Anti- epileptic Drugs

ANTI-EPILEPTIC DRUGS

•Management of various of forms of epilepsies including treatment of status epilepticus

•Status of newer anti-epileptic drugs in treatment of epilepsies CHOYTOO Shiksha

Roll No 12

CONTENTS

• Introduction

• Types of seizures

• Brief description of each type of seizures and

their management

• Status of newer anti-epileptic drugs

INTRODUCTION

• Aim : control and totally prevent all types of seizures at an

acceptable level of S/E

• Treatment should be started early with single low dose

• Simple therapy

• Drug withdrawal should be gradual

• Pregnancy : treatment not stopped

dose is reduced

folic acid is supplemented in 1st and 2nd

trimester along with vit k in last trimester

TYPES OF SEIZURES

GENERALISED SEIZURES

PARTIAL SEIZURES

Generalized Tonic ClonicSeizures

Simple partial seizure

Absence seizures Complex partial seizures

Atonic seizures Simple or complex partial seizures secondary to generalised seizures

Myoclonic seizures

Infantile spasms

GTC SEIZURE

• Sudden 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 SEIZURES

Simple 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 s

No alteration of consciousness.

MANAGEMENT OF PS AND GTCS• Carbamazepine - preferred drug in PS

Preferred in young girls – cosmetic effects

• Valproate - used in GTCS cautious with children-hepatotoxicity

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

• Complete control in 90% patients with generalised seizures but, only 50% in patients with partial seizures.

Type First choice Second choice Add on

General tonic-clonicSimle Partial seizures

Carbamazepine, phenytoin

Valproate, phenobarbitone

Lamotrigine, gabapentin, topiramate,primidone, levetiracetam

PARTIAL SEIZURE

Complex Partial Seizures

• Produces confusion and inappropriate or dazed behavior.

• Motor activity appears as non-reflex actions.

• Automatisms (repetitive coordinated movements).

• Purposeless movements like lips smacking or hand wringing

• Last for 30 s to 2 min, preceded by aura

• Consciousness is impaired or lost.

MANAGEMENT OF CPS• It is usually difficult to control

• Carbamazepine + phenytoin or valproate is

given

• Refractory cases:

levetiracetam, lamotrigine, gabapentin, topiramate or zonisamide.

Type First choice Second choice Add on

Complez partial seizure

CarbamazepineValproatePhenytoin

GabapentinLamotrigineLevetiracetam

ClobazamZonicamideTopiramate

ABSENCE SEIZURE

• Sudden onset of impaired conciousness

• With staring

• Last less than 30 min

• attack may be associated with mild clonic

jerking of the eyelids or extremities

• postural tone changes

• autonomic phenomena

MANAGEMENT OF ABSENCE SEIZURE

• Both valproate and Ethosuximide can be use

• Valproate : most commonly used - prevent kindling

& emergence of GTCS

• Lamotrigine is a good alternative

• Clonazepam limited by sedative effects, and

development of tolerance

• clobazam- more sustained response

Type First choice Second choice

Add on

absence valproate Ethosuximide, lamotrigine

Clobazam, clonazepam

ATONIC SEIZURES• Akinetic epilepsy

• Unconsciousness , Relaxation of all muscles

• Sudden loss of postural tone

• Due to excessive inhibitory discharges

• Patient may fall

MYOCLONIC SEIZURES• Sudden , brief, shock like contraction of muscles

• It may be limited to one part of the body or whole body

MANAGEMENT OF ATONIC &

MYOCLONIC SEIZURES• Valproate is preferred

• Lamotrigine preferred alternative

• Topiramate & levetiracetam may be added in unresponsive or poor response

Type First choice Second choice Add on

myoclonic valproate Lamotrigine, topiramate

Levetiracetam, clonazepam

atonic valproate Clonazepam, clobazam

lamotrigine

MANAGEMENT OF FEBRILE

CONVULSIONS AND INFANTILE SPASMS

• Rectal diazepam 0.5mg/kg

• Anti epileptics ineffective in infantile spasms

• corticosteroids provide symptomatic relief.

• Valproate, clonazepam or Vigabatrin has some efficacy

Type First choice Second choice Add on

febrile Diazepam-rectal

STATUS EPILEPTICUS

• continuous 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 mortality

Type First choice Second choice Add on

Status epilepticus Lorazepam & diazepam IV

Fosphenytoin,phenobarbitone

GA

MANAGEMENT OF STATUS EPILEPTICUS

• Lorazepam 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)

IV

• Nowadays fosphenytoin is prefered

max 1000 phenytoin equivalent

• No 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 measures

▫ Maintenance of airways , oxygenation, fluid and electrolyte balance, BP, Pulse rate

NEWER ANTI-EPILEPTIC DRUG

•LAMOTRIGINE•GABAPENTINE•TOPIRAMATE•LEVETIRACETAM•ZONISAMINE•TIAGABINE•VIGABATRINE

LAMOTRIGINE

• Dose 50mg/day initially, increase upto 300mg/day

as needed

• not to be used in children

• MOA: same as carbamazepine

• Broad spectrum anti-epileptic

• Abs orally, half life 24 hours

• Better tolerated than carbamazepine or phenytoin,

no negative effect on cognitive function

GABAPENTINE

• Modifies maximal electro shock and inh. PTZ induced

clonic seizure

• Add on to first line of drug

• Can even be used as monotherapy

• Reduces seizure frequency in refractory partial seizures

• No change in primary antiepileptic drug is required

when gabapentine is added

• Dose: start with 300 mg OD, inc up to 300- 600mg

TDS as required

TOPIRAMATE

• Weak carbonic anhydrase inhibitor

• broad spectrum anti convulsant activity in partial

tonic seizures & kindling model

• Monotherapy & adjuvant drug

• Great results in myoclonic epilepsy

• Dose: initially 25mg OD increase weekly upto 100-

200mg BD as required

ZONISAMIDE

• Weak carbonic anhydrase inhibitor

• Add on drug in refractory partial seizures

• Dose : 25-100mg BD

LEVETIRACETAM

• Unique- 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 & myoclonicepilepsy.

• Dose : 0.5mg BD, increase upto 1.0g BD

TIAGABINE & VIGABATRIN

• Tiagabine : Potentiates GABA

• Add on therapy of partial seizures

• Vigabatrin : (-) of GABA transaminase

• effective in refractory epilepsy

• only adjuvant medication.

REFERENCES

• padmaja udaykumar – med. pharmacology

•THANK YOU