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.

    Tr