EPILEPSY AND ANTI-EPILEPTIC DRUGS

By: Nimra Ashraf & Syed Usama Shayan

Contents

Epilepsy???Causes???Types Of seizuresAntiepileptic Drugs

INTRODUCTION

It is the 3rd most common neurological disorder after cerebrovascular disease and Alzheimer's disease . Epilepsy is not a single entity but the assortment of different seizure types and syndrome .

What is EPILEPSY ?

It is the sudden , excessive and synchronous discharge of cerebral neurons .

This abnormal activity result in loss of conciousness , abnormal movement or odd behaviours .

EPILEPSY CONTD.The symptoms that are produced in epilepsy depends upon the site of origin of abnormal neuronal firing .

e.g if motor cortex is involved the patient may experience abnormal movement and generalized convulsion . if it originates from parietal and occipital lobe so visual , auditory or olfactory hallucinations occur .

WHAT CAUSES EPILEPSY ?

IN CHILDRENS : Birth traumas Infections Congenital abnormalities High fever

IN MIDDLE AGE : Head injuries Infection Alcohol Drug stimulant Medication side effects

IN ELDERLY AGE

Brain tumor Strokes

OTHER :It can also occur due to chemical imbalance includes drugs like alcohol, coccaine etc

Low blood sugar , low oxygen and low blood Na and Ca can also cause seizures .

Classification of Epileptic Seizures Generalized:

1.Generalized tonic-clonic seizure

2.Absence seizure3.Tonic seizures4.Atonic Seizure5.Myoclonic seizure

Partial (focal) Seizures: 80% of Adult epilepsiesSimple Partial SeizuresComplex Partial SeizuresSimple partial or complex partial secondarily generalized

Generalized seizures1. Generalized tonic-Generalized tonic-clonic

GTCS/major epilepsy/grand mal Commonest of all Lasts for 1-2 minutes Loss of consciousness followed by tonic phase and then clonic

phase Usually occurs in both the hemispheres Seizures are followed by confusion and exhaustion due to

depletion of glucose and energy stores . 2 phases: tonic phase followed by clonic phase Tonic phase:

Sustained powerful muscle contraction (involving all body musculature) which arrests ventilation Clonic phase:

Alternating contraction and relaxation, causing a jerking movement which could be bilaterally symmetrical

Absence seizure:

Also called minor epilepsy/petit mal Generally occurs in 3 to 5 years of age last untill puberty .Momentary loss of consciousness (not convulsion), patient stares at one directionNo convulsions , rapid eye blinking which last for 3-5 seconds .No loss of postural control

Atonic Seizures : Unconsciousness with relaxation of

all muscles Patient falls down Loss of postural tone, with sagging

of the head or falling Myoclonic Seizures :

Occur at any age but generally occur at puberty .

Momentary contractions of muscles of limbs or whole body

No loss of postural control Infantile spasm:

An epileptic syndrome Characterized by brief recurrent

myoclonic jerks (muscle spasm) of the body with sudden flexion or extension of the body and limbs

Progressive mental deterioration

Partial (focal) SeizuresSimple partial seizure (Jacksonian)Lasts for 20 – 60 secondsMotor, sensory, or psychic symptomatologyTypically consciousness is preserved Seizures are caused by group of hyperactive neuron exhibiting abnormal electrical activity and cofined to single locus .

Complex partial seizure (temporal lobe/psychomotor epilepsy)

Focus is located in temporal lobeConfused behavior and purposeless movements and emotional changes lasting for 30 seconds to 2 minutesMotor dysfunction involve chewing movement , diarrhea and urination

Classification on the basis of mechanism of action

DRUGS FACILATATING GABA ACTIONS: Barbiturates , benzodiazepine , gabapentin

INHIBITORS OF GABA TRANSAMINASE: Facilitate GABA action: valproic acid , vigabatrin

DRUGS BLOCKING Na CHANNELS : Decrease axonal conduction phenytion , carbamazepine ,valproic acid , primidone.

Drug blocking T-type Ca Channels: Dec. presynaptic Ca influx Valproic acid

drud blocking “glutamate ” receptors: Dec. excitatory affects of glutamic acid. Topiramate

Drug blocking Glutamate receptors  

NMDA (N-myethyl-D-aspartate) receptor sites as targetsKetamine, phencyclidine, dizocilpine block channel and have anticonvulsant properties but also dissociative and/or hallucinogenic properties; open channel blockers.

Felbamate antagonizes strychnine-insensitive glycine site on NMDA complex

GABA InhibitorsBenzodiazepines (diazapam, clonazapam)Increase frequency of GABA-mediated chloride channel openingsBarbiturates (phenobarbital, primidone)Prolong GABA-mediated chloride channel openingsSome blockade of voltage-dependent sodium channels

GabapentinMay modulate amino acid transport into brain May interfere with GABA re-uptakeTiagabine Interferes with GABA re-uptakeVigabatrin elevates GABA levels by irreversibly inhibiting its main catabolic enzyme, GABA-transaminase

Na+ Channels BlockersPhenytoin, CarbamazepineBlock voltage-dependent sodium channels at high firing frequencies—use dependentOxcarbazepineBlocks voltage-dependent sodium channels at high firing frequenciesAlso effects K+ channelsZonisamideBlocks voltage-dependent sodium channels and T-type calcium channels

Decrease Pre-synaptic Calcium influx resulting in decrease transmitter release by neurons.

Ethosuximide : is a specific blocker of T-type currents and is highly effective in treating absence seizures

Blocking T-Type Ca Channels

References

Lippincott