1. Anti Epileptic Drugs

8/7/2019 1. Anti Epileptic Drugs

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Antiepileptic DrugsAntiepileptic Drugs

EpilepsyEpilepsy denotes any disorder characterizeddenotes any disorder characterized

by recurrent seizureby recurrent seizureSeizureSeizure is a transient disturbance of cerebralis a transient disturbance of cerebralfunction due to an abnormal paroxysmalfunction due to an abnormal paroxysmalneuronal discharge in the brainneuronal discharge in the brain


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Nature & Mechanism of SeizuresNature & Mechanism of Seizures

TheThe seizuresseizures areare causedcaused byby

occasionaloccasional ,, sudden,sudden, excessive,excessive, andand locallocaldischargesdischarges ofof greygrey matterandmatterand aa generalizedgeneralized

convulsionconvulsion resultedresulted whenwhen normalnormal brainbrain

tissuetissue waswas invadedinvaded byby thethe seizureseizure activityactivity

initiatedinitiated inin thethe abnormalabnormal focusfocus..


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Classification of Epilepsy / SeizuresClassification of Epilepsy / Seizures

A.A. Partial (Focal)Partial (Focal)

Simple PartialSimple Partial

Symptoms depend on the region of the cortexSymptoms depend on the region of the cortex

involved.Convulsions or light flashes withoutinvolved.Convulsions or light flashes without

loss of consciousness.loss of consciousness.

C

omplex PartialC

omplex PartialAuraAura--amnesiaamnesia--abnormal behaviour.abnormal behaviour.


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B.B. GeneralisedGeneralised1.1. Grand mal / Gen. Tonic Clonic EplipsyGrand mal / Gen. Tonic Clonic Eplipsy

2.2. Petit mal / Absence Seizures EpilepsyPetit mal / Absence Seizures Epilepsy

3.3. Myoclonic SeizuresMyoclonic Seizures4.4. Atonic SeizuresAtonic Seizures

5.5. Infantile SpasmInfantile Spasm


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Mechanism of ActionMechanism of Action

TheyThey actact byby twotwo waysways

1.1. SuppressingSuppressing thethe activityactivity ofof epilepticepileptic //

epileptogenicepileptogenic focusfocus..

2.2. PreventingPreventing thethe spreadspread ofof epilepticepileptic //

epileptogenicepileptogenic activityactivity..MainlyMainly theythey actact byby 22ndnd Mechanism,Mechanism, WhichWhich

isis duedue toto twotwo mainmain actionsactions..


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EnhancementEnhancement ofof GA BAsGABAs mediatedmediated synapticsynaptic

inhibitioninhibition..

UseUse dependentdependent blockblock ofof sodiumsodium channelchannel functionfunction.. thethe electricalelectrical excitibilityexcitibility..

OtherOther MechanismMechanism inin SomeSome CasesCases::--

InhibitionInhibition ofof TT.. TypeType Ca++Ca++ ChannelsChannels..

BlockBlock ofof GlutamateGlutamate ReceptorsReceptors..


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CLASSIFICATIONCLASSIFICATION

I. ChemicalI. Chemical

BarbituratesBarbiturates

PhenobarbitonePhenobarbitone

Methyl phenobarbitoneMethyl phenobarbitone

MetharbitalMetharbital

Hydantion DerivativesHydantion Derivatives

PhenytoinPhenytoin

MephenytoinMephenytoin EthotoinEthotoin


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Valproic Acid DerivativesValproic Acid Derivatives

Sodium ValproateSodium Valproate

Valproic AcidValproic Acid

IminostilbinesIminostilbines

CarbamazepineCarbamazepine

OxcarbamazepineOxcarbamazepine


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SuccinimidesSuccinimides

EthosuximideEthosuximide MethsuximideMethsuximide

PhensuximidePhensuximide

BenzodiazepinesBenzodiazepines

DiazepamDiazepam ClonazepamClonazepam

NitrazepamNitrazepam


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Newer DrugsNewer Drugs

GABA AnalogueGABA AnalogueVigabatrinVigabatrin GabapentinGabapentin

TiagabinTiagabin

MiscelleneousMiscelleneousLomotrigineLomotrigine FelbamateFelbamate

TopiramateTopiramate ZonisamideZonisamide


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II. Therapeutic ClassificationII. Therapeutic ClassificationA.A. Drugs used in Partial (Focal) EpilepsyDrugs used in Partial (Focal) Epilepsy

1.1. ForSimple

PartialFor

Simple

Partial EpilepsyEpilepsy

PhenytoinPhenytoin CarbamazepineCarbamazepine

PhenobarbitonePhenobarbitone PrimidonePrimidone

VigabatrinVigabatrin LamotrigineLamotrigine

FelbamateFelbamate GabapentineGabapentineTopiramateTopiramate

2.2. For Complex Partial or Psychomotor or TemporalFor Complex Partial or Psychomotor or Temporallobe Epilepsylobe Epilepsy andand Jacksonian EpilepsyJacksonian Epilepsy

PhenytoinC

arbamazepinePhenytoinC

arbamazepinePrimidone GabapentinePrimidone GabapentineVigabatrin TopiramateVigabatrin Topiramate


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Drugs used for Febrile Seizures in ChildrenDrugs used for Febrile Seizures in Children

PhenobarbitonePhenobarbitone

PrimidonePrimidone


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5.5.Status EpilepticusStatus Epilepticus

Diazepam I/VDiazepam I/V (20(20--30mg)30mg)

Fosphenytoin / PhynytoinFosphenytoin / Phynytoin (13(13--18 mg/kg)18 mg/kg)Phenobarbitone I/VPhenobarbitone I/V (100(100--200 mg)200 mg)

Thiopentone sodium I/VThiopentone sodium I/V


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PhenytoinPhenytoin

Has selective antiepileptic effect and do not produceHas selective antiepileptic effect and do not producesignificant drowsiness.significant drowsiness.

Mechanism of ActionMechanism of Action

Act by stabilizing the neuronal membrane and preventAct by stabilizing the neuronal membrane and preventthe spread of seizure discharges.the spread of seizure discharges.

Sodium channels exist in three forms,Sodium channels exist in three forms,

Resting,Resting,ActivatedActivated

InactivatedInactivated


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Phenytoin delays the recovery of NaPhenytoin delays the recovery of Na++ channelschannels

from inactivated state thus reducing thefrom inactivated state thus reducing theneuronal excitability.neuronal excitability.

At high concentrationAt high concentration

Inhibits calcium influx into neuron, reducesInhibits calcium influx into neuron, reduces

glutamate levels and increase response toglutamate levels and increase response toGABA.GABA.


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PharmacokineticsPharmacokinetics

Absorbed slowly through GIT, widelyAbsorbed slowly through GIT, widely

distributed and 90 % protein bound.distributed and 90 % protein bound.

Fosphenytoin is well absorbed after I/MFosphenytoin is well absorbed after I/Minjection.injection.

Metabolized in liver by hydroxylation andMetabolized in liver by hydroxylation and

glucronide conjugation.glucronide conjugation.

Phenytoin exhibit dosePhenytoin exhibit dose--dependent eliminationdependent eliminationor saturation kinetics.or saturation kinetics.


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UsesUses

Generalized tonicGeneralized tonic--clonic seizuresclonic seizures

Partial seizures.Partial seizures.

Trigeminal and other neuralgias.Trigeminal and other neuralgias. Status epilepticus.Status epilepticus.

ArrhythmiasArrhythmias


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Adverse effectsAdverse effects

Hypertrophy and hyperplasia of gums.Hypertrophy and hyperplasia of gums.

Diplopia and ataxia.Diplopia and ataxia.

H

ypersenstivity reactions.H

ypersenstivity reactions. HirsutismHirsutism

HyperglycemiaHyperglycemia

Megaloblastic anemia.Megaloblastic anemia.

OsteomalaciaOsteomalacia

Fetal Hydantoin syndrome (cleft lip, cleft palate)Fetal Hydantoin syndrome (cleft lip, cleft palate)


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At high concentrationAt high concentration

CNSCNS

Vertigo, ataxia, tremors, headache,Vertigo, ataxia, tremors, headache,

nystagmus.nystagmus.GITGIT

Nausea, vomiting and dyspepsiaNausea, vomiting and dyspepsia

CVSCVSHypotension and cardiac arrhythmiasHypotension and cardiac arrhythmias


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CarbamazepineCarbamazepine

Mech of ActionMech of Action

It slows the rate of recovery of NaIt slows the rate of recovery of Na++ channelschannels

from inactivation.from inactivation.PharmacokineticsPharmacokinetics

Absorbed slowly and erratically from GIT,Absorbed slowly and erratically from GIT,

well distributed in the bodywell distributed in the bodyCause enzyme induction.Cause enzyme induction.


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Sedation, drowsiness, vertigo, ataxia, diplopia,Sedation, drowsiness, vertigo, ataxia, diplopia,

blurred vision.blurred vision.

Hypersenstivity reactions, hepatitis.

Hypersenstivity reactions, hepatitis.

Neutropenia, aplastic anemia.Neutropenia, aplastic anemia.


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UsesUses

Generalized tonicGeneralized tonic--clonic seizures and partialclonic seizures and partial

seizures.seizures.

Trigeminal and other neuralgias.Trigeminal and other neuralgias. Bipolar disorder.Bipolar disorder.


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BARBITURATESBARBITURATES


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BARBITURATESBARBITURATES

Four derivativesFour derivatives

PhenobarbitalPhenobarbital

MephobarbitalMephobarbital MetharbitalMetharbital

PrimidonePrimidone


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PharmacokineticsPharmacokinetics

Rapidly & complete absorbed on oral admRapidly & complete absorbed on oral adm

Lipid soluble & can cross BBBBPBLipid soluble & can cross BBBBPB

Hepatic metHepatic met

Urinary excretionUrinary excretion


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Mechanism of actionMechanism of action GABAergicGABAergic

GABAmimeticGABAmimetic


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Clinical usesClinical uses

Rx of partial & gen tonic clonic seizuresRx of partial & gen tonic clonic seizures

Th. Level ranges from 10Th. Level ranges from 10--40mcg/ml40mcg/ml

ToxicityToxicity


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Sodium valproateSodium valproate

BroadBroad--spectrum antiepileptic drugspectrum antiepileptic drug

Mechanism of actionMechanism of action

Delays the recovery of sodium channels fromDelays the recovery of sodium channels frominactivation.inactivation.

Blocks TBlocks T--type calcium current in thalamictype calcium current in thalamic

neurons.neurons.Increase the activity of GABA in brain.Increase the activity of GABA in brain.


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Clinical useClinical use

Absence seizures with concomitant generalizedAbsence seizures with concomitant generalized

tonic clonic attacks.tonic clonic attacks.

Myoclonic seizures.Myoclonic seizures. Management of bipolar disorder and migraineManagement of bipolar disorder and migraine

prophylaxis.prophylaxis.


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GIT nausea, vomiting, anorexia and abdominalGIT nausea, vomiting, anorexia and abdominal

discomfort.discomfort.

C

NS

sedation, ataxia and tremors.C

NS

sedation, ataxia and tremors. Skin rash, alopeciaSkin rash, alopecia

Idiosyncratic toxicity.Idiosyncratic toxicity.

TeratogenicityTeratogenicityNeural tube defects.Neural tube defects.


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BenzodiazepinesBenzodiazepines

Diazepam and lorazepam are effective inDiazepam and lorazepam are effective in

controlling status epilepticus.controlling status epilepticus.

C

lonazepam is used in absence and myoclonicC

lonazepam is used in absence and myoclonicseizures.seizures.

I/V administration of diazepam is done inI/V administration of diazepam is done in

treatment of status epilepticus, tetanus,treatment of status epilepticus, tetanus,eclamptic convulsions, febrile and drug inducedeclamptic convulsions, febrile and drug induced

convulsions.convulsions.


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EthosuxamideEthosuxamide

Mechanism of actionMechanism of action

It reduces the lowIt reduces the low--threshold (Tthreshold (T--type)type)

calcium currents in thalamic neurons.calcium currents in thalamic neurons.Clinical useClinical use

Absence seizuresAbsence seizures

Adverse effectsAdverse effectsGastric distress, blood dyscriasias.Gastric distress, blood dyscriasias.


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PRIMIDON

EPRIMIDON

E


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PRIMIDONEPRIMIDONE

ChemicallyChemically 22--desoxyphenobarbitaldesoxyphenobarbital

Met to phenobarbital & phenylethylmelonamideMet to phenobarbital & phenylethylmelonamide

All three are activeAll three are activemetabolites/anticonvulsantssssmetabolites/anticonvulsantssss


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UsesUses

Absence seizuresAbsence seizures

MyoclonicMyoclonic

Partial and generalized tonicPartial and generalized tonic--clonic seizuresclonic seizures Mania and bipolar disorder.Mania and bipolar disorder.

1. Anti Epileptic Drugs

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