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Seizure: is a paroxysmal event due to abnormal , excessive, discharges from CNS neurons i.e., from a shift in
the normal balance of excitation and inhibition within the CNS.
Epilepsy: is a chronic clinical phenomenon in which a person has recurrent seizures; accordingly a person
with single seizure, or recurrent seizures due to corrable or avoidable causes, does not necessarily have
epilepsy.
Classification of seizure types: ‫قراءه و فهم فقط‬
Partial seizures (consciousness preserved): Partial seizures involve only a portion of the brain, typically
part of one lobe of one hemisphere.
-Simple partial seizures: (consciouness normal); The patient often exhibits abnormal activity of a single limb
or muscle group that is controlled by the region of the brain experiencing the disturbance.
-Complex partial seizures: (consciousness altered/ no memory); These seizures exhibit complex sensory
hallucinations and mental distortion. Motor dysfunction may involve chewing movements, diarrhea, and/or
urination.
Generalized seizures (consciousness lost/no memory): Generalized seizures may begin locally and then
progress to include abnormal electrical discharges throughout both hemispheres of the brain.
-Generalized tonic-clonic (grand mal) seizures: These seizures result in loss of consciousness, followed
by tonic (continuous contraction) and clonic (rapid contraction and relaxation) phases. The seizure may be
followed by a period of confusion and exhaustion due to the depletion of glucose and energy stores.
-Absence (petit mal) seizures: These seizures involve a brief, abrupt, and self-limiting loss of consciousness.
The onset generally occurs in patients at 3 to 5 years of age and lasts until puberty or beyond. The patient
stares and exhibits rapid eye-blinking, which lasts for 3 to 5 seconds.
- Febrile seizures: Young children may develop seizures with illness accompanied by high fever. Febrile
seizures consist of generalized tonic-clonic convulsions of short duration and do not necessarily lead to a
diagnosis of epilepsy.
-Status epilepticus: In status epilepticus, two or more seizures occur without recovery of full consciousness
between them. These may be partial or generalized (which is very dangerous and may cause brain death).
Mechanism of action of antiepileptic drugs:
The antiepileptic drugs appear to block the initiation or spread of seizures via one or more of 3 ways:
1-Control of neuronal membrane action potential:
A- Na+ channels blockade thereby inhibiting the generation of repetitive action potentials in the epileptic
focus and preventing their spread.: Phenytoin, Carbamazepine, Valproic acid, Lamotrigine, Topiramate.
B- Ca++ channels blockade: Phenytoin, Valproic acid & Ethosuximide.
2- Enhancing the inhibitory activity:
A-Inhibiting GABA transaminase (the enzyme that is responsible for GABA breakdown ):
Valproic acid & Vigabatrine.
B- Enhancing synthesis & release of GABA: Gabapentin.
C- Interacting with GABA receptors facilitating CL- influx leading to hyperpolarization: Benzodoazepines ,
phenobarbitone.
3- Inhibiting the excitatory activity:
A- Inhibiting the release of excitatory neurotransmitters (Glutamate): Lamotrigine.
B- Decreasing Glutamate synthesis: Gabapentin.
C- Glutamate receptor blockade: Topiramate, Levetiracetam
 ‫ اسماء تجارية لالطالع فقط‬Carbamazepine TEGRETOL, Diazepam VALIUM, Sodium Valproate
DEPAKIN, Gabapentin NEURONTIN, Levetiracetam KEPPRA, Lorazepam ATIVAN, Phenobarbital
LUMINAL, Phenytoin EPANIOTIN, Topiramate TOPAMAX.
1- Phenytoin:
Medical uses:
-Phenytoin is effective against partial seizures and generalized tonic clonic (know very little in use)
seizures.
- It is also used to treat trigeminal neuralgia.
- It is also used to treat cardiac arrhythmia (potential membrane stabilizing effect).
Phrmacokinetics:
Shows saturation kinetics, such that small increases in phenytoin doses at a standard maintenance dose
can precipitate marked side effects.
Side effects: long term use of phenytoin is associated with unfavorable cosmotic effects (hirsutism,
coarsening of facial features & gingival hypertrophy) so it is avoided in young patients who likely to
require the drug for many years.
2- Carbamazepine:
Medical uses:
a- Carbamazepine is considered a drug of choice for both partial seizures and generalized tonic-clonic
seizures.
b-It is also used to treat trigeminal neuralgia
c- Carbamazepine is also useful for controlling mania
Phrmacokinetics:
Carbamazepine is absorbed slowly and erratically following oral administration and may vary from
generic to generic, resulting in large variations in serum concentrations of the drug.
Drug Interactions
Drug interactions involving carbamazepine are almost exclusively related to the drug’s enzymeinducing properties. The increased metabolic capacity of the hepatic enzymes may cause a reduction in
carbamazepine concentration it self and an increased rate of metabolism of other drugs, eg, phenytoin.
Side effects:
- diplopia and ataxia (the most common).
-Carbamazepine should not be prescribed for patients with absence seizures because it may cause an
increase in seizures (unknown cause).
-Teratogenic in pregnancy causing neural tube defects.
- erythematous skin rash
- idiosyncratic blood dyscrasias
3- Valproic acid
a broad spectrum of activity against seizure.
Valproate is bound to albumin (greater than 90 percent), which can cause significant interactions with
other highly protein-bound drugs. Rare hepatic toxicity may cause a rise in hepatic enzymes in plasma,
which should be monitored frequently. Teratogenicity is also of great concern (cause behavioral
abnormalities and neural tube defects).Therefore, all women of childbearing age should be placed on
other therapies.
4- Lamotrigine
Medical uses:
The drug is also active against absence seizures in children .
Adverse effects include headache, diplopia, nauseaand skin rash. The rash is considered a typical
hypersensitivity reaction. Although the risk of rash may be diminished by introducing the drug slowly,
pediatric patients are at greatest risk, some studies suggest that a potentially life-threatening dermatitis
will develop in 1–2% of pediatric patients.
Pharmacokinetics
Lamotrigine is almost completely
Drug Interactions
Valproate causes a twofold increase in the drug’s half-life; in patients receiving valproate.
5- Topiramate
Clinical Uses
-Topiramate as monotherapy demonstrated efficacy against partial and generalized tonic-clonic
seizures.
-Topiramate is also approved for the treatment of migraine headaches.
Side effects:
Dose-related adverse effects occur most frequently in the first 4 weeks and include fatigue, dizziness,
cognitive slowing. Acute myopia and glaucoma may require prompt drug withdrawal. Urolithiasis has
also been reported. The drug is teratogenic.
Pharmacokinetics
Topiramate is rapidly absorbed and is 80% bioavailable.
There is no food effect on absorption
The drug is primarily excreted unchanged in the urine.
There is no autoinduction.
6-Levetiracetam
Medical uses:
Effective against partial seizures.
Phrmacokinetics:
Oral absorption of levetiracetam is nearly complete. Oral formulations include extended release
tablets; an intravenous preparation is also available.
Drug Interactions: levetiracetam is not metabolized by cytochrome P450. so no interaction.
Side effects: drowsiness at first days of use.
7- Ethosuximide: Ethosuximide was introduced in 1960. Now used in animal studies only
8- Vigabatrine:
Medical uses:
Seconed line drug only reseved for resistant cases of partial seizures and infantile spasms.
Side effects:
Typical toxicities include drowsiness, dizziness, and weight gain and reversible intramyelinic edema
9- Gabapentin, Pregabalin : Gabapentin is an amino acid, an analog of GABA, that is effective
against partial seizure. Pregabalin is another GABA analog, closely related to gabapentin. This drug
has been approved for both antiseizure activity and for its analgesic properties.
Medical uses: -Gabapentin and Pregabalin are effective as an adjunct against partial seizures and
generalized tonic-clonic seizures
and also been promoted for the treatment of neuropathic pain
including painful diabetic peripheral neuropathy and postherpetic neuralgia.
Phrmacokinetics: well absorbed , excreted really.
Drug Interactions: unique mong all antiepileptics as having no drug interactions
Side effects: The most common adverse effects of Gabapentin and Pregabalin are somnolence,
dizziness, ataxia, headache and tremor.
10- Benzodoazepines: Clonazepam, Diazepam and lorazepam are most often used as an adjunctive
therapy for for partial and generalized tonic-clonic seizures.
11- phenobarbitone:
Clinical Uses
-Phenobarbital is useful in the treatment of partial seizures and generalized tonic-clonic seizures.
-Is useful for prevention and treatment of febrile seizures.
Pharmacokinetics:
Well absorbed orally and parentrally.
Side effects:
-Cause sedation in adults, hyperactivity in children and other cognitive changes. Thus its use should be
limited in situations that no other alternative is available.