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KEDOKTERAN DAN MIPA
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Antiepileptic Drugs
Prof. DR. dr. Hadyanto Lim, MKes,SpFK,FESC,FIBA Dept.of Pharmacology, Faculty of Medicine, Methodist University of Indonesia-Medan
Blok 8 Semester IV Neuropsikiatri Kelas A 14 Juni 2011, Selasa, jam 11.00-12.00; Kelas B 14 Juni 2010, Selasa, jam 10.00-11.00
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 NMDA = N-methyl D-aspartate
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.