Epilepsy

• Angka kejadian epilepsi masih tinggi  negara berkembang 114 (70-

190) per 100.000 penduduk/tahun.
• Indonesia  bila jumlah penduduk ± 220 juta, maka diperkirakan
jumlah
penyandang epilepsi baru 250.000 /tahun.
• Prevalensi epilepsi berkisar antara 0,5 – 4%. Angka prevalensi epilepsi
aktif ± 4-10 per 1000 penyandang epilepsi.
• Epilepsi berpotensi menimbulkan masalah sosio-ekonomi &
medikolegal
 dapat menurunkan kualitas hidup penyandang epilepsi
• Penyakit epilepsi dapat diobati  55-68% kasus berhasil menunjukkan
remisi dlm jangka waktu yang cukup panjang  diperlukan
optimalisasi penanggulangan epilepsi.
PERDOSSI, 2012. Pedoman Tatalaksana Epilepsi)
Definisi
EPILEPSI suatu keadaan yang ditandai oleh bangkitan
epilepsi berulang berselang lebih dari 24 jam yg timbul tanpa
provokasi

Epileptic seizure  manifestasi klinik yg disebabkan oleh

aktivitas
listrik otak yg abnormal dan berlebihan dari sekelompok
neuron

Manifestasi Klinik:
perubahan perilaku yg (PERDOSSI,
stereotipik, dapat menimbulkan
2012. Pedoman Tatalaksana Epilepsi)
Etiologi Epilepsi

Idiopatik  penyebabnya tidak

diketahui,
predisposisi genetik

Kriptogenik  dianggap
simtomatik tetapi
penyebabnya belum
diketahui

Simtomatik  kelainan/lesi pada

susunan saraf
 Klasifikasi epilepsi ILAE
1989
• Idiopathic
Partial epilepsy • Symptomatic
• Uncertain etiology

• Idiopathic
Generalized • Symptomatic - West sy, Lennox
epilepsy gastaut

Epilepsies undertemined focal or generalized

Special • Febrile convulsion

• Acute metabolic dearengement
syndrome
 3 Mekanisme
Dasar Epilepsi
• Gangguan keseimbangan neurotransmiter
• Peningkatan glutamate ( excitatory )
• Penurunan GABA ( inhibitory )
1 • Gangguan aktivitas neuromodulator

• Gangguan homeostasis ion K, Ca, Cl

2
•Rearranged neuronal circuits
• Hilangnya hambatan pada sinap
• Overgrowrth eksitatori sinap
3 • Simplified circuits yang meningkatkan sinkronisasi neuron
 Algoritme Terapi
AntiEpilepsi

Rogers & Cavazos, 2008. Epilepsy. In:

Pharmacotherapy. A Patophysiologic Approach
7th edition. McGraww-Hill
PENATALAKSANAAN TERAPI
MEKANISME KERJA OBAT
1. Anti-seizure drug-enhanced Na+ channel
inactivation

• Meningkatkan inaktivasi kanal Na+ memiliki

mekanisme aksi menurunkan kemampuan
saraf untuk menghantarkan muatan listrik
2. Enhanced GABA
synaptic transmission
1. obat-obat agonis reseptor
GABA  meningkatkan
transmisi inhibitori
dengan mengaktifkan kerja
reseptor GABA
( benzodiazepin dan
barbiturat)
2. Obat yang menghambat GABA
transaminase - konsntrasi
GABA meningkat (vigabatrin)
3. Obat yang bekerja dengan
menghambat GABA
transporter
 meperlama aksi GABA (
Tiagabin)
4. Obat-obat meningkatkan
konsentrasi GABA pada cairan
cerebrospinal pasien
(Gabapentin)
 3. drug-induced reduction of
current through T-type Ca2+
channels

• Obat yang menurunkan nilai ambang arus ion Ca 2+ 

menghambat ion kanal CA 2+ tipe T
• Arus Ca 2+ kanal tipe T merupakan arus pacemaker dalam
neuron talamus yang bertanggung jawab terjadinya letupan
kortikal ritmik serangan kejang
 Asam Valproat
DRUGS LITERATURE DOSE PATIEN ADMINIS- ADR MONI-
T DOSE TRATION TORING
VPA 750-3000 mg/day in 3 X 250 Administer Headache (31%), LFT, CBC,
two or three doses mg orally with food dizziness (12- serum
if GI upset 25%), nausea amonia (with
occurs. (15-48%), symptom of
Give at bedtime weakness (6- lethargy,
to reduce 27%), dyspepsia mental
effects of CNS (7-23%), tremor status
depression. (≤ 57%) change)

Place in Therapy:
 Valproic acid is first-line therapy for primary generalized seizures
(myoclonic, atonic, & absence seizures.)
 It can be used as both monotherapy & adjunctive therapy for partial seizures,
and it can be very useful in patients with mixed seizure disorders.
 It has a wide therapeutic index and is considered a broad-spectrum AED.
 It is also used in other neurologic or psychiatric disorders (e.g., migraine
headache, bipolar disorder).
Algoritma Terapi Epilepsi dg Valproat
 Neuronal Sites of Action of Antiepileptics

(Lüllmann, 2000)

 Valproic Acid (VPA) is responsible for the moderate inhibition of T calcium

channel activity & it also affects GABA metabolism  VPA stimulates the GABA
synthesizing enzyme, glutamate decarboxylase, & inhibits GABA metabolizing
enzymes (GABA transaminase, succinic semialdehyde dehydrogenase, & aldehyde
reductase).
AED – Drug Interaction

Rogers & Cavazos, 2008. Epilepsy. In: Pharmacotherapy. A

Patophysiologic
 Haloperidol
Karakteristik Keterangan

Pharmacology Butyrophenone antipsychotic which can bind to dopamine D1 and D2, 5-

HT2, histamine H1 and α2 adrenergic receptors in the brain  antagonism
of dopamine receptors in the mesolimbic & mesofrontal systems.
Depresses the release of hypothalamic and hypophyseal hormones;
believed to depress the reticular activating system thus affecting basal
metabolism, body temperature, wakefulness, vasomotor tone, and emesis

Indication For the treatment of psychoses and associated behavioural disorders

Literature dose Oral: 0.5-5 mg 2-3 times/day; usual maximum: 30 mg/day

Patient dose 2x0,5 mg

Adverse effect tachycardia, impotence and dizziness. Other adverse effects include and
sedation and weight gain, which is due to histamine H1 receptor blockade.
Haloperidol: Mechanism of
Action
Antipsychotic medication & Seizure

Antipsychotic 1st generation & 2nd generation can lower the seizure
threshold  increasing the chances of seizure induction.
Antipsychotic most frequently associated with seizure:
- 1st generation  Chlorpromazine
- 2nd generation  Clozapine
Antipsychotic with a lower risk of seizure induction:
- Molindone - Fluphenazin - Trifluoperazin
- Haloperidol e e
- Pimozide
Other factors contributes - Risperidone
to seizure provocation:
 History of seizure activity; Concurrent use of other drugs that
lower seizure treshold; rapid dose titration; slow drug metabolition;
metabolic factors & drug-drug interaction

Hedges,D., 2003. Antipsychotic medication and seizures: a

Profil Farmakokinetika Antipsikosis

Rogers & Cavazos, 2008. Epilepsy. In: Pharmacotherapy. A

Patophysiologic
Approach 7th edition. McGraww-Hill
Efek Samping terkait Penggunaan
Antipsikosis
Interaksi Obat - Haloperidol

Rogers & Cavazos, 2008. Epilepsy. In: Pharmacotherapy. A

Patophysiologic
Approach 7th edition. McGraww-Hill
 TUGAS INDIVIDU
• Review jurnal obat (salah satu obat dibawah) pada pasien
epilepsi
atau kejang.
• Masing2 jurnal tidak boleh sama judul, penulis nya,
• Obat yang dicari:
• A. Phenobarbital
• B. Gol.Benzodiazepin ( Clonazepam, Lorazepam, Diazepam)
• C.Phenytoin
• D.Gol.Succinimides (Ethosuximide)
• E.Carbamazepin
• F.Gabapentin
• G.Pregabalin
• H. Asam Folat
THANK YOU….