This document provides information about epilepsy and its management. It defines epilepsy as a chronic condition characterized by recurrent seizures. Seizures occur due to abnormal electrical activity in the brain. The goals of drug treatment are to restore normal brain electrical patterns and control seizures. Several anti-epileptic drugs are discussed that work via different mechanisms such as decreasing sodium influx or increasing GABA activity. Common anti-epileptic medications mentioned include phenytoin, carbamazepine, and valproic acid.

1. ASSIGNMENT-1
TOPIC: EPILEPSY
In
PHARMACOTHERAPEUTICS- III
Submitted by:
K.GOWRI PRIYA
19AB1T0011
IV pharm D.
Under the guidance of
DR. K. LAKSHMI KAVYA
Pharm. D
Assistant professor.
Vignan pharmacy college
Affiliated to JNTUK, KAKINADA. Approved by
AICTE & PCI (NEW DELHI), VADLAMUDI, GUNTUR
DIST, ANDHRA PRADESH..., INDIA. pin:522213.

2. EPILEPSY
INTRODUCTION:
 Epilepsy is a condition characterized by Recurrent episodes
of seizures.
 Seizures result from Episodic electrical discharges in cerebral
neurons associated with prolonged depolarization during which
sustained, high-frequency repetitive firing occurs, followed by
prolonged hyper polarization.
 Goal of the Drug is to Restore Normal Patterns of Electrical activity.
DEFINITIONS:
 EPILEPSY: Epilepsy is a chronic disorder that causes unprovoked,
recurrent seizures. A seizure is a sudden rush of electrical activity in the
brain. There are two main types of seizures.
(OR)
Epilepsy includes a chronic condition of recurrent or repeated seizures. A
seizure is a transient, paroxysmal, pathophysiological disturbance of
cerebral function caused by a spontaneous excessive discharge of cortical
neurons.
 SEIZURE: A seizure is when there's an abnormal surge of electrical
activity in the brain, due to complex chemical changes in nerve cells
(this is technically known as electrochemistry, or when chemical
reactions can produce an electrical current).
(OR)
A seizure may be abnormal movements or an arrest of movement, a
disorder of sensation or perception or a disturbance of behaviour or an
impairment of consciousness. Almost any required or genetic
pathological process involving the brain may cause epilepsy. The

3. symptoms of epilepsy include falling down, shaking of hands, legs and
bodies, biting the teeth, foaming in the mouth etc.
 EPILEPTIC SEIZURE: An epileptic seizure is a transient occurrence of
signs and/or symptoms due to abnormal excessive or synchronous
neuronal activity in the brain. Epilepsy is a disease characterized by an
enduring predisposition to generate epileptic seizures and by the
neurobiological, cognitive, psychological, and social consequences of this
condition.
EPEDIOMOLOGY:
 Epilepsy is a common disorder which affects 50 million people
worldwide. As the disorder is not curable there is a very high prevalence
or existing population with this disorder. Every year several hundreds of
thousands join this pool of patients as new cases.
 It is a compilation of the most recent epidemiological studies, focusing
first on studies from France and then on those from Europe and, where
relevant, the rest of the world.
 With a conservative estimate of 1% as prevalence of epilepsy, there are
more than 12 million persons with epilepsy (PWE) in India, which
contributes to nearly one-sixth of the global burden.
AETIOLOGY:
Although there are many causes of seizures, some are more common than
others.
-Head injuries & toxins: heredity sound, head injuries, brain lesions,
biochemical disturbances also are likely to produce convulsions.
-Emotional stress
-Drug-induced

4. -Psycho-social causes: They are eccentricity, poverty of emotions,
hypersensitivity and rigidity.
-Specific Structural Causes Associated with Epilepsy
 Hypothalamic hamartoma
 Aicardi syndrome
 Focal cortical dysplasia
 Cavernous and other vascular malformations
 Dysembryoplastic neuroepitumors tumors (DNETS), gangliogliomas, and
low-grade tumors
 Mesial temporal sclerosis (MTS)
 Multiple Sclerosis
 Traumatic brain injury (TBI)
 Perinatal brain injury
 Vascular injury
 Hemimegaloencephaly
 Schizencephaly
 Periventricular nodular heterotopia (PVNH)
 Polymicrogyria (PMG)
Genetic causes of epilepsy
 CDKL5
 PCDH19
 Ring chromosome 20
-Metabolic causes of Epilepsy
 Glut 1 (Glucose Transport) Deficiency Syndrome (SLC2A1)
 Vitamin dependent
 Pyridoxine
 P5P

5.  Folinic acid
 Creatine transporter
 Mitochondrial
 Storage disorders
-Infectious causes of Epilepsy
 Neurocysticercosis
 Cerebral malaria
 TORCH infections (toxoplasmosis, other agents, rubella/German measles,
cytomegalovirus, and herpes simplex)- typically acquired during
pregnancy and present in very early life with seizures, growth and
developmental delay, small head size, cataracts or visual problems, rash
and enlargement of the liver
 Bacterial meningitis- may cause seizures during the initial presentation
however, seizures often do not persist after it is successfully treated
 Viral encephalitis
 Tuberculosis
 Human immunodeficiency virus (HIV)

6. NORMAL CNS FUNCTION:
There is a balance exists between the inhibitory (γ-aminobutyric
acid (GABA)) and the excitatory (glutamate) neurotransmission
Excitatory neurotransmitters increase the likelihood of postsynaptic
neuron depolarization and generation of an action potential Inhibitory
neurotransmitters reduce the likelihood of postsynaptic neuron depolarization
and generation of an action potential.
An imbalance between glutamate and gamma-aminobutyric acid
neurotransmitter systems can lead to hyper-excitability but catecholaminergic
neurotransmitter systems and opioid peptides were shown to play a role in
epileptogenesis as well.
 Primary Excitatory neurotransmitter – NMDA
 Primary Inhibitory neurotransmitter - GABA

7. PATHOPHYSIOLOGY:
A seizure occurs when a portion of the brain becomes overly excited
or when nerves in the brain begin to fire together in an abnormal fashion.
Seizure activity can arise in areas of the brain that are malformed from birth
defects or genetic disorders or disrupted from infection, injuries, tumors, strokes,
or inadequate oxygenation.
The seizures result from an abrupt imbalance between the
forces that excite and inhibit the nerve cells such that the excitatory forces take
precedence. This electrical signal then spreads to the surrounding normal brain
cells, which begin to fire in concert with the abnormal cells.
o Decreased inhibitory system + increased excitation  genesis of seizures
o Abnormalities in Ion Channel (Na+, K+, Ca+2) may cause seizures.

8. SYMPTOMS:
Symptoms vary from person to person. Some people may have
simple staring spells, while others have violent shaking and loss of alertness.
The type of seizure depends on the part of the brain affected and cause of
epilepsy Behavioral changes, aura or visual hallucinations before a seizure
attack.
Symptoms of Epilepsy:
 Wild, monotonous bodily movements.
 Blackouts, disorientation and periods of unresponsiveness.
 Sudden fear.
 Tongue biting.
 Speech arrest.
 Loss of consciousness.
 Loss of bladder and rectum control.
 Aspiration Pneumonia.
 Headache, muscular pains and temporary weakness post seizure.
 Difficulty learning.
 Poor self-esteem, depression and suicidal thoughts.
CLASSIFICATION OF SEIZURES:
Seizures are broadly characterized as partial seizures (caused by a
focal lesion) and generalized seizure (caused by diffuse brain dysfunction). The
psychiatric manifestations of epilepsy are divided into those associated with
seizures itself and those occurring between seizures (interictally).

9. Generalized seizures
A. Generalized Tonic- Clonic seizures
 Major Epilepsy
 Commonest
 Last for 1-2 minutes
 Unconsciousness & Tonic Spasm followed by clonic jerking &
depression of all CNS function

10. B. Absence Seizures
 Minor Epilepsy
 Last for 1/2 min
 Momentary Loss of consciousness & patient freezes and stares in one
direction.
 Little / no bilateral jerking.
i. TYPICAL: Consist of impairment of consciousness without loss of
muscles tone and posture. Often manifest as inattention, an empty stare or
interruption of speech or motion.  Attacks are often triggered by
hyperventilation.
ii. ABSENCE SEIZURE ATYPICAL: Characterized by combination of
impairment of consciousness and motor or autonomic changes. *May
have tonic (stiffness) or clonic (jerking) spells or may have automatism
(involuntary behaviour). *The EEG doesn’t have 3/sec spike and wave
pattern.
C. Atonic Seizures
 Akinetic Epilepsy
 Unconsciousness with relaxation of all muscles.
There are 2 types atonic seizures
They are:

11. I) Brief Atonic Seizure: Leads to sudden fall or droop attack. Usually
last for one or two seconds.
II) Long Atonic Seizure: Sudden loss of consciousness. Fall to floor and
remain completely flaccid for one or several minutes.
D. Myoclonic Seizure
 Shock like momentary contraction of a single muscle.
E. Infantile spasms
 In infants
 Most typical epilepsy
 Muscle spasm
 Progressive Mental Deterioration
2. Partial Seizures
A. Simple Partial Seizure
 Cortical focal Epilepsy
 Lasts for 1/2 to 1 min
 No loss of consciousness
 Convulsions are confined to a particular area of cortex
B. Complex Partial Seizure
 Temporal lobe epilepsy
 Attacks of Bizarre & confused behaviours
 Emotional changes
 Purposeless movements
 Lasts for 1-2 min
 Aura (feeling & Seizures) often precedes
C. Simple Partial / Complex Partial Seizure Secondarily Generalized
 Partial Seizure occurs first and evolves into Generalized Tonic-clonic
with loss of consciousness

12. STATUS EPILEPTICUS: A condition when consciousness does not return
between seizures for more than 30 min. This state may be life-threatening with
the development of pyrexia, deepening coma and circulatory collapse.
FEBRILE SEIZURE: A febrile seizure is a convulsion in a child that's caused by a
fever. The fever is often from an infection. Febrile seizures occur in young,
healthy children who have normal development and haven't had any
neurological symptoms before.
Infantile spasms Infantile spasms (also called epileptic spasms) are a type
of seizure. A seizure is a burst of uncontrolled electrical activity between brain
cells that causes temporary abnormalities in muscle tone or movements,
behaviours, sensations and/or states of awareness. Not all seizures are alike.

13. DIAGNOSTIC TESTS IN SEIZURE DISORDERS :
Hematological tests
• Serum
• Glucose – Hypoglycaemia.
• E & U – Electrolyte imbalances, increased blood urea nitrogen.
• Increased blood alcohol/ ammonia levels.
• Urine
• To detect medication toxicity.
• To detect Organic & Amino – aciduria.
Skull x-ray:
• Evidence of fractures.

14. • Evidences of space occupying lesions (shift in calcified pineal gland, bony
erosions, separated sutures, calcifications).
EEG:
• Tonic-clonic: high, fast voltage spiked in all leads.
• Absence: 3/s, rounded, spiked wave complexes in all leads.
• Infantile spasms: Hypsarrhythmia’s.
• Complex partial: square-topped, 4-6/s spike wave complexes over involved
lobe.
CT/ MRI:
• show Structural changes
• Indicated in Focal seizures.
• Neonatal or Early Infancy onset.
• Status Epilepticus
• Focal Slowing/ paroxysmal EEG Activity.
• Echoencephalography
• Midline shifts in brain structures
• Cerebral Angiography
• Vascular abnormalities; subdural hematoma
Syncope
• Global amnesia
• Cardiogenic (arrhythmia, ischemia, aortic stenosis)
• Breath-holding attacks • Benign paroxysmal vertigo
• Migraine
• Panic attack
• Psychogenic or Pseudo epileptic attacks
• Narcolepsy
• Cataplexy
• Sleep apnoea
MANAGEMENT:
Non pharmacological therapy:
During fits outside the hospital, the following are important:
• Place patient on the LEFT LATERAL position.
• If febrile, tepid sponge and expose to cold air.

15. • Loosen tight clothing around the neck.
• Put a soft mouth gag in between the jaws to prevent biting of the tongue.
HOME REMEDIES
• Exposure of limbs to naked flame: Risk of burns and tetanus
• Using spoon/ sticks as mouth gag: Oral ulcers, tooth dislocation, risk of
aspiration
• Instillation of pepper into the eyes: Conjunctivitis, keratitis, risk of
blindness
• Incisions and scarifications: Risk of tetanus
• Use of Cow’s urine concoction (alligator pepper, garlic, tobacco leaves):
Risk of hypoglycaemia
• Alcohol administration: Risk of hypoglycaemia
PHARMACOLOGICAL THERAPY:
CLASSIFICATION OF ANTI EPILEPTIC DRUGS:
Anti-epileptic drugs are classified as:

16. Mechanism of Action
These drugs act via various mechanisms –
 Decreased axonal conduction by preventing Na+ influx through fast
Na+ channels – Carbamazepine, Phenytoin
 Increased inhibitory tone by facilitation of GABA mediated hyper
polarization- Barbiturates, BZDs
 Decreased excitatory effects of glutamic acid – Lamotrigine,
Topiramate (blocks AMPA Receptors), Felbamate (blocks NMDA
Receptors)
 Decreased Presynaptic Ca2
+ influx through type-T channels in
thalamic neurons – Valproic acid & Ethosuximide.
SCHEMATIC REPRESENTATION

17. CLASS OF DRUG ALONG WITH THEIR MECHANISM OF
ACTION

18. ANTI-EPILEPTIC DRUGS:
1. Phenytoin
Mechanism –
Blocks axonal voltage gated Na+ channels → Prevents seizure propagation
Uses –
 GTCS
 Partial Seizures
 Status Epilepticus
 Trigeminal Neuralgia (Non-Epileptic Use)
Side Effects –
 CNS Depression
 Hirsutism
 Osteomalacia
 Gingival Hyperplasia
 Megaloblastic Anaemia
 Hypersensitivity/ Allergy
Contraindications –
 Myoclonic Seizure
 Absence Seizures
2. Carbamazepine
Mechanism –
Blocks axonal voltage gated Na+ channels → Prevents seizure propagation.
Uses –
 GTCS
 Partial Seizures [DOC]
 Trigeminal Neuralgia [DOC]
 Mania & Bipolar Disorder
 Diabetes Insidious
Side effects –
 CNS Depression
 Osteomalacia
 Megaloblastic Anaemia
 Aplastic Anaemia
 Exfoliative Dermatitis.
 Increased ADH Secretion (Dilutional hyponatremia)
 Cleft Lip & Palate
 Spina bifida (if given to pregnant mother)
 Hepatotoxic
 Allergy (Steven Jenson’s Syndrome/ Toxic Epidermal Necrolysis)

19. Contraindications –
 Myoclonic seizures
 Atonic Seizure
 Absence Seizures
3. Valproic Acid
Enzyme inhibitor
Mechanism –
 Blocks axonal voltage gated Na+ channels → Prevents seizure
propagation.
 But also, inhibition of GABA Transaminase (increases GABA levels)
 Blockade of T-Type Ca2+ channels
 Decreases Glutamate levels
Uses –
 GTCS
 Absence Seizures
 Myoclonic Seizure
 Dravet Syndrome
 Tardin Dyskinesia
 Mania & Bipolar Disorder
 Migraine Prophylaxes
 Status Epilepticus (Used IV)
Side Effects –
(MNEMONIC – VALPROATE)
V = Vomiting, Nausea (most common)
A = Alopecia, curling of hairs
L = Liver toxicity
P = Pancreatitis
R = Rashes
O = Obesity
A = increased Ammonia
T = Teratogenic (causes Neural Tube Defects), Thrombocytopenia
E = Enzyme inhibitor
4. Ethosuximide
Mechanism –
Blockade of T-type Ca2
+ channels in Thalamic neurons
Uses
 Absence Seizures
 Ethosuximide is drug of choice in children(<2yrs)

20. Other Ant seizure Drugs
1. Lamotrigine
 Blocks Na+ channels & Glutamate Receptors
 Also, T type CCB
 Used in Various Seizures
 Side effects – Stevens – Johnson Syndrome (Rashes)
 These are safer in pregnancy [NOT TERATOGENIC]
2. Levetiracetam :
 Mechanism – SV2A inhibitor
 Used in focal Onset & Generalized Tonic-clonic seizures.
 Safe in pregnancy
3. Topiramate
 Block Na+ channels and glutamate Receptors (AMPA blocker)
 Enhances GABA Activity.
 Also, mild carbonic Anhydrase inhibitor
Uses –
 In focal seizures in adults & children > 2 years.
 Migraine prophylaxis
 Decreasing craving in Alcoholics
 Obesity
4. Felbamate
 Blocks Na+ channels and glutamate receptors (NMDA blocker)
 Used in Partial Seizure
 Side effects is Aplastic Anaemia.
5. Gabapentin
 Affect Ca 2
+ channels.
Uses –
 Seizure states
 Neuropathic Pain
 Post herpetic neuralgia
Side effect – Sedation
6. Zonisamide
 Na+ channel blocker, T type Ca2+ Channel blocker
 Also, Carbonic Anhydrase inhibitor
 Used in Seizure states
 Side effect is Renal Stone formation
7. Locasamide
 Na+ channel blocker

21.  CRMP2 Protein inhibitor
8. Vigabatrin
 Inhibits Transaminase
 Used in treatment of infantile spasms with Tuberous Sclerosis
 Side effect is leads to Visual impairment
9. Ezogabine
 K+ channel opener
 Used to treat Partial Seizure
10. Barbiturates & Benzodiazepams
They block the GABA receptor
Example –
 Clonazepam – Absence Seizures
 Lorazepam – Status Epilepticus
 Carbamazepine – Partial Seizure etc.

22. SURGICAL THERAPY:
 LOBECTOMY: A lobectomy or lobe resection is a surgical procedure in
which a lobe of the brain is surgically removed. The most common form
of paediatric epilepsy surgery is temporal lobectomy. Some studies have
shown that up to 80 percent of children become seizure free after this
procedure.
 LESIONECTOMY: Lesionectomy is a type of brain surgery used to
treat people with epilepsy. The goal of lesionectomy surgery is to remove
the seizure focus while preserving vital functions such as speech,
sensation, movement, and memory.
REFERENCES:
 Clinical pharmacy & therapeutics - Roger & walker, Churchill
Livingstone publication.
 Pharmacotherapy: A pathophysiologic approach – Joseph T. Dipiro
et.al.Appleton & Lange.
 https://medical-junction.com/anti-epileptic-drugs/
 Goodman & Gilman’s The Pharmacological Basis of Therapeutics.
…. THE END ….