神经系统药理—魏尔清抗癫痫药课件

Psychomotor seizuresPsychomotor seizuresPetit mal(absence)Petit mal(absence)Grand mal(tonic-clonic)Grand mal(tonic-clonic)Epilepsy is not a single Epilepsy is not a single entity;it is a family of entity;it is a family of different recurrent seizure different recurrent seizure disorders that have in disorders that have in common the sudden,common the sudden,excessive and disorderly excessive and disorderly discharge of central neurons.discharge of central neurons.This results in abnormal This results in abnormal movement or perceptions movement or perceptions that are of short duration but that are of short duration but that tend to recur.that tend to recur.Psychomotor seizuresPetit mal 1Classification of epilepsy(older)Generalized seizures(Generalized seizures(全身发作全身发作全身发作全身发作）Grand malGrand mal（大发作大发作大发作大发作）：）：）：）：tonic-clonic seizurestonic-clonic seizures（强直阵挛强直阵挛强直阵挛强直阵挛）Petit mal Petit mal（小发作小发作小发作小发作）：absence seizures absence seizures（失神发作失神发作失神发作失神发作）Partial seizures(Partial seizures(部分性发作部分性发作部分性发作部分性发作)PshychomotorPshychomotor（精神运动性精神运动性精神运动性精神运动性）：）：）：）：temporal lobe seizurestemporal lobe seizures（颞叶癫痫颞叶癫痫颞叶癫痫颞叶癫痫）PartialPartial（部分发作部分发作部分发作部分发作）：）：）：）：motor,sensory,ANS,motor,sensory,ANS,etc.etc.（局限性发作局限性发作局限性发作局限性发作）Classification of epilepsy(ol2Classification of epilepsyClassification of epilepsy3Normal EEGNormal EEGAbsence EEGAbsence EEGNormal EEGAbsence EEG4The pathways for The pathways for seizure propagation in seizure propagation in partial seizures and partial seizures and primary generalized primary generalized seizuresseizuresThe pathways for seizure propa5神经系统药理魏尔清抗癫痫药课件6Stereotypical complex partial seizuresStereotypical complex partial 7Ineffective for petit mal(absence seizures)(3)AntiarrhythmiaNecessary to monitor plasma concentrations(1)Grand mal/Partial：Broad spectrum of antiepilepsyIneffective for petit mal(absence seizures)Phenytoin,Carbamazepine,PhenobarbitalAdverse effects：Antiepileptic drugsHepatic toxicityGrand mal,status epilepticus;Mephenytoin 美芬妥英,Ethotoin 乙苯妥英：analogues of phenytoinInduction of hepatic drug-metabolizing enzymes(3)Antiarrhythmia(3)AntiarrhythmiaAntiepileptic drugsPsychomotor seizuresLamotrigine 拉莫三嗪Primidone,Valproate sodiumPrincipals of antiepileptic drug usesMechanisms of antiepileptic drugsElectrophysiologicalElectrophysiologicalInhibiting excessive dischargesInhibiting excessive dischargesInhibiting spread of dischargesInhibiting spread of dischargesMolecularMolecularPotentiating GABA neuronal functionsPotentiating GABA neuronal functionsModulating NaModulating Na+,Ca,Ca2+2+,K,K+channel fuctionschannel fuctionsIneffective for petit mal(abs8A.Antiepileptic drugsSpecial drugsPhenytoin Sodium 苯妥英钠苯妥英钠苯妥英钠苯妥英钠A.Antiepileptic drugsSpecial91.Pharmacological effects and the mechanism Inhibiting influx of Na+and Ca2+Inhibiting spread of abnormal dischargesA.Antiepileptic drugs1.Pharmacological effects and10神经系统药理魏尔清抗癫痫药课件112.Clinical uses(1)AntiepilepsyGrand mal,status epilepticus;Grand mal,status epilepticus;Partial seizures(simple and complex);Partial seizures(simple and complex);Ineffective for petit mal(absence seizures)Ineffective for petit mal(absence seizures)(2)Trigeminal and related neuralgia(3)AntiarrhythmiaA.Antiepileptic drugs2.Clinical usesA.Antiepilep123.ADME Larger doses:non-linear kinetics（plasma concentration 10 g/ml）Necessary to monitor plasma concentrations Induction of hepatic drug-metabolizing enzymesA.Antiepileptic drugsA.Antiepileptic drugs13神经系统药理魏尔清抗癫痫药课件14神经系统药理魏尔清抗癫痫药课件153.Adverse effects(1)Local reactions GI reactions;gingival hyperplasiaGI reactions;gingival hyperplasia(2)CNS reactions Particularly in the cerebellum and vestibular systems:Particularly in the cerebellum and vestibular systems:nystagmus(nystagmus(眼球震颤眼球震颤眼球震颤眼球震颤),ataxia(),ataxia(共济失调共济失调共济失调共济失调),),etc.etc.Behavioral changes:confusion,hallucinationBehavioral changes:confusion,hallucination A.Antiepileptic drugs3.Adverse effectsA.Antiepil16(3)Hemological reactions Megaloblastic anemiaMegaloblastic anemia(4)Allergic reactions Skin reactions;blood cell abnormality(including Skin reactions;blood cell abnormality(including thrombocytopenia,agranulocytosis);thrombocytopenia,agranulocytosis);hepatic toxicity;hepatic toxicity;ect.ect.(5)Skeletal reactions Osteomalacia by abnormal vitamin D metabolism and Osteomalacia by abnormal vitamin D metabolism and calcium absorptioncalcium absorptionA.Antiepileptic drugs(3)Hemological reactionsA.A174.Drug interactions(1)Increases plasma concentrations of drugs by(1)Increases plasma concentrations of drugs by displacement of plasma protein binding displacement of plasma protein binding(salicylates)(salicylates)and inhibition of inactivation and inhibition of inactivation (isoniazid,chloramphenicol)(isoniazid,chloramphenicol)(2)Decreases plasma concentrations of drugs(2)Decreases plasma concentrations of drugs (phenobarbital,carbamazepine)(phenobarbital,carbamazepine)by enhancing by enhancing metabolismmetabolism(3)Phenytoin enhances the metabolism of(3)Phenytoin enhances the metabolism of corticosteroids and vitamin Dcorticosteroids and vitamin DA.Antiepileptic drugs4.Drug interactionsA.Antiep18Effective for psychomotor seizures,and grand malEpilepsy 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.(2)Trigeminal and related neuralgiaPhenytoin,Carbamazepine,PhenobarbitalThis results in abnormal movement or perceptions that are of short duration but that tend to recur.Other anticovulsant drugsParticularly in the cerebellum and vestibular systems:nystagmus(眼球震颤),ataxia(共济失调),etc.Adverse effectsPartial（部分发作）：Primidone,Valproate sodiumDrug interactionsPartial seizures(simple and complex);Phenytoin,Carbamazepine,PhenobarbitalInhibiting spread of dischargesCHCOOHPrincipals of antiepileptic drug usesPetit mal（小发作）：Classification of epilepsyPrincipals of antiepileptic drug usesvasodilatation,BP;(1)AntiepilepsyInhibiting both formation and spread of Inhibiting both formation and spread of dischargesdischargesEffective for grand mal,partial simple Effective for grand mal,partial simple seizures,status epilepticusseizures,status epilepticusPhenobarbital 苯巴比妥苯巴比妥苯巴比妥苯巴比妥A.Antiepileptic drugsEffective for psychomotor seiz19Effective forEffective for psychomotor seizurespsychomotor seizures,and grand maland grand malEffective for mania,depression,and neuralgiaEffective for mania,depression,and neuralgiaCarbamazepine 卡马西平卡马西平A.Antiepileptic drugsEffective for psychomotor seiz20神经系统药理魏尔清抗癫痫药课件21Broad spectrum of antiepilepsyBroad spectrum of antiepilepsyHepatic toxicityHepatic toxicityValproate sodium 丙戊酸钠丙戊酸钠丙戊酸钠丙戊酸钠A.Antiepileptic drugsCH3CH2CH2 CHCOOHCH3CH2CH2Valproate sodium 丙戊酸钠A.Ant22Other antiepileptic drugsPrimidone Primidone 扑米酮扑米酮扑米酮扑米酮：analogues of phenobarbital,used analogues of phenobarbital,used for phenobarbital-and phenytoin-ineffective patientsfor phenobarbital-and phenytoin-ineffective patientsMephenytoin Mephenytoin 美芬妥英美芬妥英美芬妥英美芬妥英,Ethotoin,Ethotoin 乙苯妥英乙苯妥英乙苯妥英乙苯妥英：analogues of analogues of phenytoinphenytoinEthosuximide Ethosuximide 乙琥胺乙琥胺乙琥胺乙琥胺：peptit malpeptit malDiazepam:Diazepam:status epilepticus(status epilepticus(i.v.i.v.)Nitrozepam Nitrozepam 硝西泮硝西泮硝西泮硝西泮,Clonazepam,Clonazepam 氯硝西泮氯硝西泮氯硝西泮氯硝西泮：peptit malpeptit malLamotrigine Lamotrigine 拉莫三嗪拉莫三嗪拉莫三嗪拉莫三嗪A.Antiepileptic drugsOther antiepileptic drugsA.A23神经系统药理魏尔清抗癫痫药课件24神经系统药理魏尔清抗癫痫药课件25神经系统药理魏尔清抗癫痫药课件26神经系统药理魏尔清抗癫痫药课件27Box Common toxicity of antiepileptic drugs:CNS reactions Hemological reactions Hepatic toxicityA.Antiepileptic drugsBox Common toxicity of A.An28(1)AntiepilepsyPrimidone,Valproate sodiumplasma concentration monitoring if necessaryClassification of epilepsy(older)CHCOOHParticularly in the cerebellum and vestibular systems:nystagmus(眼球震颤),ataxia(共济失调),etc.Antiepileptic drugsInduction of hepatic drug-metabolizing enzymes),Phenobrbital(i.Effective for psychomotor seizures,and grand malClassification of epilepsy(older)Partial seizures(simple and complex);Other anticovulsant drugs(2)Peptit mal:Ethosuximide(2)CNS reactions(3)Phenytoin enhances the metabolism of corticosteroids and vitamin DChoice of drugs(1)Increases plasma concentrations of drugs by displacement of plasma protein binding(salicylates)and inhibition of inactivation(isoniazid,chloramphenicol)hypertension crisis),Phenobrbital(i.Mechanisms of antiepileptic drugsvasodilatation,BP;small larger doses;hypertension crisistonic-clonic seizures（强直阵挛）Primidone,Valproate sodiumClinical uses(2)Peptit mal:Ethosuximiderelaxing skeletal musclesCHCOOHInhibiting both formation and spread of dischargesCHCOOHStereotypical complex partial seizures(2)CNS reactionsSpecial drugsAntiepileptic drugsNecessary to monitor plasma concentrationsOther anticovulsant drugsMechanisms of antiepileptic drugsIneffective for petit mal(absence seizures)temporal lobe seizures（颞叶癫痫）dose individualization;Principals of antiepileptic drug uses1.Choice of drugs(1)Grand mal/Partial(1)Grand mal/Partial：Phenytoin,Carbamazepine,PhenobarbitalPhenytoin,Carbamazepine,Phenobarbital Primidone,Valproate sodiumPrimidone,Valproate sodium(2)Peptit mal:(2)Peptit mal:EthosuximideEthosuximide Clonazepam,Valproate sodiumClonazepam,Valproate sodium(3)Psychomotor(3)Psychomotor：Carbamazepine,PhenytoinCarbamazepine,Phenytoin(4)Status epilepticus(4)Status epilepticus：Diazepan(i.v.)Diazepan(i.v.)Phenytoin(i.v.),Phenobrbital(i.m.)Phenytoin(i.v.),Phenobrbital(i.m.)A.Antiepileptic drugs(1)Antiepilepsyvasodilatation292.Dosage：small small larger doses;larger doses;dose individualization;dose individualization;plasma concentration monitoring if necessary plasma concentration monitoring if necessary3.Usage：drug combinationdrug combination4.Withdrawal：gradually and slowlygradually and slowlyA.Antiepileptic drugs2.Dosage：A.Antiepileptic dr301.Effects：central depression;central depression;vasodilatation,BP vasodilatation,BP ;relaxing skeletal muscles relaxing skeletal muscles2.Uses：convulsionconvulsion；hypertension crisishypertension crisis3.Adverse effects：depression of respiratory and vasomotor centers,depression of respiratory and vasomotor centers,antagonized by calcium preparations(antagonized by calcium preparations(i.v.i.v.)Magnesium Sulfate 硫酸镁硫酸镁硫酸镁硫酸镁A.Anticonvulsant drugs1.Effects：central depression;31Other anticovulsant drugsSedative-hypnotic drugsA.Anticonvulsant drugsOther anticovulsant drugsA.A32