Antiepileptic

Drugs
SEIZURES

 Transient disturbance of cerebral

function
 Abnormal paroxysmal neuronal
discharge
 It can be
a. acute
b. chronic
EPILEPSY

 Collective name for group of CNS

disorders
 With repeated occurrence of sudden and
transitory seizures
 It can be
a. primary or idiopathic
b. secondary or symptomatic
Nature of epilepsy
 Epilepsy affects about 0.5% of the
population.
 Seizure and convulsions
 Caused by an asynchronous high-frequency
discharge of a group of neurons
 Partial seizures affect localized brain regions
 Generalised seizures affect the whole brain.
Nature of epilepsy
 Two common forms of epilepsy are the tonic-
clonic fit (grand mal) and the absence seizure
(petit mal).
 Animal models
 It may be associated
 with enhanced excitatory amino acid transmission
 impaired inhibitory transmission
 abnormal electrical properties of the affected cells.
 glutamate content in areas surrounding an epileptic
focus may be increased
CLASSIFFICATION OF
SEIZURES
 Partial Seizure
 Focal area in the brain is involved
 Types:
a. Simple partial
 No impairment of consciousness
 motor or sensory symptoms
 b. complex
 with impairment of consciousness
 with automatisms
 Generalized
 Entire brain is involved
 Tonic-clonic/ Grand mal
 Tonic phase- loss of consciousness, rigidity
 Clonic phase- jerking movements of entire
body
 Absence/ Petit mal
 In children
 brief loss of consciousness (10s) blank stare,
blinking, facial twitching
 Myoclonic
 brief jerks
MOA OF DRUGS
1. Reduced the spread of excitation from
seizure foci to normal neurons
2. Enhancement of GABA mediated inhibitory
transmission
3. Prevent or reduced excessive discharge of
altered neurons of seizure foci
4. Diminution of glutaminergic excitatory
transmission
5. Modification of ionic conductance
 MOAs:
 1. Sodium channel blockers
 - Phenytoin, carbamazepine, valproic acid
 2.Calcium channel blockers
 Ethosuximide
 3. GABA-mediated
 Benzodiazepines, phenobarbital, gabapentin,
tiagabine
 Indications
 1. GTC and partial seizures
 - valproic acid, carbamazepine, phenytoin
 2. Absence
 - ethosuximide, valproic acid
 3. Myoclonic
 - clonazepam, valproic acid
 4. Status epilepticus
 - diazepam, lorazepam, phenytoin
 5. Febrile seizures- phenobarbital
Adverse effects

 Teratogenic
 valproic acid- neural tube defects
 Phenytoin- craniofacial abnormalities, spina
bifida
 Phenytoin- fetal hydantoin syndrome

 CNS, respiratory depression

Adverse effects

 Phenytoin
 Nystagmus, diplopia, ataxia, gingival
hyperplasia, hirsutism, anemia,facial
coarsening
 Carbamazepine
 Diplopia, ataxia, blood dyscrasia
 Valproic acid
 GI distress, hepatotoxicity
Gingival hyperplasia
Pharmacokinetics

 Drug metabolism inducers

 Phenytoin, carbamazepine

 Drug metabolism inhibitors

 Valproic acid
Medications by Seizure Type
(Generalized Seizures)
 Absence (petit mal)
 brief period of unresponsiveness <30 s
 1st line ethosuximide, valproic acid
 2nd line lamotrigine
 Tonic-clonic (grand mal)
 dramatic convulsions and loss of
consciousness
 1st line valproic acid,
carbamazepine,phenytoin
 2nd line lamotrigine, phenobarbital
Medications by Seizure Type
(Partial Seizures)
 Simple Partial
 Sensory seizure
 1st line carbamazepine, phenytoin
 2nd line lamotrigine, gabapentin, valproic acid
 Complex Partial
 Starts at simple partial and generalizes
 1st line carbamazepine,phenytoin
 2nd line lamotrigine, gabapentin
 Unremitting seizure  respiratory compromise
 1st line lorazepam, diazepam
 2nd line phenytoin
 LIVER- VALPROIC
 NA DEC- CARBAMAZEPINE