dr. Mara Imam Taufiq Siregar, S.

Pdi,
M.Biomed

DEPT. FARMAKOLOGI & TERAPEUTIK

FAKULTAS KEDOKTERAN DAN ILMU KESEHATAN
UNIVERSITAS JAMBI
JAMBI - 2015

PENDAHULUAN
EPILEPSY:
Epilepsy is a chronic disease, in which
seizure result from the abnormal discharge
of cerebral neurons.
A seizure is a particular behaviour produced
by an abnormal high-frequency discharge of
a group of neurons, starting focally and
spreading to a varying extent to affect other
part of the brain.

According to the focus and spread of

discharges, seizure may be classified as:

1. Partial (focal) which originate at

a spesific focus and do not spread to
involve other cortical areas
2. Generalized which usually have a focus
(often in temporal lobe) and then spread
to other areas

Classification of common
epileptic syndrome:
PARTIAL (LOCAL, FOCUS) SEIZURE

GENERALIZED SEIZURE

Psycomotor (temporal lobe)

epilepsy

Tonic clonic seizure or grandmal epilepsy

Partial motor epilepsy

Absence seizure or petit-mal

epilepsy

Common types of epileptic

syndrome:
Epileptic syndromes result from either
generalized seizures or focal seizures
Generalized seizure involves loss of
conciousness and it may be convulsive or
non-convulsive:
Tonic-clonic or grand-mal epilepsy: convulsive
generalized seizure characterized by periods of tonic
muscle rigidity followed later by massive jerking of the
body (clonus)
Absence or petit-mal seizures: generalized seizures
characterized by changes in conciousness lasting less
than 10 seconds

Common types of epileptic

syndrome:

Partial (focal, local) seizures:

Psycomotor or temporal lobe epilepsy: results from a

partial seizure with cortical activity localized to the
temporal lobe. Such seizures are characterized by features
including impaired consciousness or confusion, amnesia,
emotional instability, atypical behaviour and outbursts
Partial motor seizures: have their focus in cortical motor
regions and they present with convulsive or tonic activity
corresponding to the neurons involved, e.g. the lef arm

Common types of epileptic

syndrome:
Another type of epileptic syndrome is status
epilepticus
Status epilepticus is state in which fits follow
each other without consciousness being
regained.
Status epilepticus constitutes a medical
emergency because of possible exhaustion
of vital centres

Causes of epilepsy:
The aetiology of epilepsy is unknown in 60-70% of
cases, but heredity is an important factor.
Damage to the brain may subsequently cause of
vital centres, for example: by tumors, head injury,
infections, cerebrovascular accident
The neurochemical basis of the abnormal
discharges in epilepsy are not known, but it may
involve altered GABA metabolism

Treatment of epilepsy
Drugs used to treat epilepsy are termed
antiepileptics; the term anticonvulsant is also
used.
The aim of pharmacological treatment of epilepsy
is to minimize seizure activity/frequency, without
producing adverse drug effects.
Remember that epilepsy aberrant
electrical activity spreading throughout
an area of, orthe whole of the brain
Antiepileptic medications limit the
propagation of this spread and inhibit
development of symptoms

Mecanism of action of
antiepileptic
Antiepileptic drugs act generally to inhibit the
rapid, repetitive neuronal firing that characterizes
seizures.
There are 3 established mecanisms of action by
which the antiepileptic drugs achieves this
(figure):
1.Inhibition of ionic channels involved in neuronal
excitability
2.Inhibition of excitatory transmission
3.Enhancement of GABA-mediated inhibition

Drugs used to epilepsy classified by clinical use

Seizure type

Primary drugs

Secondary drugs

Partial and/or
generalized tonicclonic seizures

Sodium valproat
carbamazepine

Phenytoin
Vigabatrin
Gabapentin
Lamotrigine
phenobarbital

Absence seizure

Ethosuximide
Sodium valproate

Phenobarbital
Lamotrigine

Status epilepticus

Lorazepam

Diazepam
Clonazepam

Antiepileptic drugs can be classified according to

their mecanism of action, but in clinical practice it
is useful to think of the drugs according to their
use

Phenytoin
Mecanism of action:
This involves use-dependent block of voltagegated sodium channels
Reduces the spread of a seizure
Route of administration:
Oral, IV
Indication:
In all forms of epilepsy except absence seizure &
neuralgic pain

Contraindication:
Phenytoin has many contraindicatiions, mainly
because it induces the hepatic cytochrome P450
oxidase system
Increasing the metabolism of oral contraceptives,
anticoagulant, dexamethasone and pethidine
Adverse effects:
The adverse effects of phenytoin may be dosageor non-dosage-related
The dosage-related affect the
cerebrovestibular system, leading to ataxia,
blurred vision, hyperactivity
Acute toxicity causes sedation and confusion

Adverse effects:
The non-dosage-related collagen effects such
as gum hypertrophy, allergic reaction e.g. rush,
hepatitis, lymphadenopathy, hematological
effects e.g. megaloblastic anemia, endocrine
effects e.g. hirsutism (hair growth), teratogenic
effects and may cause congenital malformation

Sodium valproat
Mecanism of action:
Has 2 mecanisms of action:
1.Like phenytoin, it causes use-dependent block of
voltage-gated sodium channels
2.Increases the GABA content of the brain when
given over a prolonged period
Route of administration:
Oral, IV
Indication:
In all forms of epilepsy

Contraindication:
Acute liver disease
Has a history of hepatic dysfunction
Adverse effects:
Gastrointestinal upset
Liver failure

Carbamazepine
Mecanism of action:
Like phenytoin, causes use-dependent block of
voltage-gated sodium channels
Route of administration:
Oral, rectal
Indication:
In all forms of epilepsy except absence seizure &
neuralgic pain

Contraindication:
Like phenytoin strong enzymes inducer
Has a history of hepatic dysfunction
Adverse effects:
Really limited to the nervous systems; ataxia,
nystagmus, dysarthria, vertigo, sedation

Ethosuximide
Mecanism of action:
Inhibition of low-threshold calcium current (Tcurrents)
Route of administration:
Oral
Indication:
The drug of choise in simple absence seizures
Particularly well tolerated in children

Contraindication:
May make tonic-clonic attacks worse
Adverse effects:
Gastrointestinal upset, drowsiness, mood swings,
skin rashes

Vigabatrin
Mecanism of action:
Irreversible inhibition of GABA transaminase
Route of administration:
Oral
Indication:
Indicated in epilepsy not satisfactorily controlled
by other drugs

Contraindication:
Psycosis because of side effect of
hallucinations
Adverse effects:
Drowsiness, dizziness, depression, visual
hallucinations

Lamotrigine
Mecanism of action:
Act via an effect on sodium channels
Inhibiting the release of excitatory amino acids
Route of administration:
Oral
Indication:
Monotherapy and adjuvantive treatment of partial
seizures; neuralgic pain

Contraindication:
Hepatic impairment
Adverse effects:
Rashes, fever, malaise, drowsiness, rarely
hepatic dysfunction

Gabapentin
Mecanism of action:
Is a lipophilic drugs that was designed to act like
GABA in CNS (agonist)
Involves voltage-gated calcium channels blokade
Route of administration:
Oral
Indication:
As an adjunct to therapy in partial epilepsy with
or without secondary generalization

Contraindication:
Caution to avoid sudden withdrawal, renal
impairment (elderly)
Adverse effects:
Somnolence, dizziness, ataxia, fatique

Barbiturates
Mecanism of action:
Example of barbiturates include phenobarbital &
primidone (which itself, is largely converted to
phenobarbital)
Potentiation of chloride currents through the
GABAA / Cl-channel complex
Route of administration:
Oral, IV
Indication:
Used in all forms of epilepsy, including status
epilepticus

Contraindication:
Not used in children, elderly people & people with
respiratory depression
Adverse effects:
Sedation, potentially fatal CNS depression in
overdose, good inducer of cytochrome P450

Benzodiazepin
Mecanism of action:
Example of benzodiazepin include clonazepam &
clobazam
Cause potentiation of chloride current through
the GABAA / Cl-channel complex
Route of administration:
Oral, IV

Indication:
Clobazam for tonic-clonic & partial seizures
Lorazepam & diazepam effective in
management of status epilepticus
Contraindication:
Not used in people with respiratory depression
Adverse effects:
Sedation
Lorazepam & diazepam (IV) can depress
respiration

Other anticonvulsant
Other agents used as antiepilepticus
include levetiracetam,
tiagabine,topiramate, acetazolamide
and piracetam.
Their indication can be obtained
from the British National Formulary

Status epilepticus
Intravenous benzodiazepines (lorazepam or
diazepam) are first-line drugs in status
epilepticus.
If these fail to bring an end to seizure activity,
intravenous sadium valproate or phenytoin, or
carbamazepine via a nasogastric tube should be
attempted, ideally in ICU setting.
Alternatively intravenous fosphenytoin (a prodrug
of phenytoin) can be given more rapidly but
requires ECG monitoring.
Thiopental can be used as a final option.