EPILEPSY & ANTIEPILEPTIC

DRUGS
Dr. Siva Priya
Sonali
Thanushanthan
Tivashkar
Srinaath
Sidhantasahoo
INTRODUCTION
•The term EPILEPSY based on Greek
word “ epilambanein” ( “meaning to
seize” ) was first used by Hippocrates.

•He described epilepsy as a disease of

the brain , which should be treated
with diet.

•Hippocrates provided the first

classification on epilepsy.
DEFINITIONS
Seizure: The clinical manifestation of an abnormal and excessive
“ synchronization” of a population of cortical neurons.
Epilepsy: A tendency toward recurrent seizures unprovoked by
any systemic or acute neurologic insults.
Epileptogenesis: sequence of events that converts a normal
neuronal network into a hyperexcitable network.
 EPILEPSY??
Epilepsy is a common chronic neurological disorder
characterized by seizures.
About 50 million people worldwide have epilepsy, and
nearly two out of every three new cases are discovered in
developing countries.

Is mostly in young children, people over the age of 65 years.

As a consequence of brain surgery, epileptic seizures may

occur in recovering patients.

Epilepsy is usually controlled, but cannot be cured with

medication, although surgery may be considered in difficult
cases. However, over 30% of people with epilepsy do not have
seizure control even with the best available medications
 CAUSES
Epilepsy have number of causes. For example, it is sometimes
caused by brain damage, either through injury or infection, or it may
be caused by stroke, cerebral palsy, tumors, and problems during
birth.
Some other more common CAUSES of
epilepsy include
Genetic influence
Head trauma
Medical disorders
Dementia
Diseases 
Prenatal injury 
Developmental
disorders 
RISK FACTORS

Age Early childhood and after age 65

Sex Men are slightly more than women.
Family history
Head injuries
Stroke and other vascular diseases 
Brain infections like meningitis.
Prolonged seizures in childhood
 PATHOPHYSIOLOGY
A seizure is traceable to an unstable cell
membrane or its surrounding cells. Excess
excitability spreads either locally (focal seizure)
or more widely (generalized seizure).

Normal neuronal activity depends on normal

functioning of excitatory and neurotransmitters;
an adequate supply of glucose, oxygen, sodium,
potassium, chloride, calcium, and amino acids;
normal pH; and normal
receptor function.
CLASSIFIACTION WITH
THEIR
SYMPTOMS
TONIC-CLONIC SEIZURES
ATONIC SEIZURE

ATONIC SEIZURE
MYCLONIC SEIZURES

MYCLONIC SEIZURES
SIMPLE PARTIAL SEIZURES
COMPLEX PARTIAL SEIZURES
DIFFERENTIAL DIAGNOSIS
Syncope attacks
Cardiac arrythmias
Migraine
Hypoglycemia
Narcolepsy
Panic attacks
PSEUDOSEIZURES
 DIAGNOSTIC TESTS
People with epilepsy will often have abnormal electrical activity seen on
an electroencephalograph (EEG).
Various blood tests and other tests looking for temporary and reversible
causes of seizures, may include:
Blood chemistry
Blood sugar
CBC (complete blood count)
CSF (cerebrospinal fluid) analysis
Kidney function tests
Liver function tests
Tests for infectious diseases
Tests for the cause and location of the problem may include:
EEG
Head CT or MRI scan
Lumbar puncture (spinal tap)
 COMPLICATIONS
Difficulty learning

Inhaling fluid into the lungs, which can cause aspiration pneumonia

Injury from falls, bumps, or self-inflicted bites during a seizure.

Injury from having a seizure while driving or operating machinery.

Many epilepsy medications cause birth defects -- women wishing to become

pregnant should alert their doctor in advance in order to adjust medications.

Permanent brain damage (stroke or other damage).

Prolonged seizures or numerous seizures without complete recovery between them

Side effects of medications

 PREVENTION
Generally, there is no known way to prevent epilepsy

However, proper diet and sleep, and staying away from illegal drugs
and alcohol, may decrease the likelihood of triggering seizures in people
with epilepsy.

Reduce the risk of head injury by wearing helmets during risky

activities; this can help lessen the chance of developing epilepsy.

Persons with uncontrolled seizures should not drive.

if you have uncontrolled seizures, you should also avoid activities

where loss of awareness would cause great danger, such as climbing to
high places, biking, and swimming alone.
Treatment
and
First aid
TREATMENT
Epilepsy is usually treated with medication prescribed
by a physician; primary caregivers, neurologists, and
neurosurgeons all frequently care for people with
epilepsy.

In some cases the implantation of a stimulator of the

vagus nerve, or a special diet can be helpful.

Neurosurgical operations for epilepsy can be palliative,

reducing the frequency or severity of seizures; or, in
some patients, an operation can be curative.
First Aid Tips:
Identification / look out for :
Twitching of limbs,
shaking or rigid body.
Abnormal eye movements.
Confusion
Unconsciousness
Unusual breathing pattern.
Clenched jaw
Frothing at the mouth.
What to do??
During Seizure
1. If possible try to ease the patient's fall. 
2. Try to protect the head 
3. Try to maintain some privacy for the casualty 

After Seizure
1. Remove tight clothing. 
2. In unconscious patient use the Recovery Position 
3. Usually patient recovers on his own in his own time. 
4. If time lapsed is more than 10 minutes or if first convulsion, seek
immediate medical help / ambulance.

Do not
1. Feed (liquid or solid) by mouth. 
2. Gag the patient or put anything in the mouth. 
3. Restrain the patient during the attack.
PHARMACOLOGIC TREATMENT
Some medications can be taken daily in order to prevent
seizures or reduce the frequency of their occurrence.

These are termed "anticonvulsant" or "antiepileptic" drugs

(sometimes AEDs).

All such drugs have side effects which are idiosyncratic and
others which are dose-dependent; it is not possible to predict
who will suffer from side effects or at what dose the side
effects will appear.
Antiepileptic
Drugs
•Sodium currents/channels
•Calcium channels
•Glutamate receptors

•GABA-A receptors/channels

•Sex hormones
•Carbonic anhydrase inhibition

•Synaptic vesicle protein 2A binding

Classification of Antiepileptic Drugs
Main types of seizures and the common drugs used
Choice preference of AED’s
Some important Drugs for epilepsy
Phenytoin
It is an oldest non-sedative antiepilepsy drug & chemically it is
a diphenyl hydantoin

Mechanism of Action
At therapeutic levels (10-20 μg/ml) à blocks the use dependent
Na+ channels à inhibits the generation of repetitive action
potentials.
 
At higher doses à it also reduces the influx of Ca+2 
à suppresses repetitive firing of neurons & neurotransmitters
Pharmacokinetics

Oral absorption is slow

Adverse Effects

Gingival hyperplasia
Megaloblastic anemia
Vitamin K deficiency
Vitamin D Deficiency
Hirutism
congenital malformation
Phenytoin should not be discontinued suddenly à it may
precipitate withdrawal seizures
Carbamazepine
Mechanism of Action
It blocks the use-dependent Na+ channels à inhibits high
frequency repetitive firing of the neurons in brain
Therapeutic Uses
it is the drug of choice for partial & generalized
tonic-clonic seizures
Pharmacokinetic
It is distributed mainly in brain, liver, kidneys
 It is metablosied & excreted through urine
Adverse Effects
Drowsiness, dizziness, headache, slurred speech, vertigo,
ataxia, diplopia à tolerance develops over a period of few weeks
Teratogenecity
• Allergic reactions à rashes & fever
Valproic Acid (Sodium Valproate)
Valproic acid or Sodium Valproate or Valproate semisodium à it
is the valproate ion (C3H7)2.CHCOO- àwhich  is active form &
absorbed from GIT
Mechanism of Action
Block use dependent Na+ channels 
Inhibit GABA transaminase
Activate glutamic acid decarboxylase
At higher concentrations à it increase the membrane K+
conductance by activating K+ channels
Therapeutic uses
It is very effective against absence seizures [Basis: Inhibit
Ca+2 influx by blocking T-type Ca+2 channels]
Pharmacokinetics
well absorbed orally
Adverse Effects
 Dose related – Weight gain, increase in appetite, GIT distress,

tremors, reversible alopecia

 Causes Hepatotoxicity

 Idiosyncratic reaction
Clinical Trial Example……..
 EFFECTS OF ANTIEPILEPTIC DRUGS ON
BRAIN EXCITABILITY
This study has been completed.
First Received on February 15, 2003.   Last
Updated on March 3, 2008
PURPOSE
This study will evaluate the usefulness of transcranial magnetic stimulation (TMS) in
measuring cortical excitability. The cortex is the outer part of the brain. Patients with
seizures have increased cortical excitability and are often treated with antiepileptic
drugs to reduce this excitability.

The therapeutic effects of antiepileptic drugs are usually tracked with blood tests
that measure their blood levels. However, these blood tests may not always correctly
reflect the effects of the drugs on the brain.
TMS has been used successfully to measure cortical excitability in many
neurological diseases, including epilepsy, and may be helpful in
measuring drug effects on the brain directly.
OBJECTIVES
Transcranial magnetic stimulation (TMS) is a non-invasive technique
that allows accurate measures of this parameter. The purpose of this
protocol is to test the hypothesis that TMS measures of cortical
excitability will correlate with serum blood levels of AEDs, and reflect
clinical effects on cortical function directly in healthy volunteers.

This information is crucial to reach the ultimate goal of developing a

reliable quantitative measurement of central physiological effects of
AEDs in epileptic patients.
STUDY POPULATION :40 normal volunteers aged 18 to 55 years
will be recruited for this study.

STUDYDESIGN: Subjects will be assigned to either of two groups,

with each group receiving one of the following drugs; carbamazepine
(CBZ), and lamotrigine (LTG).

OUTCOME MEASURES:The primary outcome variables will be

MEP size, measured from recruitment curves. MEP size
difference from baseline will be compared to the
serum drug level for each drug.