEG The pathways for seizure propagation in partial seizures and primary generalized seizures Stereotypical complex partial seizures Mechanisms of antiepileptic drugs Electrophysiological Inhibiting excessive discharges Inhibiting spread of discharges Molecular Potentiating GABA neuronal functions Modulating Na+,Ca2+,K+channel fuctions A.Antiepileptic drugs Special drugs Phenytoin Sodium 苯妥英钠苯妥英钠 CONNHC6H5C6H5NaO 1.Pharmacological effects and the mechanism Inhibiting influx of Na+and Ca2+Inhibiting spread of abnormal discharges A.Antiepileptic drugs 2.Clinical uses (1)Antiepilepsy Grand mal,status epilepticus;Partial seizures(simple and complex);Ineffective for petit mal(absence seizures)(2)Trigeminal and related neuralgia (3)Antiarrhythmia A.Antiepileptic drugs 3.ADME Larger doses:non-linear kinetics（plasma concentration 10 g/ml）Necessary to monitor plasma concentrations Induction of hepatic drug-metabolizing enzymes A.Antiepileptic drugs 3.Adverse effects (1)Local reactions GI reactions;gingival hyperplasia (2)CNS reactions Particularly in the cerebellum and vestibular systems:nystagmus(眼球震颤眼球震颤),ataxia(共济失调共济失调),etc.Behavioral changes:confusion,hallucination A.Antiepileptic drugs (3)Hemological reactions Megaloblastic anemia (4)Allergic reactions Skin reactions;blood cell abnormality(including thrombocytopenia,agranulocytosis);hepatic toxicity;ect.(5)Skeletal reactions Osteomalacia by abnormal vitamin D metabolism and calcium absorption A.Antiepileptic drugs 4.Drug interactions (1)Increases plasma concentrations of drugs by displacement of plasma protein binding(salicylates)and inhibition of inactivation(isoniazid,chloramphenicol)(2)Decreases plasma concentrations of drugs(phenobarbital,carbamazepine)by enhancing metabolism (3)Phenytoin enhances the metabolism of corticosteroids and vitamin D A.Antiepileptic drugs Inhibiting both formation and spread of discharges Effective for grand mal,partial simple seizures,status epilepticus Phenobarbital 苯巴比妥苯巴比妥 A.Antiepileptic drugs C2H5CONHNHCOCOCC6H5 Effective for psychomotor seizures,and grand mal Effective for mania,depression,and neuralgia Carbamazepine 卡马西平卡马西平 NCONH2A.Antiepileptic drugs Broad spectrum of antiepilepsy Hepatic toxicity Valproate sodium 丙戊酸钠丙戊酸钠 A.Antiepileptic drugs CH3CH2CH2 CHCOOH CH3CH2CH2 Other antiepileptic drugs Primidone 扑米酮扑米酮：analogues of phenobarbital,used for phenobarbital-and phenytoin-ineffective patients Mephenytoin 美芬妥英美芬妥英,Ethotoin 乙苯妥英乙苯妥英：analogues of phenytoin Ethosuximide 乙琥胺乙琥胺：peptit mal Diazepam:status epilepticus(i.v.)Nitrozepam 硝西泮硝西泮,Clonazepam 氯硝西泮氯硝西泮：peptit mal Lamotrigine 拉莫三嗪拉莫三嗪 A.Antiepileptic drugs Box Common toxicity of antiepileptic drugs:CNS reactions Hemological reactions Hepatic toxicity A.Antiepileptic drugs Principals of antiepileptic drug uses 1.Choice of drugs (1)Grand mal/Partial：Phenytoin,Carbamazepine,Phenobarbital Primidone,Valproate sodium (2)Peptit mal:Ethosuximide Clonazepam,Valproate sodium (3)Psychomotor：Carbamazepine,Phenytoin (4)Status epilepticus：Diazepan(i.v.)Phenytoin(i.v.),Phenobrbital(i.m.)A.Antiepileptic drugs 2.Dosage：small larger doses;dose individualization;plasma concentration monitoring if necessary 3.Usage：drug combination 4.Withdrawal：gradually and slowly A.Antiepileptic drugs 1.Effects：central depression;vasodilatation,BP ;relaxing skeletal muscles 2.Uses：convulsion；hypertension crisis 3.Adverse effects：depression of respiratory and vasomotor centers,antagonized by calcium preparations(i.v.)Magnesium Sulfate 硫酸镁硫酸镁 A.Anticonvulsant drugs Other anticovulsant drugs Sedative-hypnotic drugs A.Anticonvulsant drugs