藥理學(xué)英文版教學(xué)課件：Chapter 15 Antiepileptics-Anticonvulsants

DrugsforEpilepsy&SeizureCase116yrsoldyoungmanParoxysmal（陣發(fā)性）convulsionfor8years.Fallfromatree8yrsagoandbeganparoxysmalconvulsion2monthslater.Diagnosedasmajorepilepsy.§1introductiontoepilepsyEpilepticseizureclassificationPartialseizures(局限性發(fā)作):consciousGeneralizedseizures(大發(fā)作):temporarylossofconsciousnessandtwitching（抽搐）ClassificationofGeneralizedSeizuresTonic–clonicseizures(grandmalseizures,大發(fā)作)Absenceseizures(petitmalseizures,小發(fā)作)Myoclonicseizures(肌陣攣性發(fā)作)Febrileseizures(熱驚厥)Statusepilepticus(持續(xù)狀態(tài))GrandMalEpilepsy(大發(fā)作)majorseizures,fullbodyconvulsionsunconscious,fallsdowntonic/clonicconvulsionsuncontrolledurination,defecation(二便失禁)usuallylasts1-2minutes,followedbyfatique,musclesorenessaseriesofstatusepilepticus（癲癇持續(xù)狀態(tài)）isseriousandcouldbefatalPetitMal（小發(fā)作）minorepilepsyusuallychildhoodandadolescenceStaring（凝視）,rapideyeblinking(眨眼10sec.to2min.)lossofconsciousness,usuallynofallingormotorconvulsionsupto100petitmalseizuresperdayClassificationofPartialSeizuresSimplepartialseizures

（簡(jiǎn)單局限發(fā)作）OccurinasingleareaofthebrainandmayinvolveasinglemusclemovementorsensoryalterationComplexpartialseizuresInvolvecomplexsensorychangesMotorchangesmayincludeinvoluntaryurination,chewingmotions,diarrhea,etc.FactorsAffectingtheFormofaSeizure

LocationofthecellsthatinitiatetheelectricaldischargeNeuralpathwaysthatarestimulatedbytheinitialvolley（齊射）ofelectricalimpulsesMechanismofseizuresGeneralizedseizuresBegininoneareaofthebrainandrapidlyspreadthroughoutbothhemispheresofthebrainPartialseizuresorfocalseizuresInvolveoneareaofthebrainanddonotspreadthroughouttheentirebrain§2DrugsforEpilepsy(p97)DrugmechanismsforEpilepsyBlocktheinitiationoftheelectricaldischargefromthefocalarea,orpreventthespreadoftheabnormalelectricaldischargetoadjacentbrainareasHowtodo:Blockadeofvoltage-gatedchannels:Na+,Ca++EnhancementofinhibitoryGABAimpulsesInterferencewithexicitatoryglutamatetransmissionDrugsforTreatingTonic–ClonicSeizures

Hydantoins(乙內(nèi)酰脲類,Phenytoin)BarbituratesBarbiturate-likedrugsHydantoins

乙酰脲類藥物Phenytoin(Dilantin,大侖丁，苯妥英鈉)Treatstonic–clonicseizuresandstatusepilepticus;preventandtreatseizuresafterneurosurgeryPharmacodynemics&Clinicaluses1.firstchoicefortonic-clonicseizureandpartialepilepsy2.trigeminalneuralgia(三叉神經(jīng)痛),glossopharyngealneuralgia（舌咽神經(jīng)痛）3.antiarrhythmiaMechanismsInhibitposttetanicpotentiation(PTP)membranestablizationInhibitvoltage-dependentNa+channelsInhibitvoltage-dependentCa++channelsInhibiteffectsoncalmodulincekinasesystemPharmacokineticsofPhenytoinAweakacid,irregularabsorptionbyp.oEffectiveconcentration:10~20ug/mlElimination:<10ug/ml1storder,t1/2=20h>10ug/ml0order,t1/2=60hAdverseEffectsofphenytoindizziness,visualdisturbances,postureimbalances（共濟(jì)失調(diào)）,Gingival（牙齦）hyperplasia,folicacidmetabolismdisorderAnaphylactic（過(guò)敏）reaction:skinrashes,Fetal（胎兒）hydantoinsyndromeEnzymeinducerOtherantiepilepticdrugsCarbamazepine(Tegretol，卡馬西平)relatedtotricyclicantidepressantsanticonvulsantproperties:excellentinstoppingseizuresAnalgesic（止痛）properties:trigeminalneuralgia（三叉神經(jīng)痛）S/E:drowsiness,dizziness,nausea,vomiting,liverdisorders,CVdisorders,bonemarrowdepressionBarbituratesexcellentanticonvulsantsreducesexcitabilityofnervecellsPhenobarbital(苯巴比妥，Luminal)Emergencycontrolofstatusepilepticusandacuteseizures;managementoftonic–clonicandcorticalfocalseizures;treatmentofsimplepartialseizuresPrimidone（撲癇酮）

Treatmentoftonic–clonicorpartialseizuresEthosoximide(乙琥胺)InhibittheTtypeCa++channelsFirstdrugofchoiceforabsenceseizure（小發(fā)作）HasrelativelyfewadverseeffectscomparedwithmanyotherantiepilepticdrugsValproicAcid(丙戊酸鈉)petitmalseizuresincreasesGABA(inhibitoryneurotransmitter)S/E:nausea,vomiting,diarrhea,interfereswithplatelets,livertoxicityBenzodiazepinesdrugsofchoicetostopconvulsionsDiazepam(地西泮,安定Valium)Emergencycontrolofstatusepilepticus（癲癇持續(xù)狀態(tài)）andacuteseizures;Clonazepam(氯硝西泮，Klonopin)Usedforthetreatmentofabsence(petitmal)seizures.Flunarizine（氟利桂嗪）Antiepilepsirin（抗癇靈）Lamotrigine（拉莫三嗪）Topiramate（托吡酯）PatientTeachingforPatientsTakingAntiepilepticAgentsDrugnameandprescribeddosageMeasuresforavoidanceofadverseeffectsWarningsignsthatmayindicatepossibleproblemsNeedformonitoringandevaluation§3Anticonvuls