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Antiseizure Drugs,

Anticonvulsants,

antiepileptics

Prof.Dr.Mulyohadi Ali, dr., SpFK

You should be able to:

Defined epilepsy,

Different seizure type ,

List the major drugs used for generalized tonic- clonic, partial seizure; absence seizure and status epilepticus,

Recommended drugs of choice and alternative therapy

Identify the mechanisms of antiseizure drug action

Identify the main pharmacokinetics and the most common adverse effects , and monitoring

parameters for anticonvulsants.

Term

Defination

Seizures

Finite episodes of brain dysfunction resulting

from abnormal discharge of

cerebral neuron

Partial

Conciousnes preserved, manifested

seizures,

variously as convulsive jerking, paresthesias,

autonomic dysfunction

simple

psychic symptom ( sensory perception, illusions, hallucinations, affect changes) and

Partial

Impaired conciousness that is preceded ,

Seizures,

accompanied, or followed by psychologic

Complex

symptoms.

Term

Defination

Tonic-Clonic

Loss of conciousness, tonic phase ( < 1

seizures,

minute), clonic phase ( 2 3 minutes), , tounge

generalized /

bitting, fecal and urinary incontinence.

Grand mal

epilepsy

Absence seizure, generalized /

Impaired conciusness ( often abrupt onset and brief) . automatisms, loss of postural tone, enuresis, begin in childhood, usually cease by

Petitmal

age 20 years.

epilepsy

Myoclonic

Single or multiple myoclonic muscle jerks

seizures

Status

A series of seizures ( usually tonic clonic)

epiepticus

without recovery of conciousness between attacks; it is a life-threatening emergency.

Term

Partial

seizures,

simple

Partial Seizures, Complex

grand mal

epilepsy

Subclass / prototype drug

Drug of choice:

Carboxylic acid ( valproic acid, sodium valproate) Tricyclics compounds (carbamazepine) Hydantoins ( phenytoin ) Alternative:

Barbiturates (Phenobarbital , or pirimidone ) ----- idem -----

------ idem ------

Term

Subclass / prototype drug

Absence

Drug of choice:

seizure,

Succinimides ( ethosuximide )

generalized

/ petitmal

epilepsy

Valproic acid if concomitant with

generalized tonic-clonic or myoclonic

seizures

Myoclonic

Valproic acid

seizures

Benzodiazpines ( clonazepam )

Status

Diazepam or lorazepam i.v.

epiepticus

General anesthesia may be employed

in very severe case and does not

response with conventional drugs

Pharmacokinetic principles

Phenytoin : first pass effects / oral bioavailability is variable,

inducers liver metabolisms

Phenytoin metabolism is nonlinier, Plasma protein binding 97 98 %, Carbamazepine Inducer liver metabolisms Valproic acid Inhibits the metabolisms of phenytoin, phenobarbital,

A toxic metabolite --- hepatotoxicity

Mechanisms of action

To suppress repetitive action potentials in epileptic focus

Sodium Channel Blockade:

Carbamazepine Phenytoin

GABA Receptor:

Diazepam Phenobarbital

Calcium Channel Blockade

Ethosuximde