Antiepilepticdrugs

Dr.Hj.RikaYuliwulandari,PhD

Types of s (focal)

Primary

Definisi Tujuan antiepilepticdrugs Classificationofantiepilepticdrugs Pharmacologyofantiepilepticdrugs

Definition
Epilepsy:
Recurrentseizuredisorders Sudden Excessive Symptomsdependonthesiteofelectricaldischarge

Convulsion motorcortex 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

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,

PrincipleMechanismsofActionof AntiepilepticDrugs
DecreaseactivityofvoltagedependentNa+ channels DecreaseactivityofvoltagedependentCa+ channels AugmentGABA activity Decreaseglutamatereceptoractivity Drugtreatmentdeppends onthespecifictype ofseizure

ClinicalApplicationof AntiepilepticDrugs
Typesofepilepsy PARTIAL Simple Complex GENERALIZED TonicClonic (grandmal) Absence(Petit mal) Myoclonic Febrile Seizures inchildren Status epilepticus Phenytoin, CBZ Ethosuximide Valproic acid, Clonazepam Phenobarbital Phenitoin,Diazepam Primidone Phenobarbital Phenobarbital,Primidone,Valproic acid Valproic acid,Clonazepam Phenitoin,CBZ Phenitoin,CBZ Phenobarbital,Primidone Primidone Drugs1 Drugs2

WhentoWithdrawAntiepilepticDrugs?

Normalneurologicalexamination NormalIQ NormalEEGpriortowithdrawal Seizure freefor25yrs orlonger NOjuvenilemyoclonicepilepsy

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%

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

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,blurred vision GIproblem:nausea,vomiting Aplastic anemia,agranulocytosis,thrombocytopenia Potentiallyinducelivertoxicity(needfrequentliverfunctiontest!!!!)

Druginteraction:

Allert:Carbamazepine andmostotherantiepilepticdrugsrequiredgradual dosetitrationtofulldoseoverdaystoweeks,exceptPhenytoin

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

Primidone
ResemblesPhenobarbital Orallywellabsorbed Poorproteinbinding

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 metabolismcausingincreasecirculatinglevelofthe drug

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

Diazepam
FamilyofBenzodiazepine
Diazepam,Klonazepam,Nitrazepam

Pharmacology:
Docofacutetreatmentinstatusepilepticus Dose:
520mgiv(slow) canberepeatedafter1520mnt Infant:0.5mg/kgbw perrectal,child<11yr:1mg/kgbw

Se:respiratorytractobstruction,respiratory depression,hypotension,cardiacarrest,sleepy

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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Patophysiology ofconvulsion