Epilepsy Treatment1

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Epilepsy and antiepileptic drugs

Epilepsy: is a very common chronicdisorder characterized by recurrent

seizures.

Seizure: excessive discharge of cortical

neuron

Convulsion: involuntary contraction of

voluntary muscles

Patients may have epilepsy or seizure

disorders without convulsions

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Any Seizure Result From

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Types Of Ion Channels

Voltage-gated

Channels Na+ & ca ++

depolarize the

cell membrane

(E)

K+ hyperpolarize

the cell membrane

(I)

Ion Channels

Ligand -gated

channels

Glutamate (E)

GABA (I)

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Primary

Types of

s

(focal)


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International Classification Of Seizures

a. Partial focal :

In which the discharge involves one part

of the cortex.

1.Simple: consciousness is preserved

2.Complex: consciousness is impaired


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b. Generalized

In which the discharge involves the whole

cortex

1. Tonic-Clonic: Grandmal seizures

Tonic: abrupt loss of consciousness (less than

1 min)

Clonic: jerking of body muscles with lip or

tongue biting, fecal & urinary incontinence


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2. Absence or petit mal: altering of

consciousness lasting 10-30 seconds,

onset of this type occurs from ages 3-16

years

3. Myoclonic: Single or Multiple muscle jerk


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c. Status epilepticus:

Series of seizures without recovery ofconsciousness between attacks

It is life threatening emergency


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Febrile seizures

Young child (3 months to 5 years)

frequently develop seizures with illnessaccompanied by high fever

Treatment: acute case Diazepamrectally

Diagnosis of specific seizure type is importantfor prescribing the most appropriate anti-seizure drug

Treatment may involve combination of drugs


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Generalized tonic clonic seizures

(grand mal seizures)

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Generalized Seizure (Absence or Petit Mal )

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ATONIC SEIZURE


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Aim of Treatment

a: Complete suppression of fits and if not

possible.

b: Reduction of fit frequency as much as

possible, with minimum and tolerable

ADRs.


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The management of patients with epilepsy is

focused on 3 main goals:

Goals

Improve

Quality Of

Life

Avoiding

Side

Effects

Controlling

Seizures

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Etiology of epilepsy

Some seizures arise secondary to other

conditions. However, in most cases, the

cause of the seizure is unknown.

1. Primary (idiopathic) seizures have noidentifiable cause.


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2.Secondary seizures (symptomatic or acquires

seizures) occur secondary to an identifiable cause.* Intracranial neoplasms.

* Infectious diseases, such as meningitis, influenza,

* High fever (in children)* Head trauma.

* Metabolic disorders, such as hypoglycemia and

hypocalcemia.

* Alcohol or drug withdrawal.


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Clinical evaluation

Historyincludes an evaluation of the

seizure, including interviews of the

patients family

Laboratory testmay also identify an

underlying etiology

Neurological imagingstudies


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EEG studies measure the electrical activity

of the brain.

- An EEG is useful for classifying the

seizure, but the EEG by itself cannot rule

seizures in or out, as there are patients

with normal EEGs who have seizure

disorders.


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Therapy

Principles of drug therapy

Seizure control.

Approximately 50% of epileptics achievecomplete seizure control through drug

therapy. In another 25% drugs reduce the

frequency of seizures. Epileptics generally

require continuous drug therapy for at

least 4 seizure-free years before the drug

can be discontinued.


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Antiepileptics are indicated when there is

two or more seizures occurred in short

interval

An initial therapeutic aim is to use only one

drug (monotherapy)


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Before any drug treatment is instituted,

remedial causes of the seizure activity

should be excluded.

A single primary drug that is most

appropriate for the seizure type must be

selected. If there is more than one

appropriate primary drug, age, sex, and

compliance of the patient must be

considered

Treatment:


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Treatment

Additional therapy. If seizures recur after themaximal tolerated dose is reached; a second

drug is added at a low dose.

The dose of the second drug is increased until a

therapeutic level is reached.

The first drug is maintained until the optimaldose of the second drug is determined; then the

first drug is discontinued gradually to avoid

triggering seizure activity.


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The sudden withdrawal of drugs should be

avoided

withdrawal may be considered after

seizure- free period of 2-3 or more years


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MOA of antiepleptic drugs:

inhibitory tone by facilitation of GABA-mediatedhyperpolarization-barbiturates, benzodiazepines

axonal conduction by preventing Na' influx

through fast Na channels-carbamazepine,phenytoin; also, at high doses, barbiturates andvalproic acid

presynaptic ca2 + influx through type-Tchannels in thalamic neurons-ethosuximide andvalproic acid


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DRUG THAT BLOCK VOLTAGE-DEPENDENT SODIUM

CHANNELS

Pharmacology of antiepileptic drug

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Anti-epileptic drugs

Phenytoin

MOA: blocks voltage gated sodium channels in

neuronal membrane

Clinical uses: partial seizures & generalized

tonic-clonic seizures

It has narrow therapeutic index


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Phenytoin

the relation between thedose & plasma

concentration is not

linear.

Has high drug

Interactions.

Induction of dug

metabolizing enzymes


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S/Es

1. CNS: ataxia, diplopia, nystagmus

2. Gingival hyperplasia

3. Hairsutism

4. Teratogenic effect (not given during

pregnancy)5. Abnormalities of vitamin D catabolism

6. folate levels megaloblastic anemia


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Gingival hyperplasia

Carbamazepine
http://jorthod.maneyjournals.org/content/vol30/issue1/images/large/ClocFig1b.jpeg


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Carbamazepine

MOA: blocks sodium channels

Uses: as phenytoin & for Trigeminal

Neuralgia & Rx of mania Similarities between phenytoin & carbamazepine:

Both are liver enzyme inducers

Both enhance catabolism of vitamin D

Both cause megaloblastic anemia but morewith phenytoin

Both are not used in absence seizures

S/Es

CNS: ataxia, diplopia


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Valproic acid

MOA

Interfere with sodium channels at high doses

Can potentiate the inhibitory effect of GABA Therapeutic uses

Generalized Tonic-Clonic, partial & can beused in absence seizure S/Es

Alopecia (hair loss)

Teratogenicity

Liver damage


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Ethosuximide

MOA: act by blocking T-calcium channel

The main drug used to treat absence seizures

S/Es: nausea & anorexia

Phenobarbital

clinical use: the same as phenytoin, for Tonic-

Clonic seizures


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Benzodiazepines

1. Diazepam: given I.V. to treat status

epilepticus

2. Clonazepam


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Drugs Used in Seizure Disorders

Tonic-Clonic & Partial Seizure Absence Seizure Myoclonic

CarbamazepinePhenytoin

Valproic acid

phenobarbital

EthosuximideValproic acid

Clonazepam

ClonazepamValproic acid


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Management of status epilepticus

1.Establish airway, oxygenate, recoveryposition

2. Establish IV access and give IVlorazepam 2-4mg (IV diazepam 5-10mgalternative; Buccal midazolam 10mgpreferred over rectal diazepam)

3. Check blood for: glucose, urea andelectrolytes, Calcium, anticonvulsant

levels, and arterial blood gas and pH.


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4.If seizures continue, administerintravenous phenobarbital orphenytoin assecond-line treatment

5. In sever status epilepticus especially thatnot respond to these meausres, generalanesthesia and neuromuscular blocker

and artificial respiration.
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Epilepsy Treatment1

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