AnticonvulsantTherapy-BCEpilepsySociety：抗惊厥疗法-公元前癫痫协会课件.ppt

1、Anticonvulsant TherapyDr.Sia MichoulasPediatric Epilepsy FellowBC Childrens HospitalOutlinenIntroductionnWhy do we treat seizuresnHow do we select anticonvulsant medicationsnAdverse EffectsnDrug InteractionsnAnticonvulsants and PregnancyEpidemiology of Epilepsyn1-2%of Canadians40,000 people in BCnCe

2、rebral Palsy 20%nAutism 20-30%nDevelopmental Delay-20%n3rd most common neurologic disorderAfter Stroke and AlzheimersSeizure ManifestationsSeizure OccurrencenUp to 10%of the population will experience a single seizure during their lifetimemajority due to an acute reversible cause:fever,metabolic cha

3、nges,drug intoxication/withdrawal.nSince seizures dont recur in these patients after the provoking factor has been corrected,they dont have a diagnosis of epilepsy.nA diagnosis of epilepsy is made after a patient has had 2 or more unprovoked seizuresWhat was the cause of the seizure?nEpileptic seizu

4、res are symptoms due to a variety of causesnDetermining the underlying cause has implications for both treatment and prognosisCauses epileptic seizuresIdiopathic(Genetic)-50%of casesChildhood and Juvenile absence epilepsyBenign rolandic epilepsy of childhoodJuvenile myoclonic epilepsy(JME)Symptomati

5、c-50%of casesMalformations of brain developmental Tuberous Sclerosis Brain InfectionStrokeTraumatic brain injuryTumor Clinical Factors Associated With Genetic Versus Symptomatic EpilepsyWhy Do We Treat Seizures?nPrevent Falls&InjuriesnEmployment&EducationnPsychosocial well-beingAnxietyEmbarrassmentL

6、oss of self-controlDrivingLife-style restrictionMedicationsnVery OldBromides(1861)nOldPhenobarbital(1912)Phenytoin(DilantinR)(1936)Diazepam(ValiumR)(1960s)Carbamazepine(TegratolR)(1974)Valproic Acid(DepakoteR)(1978)nNewClobazam(FrisiumR)Lamotrigine(LamictalR)Topiramate(TopamaxR)Vigabatrin(SabrilR)nE

7、ven NewerLevetiracetam(KeppraR)Oxcarbazepine(TrileptalR)nThe NewestLacosamide(VimpatR)Rufinamide(BanzelR)Ezogabine(PotigaR)n(Retigabine in Europe)When do you consider starting treatment?nAfter first unprovoked seizure 50%of patients will have a 2nd seizure.This needs to be balanced against the poten

8、tial side-effects and cost of medication.nIn general treatment is started after the 2nd seizure.How effective are medications?n70%of patients will respond(1st or 2nd drug)nIf 2 appropriate drugs fail3rd drug:approximate 5%success ratenIf 3rd drug fails:“refractory epilepsy”Other treatmentsnKetogenic

9、 dietnEpilepsy SurgeryGoals of TreatmentnComplete Suppression of Seizures with NO side-effectsnMaintain/Restore patients lifestyleCase#1nMark is an 7 year boy seen in the neurology clinic accompanied by his mom.Teachers have noticed“staring spells”at school.VIDEOPanayiotopoulos CP.Typical Absence.Ne

10、urology Medlink.June 2007Principles of AED therapy1.Select most appropriate drugSeizure typeEpilepsy SyndromeIndividual patient factorsadverse effect,cost,patient-lifestyledosing scheduleCo-morbiditiesPrinciples of AED therapy2.Optimize Dosagestart low dose,titrate up to maximum doseMinimize initiat

11、ion related side-effectsEnd Point:nseizures controlled or side-effects occurPrinciples of AED therapynDrug level monitoringTarget blood drug level nHelpful in guiding dose adjustmentsTreat the INDIVIDUALnNOT the therapeutic rangeAdverse EffectsAdverse EffectsnInitiation&Dose related adverse effectsn

12、Idiosyncratic“allergic”reactionsCase#1 continuednMarks mom calls your office 2 weeks later.Patient has been increasing the medication every 5 days but noticing that she is more“sleepy”during the day.Adverse EffectsnInitiation&Dose related adverse effectsImportant to recognizeSeldom are serious rever

13、siblenDecreasing medicationnDiscontinuing medicationValproic Acid(DepakoteR)nAdvantagesWell toleratedBroad spectrumNo effect on BCPnDisadvantagesWeight gainTremorHair thinningPlatelet dysfunctionDrug interactions“allergic”reactionsAvoid in PregnancyCase#2nSarah 14 year old girl.She has experience 2

14、brief generalized tonic-clonic seizures.nDecision is made start anticonvulsant medication.nShe is started on lamotrigine(LamictalR)Lamotrigine(LamictalR)nAdvantagesEffectiveWell-toleratedTwice dailynDisadvantagesAllergic RashTitrate SlowlyCase#2 continuednSarah returns to your office 3 weeks later.n

15、She has developed a rash and fever.Idiosyncratic“allergic”reactionsnUnpredictablenNOT dose-dependentnUsually occur early in the course of treatmentnRange:Mild-severenRare:1 in 20,000 50,000Idiosyncratic“allergic”reactionsnSkin RashUsually within 4 6 weeksTitrate dose up slowlyMild-SeverenReversible

16、if discontinued early!AED:lamotrigine 1:1000-2000Others:phenytoin,carbamazepine,phenobarbitalIdiosyncratic“allergic”reactionsnLiverUsually occurs early in treatmentCan be reversible if medication is stopped earlynBloodSymptoms:nBleeding,bruising,persistent infectionsCarbamazepine(TegratolR)nAdvantag

17、esEffectiveWell toleratednDisadvantagesDizziness/unsteady“allergic”reactionDrug InteractionsMay exacerbate seizuresnMyoclonic,absenceCarbamazepinenRare serious&potentially fatal skin reactions:n1 to 6 per 10,000 patientnAsian Ancestry:risk 10 times higherCarbamazepinenGenetic MarkerInherited variant

18、 of a gene(HLA-B 1502 allele),an immune system genePatients with this variant are at a higher riskIt is possible to screen:blood testnAsian Ancestry:prevalence of this allelenHigh Risk:(10-15%)China(Han Chinese),Thailand,Malaysia,Indonesia,Philippines,TaiwannModerate Risk:(5-10%)South AsianLow Risk:

19、(90%of women with epilepsy will have a healthy babynSlightly higher risk for congenital malformationsGeneral population:2-3%Untreated epilepsy:2-5%All anticonvulsant drugs:4-7%Anticonvulsants and PregnancynPlanned PregnancyTalk to doctornIdeally one drug at lowest possible doseMonotherapy:4.5%vs pol

20、ytherapy 7%nFolic Acid0.4mg/day all women of child baring ageHigher dose(4-5mg/day):women with epilepsy of child baring ageConclusionnEpilepsy is commonnWe treat seizures to prevent injury and maintain active lifestylenWe select anticonvulsant medicationsSeizure types,drug profile,individual factorsnAdverse EffectsnDrug InteractionsnAnticonvulsants and Pregnancy