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Antiseizure Drugs, Anticonvulsants, antiepileptics

Prof.Dr.Mulyohadi Ali, dr., SpFK Lab. Farmakologi FKUB

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.

Level of Competency of Epilepsy and other seizures: ( attach KKI, appendix 1 and 2 ) Focal epilepsy 2 Generalized epilepsy 3A Absence seizure 3A Status epilepticus 3B Narcolepsy 2 Sleep apnea syndrome 1

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

Task : Classification & Dosing antiseizurre


Generic brand name Presention Dosage Comment

Phenyto Dilantin in

Tab 50 mg Cap 100 mg Amp 2ml, 50mg/ml; iv

A : 300 mg / Therapeutic drug C : 5 mg/Kg/d monitoring Effective level 1020ug/ml Tpxic level > 20 ug/ml hyperplasia Ginggiva diplopia teratogenic with drawl

Carbam Etc azepine etc

Antiparkinson
Level of Competency of Movement Disorders ( see, appendix 1 and 2 ) Parkinson's disease 3A Tremor 3A Secondary parkinsonism 3A

You should be able to : Describe the neurochemical imbalance underlying the symptoms of Parkinsons disease Identify the mechanisms of levodopa, dopamine receptor agonists and muscarinic blocking drugs alleviate parkinsonism Describe the adverse drug reaction of antiparkinsons drugs

Task : Classification & Dosing antiparkinson


Generic brand name Levodo pa Bromo criptine etc Etc Presentaon Dosage Comment