Professional Documents
Culture Documents
Kuliah Antiepilepsi
Kuliah Antiepilepsi
Kuliah Antiepilepsi
The Synapse
ions
The Brain
Complex Secondarily
Generalized Partial Seizures
Goals:
Strategies:
A.
Resting State
B.
Arrival of Action
Potential causes
depolarization and
channel opens
allowing sodium to
flow in.
C.
Refractory State,
Sustain channel in
this conformation
Inactivation
Na+
Na+
Na+
GABA agonists
GABA antagonists
Barbiturates
Benzodiazepines
GABA uptake
inhibitors
Na+
Ca2+
AGONISTS
GLU
GLY
Mg++
Excitatory Synapse.
Permeable to Na+, Ca2+
and K+.
Magnesium ions block
channel in resting state.
Glycine (GLY) binding
enhances the ability of
GLU or NMDA to open
the channel.
Agonists: NMDA, AMPA,
Kianate.
Phenytoin
Carbamazepine
Oxcarbamazepine
Primione
Valproic acid
Lamotrigine
Topitramate
Zonisamide
Phenobarbital
Gabapentin
Felbamacte
Ethosuxamide
Phenobarbital
Zonisamide
BARBITURATES:
Phenobarbital
BENZODIAZEPINES:
Diazepam
Lorazepam
Clonazepam
Valproic Acid
Gabapentin
Gabapentin
Vigabatrin
Valproic Acid
Tiagabine
Facilitate GAD
(Glutamic acid decarboxylase)
Increase GABA synthesis
Valproic Acid
Topiramate
1)
2)
3)
4)
5)
6)
7)
8)
Hydantoins: phenytoin
Barbiturates: phenobarbital
Oxazolidinediones: trimethadione
Succinimides: ethosuximide
Acetylureas: phenacemide
Other: carbamazepine, lamotrigine,
vigabatrin, etc.
Diet
Surgery, Vagus Nerve Stimulation (VNS).
.
Block of sustained high frequency repetitive firing of
action potentials.
(From Katzung B.G., 2001)
Oldest nonsedative
antiepileptic drug.
Fosphenytoin, a more
soluble prodrug is used for
Toxicity:
parenteral use.
Ataxia
Fetal hydantoin
Cognitive impairment.
syndrome
Hirsutism
It alters Na+, Ca2+ and K+
Gingival hyperplasia.
conductances.
Inhibits high frequency
Coarsening of facial
repetitive firing.
features.
Dose-dependent zero order Alters membrane
potentials.
kinetics.
Alters a.a. concentration.
Exacerbates absence
Alters NTs (NE, ACh, GABA)
seizures.
Tricyclic, antidepressant
(bipolar)
3-D conformation similar to
phenytoin.
Mechanism of action, similar
to phenytoin. Inhibits high
frequency repetitive firing.
Decreases synaptic activity
Toxicity:
presynaptically.
Autoinduction of
Binds to adenosine receptors
metabolism.
(?).
Nausea and visual
Inh. uptake and release of
disturbances.
Granulocyte supression. NE, but not GABA.
Potentiates postsynaptic
Aplastic anemia.
effects of GABA.
Exacerbates absence
Metabolite is active.
seizures.
Closely related to
carbamazepine.
With improved toxicity
profile.
Less potent than
carbamazepine.
Active metabolite.
Mechanism of action, similar
Toxicity:
Hyponatremia
to carbamazepine It alters
Less hypersensitivity
Na+ conductance and inhibits
and induction of hepatic
high frequency repetitive
enzymes than with carb.
firing.
Toxicity:
Sedation.
Cognitive
impairment.
Behavioral
changes.
Induction of liver
enzymes.
May worsen
absence and
atonic seizures.
Toxicity:
Same as phenobarbital
Sedation occurs early.
Gastrointestinal complaints.
Metabolized to phenobarbital
and phenylethylmalonamide
(PEMA), both active
metabolites.
Effective against partial and
generalized tonic-clonic
seizures.
Absorbed completely, low
binding to plasma proteins.
Should be started slowly to
avoid sedation and GI
problems.
Its mechanism of action may
be closer to phenytoin than
the barbiturates.
hepatotoxicity.
[aspartate]Brain?
Negative interactions with May
increase
membrane
other antiepileptics.
potassium conductance.
Skin rashes
Lupus erythematosus (?)
A benzodiazepine.
Long acting drug with
efficacy for absence
seizures.
One of the most potent
antiepileptic agents
known.
Also effective in some
Toxicity:
cases of myoclonic
Sedation is prominent.
seizures.
Ataxia.
Has been tried in
Behavior disorders.
infantile spasms.
Doses should start small.
Increases the frequency
of Cl- channel opening.
Toxicity:
Drowsiness
Dizziness
Weight gain
Agitation
Confusion
Psychosis
Absorption is rapid,
bioavailability is ~ 60%, T 1/2
6-8 hrs, eliminated by the
kidneys.
Use for partial seizures and
Wests syndrome.
Contraindicated if preexisting
mental illness is present.
Irreversible inhibitor of GABAaminotransferase (enzyme
responsible for metabolism of
GABA) => Increases
inhibitory effects of GABA.
S(+) enantiomer is active.
Toxicity:
Dizziness
Headache
Diplopia
Nausea
Somnolence
Rash
Toxicity:
Aplastic anemia
Severe hepatitis
Toxicity:
Somnolence
Fatigue
Dizziness
Cognitive
slowing
Paresthesias
Nervousness
Confusion
Urolithiasis
Asthenia
Emotional lability
Psychosis
Skin rash
Sulfonamide derivative.
Marketed in Japan.
Good bioavailability, low
pb.
T1/2 = 1 - 3 days
Effective against partial
and generalized tonicToxicity:
clonic seizures.
Mechanism of action
Drowsiness
Cognitive impairment involves voltage and usedependent inactivation of
High incidence of
sodium channels (?).
renal stones (?).
May also involve Ca2+
channels.
Toxicity:
Somnolence.
Dizziness.
Ataxia.
Headache.
Tremor.
Toxicity
Sedation
Children may
manifest a
paradoxical
hyperactivity.
Tolerance
Benzodiazepines.
Will also be discussed with
Sedative hypnotics.
Given I.V.
Lorazepam may be longer
acting.
1 for treating status
epilepticus
Have muscle relaxant
activity.
Allosteric modulators of
GABA receptors.
Potentiates GABA function,
by increasing the frequency
of channel opening.
Initial
Diazepam, i.v. 5-10 mg (1-2 mg/min)
repeat dose (5-10 mg) every 20-30 min.
Lorazepam, i.v. 2-6 mg (1 mg/min)
repeat dose (2-6 mg) every 20-30 min.
Follow-up
Phenytoin, i.v. 15-20 mg/Kg (30-50 mg/min).
repeat dose (100-150 mg) every 30 min.
Phenobarbital, i.v. 10-20 mg/Kg (2530mg/min).
repeat dose (120-240 mg) every 20 min.
PARTIAL SEIZURES
( Simple and
Complex, including secondarily
generalized)
Drugs of choice: Carbamazepine
Phenytoin
Valproate
Alternatives: Lamotrigine, phenobarbital,
primidone, oxcarbamazepine.
Add-on therapy: Gabapentin, topiramate,
tiagabine, levetiracetam, zonisamide.
INFANTILE SPASMS
Drugs of choice: Corticotropin (IM) or
Corticosteroids (Prednisone)
Zonisamide
Alternatives: Clonazepam, nitrazepam,
vigabatrin, phenobarbital.