Blok 8 Semester IV Neuropsikiatri
Kelas A 14 Juni 2011, Selasa, jam 11.0012.00;
Kelas B 14 Juni 2010, Selasa, jam 10.0011.00
Antiepileptic Drugs
Prof. DR. dr. Hadyanto Lim, MKes,SpFK,FESC,FIBA
Dept.of Pharmacology, Faculty of Medicine,
Methodist University of Indonesia-Medan
Seizure
Episodes of abnormal electrical activitiy in
the brain that cause involuntary
movements, sensations, or thoughts. It can
result from : head trauma, stroke, brain
tumors, hypoxia, hypoglycemia, fever,
alkohol withdrawal, infection, genetic,
hyperthermia in children, idiopathic.
Epilepsy : chronic disorder characterized by
recurrent , self limited seizures.
Neurobiology of Seizure
Glu
= Glutamate
aspartate
NMDA= N-methyl D-
Other Mechanisms of
Seizure
Suppression of inhibitory
neurotransmission of -aminobutyric
acid (GABA).
Increase in calcium influx via T-type
calcium channel in thalamic neuron.
Classification of Seizure
Partial (Focal) seizure : 60%
- Originates in one cerebral hemisphere
- Does not lose consciousness during the seizure.
- In simple partial seizures : consciousness is
not
altered, in complex partial seizures, altered
consciousness and repetitive behaviors
(automatism)
Generalized seizure : 40%
- Arises in both cerebral hemispheres and involves
loss of consciousness.
Generalized Seizures
Tonic-clonic seizures : grand mal seizures
A brief tonic phase that is followed by a
clonic phase with muscle spasms lasting 3 to
5 minutes.
Absence seizures : petit mal seizures
- abrupt loss of consciousness
- decreased muscle tone.
Partial and Generalized Seizures
Cellular and Synaptic Mechanisms
Generating Seizures
Mechanisms of Antiepileptic
Drugs
Inhibition of the sodium or calcium influx
responsible for neuronal depolarization.
Augmentation of inhibitory GABA
neurotransmission.
Inhibition of excitatory glutamate
neurotransmission.
Action of Phenytoin on
Na+ Channel
By prolonging the
inactivated state of
the Na+ Channel.
Thereby, reducing
the likelihood of
repetitive action
potentials
Drugs for Partial and Generalized
Tonic-Clonic Seizures
Phenytoin
- A hydantoin derivative formerly called
diphenylhydantoin.
- Phenytoin is converted to an inactive
hydroxylated metabolite by cytochrome P
450 enzymes.
- Interferes with folate metabolism, and can lead
to megaloblastic anemia.
- Adversely affects collagen metabolism and
thereby
contributes to gingival hyperplasia.
Phenytoin
Impairing cerebellar function, and can
cause ataxia, diplopia, nystagmus, and
slurred speech.
It can cause hirsutism (excessive hair
growth). Thus, phenytoin use in
children should be avoided.
Drugs for Partial and Generalized
Tonic-Clonic Seizures
Carbamazepine
- Adequately absorbed after oral
administration.
- Biotransformed to an active metabolite,
carbamazepine epoxide.
- Excreted as metabolites in the urine and
feces.
- Cause drowsiness, ataxia and CNS depression.
- Drug of choice for trigeminal neuralgia.
Phenobarbital
Phenobarbital
Well absorbed from the gut (usus)
Can cause ataxia, dizziness (pusing
kepala/pening), drowsiness, and
cognitive impairment.
In excessive doses, it can depress
respiration.
Onset of action is slow, but long
duration.
Second line drug for partial and
generalized tonic-clonic seizures.
