神經(jīng)系統(tǒng)藥理魏爾清抗癲癇藥

1、神經(jīng)系統(tǒng)藥理魏爾清抗癲癇藥Psychomotor seizuresPetit 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

2、 that are of short duration but that tend to recur.Classification of epilepsy (older)Generalized seizures (全身發(fā)作）Grand mal（大發(fā)作）： tonic-clonic seizures（強(qiáng)直陣攣）Petit mal （小發(fā)作） ： absence seizures （失神發(fā)作）Partial seizures (部分性發(fā)作)Pshychomotor（精神運(yùn)動(dòng)性）： temporal lobe seizures（顳葉癲癇）Partial（部分發(fā)作）： motor, sensory,

3、ANS, etc.（局限性發(fā)作）Classification of epilepsyNormal EEGAbsence EEGThe pathways for seizure propagation in partial seizures and primary generalized seizuresStereotypical complex partial seizuresMechanisms of antiepileptic drugsElectrophysiologicalInhibiting excessive dischargesInhibiting spread of disch

4、argesMolecularPotentiating GABA neuronal functionsModulating Na+, Ca2+, K+channel fuctionsA. Antiepileptic drugsSpecial drugsPhenytoin Sodium 苯妥英鈉1. Pharmacological effects and the mechanism Inhibiting influx of Na+ and Ca2+ Inhibiting spread of abnormal dischargesA. Antiepileptic drugs2. Clinical u

5、ses(1) AntiepilepsyGrand mal, status epilepticus; Partial seizures (simple and complex);Ineffective for petit mal (absence seizures)(2) Trigeminal and related neuralgia(3) AntiarrhythmiaA. Antiepileptic drugs3. ADME Larger doses: non-linear kinetics（plasma concentration 10 g/ml）Necessary to monitor

6、plasma concentrations Induction of hepatic drug-metabolizing enzymesA. Antiepileptic drugs3. Adverse effects(1) Local reactionsGI reactions; gingival hyperplasia(2) CNS reactionsParticularly in the cerebellum and vestibular systems: nystagmus (眼球震顫), ataxia (共濟(jì)失調(diào)), etc.Behavioral changes: confusion,

7、 hallucination A. Antiepileptic drugs(3) Hemological reactionsMegaloblastic anemia(4) Allergic reactionsSkin reactions; blood cell abnormality (including thrombocytopenia, agranulocytosis);hepatic toxicity; ect.(5) Skeletal reactionsOsteomalacia by abnormal vitamin D metabolism and calcium absorptio

8、nA. Antiepileptic drugs4. 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 metaboli

9、sm(3) Phenytoin enhances the metabolism of corticosteroids and vitamin DA. Antiepileptic drugsInhibiting both formation and spread of dischargesEffective for grand mal, partial simple seizures, status epilepticusPhenobarbital 苯巴比妥A. Antiepileptic drugsEffective for psychomotor seizures, and grand ma

10、lEffective for mania, depression, and neuralgiaCarbamazepine 卡馬西平A. Antiepileptic drugsBroad spectrum of antiepilepsyHepatic toxicityValproate sodium 丙戊酸鈉A. Antiepileptic drugsCH3CH2CH2 CHCOOHCH3CH2CH2Other antiepileptic drugsPrimidone 撲米酮：analogues of phenobarbital, used for phenobarbital- and phen

11、ytoin-ineffective patientsMephenytoin 美芬妥英, Ethotoin 乙苯妥英： analogues of phenytoinEthosuximide 乙琥胺：peptit malDiazepam: status epilepticus (i.v.)Nitrozepam 硝西泮, Clonazepam 氯硝西泮：peptit malLamotrigine 拉莫三嗪A. Antiepileptic drugsBox Common toxicity of antiepileptic drugs: CNS reactions Hemological reactio

12、ns Hepatic toxicityA. Antiepileptic drugsPrincipals of antiepileptic drug uses1. 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 epil

13、epticus：Diazepan (i.v.) Phenytoin (i.v.), Phenobrbital (i.m.)A. Antiepileptic drugs2. Dosage： small larger doses; dose individualization; plasma concentration monitoring if necessary3. Usage： drug combination4. Withdrawal：gradually and slowlyA. Antiepileptic drugs1. Effects：central depression; vasodilatation, BP ; relaxing skeletal muscles2. Uses：convulsion；hypertension crisis3. Adverse effects：depre