Antiepileptics

Antiepileptics
What is seizure?
An abnormal, synchronized, electrical
depolarization of neurons in the CNS
Major causes of seizures
1. Idiopathic
2. CNS infections
3. Fever
4. Metabolic defects
5. Cerebral trauma
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Types of seizures
1. Partial
2. Generalized tonic-clonic
3. Status epilepticus
4. Absence
5. Febrile
6. Myoclonic
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Partial (focal)seizure
A seizure in which abnormal discharges occur from a
focal area with in the brain
There are two types of partial seizure
Simple and complex
Characterstics of simple partial seizure
Involves a focal neurologic symptom that can be sensory (for
example, auditory or visual hallucinations), motor, or
psychomotor
Consciousness is always retained
What happens in complex partial seizure?
The initial focus of abnormal discharge spreads so that the
patient will lose consciousness and have postictal (post-
seizure) confusion
The majority originate in the temporal lobe
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Generalized tonic-clonic (grand mal) seizure

What part of the brain is involved?
The entire cerebral cortex
Typical phases of grand mal seizure
Tonic phaseloss of consciousness, rigidity, loss of
bowel and bladder control
Clonic phasejerking movements of the entire body
A partial seizure can develop into a grand mal
seizure
This is known as partial seizure with secondary
generalization
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Status epilepticus
Continuous seizures not separated by any periods of
regained consciousness
This condition is a medical emergency
Absence (petit mal) seizures
They usually occur in children 2 to 12 years of age
Characterized by a very brief (10 seconds) loss of
consciousness
The child will stop whatever he is doing and stare or
have some facial twitching
Following the attack, the child becomes immediately
alert and is seldom even aware that it has occurred.
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Febrile seizure
They occur in children
Usually last less than 10 minutes
The child has a fever, but there is no apparent
infection or other defined cause
Myoclonic seizure
They are sudden, short episodes of either local or
generalized muscle contractions
Can occur at any age
Associated with a variety of rare hereditary
neurodegenerative disorders
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What is epilepsy?
A group of chronic syndromes characterized by
recurrent seizures with periods of consciousness
About 1% of the population is affected by epilepsy
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The pharmacological treatment options for seizures:
Phenytoin
Carbamazepine
Phenobarbital
Primidone
Valproic acid
Ethosuximide
Benzodiazepines
Gabapentin
Lamotrigine
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Phenytoin
Therapeutic uses
Effective in treating tonic-clonic seizures and partial seizures but not
absence seizures
It is also used in the treatment of status epilepticus after the
administration of diazepam
MOA: binds to and prolongs the inactivated state of Na+
channels
Toxic effects:
Gingival hyperplasia
Megaloblastic anemia secondary to interference with folate metabolism
Hirsutism
CNS depression
Endocrine disturbancesdiabetes insipidus, hyperglycemia, glycosurea,
osteomalacia
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Drugs that increase plasma concentration of

phenytoin
Chloramphenicol
Isoniazid
Cimetidine
A well known drug to decrease plasma
concentration of phenytoin
Carbamazepine
Is phenytoin teratogenic?
Yes. It produces fetal hydantoin syndrome, which is
characterized by prenatal growth deficiency and mental
deficiencies. There is also increased incidence of
congenital malformations such as cleft palate and heart
malformations
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Carbamazepine
Therapeutic use: for t/t of parial and tonic-clonic
seizure
MOA: prolongs the inactivated state of Na+ channels
Drugs that inhibits the metabolism of carbamazepine:
Erythromycin
Isoniazid
Propoxyphene
Verapamil
Cimetidine
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Phenobarbital
Class: it is a barbiturate
MOA: ?????
Therapeutic uses:
It is the drug of choice for treating febrile seizures
Good for treating partial and tonic-clonic seizures;
however, its sedative effects have reduced its use as a
primary agent
Primidone
It is related to phenobarbital and it works the same
way as phenobarbital
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Valproic acid
It is the most effective agent in treating myoclonic
seizures
Also used in the treatment of absence seizures
How?it prolongs the inactivated state of Na+
channels.
---It may also increase GABA concentration in
the brain
Should pregnant moms be given valproic acid?
No! The incidence of neural tube defects is very high if
this drug is taken during the first trimister
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Ethosuximide
Usedrug of choice for treating absence seizures
Mechanisminhibits Ca2+ influx through T-type
channels in the thalamic neurons
Benzodiazepines
Examples of BDZ for epilepsy
Diazepam, clonazepam, clorazepate
Therapeutic uses of these drugs:
IV diazepam is the drug of choice for initiating treatment of
status epilepticus
Clonazepam can be used for treating myoclonic seizures in
children
Clorazepate may be used for parial seizures in combination
with other drugs
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Gabapentin
Used to treat partial seizures with and without
secondary generalization
Mechanismpromote release of GABA
Lamotrigine
To treat partial seizures in adults in combination
with other drugs
Mechanismblocks sustained repetitive firing by
blocking voltage-dependent Na+ channels