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EPILEPSY

Presented By Amol.B.Lavate
(M.Pharm)1st year Pharmacy Practice,
KLES University Belgaum.

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CONTENT
 INTRODUCTION
 FACTS
 CAUSES OF SEIZURES
 POSSIBLE SEIZURE TRIGGERS
 PATHOPHYSIOLOGY
 TYPES OF EPILEPSY
 CLASSIFICATION OF SEIZURES
 PREVALENCE
 SYMPTOMS OF EPILEPSY
 SCREENING & DIAGNOSIS
 TREATMENT
 ACTIONS OF ANTISEIZURE DRUGS
 USE OF ANTISEIZURE DRUGS 2
INTRODUCTION

 Epilepsy: Periodic and unpredictable seizures
caused by the rhythmic firing of large groups of
neurons may range from mild twitching to loss of
consciousness and uncontrollable convulsion

• Seizures-:A seizure is a paroxysmal behavioral spell
generally caused by an excessive disorderly
discharge of cortical or sub cortical nerve cells

 Seizures usually occurs without warning and
without the person's awareness of what is
happening. Some people with epilepsy will have
only an occasional seizure, while others will have
many on a daily basis.
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Facts about Epilepsy
 Epilepsy affects 2.7 million Americans, more Americans than cerebral
palsy, multiple sclerosis and Parkinson’s Disease combined.
 Approximately 200,000 new cases of epilepsy occur each year.
 Everyone's brain has the ability to produce a seizure under the right
conditions.
 Epilepsy can develop at any age. However, it is diagnosed most often
before the age of 20 and after the age of 60.
 With the appropriate treatment, up to 70% of people with epilepsy could
be seizure free.
 Only a few percent of people with epilepsy are affected by flashing
lights– this is called photosensitivity.
 The Greek philosopher Hippocrates (460-377 BC) was the first person to
recognize that epilepsy starts in the brain.
 Ten percent of the American population will experience a seizure at
least once in their lifetime. 1 person in 20 will have a seizure at some
time in their life

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Causes of seizures

•Heredity - th e risk o f g e ttin g e p ile p sy
is 2.5 times greater with a family Vascular, Congenital,
history of seizures than when no family 10% 8%
member has had the disorder
•Head trauma - the more severe the
injury, the greater the risk of
developing epilepsy Trauma,
6%
•Brain tumor and stroke Tumor, 4%
•Poisoning - such as lead poisoning. Degene-
More than 5,000 people annually suffer rative, 4%
seizures caused by alcoholism. Unknown, Infection,
•Infections - such as meningitis, viral 65%
3%
encephalitis, mumps, measles and
diphtheria
•Maternal injury - such as infection
or systemic illness affecting the
fetus' developing brain during
pregnancy
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Possible seizure triggers

S tre ss Alcohol U n h e a lth y n u tritio n Skipping meals

Irregular medication Flickering lightsIllness and allergies
Lack of sleep, exhaustion

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PATHOPHYSIOLOGY (I)

•Normal brain function involves "communication"
between millions of nerve cells (neurons)
•A nerve cell is made up of a cell body and branches
called axons and dendrites which join other
neurons at junctions called synapses
•At any one time, there are nerve cells which are
resting, exciting or inhibiting other nerve cells
•Electrical signals are sent from the cell body along
the axon to the synapse, these electrical signals
being the result of ion (Na+, K+ , Ca2+) currents
across channels in the nerve cell membrane
•Chemical signals (neurotransmitters) pass across
synapses between neurons

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PATHOPHYSIOLOGY (II)
•Neurotransmitters cross the synaptic gap between neurons
and fix to receptor points of the adjoining neuron
•Some neurotransmitters function to excite the joining
neuron (eg. glutamate) to send a further electrical signal.
Other neurotransmitters function to inhibit the joining
neuron (eg. GABA) and inhibit electrical signals passing
down that neuron
•It is by these electrical and chemical pathways that the
millions of neurons within the brain communicate and
function normally
•seizures occur when there is an imbalance within these
excitatory and inhibitory circuits in the brain, either
throughout the brain (generalized epilepsy) or in a
localized part of the brain (focal epilepsy), such that
neurons fire off in an abnormal fashion
•Mechanism of AEDs to prevent
–Altering electrical transmission along neurons
by affecting ion (Na+, K+ , Ca2+) channels in
the cell membrane.
–Altering chemical transmission between
neurons by affecting neurotransmitters
(GABA,glutamate) in the synapse
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CLASSIFICATION OF SEIZURES
Seizure Classification

Partial Generalized
seizure activity starts in one seizure involves whole brain &
area of the brain consciousness is affected

Simple Complex
Retains awareness Altered awareness and
behavior

Secondary
generalization
( spreading from one area to
the whole brain )

Tonic Clonic Absence Tonic or Myoclonic
“grand - mal ” or “petit mal ” or
Atonic Sudden muscle jerks
‘ drop attack ”
convulsion starting fit or Abrupt fall , either
Loss of trance like state with stiffening
consciousness , ( tonic ) or with loss
stiffening of body of muscle tone
then jerking of ( atonic or “ astatic ”
limbs attacks )

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SEIZURE CLASSIFICATIONS:

Generalized Jacksonian Focal
PARTIAL SEIZURES
Simple partial seizures.
• These seizures don't result in loss of consciousness.
They may alter emotions or change the way things
look, smell, feel, taste or sound.

Complex partial seizures.
• These seizures alter consciousness, causing you to
lose awareness for a period of time. Complex partial
seizures often result in staring and non purposeful
movements — such as hand rubbing, lip smacking,
arm positioning, vocalization or swallowing.

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Generalized Seizures
 Absence seizures (petit mal)
• These seizures are characterized by staring, subtle body movement and
brief lapses of awareness.

 Myoclonic seizures
• These seizures usually appear as sudden jerks of your arms and legs.

 Atonic seizures
• Also known as drop attacks, these seizures cause you to suddenly
collapse or fall down.

 Tonic- clonic seizures (grand mal)
• The most intense of all types of seizures, usual sequence is aura-cry-
unconsciousness -tonic spasm of all body muscles –clonic jerk
followed by prolong sleep & depression of all CNS functions.

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Prevalence of seizure types
Generalized Simple Partial,
tonic clonic, 14%
23%

Other
generalized,
8%

Partial
unknown, 7%

Absence, 6%
Complex
Partial, 36% Myoclonic, 3%
Unclassified, 13
3%
Symptoms of Epilepsy

lsion with or
Blackout
withoutoraSudden
confused
fever fear , anger for Blank
memory staring
no reason SuddenMuscle
stiffening
jerks of arms, legs o

Conditions that may be mistaken for epilepsy
•Seizures associated with high fever
•Fainting
•Sleep disorders: nightmares, narcolepsy, cataplexy
•Psychiatric disorders: panic attacks, fugue states, psychogenic
seizures
•Migraine headaches
•Childhood breath-holding episodes

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Screening & Diagnosis

Electroencephalogram (EEG)

Computerized tomography (CT)

Magnetic resonance imaging (MRI)

Positron emission tomography (PET)

Single-photon emission computerized tomography

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electroencephalography
The EEG or electroencephalography,
developed by Professor Hans Berger in
the 1920’s is one of the most
determinant and specific diagnostic
tests due to the fact that it records the
electrical activity of the brain in a safe
and painless graphical manner. Each
trace of its recording corresponds to a
different region of the brain and they
could be easily interpreted by the
specialists.
Computerized tomography (CT)
The CT scan, which stands for
computed tomography, is
equivalent to an X-Ray of the
head which would usually appear
normal in most patients with
Epilepsy. Decreases in brain
substance, scar tissue, tumors,
abnormal blood vessels or
abnormal spinal fluid circulation
are a few of the abnormalities
that might be projected with this
kind of test.
MAGNETIC RESONANCE IMAGING(MRI)
Magnetic Resonance Imaging [MRI] was first introduced in the USA in the
early 1980s revolutionizing the practice of neurology and neurosurgery
because of the excellent detail resemblance of the brain’s structure.
This is extremely helpful because it identifies brain scar tissue, areas
of abnormal brain development or dysplasia, small brain tumors, blood
vessel abnormalities, and changes in the brain’s white matter.
Positron emission tomography
 PET scans use injected radioactive material to help visualize
active areas of the brain. The radioactive material is
tagged in a way that makes it attracted to glucose.
Because the brain uses glucose for energy, the parts that
are working harder will be brighter on a PET image.
•• After the radioactive material is injected, it will take between

30 and 90 minutes for the substance to accumulate in your
brain tissue. During this waiting period, you will be asked to
rest quietly and not talk or move around much. The actual
scan takes 30 to 45 minutes. The amount of radioactive
material used in the test is very small, and its glucose
binding activity in the brain lasts only a short period of
time.
Single-photon emission computerized
tomography(SPECT)

• This type of test is used primarily in people
being evaluated for epilepsy surgery
when the area of seizure onset is unclear
on MRIs or EEGs. SPECT imaging
requires two scans — one during a
seizure and one 24 hours later.
Radioactive material is injected for both
scans and then the two results are
compared. The area of the brain with the
greatest activity during the seizure can
be superimposed onto the person's MRI,
to show surgeons exactly what portion of
the brain should be removed
Treatment Algorithm
Treatment Options
 There are four main categories of epilepsy
treatments

Ø Medications 
Ø
Ø Surgery 
Ø
Ø Ketogenic Diet
Ø
Ø Vagus Nerve Stimulation
Ø
Ø Other treatments for epilepsy 22
Medications
 Each medication has benefits and side effects and different
medications are appropriate for different types of
epilepsy.

 No one medication is proven to be the best treatment for
epilepsy. Only a complete evaluation can determine
which medication will work best for each patient.

 Approximately

 50% of seizures are eliminated by medication

 30% of seizures are reduced in intensity and frequency by
medication
 23
Seizure type and Drug selection
Seizure type First line drugs Second line drugs
Partial ,simple, complex, •Lacosimide •Clobazam
with or without secondary •Leveiiracetam •Clonazepam
generalization •Carbamazepine •Gabapentin

•Sodium valproate •Lamotrigine

•Phenytoin

•Tiagabine

•Topiramate

•Vigabatrin

•Pregabalin

•Zonisamide

Generalized absence Sodium valproate •Clobazam
Ethosuximide •Clonazepam
•Lamotrigine

Generalized tonic-clonic Levetiracetam •Carbamazepine

Sodium valproate •Clobazam

•Gabapentin

•Lamotrigine

•Phenytoin

•Topiramate

•Vigabatrin

Myoclonic Leveitiracetam • Phenobarbital
Sodium valproate

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Actions of antiseizure drugs

•Antiseizure Drugs act by distinct
mechanisms:
•increasing effect of GABA , inhibitory

neurotransmitter
•delaying the influx of sodium and calcium

ions into neurons
•Major Chemical categories of

antiseizure meds:
•1. Barbiturates

•2. Benzodiazepines
Barbiturates
 phenobarbital ( Luminal ) 60 - 180mg / day
 primidone750 - 1000mg / day
MOA : potentiate the effects of GABA
Indication :
 tonic- clonic seizures ,status epilepticus
 adjuncts to anesthesia
SE :
 drowsiness
 dizziness
 hypotension
 respiratory depression
 drug tolerance
 physical drug dependency & withdrawal syndrome
Benzodiazepines
 diazepam ( Valium ) 4 - 40mg / day
 clonazepam (Klonopin)1-12mg/day
 lorazepam (Ativan)2-6mg/day
 clorazepate (Tranxene)7.5-22.5mg/day
MOA : intensify GABA action
Indication :
 short -term severe convulsions, status epilepticus
 relieve tension , anxiety & skeletal muscle spasms
SE :
 ataxia
 cardiac depression
 drug tolerance
 physical drug dependency with withdrawal syndrome
Hydantoin
 phenytoin ( Dilantin ) 300 - 400mg / day
MOA : delay influx of sodium ions into neurons
Indication :
 all types of seizure except for absence seizures
Side Effects :
 gingival hyperplasia
 slurred speech
 confusion , headache & depression
 blood dyscrasias
 severe liver toxicity
 alopecia
 hirsutism
 Stevens –Johnson syndrome
Succinimides

Ethosuximide (Zarontin)750-1250mg/day
MOA : delay calcium influx into neurons
Indication : DOC for absence seizures
SE ;
 anorexia & vomiting
 blood dyscrasia
 Stevens- johnson syndrome
Other antiseizure drugs
 Valproates750-2000mg/day  Iminostilbenes
  valporic acid ( Depakene)   carbamazepine
  divalproex Na (Depakote) (Tegretol)600-1800mg/day
 Indication:
  gabapentin (Neurontin)900-
2400mg/day
  absence seizures   lamotrigine150-500mg/day
  mania   topiramate200-400mg/day
  migraine headache  Indication:
 SE:   seizure DO that have not
  GI upset responded to other convulsants
  Hepatotoxic   trigeminal neuralgia
  DOC for partial seizures
 SE;
  Blood dyscrasia
  CNS depression
  GI upset
  Stevens- johnson syndrome
OPERATIVE
STATISTICS SHOW THAT…

70% of patients manage But the other 30% are
their epileptic attacks with treated with surgery.
the use of drugs
LOBE
RESECTION
st common procedure among adults and adolescents, is the removal of the lobe where the o

LESIONECTOM
in lesions, such as areas of injury, tumors, or malformed blood vessels.

Y
In a FUNCTIONAL
HEMISPHERECTOMY, one
hemisphere is disconnected
from the rest of the brain, but
only a specific area of brain
tissue is removed. This surgery
is typically done on children
younger than 13 years old who
have one hemisphere that is
not functioning normally.

FUNCTIONAL
HEMISPHERECTOMY
MULTIPLE SUBPIAL
MULTIPLE TRANSECTION (MST) is
used to help control
SUBPIAL seizures that begin in
areas of the brain that
TRANSECTION cannot be safely
removed. The surgeon
makes a series of
shallow cuts or
transections in the brain
tissue to interrupt the
course of seizure
impulses but do not
disturb normal brain
activity, leaving the
person's abilities intact.
Ketogenic Diet
 The ketogenic diet is primarily used in childhood
epilepsy.

 The mechanism of ketogenic diet is unknown. The
high-fat, low-protein, no-carbohydrate diet
mimics some effects of starvation that seem to
inhibit seizures.

 The diet is very rigid and carefully controlled and
must be supervised by a physician -- sometimes
in a hospital setting.

 Ketogenic diets have been used for children with
epilepsy for many years with a success rate of 36
approximately 50 percent.
Vagus Nerve Stimulation (VNS)
•Vagus nerve stimulation (VNS) is approved
to treat partial seizures in patients 12
years of age or older
•Approximately 30 to 50 percent of patients
can be expected to have less seizure
activity with VNS
•The vagus nerve stimulator is surgically
implanted under the skin in the chest. The
device is attached to a wire that is
tunneled under the skin and attached to
the vagus nerve, which is located in the
left side of the neck
•The vagus nerve stimulator is adjusted to
automatically stimulate the vagus nerve
from every few seconds to every few
minutes.
•The device does not detect seizure activity.
It can be adjusted easily in a physician's
office using a laptop computer
OTHER TREATMENTS FOR
EPILEPSY
 NATUROPATHY
 YOGA THERAPY
 ACUPUNCTURE
 HYPNOTISM
 COLLOIDAL SILVER
Naturopathy
 NATUROPATHY is the belief that avoiding
certain drugs such as caffeine and alcohol;
chemicals; and maintaining a well-balanced
diet high in vitamins D and B6, as well as
zinc, calcium, and magnesium, which have
anticonvulsant properties, and the amino
acid taurine, would help control seizures.

Yoga therapy

Yoga therapy aims at
developing control over the
neuron excitations that
triggers the seizure by
training the individual to
develop an internal balance
through techniques of
decreasing activity rates at
all levels, reaching a deep
resting state that heals the
mind and body complex.
Acupuncture
Acupuncture, China's medical heritage for over 3,000
years, which was introduced into the USA and
Canada in the 1970's and that people find helpful
when trying to control seizures but that in rare cases
may also cause them, seeks to help the body to heal
itself but not as a self-help treatment. This
therapeutic mode relieves some of the problems
which provoke Epilepsy such as stress and poor
sleep by restoring the harmony within the
individual’s body by concentrating on the patterns
of energy that flow through the body just below the
surface of the skin. Steel needles are inserted in
vital specific areas of the body of the epileptic
person that influence the brain energy and flow of
blood to the head. Acupuncture treatments usually
last from 1 - 18 months, and 65 people showed
marked improvements with an absence of seizures
during a one year period without the use of
standardized drugs.


Hypnotism
Hypnotism has been proven to be a mean of
relief that is normally safe and beneficial for
patients with partial seizures. Commonly, to
be in a hypnotic state it takes an effort of
intense concentration and some studies
found a degree of high arousal in the EEGs
of people being hypnotized, which means
that this could, in certain cases induce a
seizure.
Colloidal Silver
Colloidal Silver, composed mainly of silver
proteins suspended in a liquid, most likely
water that are used to treat disorders such as
Epilepsy, gonorrhea, and colds. This type of
therapy was uncommon until the mid-20th
century but is now promoted as a cure for
AIDS, cancer, and diabetes. No human
clinical data has been found to support its
oral use even if it is composed of an essential
mineral, and apparently it does not serve
any physiological function in the body. Its
long term use can cause silver deposition in
the skin and mucous membranes leading to
an irreversible condition called argyria;
therefore pregnant women should abstain
from the use of it.
Prognosis
 Certain types of childhood epilepsy resolve or improve with
age.

 A seizure-free period of 4 years may indicate that
reduction or elimination of medications is possible.

 Death or permanent brain damage from seizures is rare,
but can occur if the seizure is prolonged.

 Death or brain damage are most often caused by
prolonged lack of breathing and resultant death of brain
tissue from lack of oxygen.

)  Infrequent seizures may not severely restrict the person's
lifestyle. 44
References
1. Joseph T.Dipiro,Barbera G.Wells,Terry L
Schwinghamar,CindyW.Hamlilton-Pharmacotherapy
handbook,5th edition2003; 505-22
2. Roger Walkar,Clive Edwards-Clinical pharmacay and
Therapeutics 3rd edition 2003;465-81
3. Eric T. Herfindal,Dick R. Gourley-Textbook of Therapeutics drug
and disease management,7th edition 2002;1107-11
4. www.unisanet.unisa.edu.au/12163/undlecs2002
5. www.sfn.org/.../epilepsy_illus_large.gif
6. thebrain.mcgill.ca
7. www.aesnet.org/go/professionaldevelopement/educational-opportu
8. www.wellsphere.com/wellpage/epilepsy
9. www.med.uc.edu/neurology/epilepsyinfo.htm
10.
11. 45
Thank You

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