ANTIEPILEPTICS

Dr. Rukhsana Anwar

 WHAT IS EPILEPSY ?
 A neurological disorder,
marked by sudden recurrent
episodes of sensory disturbance, loss of
consciousness, or convulsions, associated with
abnormal electrical activity in the brain.
Due to :
 abnormally high level of excitatory ; Glutamate.
 abnormally low level of inhibitory ;GABA.
 Abnormal electrical properties of the effected
cell.
 Difference Between Epilepsy,
Seizures & epilepsy syndrome
 Epilepsy is a disorder characterized by
recurring seizures (also known as “seizure
disorder”)
 A seizure is a brief, temporary disturbance in
the electrical activity of the brain
 Epilepsy syndrome is a cluster of signs and

symptoms that may involve two or

more epilepsies.
A seizure is a symptom of epilepsy
CAUSES :
 Trauma.
 Infections.
 Head injury.
 Stroke.
 Metabolic disorders ; Hypoglycemia.
 Antidepressants (overdoses)
 Poisons ; lead, CO. TRIGERS OF SEIZURES
 Genetic factors. Sleep disturbances/extreme fatigue
 Other disorders : Alcoholism
Cigarette smoking
 Brain tumors.
Stress/ anxiety
 Meningitis Photosensitivity
 Alzheimer’s disease. Hormonal changes
Missed medication
Dehydration
Drug interactions, etc.
CLASSIFICATION OF SEIZURES :

PARTIAL SEIZURES: GENERALIZED SEIZURES:

 Simple partial seizures  Absence seizures

 Complex partial  Myoclonic seizures
seizures  Atonic seizures
 Secondarily  Tonic seizures
generalized seizures  Clonic seizures
 Tonic-clonic seizures
 Febrile seizures
PARTIAL SEIZURES (Focal) :
 Begin with an electrical discharge in localized
area of the brain. (EEG Discharge confined to
1 hemisphere)
 SIMPLE PARTIAL :
 Remain localized. Normal consciousness
 Involve involuntary muscle contractions
and effects on mood and behavior
(Psychomotor Epilepsy) i.e. clonic jerking
of an extremity lasting for 6o-90 sec.
COMPLEX PARTIAL:

 Localized onset but spreads towards

brainstem reticular formation.
 Involves limbic system
 Arise from temporal or frontal lobe
 Patient is warned before attack
Altered awareness and consciousness
 Lasts for 30-120 sec.
SECONDARILY GENERALISED SEIZURES :
Burst of electrical activity in a limited area (the
partial seizure) spreads throughout the brain.
 Precedes generalized tonic clonic seizures.
PRIMARY GENERALIZED SEIZURES
 ABSENCE SEIZURES : (petit mal)
 Brief periods of unconsciousness ( stares
vacantly)
 Mild clonic jerking of eyelids or extremities.
 Begin in childhood or adolescence.
 EEG shows highly specific 2.5-3.5 Hz spike and
wave pattern.
 Lasts for 10-45 sec.
 MYOCLONIC SEIZURES :
 Short episodes of muscle contraction for
several minutes . As a result of permanent
neurologic damage.
 ATONIC SEIZURES :(Drop attack )
 Sudden loss of postural tone.
.

 eyelids may droop, the head may nod, and the person
often falls to the ground.
 remains conscious.
 TONIC CLONIC SEIZURES : (grand mal)
 Most dramatic.
 Tonic rigidity of all extremities (rigid extensor spasm) with
involuntary cry, for 15-30 sec
 Followed by clonic phase ; massive jerking of body for 60-120
sec.
 Tongue or cheek may be bitten;
bloody saliva.
 Defecation, micturition.
 FEBRILE SEIZURES :
 In children 3 months to 5 yrs of age
 Due to illness by high fever
 PARTIAL SEIZURE

ABSENCE SEIZURE ATONIC SEIZURE HELMETS

Antiepileptic drugs categorized by
mechanism of action
 Sodium channel blockers  GABA enhancers
 Phenytoin  Benzodiazepines
 Carbamazepine  Tiagabine &
 Lamotrigine Vigabatrin
 Zonisamide  Phenobarbital
 Calcium channel blockers  Potassium channel
 Topiramate openers
 Lamotrigine  Retigabine
 Ethosuximide  Diuretics
 Glutamate receptor  Bumetanide
antagonists  Acetazolamide
 Topiramate & Felbamate
Sodium channel blockers :
 Use-dependant blockage.
 Bind preferentially to the inactivated state.
 Prevent the return of the channels to the
active state by stabilizing the inactive form.
 Block high-frequency discharge without
affecting low-frequency normal discharge.
 Presynaptic and postsynaptic blockade.
.
Calcium channel blockers
 Low-voltage calcium (Ca2+) currents (T-
type) are responsible for rhythmic
thalamocortical (discharge) spike and
wave patterns of generalized absence
seizures. Some antiepileptic drugs lock
these channels, inhibiting underlying slow
depolarization necessary to generate
spike-wave bursts.
.
 GABA Enhancers :
 GABA agonist: AED’s bind to (GABA)-A receptor,
enhances chloride (Cl-) influx, hyperpolarization
of cell and enhanced inhibition.
 Uptake Blocker : block presynaptic GABA uptake
by blocking GAT-1 transporter.
 GABA- T-Inhibitors : Inhibit the metabolism of
GABA by GABA transaminase
 GAD Modulator : GABA is produced by
decarboxylation of glutamate mediated by the
enzyme glutamic acid decarboxylase (GAD).
Some AEDs may act as modulators of this
enzyme, enhancing the production of GABA and
down-regulating glutamate.
.
Glutamate blockers :
 AED’s block three main sites on glutamate
receptors.
 NMDA site.
 Kainate site.
 AMPA site.
Upon binding glutamate, the receptors facilitate
the flow of both sodium and calcium ions into
the cell, while potassium ions flow out of the
cell, resulting in excitation.
Responses to glutamate antagonists differ,
depending on the site being affected.
Carbonic anhydrase inhibitors
 Inhibition of CA increases the Conc. of H+
ions intracellularly and decreases the pH.
 Potassium ions shift to the extracellular
compartment to buffer the acid-base status.
 hyperpolarization occurs
DRUGS USED IN PARTIAL SEIZURES
AND GENERALIZED TONIC CLONIC
SEIZURES.
Phenytoin :
 Given orally or IV.
 Absorption dependant on dosage
form.
 Use-dependant block of Na-channels
 ADR’s
 I/V administration of fosphentoin produces
cardiac arrhythmia.

 Gingival hyperplasia ,coarsening of the facial

features & hirsutism.
 Nystagmus , ataxia, teratogenic effect, double
vision, cognitive impairment
Carbamezipine:
 Enhance inactivation of Na channels. can
produce voltage-use and time dependant block
of the Na dependant action potential
 Has anti diuretic effect associated with reduced
ADH in plasma
 Also used in :
 Trigeminal neuralgia & manic depressive
patients (whom Li carbonate is not effective).
 ADR’s
 Drowsiness, vertigo, allergic reaction, fever, rash
 Urinary retention
DRUGS USED IN GENERALISED
SEIZURES
Ethosuximide :
 Inhibit T-Type Ca-channels reducing low
threshold Ca-currents.
 Used in Absence seizures
 ADR’s
 Dizziness, lethargy, euphoria
 Skin rashes & systemic lupus erythmatosus.
 Valproic acid reduces Ethosuximide clearance
increasing its toxicity.
Trimethadone :
 Absence seizures
 Valproic acid :
 Na-channel blocker
 NMDA-receptor blocker
 GABA modulator
 Facilitate GAD
 Inhibits GAT-1 & GABA-T
 Used in :
 Broad anticonvulsant activity
 Partial, Tonic Clonic (Grand Mal epilepsy), Absence seizures (Petit
epilepsy)
 ADR’s
 Abdominal pain, heart burn, tremors, sedation and ataxia
 Skin rashes and alopecia
 Idiosyncratic hepatotoxicity.
 Valproic acid inhibits the metabolism of several drugs
Carbamazepine, phenytoin and Primidone etc
Benzodiazepines :

 I/V Diazepam & Lorazepam :

 Generalised tonic-clonic, status epilepticus
 Clonazepam :
 Absence & myoclonic seizures
 Clorazepate dipotassium :
 As adjunct in complex partial seizures
.