ANTIEPILEPTIC DRUGS

EPILEPSY:

Chronic neurological disorder characterized by sudden onset of seizures

SEIZURES:

Seizures are episodes of sudden, transient disturbances in cerebral

excitation that occur when a sufficient number of cerebral neurons
begin to fire rapidly and in synchronized bursts.
Depending on the type of seizure, neuronal activity may remain
localized in a specific area of the brain, or it may spread to other areas
of the brain.

CONVULSIONS:

Abnormal muscle movements due to seizure.

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 Cause of EPILEPSY

 BRAIN PATHOLOGY: stroke, tumor,

encephalopathy, head trauma.

 METOBOLIC DISORDER: infection, hypoglycemia,

hypoxia.

 IDIOPATHIC

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TYPES OF EPILEPTIC SEIZURES

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Cont…

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Cont…

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 BARBITURATES

Phenobarbitol, pentobarbitol, amobarbitol,

USE
 Generalized tonic clonic seizures
 Partial simple and complex seizures
MECHANISM OF ACTION
 Potentiate GABA inhibition.
 Decrease release of excitatory neurotransmitter.
Side effects
 Sedation, tremors.

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 Benzodiazepines
 Diazepam, lorazepam, clonazepam, clorazepate.

 Mech: Increase GABA activity.

 More sedation and tolerance.

 Sedation, ataxia, behavioural symptoms.

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 HYDANTOINS
USES
 Phenytoin first choice drug for Generalized tonic clonic epilepsy.
 Ethotoin is used in absence epilepsy
 Fosphenytoin in status epileptics

MECHANISM OF ACTION
 Phenytoin stabilizes neural membranes and decreases neuronal
excitability by decreasing sodium entry into rapidly firing neurons. This
drug basically inhibits the ability of sodium channels to reset from an
inactive to active state after the neuron has fired an action potential. By
inhibiting the reactivation of sodium channels, phenytoin prolongs the
time between action potentials (absolute refractory period) so that
neurons must slow their firing rate to a normal level.
 Side effects
 Sedation,confusion,gastric irritation.
 Hirsutism
 Cerebellar signs
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 SUCCINAMIDES
 Ethosuximide, methsuximide, and phensuximide.
USES
 Absence epilepsy
MECHANISM OF ACTION
 Ca influx inhibition in thalamic neurons:The spontaneous,
rhythmic entry of calcium into thalamic neurons may be
responsible for initiating partial seizures, and the
succinimides prevent their onset by blunting calcium
influx.
Side effects
GIT irritation, headache, dyskinesia, bradykinesia, itching
and rashes. 9
Iminostilbenes(CARBAMAZAPINE)
USES
 All types of epilepsy except absence epilepsy
MECHANISM OF ACTION
 Membrane stabilizing effect…by slowing the
recovery of sodium channels firing too rapidly.
 Inhibit pre synaptic release of nor epinephrine…
 SIDE EFFECTS
 CCF, cardiac arrhythmias
 Headache, ataxia, blurred vision.

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 VALPROIC ACID
USES
 Primarily absence seizure
 Generalized tonic clonic seizures
 Bipolar syndrome
MECHANISM OF ACTION
 Increase GABA activities
 Membrane stabilizing activities: increase potassium
conductance and efflux from certain neurons, thereby
hyperpolarizing the neuron and decreasing its
excitability…also it limits sodium entry into rapidly firing
neurons.
SIDE EFFECTS
 Weight gain, Hair loss, GIT symptoms, impaired platelets
function 11
 Newer “Second-Generation” Agents
 Felbamate is indicated for treatment of partial seizures in adults
and children as well as generalized absence seizures in children.
 Felbamate appears to bind to specific receptors in the brain (the
N-methyl-D aspartate receptor) and block the effects of
excitatory amino acids such as glutamate. Reduced influence of
these excitatory amino acids results in decreased seizure
activity.
 first “new generation” antiseizure agent.
 may cause severe toxic effects such as aplastic anemia and liver
failure.
 Typically limited to patients with severe epilepsy who fail to
respond to other antiseizure drugs.
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Cont…

 Gabapentin is used primarily to treat partial

seizures in adults and partial seizures in
children that have not responded to other
treatments.
 act as a GABA agonist.

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 Cont…

 Lamotrigine is used primarily as an adjunct to other

medications in adults with partial seizures,
although it has also been used alone to treat partial
and generalized seizures in adults and children.
 stabilizing sodium channels in a manner similar to
carbamazepine and phenytoin.

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 Others…
 Levetiracetam: mechanism of this drug is unknown.

 Tiagabine: inhibits the reuptake of GABA after it is released.

 Topiramate: inhibition of sodium channel opening, blockade

of excitatory amino acid receptors, and stimulation of GABA
receptors

 Zonisamide: stabilizes sodium channels in a manner similar

to carbamazepine and phenytoin, and may also exert some
of its antiseizure effects by inhibiting calcium entry into
rapidly firing neurons.
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 Drug Combinations in Epilepsy
The use of a single drug (monotherapy) offers several
advantages, including
 fewer side effects,
 a lack of drug interactions,
 better ability of the patient to adhere to the drug
regimen,
 lower cost, and better seizure control because the patient
was able to tolerate a higher dose of a single agent.
Likewise, management of adverse side effects in single-
drug therapy is easier because there is no question about
which drug is producing the adverse effect.
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 newer antiseizure medications…relatively
predictable pharmacokinetic and side-effect
profiles.
 Combination therapy is therefore a more
common approach to treating seizure
disorders than it was in the past.

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 PHARMAKOKINETICS
 Give orally: divided into three or four equal
quantities, and the amount of each dose varies
widely depending on the specific drug and the
severity of patient seizures.
 Distribution within the body is fairly extensive,
with all antiepileptic drugs eventually reaching the
brain to exert their beneficial effects.
 Metobolized by liver
 Liver enzyme induction

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 Special Precautions During Pregnancy

 Most women with epilepsy continue to take their

antiseizure medications when they become
pregnant, and eventually give birth to normal,
healthy babies.
 Birth defects: Problems such as stillbirth,
microencephaly, mental retardation, infant
seizures, and congenital malformations (cleft
palate, cardiac defects, neural tube defects) occur
more frequently in children of women with seizure
disorders.
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 Cont…
 If an expectant mother continues to take her
medication(s), using one drug (monotherapy) at the
lowest effective dose will help reduce the risk of harmful
effects on the fetus.
 In addition, mothers should receive optimal prenatal care
(folic acid supplementation, proper amounts of exercise,
rest, and so forth) to help ensure the baby’s health.
 After delivery, the baby should be monitored initially for
drug-related effects such as withdrawal symptoms, and
should be subsequently evaluated for developmental
delays that might become apparent later in childhood.
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 Status epilepticus
 series of seizures occurring without any appreciable period of
recovery between individual seizures.
 Essentially the patient experiences one long, extended seizure.
 sudden withdrawal from antiepileptic drugs,
 cerebral infarct,
 systemic or
 intracranial infection, or
 withdrawal from addictive drugs including alcohol.
 If untreated, status epilepticus will result in permanent damage
or death, especially if the seizures are generalized tonic-clonic
in nature.Consequently, this event is regarded as a medical
emergency that should be resolved as rapidly as possible.
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TREATMENT OF STATUS EPILEPTICUS
MANAGEMENT
 maintaining an airway, starting an IV line for
blood sampling and drug administration
 IV BENZODIAZEPINE: lorazepam or
diazepam
 IV PHENYTOINS(given concurrently with or
immediately after the benzodiazepine so that
seizures are controlled when the relatively
short-acting benzodiazepine is metabolized.
 IV PHENOBARBITOL
 GENERAL ANEASTHESIA (e.g., halothane)
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 Withdrawal of Antiseizure
Medications
 Many people with seizure disorders will need to adhere to a regimen of
antiseizure medications throughout their lifetime. There appears, however,
to be a certain percentage of patients who can discontinue their
medications once their seizures are under control.
 It is estimated, for example, that as many as 60 to 70 percent of people who
have epilepsy can remain seizure-free after their medication is withdrawn.
 Factors associated with successful medication withdrawal include being
free of seizures for at least 2 years while on medication(s), having a normal
neurologic examination prior to withdrawal, and being young when the
seizures started.
 Withdrawal of medications must, of course, be done under close medical
supervision. Likewise, medications are usually tapered-off over an
extended period of time (6 months) rather than being suddenly
discontinued.
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 Special Concerns in Rehabilitation
Patients
 a thorough medical history of all patients.
 therapists may help determine the efficacy of
antiepileptic drug therapy.
 Headache, dizziness, sedation, and gastric
disturbances (nausea, vomiting)…. The optimal
treatment time will vary from patient to patient,
depending on the particular drug, dosing schedule,
and age of the patient.

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 Cont…
 Cerebellar side effects such as ataxia also occur
frequently and may impair the patient’s ability to
participate in various functional activities…
coordination exercises.
 Skin conditions (dermatitis, rashes, etc.) are
another frequent problem in long-term
antiepileptic therapy. Any therapeutic modalities
that might exacerbate these conditions should be
discontinued.
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Cont…

 environmental stimuli such as lights and

sound… conducting the therapy session in a
busy, noisy clinic may be sufficient to
precipitate a seizure…quite setting.

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Thank You

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