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 tonicclonic, 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 Seizures

Defination
Finite episodes of brain dysfunction resulting from abnormal discharge of cerebral neuron

Partial seizures, simple

Partial Seizures, Complex

Conciousnes preserved, manifested variously as convulsive jerking, paresthesias, psychic symptom ( sensory perception, illusions, hallucinations, affect changes) and autonomic dysfunction Impaired conciousness that is preceded , accompanied, or followed by psychologic symptoms.

Term
Tonic-Clonic seizures, generalized / Grand mal epilepsy Absence seizure, generalized / Petitmal epilepsy Myoclonic seizures Status epiepticus

Defination
Loss of conciousness, tonic phase ( < 1 minute), clonic phase ( 2 3 minutes), , tounge bitting, fecal and urinary incontinence.

Impaired conciusness ( often abrupt onset and brief) . automatisms, loss of postural tone, enuresis, begin in childhood, usually cease by age 20 years. Single or multiple myoclonic muscle jerks A series of seizures ( usually tonic clonic) without recovery of conciousness between attacks; it is a life-threatening emergency.

Term
Partial seizures, simple

Subclass / prototype drug

Drug of choice: Carboxylic acid ( valproic acid, sodium valproate) Tricyclics compounds (carbamazepine) Hydantoins ( phenytoin ) Alternative: Barbiturates (Phenobarbital , or pirimidone ) Partial Seizures, ----- idem ----Complex

grand mal epilepsy

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

Term Absence seizure, generalized / petitmal epilepsy Myoclonic seizures Status epiepticus

Subclass / prototype drug Drug of choice: Succinimides ( ethosuximide ) Valproic acid if concomitant with generalized tonic-clonic or myoclonic seizures Valproic acid Benzodiazpines ( clonazepam ) Diazepam or lorazepam i.v. 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