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Antiepilepticdrugs
Dr.Hj.RikaYuliwulandari,PhD
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Primary
Types of s
(focal)
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Definisi Tujuan antiepilepticdrugs Classificationofantiepilepticdrugs Pharmacologyofantiepilepticdrugs
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Definition Epilepsy:
Recurrentseizuredisorders Sudden Excessive Symptomsdependonthesiteofelectricaldischarge
Convulsionmotorcortex Visual,auditory,olfactoryhallucinations parietaloroccipitalcortex
Antiepilepticdrugs: Treat50%ofpatientwithconvulsion Tappering on tappering off Mekanisme:blok inisiasi lonjakan elektrik dari focalareaatau
mencegah penyebaran lonjakan elektrik abnormalke areaotak lainnya Goal:
Stopconvulsion Notharmfulforcerebralneurons Normalactivityposttreatment
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Antiepileptic Drugs Classification
Golongan hidantoin Fenitoin (difenilhidantoin), mefenitoin, etotoin
Golongan barbiturat Fenobarbital, primidon
Golongan suksinimid Etosuksimid, metsuksimid, fensuksimid
Karbamazepin Golongan benzodiazepin
Diazepam, klonazepam, nitrazepam Asam valproat Antiepilepsi lain
Lamotrigin, gabapentin, Asetazolamid, vigabatrin,
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PrincipleMechanismsofActionofAntiepilepticDrugs
DecreaseactivityofvoltagedependentNa+channels
DecreaseactivityofvoltagedependentCa+channels
AugmentGABA activity Decreaseglutamatereceptoractivity Drugtreatmentdeppends onthespecifictypeofseizure
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ClinicalApplicationofAntiepilepticDrugs
Typesofepilepsy Drugs1 Drugs2
PARTIAL
Simple Phenitoin,CBZ Phenobarbital,Primidone
Complex Phenitoin,CBZ Primidone
GENERALIZED
TonicClonic(grandmal)
Phenytoin, CBZ Phenobarbital,Primidone,Valproic acid
Absence(Petitmal)
Ethosuximide Valproic acid,Clonazepam
Myoclonic Valproic acid,Clonazepam
Febrile Seizuresinchildren
Phenobarbital Primidone
Statusepilepticus
Phenitoin,Diazepam Phenobarbital
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WhentoWithdrawAntiepilepticDrugs?
Normalneurologicalexamination NormalIQ NormalEEGpriortowithdrawal Seizure freefor25yrs orlonger NOjuvenilemyoclonicepilepsy
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Phenytoin Hydantoin group
Phenytoin (Dephenylhydantoin) Mefenytoin Etotoin
Pharmacology: Nafluxinneurons stabilizesneuronalmembranesto
depolarization Ca influx Effect:Drowsiness,lethargywithouthypnosis Absorption:slow(i.m.isdepositedininjectionsitefor5days) Distributionisrapid Highconcentrationinbrain Mostlyboundtoplasmaalbumin T1/2:742hrs Proteinbinding:90%
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Metabolism:hepatichydroxylationsystem Druginducedtoxicityiseasytooccur(needtightmonitoring!!!) Geneticvariationaffectthedrugmetabolisms Dose:200400mg(510mg/kgbw) Se:
GIproblems:nausea,vomiting Gingivalhyperplasiaandcoarseningoffacialfeaturesesp.inchildren Megaloblastic anemia Behavioralchanges:confusion,hallucination,drowsiness Inhibitinsulinsecretioncausinghyperglycemiaandglycosuria Pregnancy:teratogenic effect fetalhydantoin syndrome(cleftlip,cleft
palate,congenitalheartdisease,slowgrowthandmentaldeficiency) Indication:allpartialseizures,tonicclonic seizures,statusepilepticus
(noteffectiveforabsenceseizures) Druginteraction:
InhibitionofPhenytoin:Chloramphenicol,Dicumarol,Cimetidine,Sulfonamide,Isoniazid
IncreasePhenytoin metabolism:Carbamazepine,Teophylline,Phenobarbital Phenytoin induceP450system increasemetabolismofotherantiepileptics,
anticoagulants,oralcontraceptives,quinidine,Doxycycline,Cyclosporin,Mexiletine,Methadone,Levodopa
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Carbamazepine Moa:blockingNachannel inhibitpropagationofabnormalimpulsesin
thebrain Pharmacology:
Absorption:slow Highlipidsolubility rapidlyenterthebrain EnhancehepaticP450system inchronicadministration,t1/2decrease Dose:4001200mg(Child:1030mg/kgbw) T1/2:824hrs Proteinbinding:75% Poonly Se:
Chronicuse:stupor,coma,respiratorydepression,drowsiness,vertigo,ataxia,blurredvision
GIproblem:nausea,vomiting Aplastic anemia,agranulocytosis,thrombocytopenia Potentiallyinducelivertoxicity(needfrequentliverfunctiontest!!!!)
Druginteraction: Allert:Carbamazepine andmostotherantiepilepticdrugsrequiredgradual
dosetitrationtofulldoseoverdaystoweeks,exceptPhenytoin
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Phenobarbital Familyofbarbiturate:
Phenobarbital Primidone
Pharmacology: Moa:Potentiateinhibiton effectofGABA (gammaaminobutyric
acid)mediatedneurons Absorption:
Oral:wellabsorbed PotentinducerofP450 Almost75%isinactivatedinliver,therestisexcretedthroughkidney
Se: Sedation,ataxia,nystagmus,vertigo,acutepsychoticreactions Sensitiveindividual:nausea,vomiting,morbiliform rash Highdose:agitation,confusion Discontinuation:reboundseizures
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Primidone
ResemblesPhenobarbital Orallywellabsorbed Poorproteinbinding
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Valproic acid Moa:enhanceGABA actionatinhibitorysynapses Uses:mosteffectiveformyoclonic seizures Pharmacology:
Orallywellandrapidabsorbed Proteinbinding:90% 3%excretedunchanged,therestbecomeactivemetabolite MetabolizedinliverbyP450system Dose:7503000mg(child:1560mg/kgbw) T1/2:616hrs Se:
nausea,vomiting,sedation,ataxia,tremor Rashandalopeciainsomeindividuals Increasebleedingtimeduetothrombocytopeniaandinhibitionofplatelet
aggregation Druginteraction:
Inhibitsphenobarbital metabolismcausingincreasecirculatinglevelofthedrug
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Ethosuximide FamilyofSuximide
Ethosuximide,Metsuximide,Fensuximide Pharmacology:
Moa:inhibitCachannelinneuronTcellofthalamus Wellabsorbedorally Proteinbinding:0% 25%excretedunchangedinurine 75%isinactivatedinliver DoesnotinduceP450system Dose:5001500mg(child:1530mg/kgbw) T:2060hrs Se:
stomachirritation,nausea,vomiting,drowsiness,lethargy,dixxiness,restlessness,agitation,anxiety,inabilitytoconcentrate
Sensitiveindividual:StevensJohnsonssyndrome,urticatia,leukopenia,aplastic anemia,thrombocytopenia
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Diazepam
FamilyofBenzodiazepine Diazepam,Klonazepam,Nitrazepam
Pharmacology: Docofacutetreatmentinstatusepilepticus Dose:
520mgiv(slow) canberepeatedafter1520mnt Infant:0.5mg/kgbw perrectal,child
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Otherantiepilepticdrugs Gabapentin:
AnalogofGABA Proteinbinding:0% Excretedunchangedinurine minimizedruginteraction Dose:9003600mg T1/2:57hrs Se:mildCNS
Lamotrigine: Moa:inhibitglutamateandaspartate release,blockssodiumchannels,
preventsrepetitivefiring Proteinbinding:55% Metabolizedinliver Dose:100600mg T1/2:1570hrs Se:mildCNSeffect,rash Druginteraction:
T1/2isinhibitedbyP450enzymeinducingdrug(CBZ,Phenytoin) TisIncreasedbyvalproic acid
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