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ANTI-EPILEPTIC DRUGS
EPILEPSY: - It is a chronic disorder characterized by repeated attacks of abnormal
electrical discharge of cerebral neurons resulting in EEG, sensory, motor, autonomic and
physiological changes. Each attack is a fit or a seizure.

Causes of Epilepsy:
I- Primary Epilepsy: - No known cause (idiopathic).
II- Secondary Epilepsy: - (Cryptogenic)
- Local causes: - Trauma, meningitis or tumors in the brain.
- Systemic causes: - Hypoglycemia, hypocalcemia, fevers.
- Drugs: - Insulin, Tricyclic antidepressants, CNS stimulants and
Antipsychotics.

Classification of Epilepsy: - Epilepsy is caused by a group of hyperexcitable

neurons which undergo excessive electrical discharge which might remain localized
(Partial Seizures) or may spread (Generalized seizure).
I- Partial Seizures: -
- Simple Partial Epilepsy: - localized motor (convulsions) or sensory
disturbances.
- Complex Partial Epilepsy: - (Psychomotor) Attacks of confused behavior
with disturbances of consciousness and hallucinations.
III- Generalized Seizures: -
- Grand-mal Epilepsy: - Tonic-clonic convulsions involving the whole
body with loss of consciousness.
- Petit-mal Epilepsy (Absence Seizures): - brief abrupt loss of
consciousness (10-15 seconds) with blinking of the eyelids or staring in
children).
- Myoclonic Epilepsy: - Sudden brief single or repetitive muscle
contractions without loss of consciousness.

STATUS EPILETICUS: - Continuous successions of seizures (>20 minutes) without

any period of recovery.

Pathophysiology of Epilepsy
The hyperexcitability of cerebral neurons in epilepsy might be due to:
1- Change in brain transmitters.
- Increase in excitatory brain transmitters (Glutamate).
- Decrease in inhibitory brain transmitters (GABA).
2- Increased membrane permeability to ions (Ca++, Na+).
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Mechanism of action of Anti-epileptic drugs

They decrease the hyperexcitability of cerebral neurons by one of the following
mechanisms:
I- Change in brain transmitters:
- Facilitation of GABA action (Phenobarbital and Benzodiazepines).
- Increasing the GABA level by decreasing the breakdown through
inhibiting the transaminase enzyme (Valproate and Vigabatrin).
II- Decreased membrane ion permeability:
- Block Na+ channels (Phenytoin, Carbamazepine and Valproate).
- Block Ca++ channels in the thalamus (Ethosuximide).

N.B: - Acetazolamide is a carbonic anhydrase inhibitor which potentiates other Anti-

epileptic drugs by inducing acidosis resulting in increase in seizure threshold. However,
tolerance develops quickly.

Therapeutic uses of Anti-epileptic drugs

1) Epilepsy
2) Other uses:
- Carbamazepine: - Mood stabilizer in Manic-depressive disorder.
- Trigeminal neuralgia.
- Valproate: - Mood stabilizer in Manic-depressive disorder.
- Phenytoin: - Anti-arrhythmic.

v Choice of Anti-epileptic drugs differs in different types of Epilepsy i.e.

I- Partial and Grand-mal Epilepsy: -
Drugs of choice: - Phenytoin, Carbamazepine, Valproate.
Second line drugs: - Phenobarbital (Sedation and Tolerance limit its use).

II – Petit-mal Epilepsy: -
First line drugs: - Ethosuximide (safest), Valproate (Hepatotoxic).
Second line drugs: - Clonazepam (Sedation and Tolerance limit its use).

II- Myoclonic Epilepsy: -

First line drugs: - Valproate.
Second line drugs: - Clonazepam.

TREATMENT OF STATUS EPILEPTICUS

1) Diazepam I.V (rapid control) followed by I.V Phenytoin (long acting).

2) General anaesthesia and neuromuscular blockers in resistant cases.
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General Giudelines for Anti-epileptic drug therapy

§ Proper diagnosis of the type of epilepsy and prescription of appropriate drugs:
- Phenytoin precipitates Petit-mal seizures.
- Ethosuximide precipitates Grand-mal seizures.
§ Monotherapy is preferred since Anti-epileptic drugs are either enzyme-inducers
(Phenytoin, Carbamazepine, Phenobarbitone) or enzyme-inhibitors (Valproate).
Therefore, combination therapy would result in changes in serum levels of anti-
epileptic drugs administered together.
§ Start with small dose and a single drug then gradually increase the dose. If no
effect, gradually substitute or add another drug.
§ Long duration of treatment: - If epileptic fits are absent for two years, consider
terminating therapy. If epileptic fits recur, then treatment should be repeated
another two years.
§ Termination therapy should be gradual (should be done over a period of six
months) to avoid Status epilepticus.
§ Pregnant females should receive the least possible dose to reduce the risk of
teratogenicity. Carbamazepine (least teratogenic), Phenytoin can produce cleft
palate, cleft lip and heart anomalies. Valproate can produce spinal bifida.
§ Monitoring the serum level: - The serum level of anti-epileptic drugs should be
within therapeutic range since drop below the therapeutic range would result in
loss of seizure control and increase in its level would result in toxicity (CNS
depression: stupor, coma, respiratory depression).
§ The serum level of Phenytoin is unpredictable. It is affected by the following
factors:
1) Irregular bioavailability: - Use of one formulation from a single
manufacturer.
2) Saturation kinetics: - on increasing the dose of the drug, its serum level
tends to accumulate to toxic levels.
3) Enzyme-inducers: - decrease level (e.g. Carbamazepine and
Phenobarbital).
4) Enzyme-inhibitors: - increase level (e.g. Cimetidine and Valproate).
5) Displacement from plasma-proteins: - increase free form (e.g. Valproate
and Aspirin).

Major Anti-epileptic drugs: - Side effects and Precautions

I- Phenytoin: -
1) Hypersensitivity reactions e.g. skin rash. (Stop the drug).
2) Gastro-intestinal upsets e.g. Nausea, vomiting, epigastric pain. (Give small
doses after meal).
3) Neurological disturbances e.g. Nyastagmus, diplopia, ataxia, drowsiness,
decreased learning abilities in children.
4) Enzyme-inducer:
- Increases the metabolism of anti-epileptic drugs and other drugs e.g.
Warfarin.
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- Osteomalasia due to increased Vitamin-D metabolism. (Supplements

of Vitamin-D and Ca++ are required).
5) Megaloblastic anaemia due to increased folic acid. (Routine blood picture
and supplements of folic acid when necessary).
6) Cosmetic disturbances: (Not preferred in females).
- Gingival hyperplasia. (Gum Hygiene is required).
- Coarse facial features.
- Hirsutism.
- Acne.
7) Unpredictable serum level. (Monitor the serum level).

II- Carbamazepine:
1) Hypersensitivity reactions e.g. skin rash. (Stop the drug).
2) Gastro-intestinal upsets; - Nausea, vomiting, epigastric pain. (Use small
dose after meal).
3) Neurological disturbances e.g. Diplopia, ataxia, drowsiness.
4) Hepatotoxicity. (Monitor liver functions).
5) Enzyme-inducer: - increases the metabolism of Anti-epileptic drugs and
other drugs e.g. Warfarin.
6) Agranulocytosis. (Routine blood picture monitoring).
7) Water intoxication and dilutional hyponatremia.

III- Valproate:
1) Hypersensitivity reactions e.g. skin rash. (Stop the drug).
2) Gastro-intestinal upsets: - Nausea, vomiting, epigastric pain. (Give small
dose after meal).
3) Neurological disturbances e.g. fine hand tremors, ataxia (less sedative).
4) Rare but fetal hepatotoxicity.
5) Enzyme-inhibitor: - Decreases metabolism of anti-epileptic drugs and
other drugs e.g. Warfarin.
6) Hair loss.
7) Increased appetite.
8) Increased body weight.

IV- Ethosuximide:
1) Hypersensitivity reactions.
2) Gastro-intestinal upsets.
3) Dizziness.
4) Drowsiness.
5) Headache.