Anti- epileptic Drugs

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ANTI-EPILEPTIC DRUGSManagement of various of forms of epilepsies including treatment of status epilepticus Status of newer anti-epileptic drugs in treatment of epilepsiesCHOYTOO ShikshaRoll No 12CONTENTSIntroductionTypes of seizuresBrief description of each type of seizures and their managementStatus of newer anti-epileptic drugsINTRODUCTIONAim : control and totally prevent all types of seizures at an acceptable level of S/ETreatment should be started early with single low doseSimple therapyDrug withdrawal should be gradualPregnancy : treatment not stopped dose is reduced folic acid is supplemented in 1st and 2nd trimester along with vit k in last trimesterTYPES OF SEIZURESGENERALISED SEIZURESPARTIAL SEIZURESGeneralized Tonic Clonic SeizuresSimple partial seizureAbsence seizuresComplex partial seizuresAtonic seizuresSimple or complex partial seizures secondary to generalised seizuresMyoclonic seizuresInfantile spasmsGTC SEIZURESudden loss of consciousness

Tonic phase - 1min - sustained muscle contraction

Clonic phase - 2-4 min - muscle relaxation

CNS depression follows and patient goes into sleep

PARTIAL SEIZURESSimple Partial Seizures (Jacksonian)

Involves one side of the brain at onset.motor, sensory or speech disturbances.Confined to a single limb or muscle group.Last for 20-60 sNo alteration of consciousness.

MANAGEMENT OF PS AND GTCSCarbamazepine - preferred drug in PSPreferred in young girls cosmetic effects

Valproate - used in GTCScautious with children-hepatotoxicity

Alternative s- Lamotrigine, gabapentin & topiramate are good alternatives (either add on or as monotherapy)

Complete control in 90% patients with generalised seizures but, only 50% in patients with partial seizures.TypeFirst choiceSecond choiceAdd onGeneral tonic-clonic Simle Partial seizuresCarbamazepine, phenytoinValproate, phenobarbitoneLamotrigine, gabapentin, topiramate, primidone, levetiracetamPARTIAL SEIZUREComplex Partial SeizuresProduces confusion and inappropriate or dazed behavior.Motor activity appears as non-reflex actions.Automatisms (repetitive coordinated movements). Purposeless movements like lips smacking or hand wringingLast for 30 s to 2 min, preceded by auraConsciousness is impaired or lost.

MANAGEMENT OF CPSIt is usually difficult to controlCarbamazepine + phenytoin or valproate is givenRefractory cases: levetiracetam, lamotrigine, gabapentin, topiramate or zonisamide.

TypeFirst choiceSecond choiceAdd onComplez partial seizureCarbamazepine ValproatePhenytoin

Gabapentin LamotrigineLevetiracetam

ClobazamZonicamideTopiramateABSENCE SEIZURESudden onset of impaired conciousnessWith staringLast less than 30 min attack may be associated with mild clonic jerking of the eyelids or extremitiespostural tone changesautonomic phenomena

MANAGEMENT OF ABSENCE SEIZUREBoth valproate and Ethosuximide can be useValproate : most commonly used - prevent kindling & emergence of GTCSLamotrigine is a good alternativeClonazepam limited by sedative effects, and development of toleranceclobazam- more sustained response

TypeFirst choiceSecond choiceAdd onabsencevalproateEthosuximide, lamotrigineClobazam, clonazepamATONIC SEIZURESAkinetic epilepsyUnconsciousness , Relaxation of all musclesSudden loss of postural toneDue to excessive inhibitory discharges Patient may fallMYOCLONIC SEIZURESSudden , brief, shock like contraction of musclesIt may be limited to one part of the body or whole body

MANAGEMENT OF ATONIC & MYOCLONIC SEIZURESValproate is preferredLamotrigine preferred alternativeTopiramate & levetiracetam may be added in unresponsive or poor response

TypeFirst choiceSecond choiceAdd onmyoclonicvalproateLamotrigine, topiramateLevetiracetam, clonazepamatonicvalproateClonazepam, clobazamlamotrigineMANAGEMENT OF FEBRILE CONVULSIONS AND INFANTILE SPASMSRectal diazepam 0.5mg/kg

Anti epileptics ineffective in infantile spasms

corticosteroids provide symptomatic relief.

Valproate, clonazepam or Vigabatrin has some efficacyTypeFirst choiceSecond choiceAdd onfebrileDiazepam-rectalSTATUS EPILEPTICUScontinuous seizure lasting more than 30 min, or two or more seizures without full recovery of consciousness between any of them.medical emergency associated with significant morbidity and mortalityTypeFirst choiceSecond choiceAdd onStatus epilepticusLorazepam & diazepam IVFosphenytoin, phenobarbitoneGAMANAGEMENT OF STATUS EPILEPTICUSLorazepam 0.1 mg/kg IV inj at 2mg/min (effective and longer acting anticonvulsant)If lorazepam is unavailable,Diazepam 5-10 mg every 10-15 min (max. 30 mg)Phenytoin 500 1000 mg (max 1000 in 24 hr) IVNowadays fosphenytoin is preferedmax 1000 phenytoin equivalentNo respond to phenytoin, phenobarbitone is used , 100 -200 mg

Seizure continues GA with propofol or thiopental in the last resort.This is guided by EEG.General measuresMaintenance of airways , oxygenation, fluid and electrolyte balance, BP, Pulse rate

NEWER ANTI-EPILEPTIC DRUGLAMOTRIGINEGABAPENTINETOPIRAMATELEVETIRACETAMZONISAMINETIAGABINEVIGABATRINE

LAMOTRIGINEDose 50mg/day initially, increase upto 300mg/day as needed not to be used in childrenMOA: same as carbamazepineBroad spectrum anti-epilepticAbs orally, half life 24 hoursBetter tolerated than carbamazepine or phenytoin, no negative effect on cognitive function

GABAPENTINEModifies maximal electro shock and inh. PTZ induced clonic seizureAdd on to first line of drugCan even be used as monotherapyReduces seizure frequency in refractory partial seizuresNo change in primary antiepileptic drug is required when gabapentine is addedDose: start with 300 mg OD, inc up to 300- 600mg TDS as requiredTOPIRAMATEWeak carbonic anhydrase inhibitor broad spectrum anti convulsant activity in partial tonic seizures & kindling modelMonotherapy & adjuvant drugGreat results in myoclonic epilepsyDose: initially 25mg OD increase weekly upto 100-200mg BD as required

ZONISAMIDEWeak carbonic anhydrase inhibitorAdd on drug in refractory partial seizuresDose : 25-100mg BD

LEVETIRACETAMUnique- suppresses kindled seizures but ineffective against PTZ or maximal electroshock.

Free of drug interactions. Good tolerability hence, use increasing in complex partial seizures, grand mal epilepsy & myoclonic epilepsy.

Dose : 0.5mg BD, increase upto 1.0g BD

TIAGABINE & VIGABATRINTiagabine : Potentiates GABA

Add on therapy of partial seizures

Vigabatrin : (-) of GABA transaminase

effective in refractory epilepsy

only adjuvant medication.

REFERENCES

padmaja udaykumar med. pharmacologyTHANK YOU