1、抗癫痫药抗癫痫药AntiepilepticDrugsDefinitions in epilepsy:Definitions in epilepsy:nEpilepsy comprises recurrent episodes of Epilepsy comprises recurrent episodes of abnormal cerebral neuronal discharge.The abnormal cerebral neuronal discharge.The resulting seizures are usually clinically obvious resulting s
2、eizures are usually clinically obvious and vary in pattern according to which parts of and vary in pattern according to which parts of the brain are affected.the brain are affected.nEpilepsy can be caused by many neurological Epilepsy can be caused by many neurological diseases,including infection,t
3、rauma,infarction diseases,including infection,trauma,infarction and neoplasia.and neoplasia.nHeredity has an important role(especially in Heredity has an important role(especially in the idiopathic generalised epilepsies).the idiopathic generalised epilepsies).Normal brain cellNormal brain cellAbnor
4、mal high-Abnormal high-frequency frequency dischargedischargeFocusFocusDrug actionDrug actionInhibit dischargeInhibit dischargeStabilize membrane,inhibit the Stabilize membrane,inhibit the diffusion of discharge(primary)diffusion of discharge(primary)EpilepsyEpilepsyTherapeutic principle:nChange the
5、 permeability of NaChange the permeability of Na+,CaCa2+2+and and K K+in nerve cell membrane,degrade in nerve cell membrane,degrade excitement stage,extend refractory excitement stage,extend refractory phase.phase.nDirectly or indirectly increase CNS levels Directly or indirectly increase CNS levels
6、 of GABA.of GABA.epilepticepilepticgrand mal.grand mal.convulsion model:convulsion model:petit mal.petit mal.grand mal.S Spontaneously epileptic rat(SER)modelpontaneously epileptic rat(SER)model：epilepticClassification of Antiepileptic DrugsClassification of Antiepileptic DrugsnHydantoinsHydantoins：
7、SodiumSodium PhenytoinPhenytoinnBarbituratesBarbiturates：Phenobarbital,PrimidonePhenobarbital,PrimidonenSuccinimideSuccinimide：EthosuximideEthosuximidenBenzodiazepine:Benzodiazepine:Diazepam,NitrazepamDiazepam,NitrazepamnOthers:Others:Sodium ValproateSodium ValproateSodium Phenytoin(Sodium Phenytoin
8、(苯妥英钠苯妥英钠)【Physiological dispositionPhysiological disposition】nSodium Phenytoin is absorbed slowly Sodium Phenytoin is absorbed slowly after oral administration.After 6-10 after oral administration.After 6-10 days,its plasma concentration can days,its plasma concentration can achieve effect levels.T
9、his drug has achieve effect levels.This drug has variable interpatient plasma variable interpatient plasma concentration.concentration.Sodium Phenytoin Sodium PhenytoinMechanism of action:Mechanism of action:It can block sodium channels(voltage-It can block sodium channels(voltage-,frequency-,and ti
10、me dependent fashion)and,frequency-,and time dependent fashion)and inhibit the generation of action potentials.inhibit the generation of action potentials.It can increase the function of inhibitory It can increase the function of inhibitory transmitter GABA,inhibit nerve terminal to transmitter GABA
11、,inhibit nerve terminal to uptake GABA and induce the increasing of uptake GABA and induce the increasing of GABA receptor,thereby enhance GABA-GABA receptor,thereby enhance GABA-mediated postsynaptic inhibition.mediated postsynaptic inhibition.Sodium PhenytoinSodium Phenytoin【Pharmacologic properti
12、es and clinical Pharmacologic properties and clinical applicationapplication】nAnti-epilepticAnti-epileptic：It can be used for partial It can be used for partial seizures and tonic/clonic seizures,but not for seizures and tonic/clonic seizures,but not for other generalised seizure types.other general
13、ised seizure types.nPeripheral neuralgiaPeripheral neuralgia：cranial nerve,ischiadic cranial nerve,ischiadic nerve and cranial nerve.nerve and cranial nerve.nArrhythmia:Arrhythmia:membrane-stabilizing action.membrane-stabilizing action.Sodium PhenytoinSodium PhenytoinnDigestive system Digestive syst
14、em nGingival hyperplasiaGingival hyperplasianNervous systemNervous systemnHematological systemHematological systemnSkeletal systemSkeletal systemnAllergic responseAllergic responsenOthersOthers【Adverse effectsAdverse effects】Sodium PhenytoinSodium Phenytoin【Adverse effects】nDigestive system:Digestiv
15、e system:anorexia,nausea,vomiting and anorexia,nausea,vomiting and abdominal pain(recommend to take it after meal).abdominal pain(recommend to take it after meal).It may cause phlebitis after IV.It may cause phlebitis after IV.nGingival hyperplasia:Gingival hyperplasia:It common occurs in It common
16、occurs in children and teenagers after long term use,the children and teenagers after long term use,the incidence rate is about 20%.Generally,this effect incidence rate is about 20%.Generally,this effect can resolve after drug withdraw 3 to 6 months.can resolve after drug withdraw 3 to 6 months.Sodi
17、um PhenytoinSodium Phenytoin【Adverse effects】nNervous system:Nervous system:nystagmus,diplopia,vertigo,nystagmus,diplopia,vertigo,ataxia(usually only at very high ataxia(usually only at very high concentration).Severe patient occurs language concentration).Severe patient occurs language disorder,men
18、tal confusion and cataphora.disorder,mental confusion and cataphora.nHematological system:Hematological system:Because it can inhibit Because it can inhibit the absorption of folinic acid and accelerate its the absorption of folinic acid and accelerate its metabolism.This drug also can inhibit folic
19、 acid metabolism.This drug also can inhibit folic acid reductase.So it may cause megaloblastic reductase.So it may cause megaloblastic anemia after long-term use(recommend to anemia after long-term use(recommend to pretreat with folinic acid).pretreat with folinic acid).Sodium PhenytoinSodium Phenyt
20、oin【Adverse effects】nSkeletal system:Skeletal system:It can enhance vitamin D It can enhance vitamin D metabolism,so Phenytoin may increase the risk metabolism,so Phenytoin may increase the risk of hypocalcemia,rickets and osteomalacia after of hypocalcemia,rickets and osteomalacia after long-term t
21、reatment(pretreat with vitamin D if long-term treatment(pretreat with vitamin D if necessary).necessary).nAllergic response:Allergic response:rash,thrombocytopeniarash,thrombocytopenia,agranulocytosis and aplastic anemia.,agranulocytosis and aplastic anemia.nOthers:Others:rarely appear male barymast
22、ia,female rarely appear male barymastia,female hirsutism and lymphadenectasis.hirsutism and lymphadenectasis.Phenobarbital(Phenobarbital(苯巴比妥苯巴比妥)Mechanism of action:Mechanism of action:nPhenobarbital can inhibit the paradoxical discharge Phenobarbital can inhibit the paradoxical discharge of epilep
23、sy focus selectively,enhance stimulation of of epilepsy focus selectively,enhance stimulation of surrounding tissues and block discharge diffuse to surrounding tissues and block discharge diffuse to normal tissues.normal tissues.nPhenobarbital facilitate GABA-mediated inhibition of Phenobarbital fac
24、ilitate GABA-mediated inhibition of neuronal activity.neuronal activity.PhenobarbitalPhenobarbitalPharmacologic properties:Pharmacologic properties:nPhenobarbital can be used for all types of Phenobarbital can be used for all types of epilepsy.The effects by turns are:grand epilepsy.The effects by t
25、urns are:grand mal and status epilepticsmal and status epilepticslocal local psychomotor seizurepsychomotor seizurepetit mal.petit mal.nTake effect rapidlyTake effect rapidly（1 12 hr),the first 2 hr),the first choice of grand mal.choice of grand mal.nPrevent convulsive and eliminate Prevent convulsi
26、ve and eliminate precursory symptom.precursory symptom.PhenobarbitalPhenobarbital【Adverse effects】nSomnolenceSomnolence、depression.depression.nTolerance develops after long-term Tolerance develops after long-term treatment.treatment.Primidone(Primidone(去氧苯比妥去氧苯比妥)Primidone(Primidone(扑米酮扑米酮)nPharmaco
27、logic properties:Pharmacologic properties:Absorption after oral administration is Absorption after oral administration is rapid,and the plasma peak concentration rapid,and the plasma peak concentration is approximately 3 hours at therapeutic is approximately 3 hours at therapeutic doses.It can be us
28、ed for all types of doses.It can be used for all types of epilepsy except petit mal.Its better to epilepsy except petit mal.Its better to use this drug with sodium phenytoin.With use this drug with sodium phenytoin.With regard to grand mal,the effect of regard to grand mal,the effect of primidone is
29、 better than phenobarbital,this primidone is better than phenobarbital,this drug is useless to petit mal.drug is useless to petit mal.Primidone(Primidone)Primidone(Primidone)【Adverse effects】nCommon:Common:somnolence,vertigo,nausea somnolence,vertigo,nausea and vomiting.and vomiting.n Rare:Rare:mega
30、loblastic anemia,leucopenia megaloblastic anemia,leucopenia and thrombocytopenia.and thrombocytopenia.Ethosuximide(Ethosuximide(乙琥胺乙琥胺 )nPetit mal(first choice),Petit mal(first choice),useless to other types of useless to other types of seizure.seizure.Common adverse effect Common adverse effectnGas
31、trointestinal tract:Gastrointestinal tract:anorexia,nausea,anorexia,nausea,vomiting.vomiting.nCNS:CNS:headache,headache,dizziness and somnolence.dizziness and somnolence.nRarely appear Rarely appear agranulemia and aplastic agranulemia and aplastic anemia.anemia.Diazepem(Diazepem(安定安定)&)&Nitrazepem(
32、Nitrazepem(硝基安定硝基安定)DiazepemDiazepem：nDiazepem is indicated for status epilepticus.Diazepem is indicated for status epilepticus.NitrazepemNitrazepem:nIts highly effective in controlling petit mal Its highly effective in controlling petit mal and myoclonus epilepsy.and myoclonus epilepsy.nSudden with
33、drawal of nitrazepem is likely to Sudden withdrawal of nitrazepem is likely to aggravate seizure and induced symptom.aggravate seizure and induced symptom.Sodium Valproate(丙戊酸钠丙戊酸钠)Pharmacologic propertiesPharmacologic properties:nEnhance the enzymatic activity of glutamate Enhance the enzymatic act
34、ivity of glutamate decarboxylase.GABAdecarboxylase.GABAnInhibit GABA reuptake and synapse inactivationsynapse Inhibit GABA reuptake and synapse inactivationsynapse frontal membrane GABA enhance GABA postsynaptic frontal membrane GABA enhance GABA postsynaptic inhibitioninhibitionnBroad spectrum anti
35、epileptic drug,use to all types of Broad spectrum antiepileptic drug,use to all types of epilepsy.epilepsy.nCNS:CNS:somnolence,disequilibrium,acratia and tremor.somnolence,disequilibrium,acratia and tremor.nHepatic lesionHepatic lesion(20%patients).(20%patients).nGastrointestinal tract:Gastrointesti
36、nal tract:nausea,vomiting and anorexia.nausea,vomiting and anorexia.Carbamzepine(Carbamzepine(卡马西平卡马西平)Pharmacologic propertiesPharmacologic properties:nCarbamazepine can block sodium channel,inhibit paradoxical discharge and discharge diffusion.It may relate to the postsynaptic inhibition of GABA.p
37、ostsynaptic inhibition of GABA.nBroad spectrum antiepileptic drug,use to all types Broad spectrum antiepileptic drug,use to all types of epilepsy.of epilepsy.nTrigeminal neuralgia(therapeutic effect is good).nAntidiuresisdiabetes insipidus.Carbamzepine Carbamzepine【Adverse effectsAdverse effects】nCN
38、S:CNS:somnolence,disequilibrium somnolence,disequilibriumnGastrointestinal tract:Gastrointestinal tract:nausea,vomiting and nausea,vomiting and anorexia.anorexia.nRashRash，leucopenia leucopenia，thrombocytopeniathrombocytopenia，aplastic anemia and hepatic lesion.aplastic anemia and hepatic lesion.Pri
39、nciple of MedicationPrinciple of Medication n1 12 times/year2 times/year，no drugs are neededno drugs are needednGrand pit(first choice):Grand pit(first choice):Sodium phenytoin or Sodium phenytoin or phenobarbital,carbamzepine,Primidone.phenobarbital,carbamzepine,Primidone.nPetit mal(first choice):P
40、etit mal(first choice):Ethosuximide,Ethosuximide,clonazepam and sodium valproate.clonazepam and sodium valproate.nStatus epilepticus:Status epilepticus:Diazepam or sodium Diazepam or sodium phenytoin(IV),phenobarbital,diazepam,phenytoin(IV),phenobarbital,diazepam,clonazepam.clonazepam.nPsychomotor:P
41、sychomotor:Sodium phenytoin or combine Sodium phenytoin or combine with desoxybarbital or carbamazepine.with desoxybarbital or carbamazepine.Principle of Medication(I)Principle of Medication(I)nThe dose can be gradually increased from a The dose can be gradually increased from a low starting dose un
42、til reach the best effect.low starting dose until reach the best effect.nIn the initial stage,the patients should only be In the initial stage,the patients should only be treated with a single antiepileptic drug,if the treated with a single antiepileptic drug,if the drug is useless,then it can be ch
43、anged.When drug is useless,then it can be changed.When drug changing is necessary,it should be drug changing is necessary,it should be gradually withdrawn after the effect of new gradually withdrawn after the effect of new drug occurs.drug occurs.nAfter the symptom is fully controlled,the After the
44、symptom is fully controlled,the patients should continuing be treated for 2 or patients should continuing be treated for 2 or 3 years.Sudden withdrawal of drugs are likely 3 years.Sudden withdrawal of drugs are likely to precipitate relapse.to precipitate relapse.Principle of Medication(II)Principle
45、 of Medication(II)nEnhance therapeutic effect:dosing Enhance therapeutic effect:dosing individually,monitoring drug plasma individually,monitoring drug plasma concentration,examining regularly.concentration,examining regularly.nEvaluating efficacy and safety.Evaluating efficacy and safety.nAdjusting
46、 drug dosage:the therapeutic Adjusting drug dosage:the therapeutic index of antiepileptic drug is loweasy index of antiepileptic drug is loweasy to be poisoning Therapeutic dose is get to be poisoning Therapeutic dose is get close to toxic dose.close to toxic dose.Anticonvulsant DrugsAnticonvulsant
47、DrugsnConvulsions are involuntary skeletal muscular Convulsions are involuntary skeletal muscular contractions.Convulsions can arise from contractions.Convulsions can arise from pathological processes within or outside the pathological processes within or outside the brain,toxins,drug overdose,or wi
48、thdrawal brain,toxins,drug overdose,or withdrawal from drug dependence.from drug dependence.nCommonly used anticonvulsant drugs are Commonly used anticonvulsant drugs are sedative and hypnotic drugs.Magnesium sedative and hypnotic drugs.Magnesium Sulfate is also used on this disease.Sulfate is also used on this disease.Thanks!35结束语结束语
