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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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Adverse effectsAdverse effects
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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Adverse effectsAdverse effects
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.