AnticonvulsantTherapy-BCEpilepsySociety：抗驚厥療法-公元前癲癇協(xié)會課件

1、Anticonvulsant TherapyDr. Sia MichoulasPediatric Epilepsy FellowBC Childrens HospitalOutlineIntroductionWhy do we treat seizuresHow do we select anticonvulsant medicationsAdverse EffectsDrug InteractionsAnticonvulsants and PregnancyEpidemiology of Epilepsy1- 2 % of Canadians40, 000 people in BCCereb

2、ral Palsy 20%Autism 20-30%Developmental Delay - 20%3rd most common neurologic disorderAfter Stroke and AlzheimersSeizure ManifestationsSeizure OccurrenceUp to 10% of the population will experience a single seizure during their lifetimemajority due to an acute reversible cause: fever, metabolic chang

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

4、s are symptoms due to a variety of causesDetermining 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)Symptoma

5、tic - 50% of casesMalformations of brain developmental Tuberous Sclerosis Brain InfectionStrokeTraumatic brain injuryTumor Clinical Factors Associated With Genetic Versus Symptomatic EpilepsyWhy Do We Treat Seizures?Prevent Falls & InjuriesEmployment & EducationPsychosocial well-beingAnxietyEmbarras

6、smentLoss of self-controlDrivingLife-style restrictionMedicationsVery OldBromides (1861)OldPhenobarbital (1912)Phenytoin (DilantinR)(1936)Diazepam (ValiumR)(1960s)Carbamazepine (TegratolR) (1974)Valproic Acid (DepakoteR) (1978)NewClobazam (FrisiumR)Lamotrigine (LamictalR)Topiramate (TopamaxR)Vigabat

7、rin (SabrilR)Even NewerLevetiracetam (KeppraR)Oxcarbazepine (TrileptalR)The NewestLacosamide (VimpatR)Rufinamide (BanzelR)Ezogabine (PotigaR)(Retigabine in Europe)When do you consider starting treatment?After first unprovoked seizure 50% of patients will have a 2nd seizure. This needs to be balanced

8、 against the potential side-effects and cost of medication.In general treatment is started after the 2nd seizure.How effective are medications?70% of patients will respond(1st or 2nd drug)If 2 appropriate drugs fail3rd drug: approximate 5% success rateIf 3rd drug fails: “ refractory epilepsy”O(jiān)ther t

9、reatmentsKetogenic dietEpilepsy SurgeryGoals of TreatmentComplete Suppression of Seizures with NO side-effectsMaintain/Restore patients lifestyleCase #1Mark is an 7 year boy seen in the neurology clinic accompanied by his mom. Teachers have noticed “staring spells” at school.VIDEOPanayiotopoulos CP.

10、 Typical Absence. Neurology Medlink. June 2007Principles of AED therapySelect most appropriate drugSeizure typeEpilepsy SyndromeIndividual patient factorsadverse effect, cost, patient-lifestyledosing scheduleCo-morbiditiesPrinciples of AED therapy2. Optimize Dosagestart low dose, titrate up to maxim

11、um doseMinimize initiation related side-effectsEnd Point: seizures controlled or side-effects occurPrinciples of AED therapyDrug level monitoringTarget blood drug level Helpful in guiding dose adjustmentsTreat the INDIVIDUALNOT the therapeutic rangeAdverse EffectsAdverse EffectsInitiation & Dose rel

12、ated adverse effectsIdiosyncratic “allergic” reactionsCase #1 continuedMarks 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 EffectsInitiation & Dose related adverse effectsImportant to recogni

13、zeSeldom are serious reversibleDecreasing medicationDiscontinuing medicationValproic Acid (DepakoteR)AdvantagesWell toleratedBroad spectrumNo effect on BCPDisadvantagesWeight gainTremorHair thinningPlatelet dysfunctionDrug interactions“allergic” reactionsAvoid in PregnancyCase # 2Sarah 14 year old g

14、irl. She has experience 2 brief generalized tonic-clonic seizures.Decision is made start anticonvulsant medication.She is started on lamotrigine (LamictalR)Lamotrigine (LamictalR)AdvantagesEffectiveWell-toleratedTwice dailyDisadvantagesAllergic RashTitrate SlowlyCase #2 continuedSarah returns to you

15、r office 3 weeks later.She has developed a rash and fever.Idiosyncratic “allergic” reactionsUnpredictableNOT dose-dependentUsually occur early in the course of treatmentRange: Mild- severeRare: 1 in 20,000 50,000Idiosyncratic “allergic” reactionsSkin RashUsually within 4 6 weeksTitrate dose up slowl

16、yMild - SevereReversible if discontinued early!AED: lamotrigine 1:1000-2000Others: phenytoin, carbamazepine, phenobarbitalIdiosyncratic “allergic” reactionsLiverUsually occurs early in treatmentCan be reversible if medication is stopped earlyBloodSymptoms:Bleeding, bruising, persistent infectionsCar

17、bamazepine (TegratolR)AdvantagesEffectiveWell toleratedDisadvantagesDizziness/unsteady“allergic” reactionDrug InteractionsMay exacerbate seizuresMyoclonic, absenceCarbamazepineRare serious & potentially fatal skin reactions: 1 to 6 per 10, 000 patientAsian Ancestry: risk 10 times higherCarbamazepine

18、Genetic MarkerInherited variant of a gene (HLA-B 1502 allele), an immune system genePatients with this variant are at a higher riskIt is possible to screen: blood testAsian Ancestry: prevalence of this alleleHigh Risk: (10-15%)China (Han Chinese), Thailand, Malaysia, Indonesia, Philippines, TaiwanModerate Risk: (5-10%)South AsiaLow Risk: ( 90% of women with epilepsy will have a healthy babySl