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.