ANTICONVULSAN

T
 “ANTICONVULSANT”

• also known as: antiepileptic drugs, antiseizure drugs

• used in the treatment of seizure disorders, in particular
grand mal, petit mal, and psychomotor seizures and other
specialized seizure disorders such as tic douloureux
(trigeminal neuralgia)
• Also used for treatment of bipolar disorder; act as mood
stabilizers
• Used for treatment of neuropathic pain.
• Goal: to suppress the rapid and excessive firing of neurons
that start a seizure
EPILEPS
Y
• a chronic medical condition produced by sudden changes in
the electrical function of the brain
• is defined as two or more than two unprovoked seizures
occurring in an individual
• characterized by recurrent paroxysmal episodes of
uncontrolled excitation of brain neurons
• causes: head trauma, meningitis, childhood fevers, brain
tumor, degenerative diseases of the cerebral circulation
 SEIZURE
• defined by a release of excessive and uncontrolled electrical
activity in the brain
• can range from tingling in a finger to grand mal
(generalized) seizures, during which people lose
consciousness, become stiff, and jerk
• not a disease, they are an event

CONVULSION
• a medical condition where body muscles contract and relax
rapidly and repeatedly, resulting in an uncontrolled shaking of
the body
 TYPES OF
SEIZURES
A. Partial (focal/local) seizure
• Simple partial (Jacksonian)
• Complex partial (psychomotor)
• With secondary generalization
B. Generalized seizure
• Absence seizures (Petit mal epilepsy)
• Myoclonic seizures
• Clonic seizures
• Tonic seizures
• Tonic-clonic seizures (Grand mal epilepsy)
• Atonic seizures
• Photosensitive seizures
 PARTIAL
SEIZURE
1. SIMPLE PARTIAL SEIZURE
• affects a small part of the brain
• these seizures can cause twitching or a change in
sensation, such as a strange taste or smell
• seizures may be limited to a single limb or muscle group
may show sequential involvement of body parts
(epileptic march)
• may have autonomic symptoms or signs such as
epigastric sensations, sweating, papillary dilation.
• Consciousness is not impaired
 PARTIAL
SEIZURE
2. COMPLEX PARTIAL SEIZURE
• the electrical discharge is confined in certain parts
of the temporal lobe concerned with mood as well as
muscle
• may have autonomic activity such as pupil dilation
and flushing
• consciousness is impaired (lasting 30 seconds to 2
minutes)
 GENERALIZED
SEIZURE
1. ABSENCE SEIZURES / PETIT MAL SEIZURES
• loss of consciousness without involving motor area
• most common in children (4 - 12 years)
• can be typical or atypical
a. Typical absence seizures – non-convulsive with muscle
tone preserved; seizure usually lasts less than 10 seconds
b. Atypical absence seizures – convulsive, longer in duration
(up to 20 seconds), a change in muscle tone and
movement is usually observed (smacking the lips or
chewing movements, rubbing fingers together or making
other hand motions, etc.)
 GENERALIZED
SEIZURE
2. MYOCLONIC SEIZURE
• a sudden and brief shock-like contraction which may
involve the entire body or be confined to the face, trunk
or extremities
3. CLONIC SEIZURE
• repetitive jerking and twitching of the body extremities
4. TONIC SEIZURE
• muscles stiffen up, person loses consciousness, body
grows rigid
 GENERALIZED
SEIZURE
5. TONIC-CLONIC SEIZURES (GRAND MAL
EPILEPSY)
• Generalized convulsion occurring in the tonic phase and
the clonic phase
• Loss of consciousness ; sudden sharp tonic contractions
of muscles, falling to ground, followed by clonic
convulsive movements
• Patient may bite his tongue & may lose control of his
bladder or bowel
 GENERALIZED
SEIZURE
6. ATONIC SEIZURES / AKINETIC SEIZURE
• Sudden lack of muscle tone (muscle is relax), causing the
inability to sit and stand
7. PHOTOSENSITIVE SEIZURES
• These are very rare, even for people with epilepsy (<
5%).
• A light related stimulus may trigger this seizure, hence
the warning labels on electronic devices, theme park
rides, and even video games
 TREATMENT OF SEIZURES

Drugs Seizure disorder

:Drug of choice
Carbamazepine or Valproate or
Phenytoin or Phenobarbital Tonic-clonic (Grand mal)
:Alternatives
Topiramate
Lamotrigine (as adjunct or alone)
Gabapentin (as adjunct)

:Drug of choice
Carbamazepine or Topiramate or
Phenytoin or Valproate Partial (simple or complex)
:Alternatives
Phenobarbital
Lamotrigine (as adjunct or alone)
Gabapentin (as adjunct)
 TREATMENT OF SEIZURES
Drug of choice:
Valproate or Ethosuximide
Alternatives: Absence (petit mal)
Clonazepam, Lamotrigine

Drug of choice:
Valproate Myoclonic, Atonic
Alternatives:
Clonazepam

Drug of choice Status Epilepticus

Diazepam, i.v. or Phenytoin, i.v. or Vaproate
Alternatives:
Phenobarbital, i.v

Diazepam, rectal*,
Diazepam ,i.v or Valproate Febrile Seizures
 MECHANISMS OF ACTION

• An effect mediated by promoting the inactivated

state of voltage-activated Na+ channels by blocking
those channels.
• A second mechanism appears to involve enhanced
g-aminobutyric acid (GABA)-mediated synaptic
inhibition
• limit activation of a particular voltage-activated
Ca2+ channel known as the T current channels by
blocking the channels.
 PHENYTOIN

• Brand name: Dilantin

• Used for partial seizures & generalized tonic-clonic seizures
• NOT effective for absence seizures.
• Also can be used for treatment of ventricular fibrillation
• Used as short-term prophylactic agent in brain injury to
prevent loss of functional tissue.
• Injectable proform: fosphenytoin
 P H EN Y TO IN

• Well absorbed when given

orally, however, it is also
available as intravascularly
(for emergency).
• Approximately 90 - 95%
protein bound
• Half life: approximately 20
hours
• Therapeutic range: 10-20
µg/ml
• Toxic level: >20 µg/ml
 P H EN Y TO IN

• Side effects
• Dose Related: GI upset, neurological (headache, vertigo,
ataxia, diplopia, nystagmus), sedation
• Non-dose related: gingival hyperplasia, hirsutism,
megaloblastic anemia (folate deficiency), hypersensitivity
reactions (mainly skin rashes and lesions, mouth ulcer),
hepatitis, fetal malformations (cleft palate), bleeding
disorders (in infants), impaired vitamin D metabolism
leading to osteomalacia
 CARBAMAZEPIN
E
• Brand name: Tegretol
• Its mechanism of action and clinical uses are similar to that of
phenytoin.
• A Tricyclic compound that is commonly used for treatment of
mania and trigeminal neuralgia.
• Less frequently used
• available as an oral form only
• Metabolized by the liver to
• CBZ 10.11 – epioxide (active)
• CBZ 10.11 – dihydroxide (inactive)
• Excreted in urine as glucuronide conjugate
• Half life: approximately 30 hours
• Therapeutic range: 4 – 12 ug/ml
 ETHOSUXIMIDE
(ZARONTIN)
• Used for control of petit mal seizure and it is administered as an
oral preparation
• Drug of choice for petit mal seizures

VA L PR O IC A C ID

• Brand name: Sodium Valproate, Depakene, Depakote

• Very effective against absence seizure, myoclonic seizure, tonic-
clonic seizure
• Less effective as compared to carbamazepine for partial
seizures
• Like carbamazepine, it can also be used for treatment of mania
 VA L PR O IC A C ID

• Available as capsule, syrup, IV

• 93% protein bound with high oral bioavailability
• Inhibits metabolism of several drugs such as phenytoin,
carbamazepine, topiramate and phenobarbital
• Excreted in urine (glucuronide)
• Half life: approximately 15 hours
• Therapeutic range: 50 – 120 ug/ml
• Side effects: nausea, vomiting and GIT disturbances (start with
low doses), increased appetite & weight gain, transient hair
loss, hepatotoxicity, thrombocytopenia, neural tube defect (e.g.
spina bifida) in the offspring of women, pancreatitis,
hyperammonemia, hallucination
 PH E N O B A R B ITA L

• Long-acting barbiturate that controls grand-mal tonic-

clonic seizure and focal epileptic
• NOT USED for Petit mal seizure
• Inactive proform: primidone (mysoline)
• After absorption of an oral dose, this drug is rapidly
converted to its active form, phenobarbital. Primidone is
rapidly absorbed and converted to the active drug. Both
primidone and phenobarbital need to be measured to
assess the total potential amount of phenobarbital in
circulation.
 PH E N O B A R B ITA L

• Oral absorption is slow but

complete
• Peak serum concentration: 10
hours after an oral dose
• 50% protein bound
• Eliminate primarily by
hepatic metabolism
• Serum half-life: 70 - 100 hours
• Therapeutic range: 15 - 30
ug/dL
• Toxic level: > 40 ug/dL
NEWER ANTIEPILEPTIC
DRUGS (SECOND -
GENERATION )
• Vigabatrin
• Felbamate
• Gabapentin
• Lamotrigine
• Topiramate
• Tiagabine
• Levetiracetam
• Oxcarbazepine
• safety profile similar to CBZ
• hyponatremia is also problem, however it is less likely to
cause rash than CBZ
• Zonisamide
 F ELB A M AT E

• orally administered drug

• peak serum concentrations: 1 - 4 hours
• indicated in severe epilepsies such as children
with the mixed seizure disorder Lennox-
Gastaut syndrome and in adults with refractory
epilepsy
• half-life: 14-22 hours in adults
• therapeutic range : 30 - 60 ug/ml
• Side effects includes fatal aplastic anemia and
hepatic failure
 G A BA P EN T IN

• chemically similar to neurotransmitter gamma

aminobutyric acid (GABA)
• administered orally in which it is reduced when antacids
are administered concurrently.
• half-life: approximately 5 - 9 hours (patient with normal
renal function)
• therapeutic range: 12 - 20 ug/mL
• may be the most likely treatment consideration in patients
with liver disease and in treating partial-onset seizures in
patient with acute intermittent porphyria
• toxic effects: ataxia, somnolence (drowsiness)
 LA M O T R IG IN E

• orally administered
• indicated in patients with partial and generalized
seizures
• hepatic metabolism accounts for the majority of
elimination
• half-life: 15 - 30 hours
• therapeutic ranges : 2.5 - 15 ug/ml
 TO P IR A M ATE

• nearly completely available after oral

administration
• peak concentration: 1 - 4 hours
• majority is eliminated by renal filtration; the
remainder is eliminated by hepatic
metabolism
• indicated in partial and generalized seizures
 TIA G A BIN E

• peaks at 0.5-2 hours

• approximately 96% protein bound
• half-life: 4 - 13 hours
• highly metabolized by the hepatic mixed-function oxidase
pathway
• indicated in treating partial seizures.
• Therapeutic range: 20 – 100 ng/ml
• Side effects: symptoms of confusion, difficulty speaking
clearly(stuttering), mild sedation, and a tingling sensation in the
body’s extremities (paresthenia), especially in the hands and
fingers.
 LE V ET IR A C ETA M

• orally administered
• indicated in partial and generalized seizures
• does not bind to serum proteins
• half-life: 6 - 8 hours
• therapeutic range: 8 - 26 ug/ml
 O X C A R B A ZE PI N E

• Prodrug, almost immediately metabolized to licarbazepine

• indicated for the monotherapy of partial seizures and in
secondarily generalized tonic-clonic seizures
• 40% protein bound
• peak concentration: 8 hours
• half-life: 8 - 10 hours in normal adults
• metabolized in the liver
 ZO N I SA M I D E

• orally administered
• absorbed from the gastrointestinal tract on the order of
65% or higher
• peak serum concentrations: 4 - 7 hours
• accumulates extensive in erythrocytes
• half-life: 50 - 70 hours
• may reduce to 23 - 35 hours when other enzyme-
inducing AEDs are being administered concurrently
• Therapeutic range: 10 - 38 ug/ml
 D IA G N O ST I C

• Electroencephalogram (EEG)
• Brain Scan
• Ketogenic Diet
• Vagus Nerve Stimulation
• Surgery
• For partial seizures (sometimes)
• If brain tumor is the cause of seizure
 ELECTROENCEPHALOGRAM
(EEG)
• a painless procedure that records the brain’s electrical
activity as wavy lines
• reveals which part of the brain is prone to seizure
• can confirm the diagnosis and offer more information
about the seizures

BRAIN SCAN
• reveals the detailed images of the brain
• helps rule out tumors or blood clots: possible cause of
seizures
 K ETO G EN IC D I E T

• Very high in fat, low in carbs diet: makes the body burn
more fat instead of sugar
• Reduce / eliminate seizures
• May be recommended when medication fails or cause
unacceptable side effects

VAGUS NERVE
STIMULATION
• “Pacemaker of the brain”
• Uses a small surgically implanted device to send
electrical pulses to the brain