OVERVIEW

Epilepsy affects approximately 3 percent of individuals by the time they are 80 years old. Globally epilepsy is the third most common neurologic disorder after cerebrovascular and Alzheimers disease. It is not a single entity but, instead, an assortment of different seizure types and syndromes originating from several mechanisms that have in common the sudden, excessive, and synchronous discharge of cerebral neurons.

Barbiturates Benzodiazepines Carbamazepine Divalproex

Ethosuximide
Felbamate

Gabapentin Lamotrigine Levetiracetam Oxcarbazepine

Phenytoin
Pregabalin

Primidone

Tiagabine
Topiramate Zonisamide

 When

no specific anatomic cause for the seizure, such as trauma or neoplasm, is evident, a patient may be diagnosed with idiopathic or cryptogenic(primary) epilepsy. Patients are treated chronically with antiseizure drugs or vagal nerve stinulation. Most cases of epilepsy are idiopathic.

 When

two or more seizures occur, then the patient may be diagnosed with symptomatic (secondary) epilepsy. Chronic treatment with antiseizure medications, vagal nerve stimulation and surgery are all appropriate treatments and maybe used alone or in combination.

Seizures have been categorized by site of origin, etiology, electro-physiologic correlation, and clinical presentation. Seizures have been classified into two broad groups; Partial (or Focal) Generalized

CLASSIFICATION OF SEIZURES
PARTIAL

It involves only a portion of the brain, typically part of one lobe of hemisphere. Consciousness is usually preserved.
Simple Partial(consciousness normal)
These seizures are caused by a group of hyperactive neurons exhibiting abnormal electrical activity, which are confined to a single locus in the brain. 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.

CLASSIFICATION OF SEIZURES
PARTIAL

Complex Partial (consciousness altered/no memory) These seizures exhibit complex sensory hallucinations, mental distortion, and loss of consciousness. Motor dysfunction may involve chewing movements, diarrhea, and/or urination.

CLASSIFICATION OF SEIZURES
GENERALIZED

It may begin locally, producing abnormal electrical discharges throughout both hemispheres of the brain. Consciousness is usually lost/no memory. Primary generalized seizures may be convulsive or non convulsive, and the patient usually has an immediate loss of consciousness.

CLASSIFICATION OF SEIZURES
GENERALIZED
Tonic-Clonic:

Seizures resultin loss of consciousness, followed by tonic (continuous contraction) and clonic (rapid contraction and relaxation) phases. It may be followed by a period of confusion and exhaustion due to the depletion of glucose and energy stores. It involve a brief, abrupt, and self-limiting loss of consciousness. The patient stares and exhibits rapid eye-blinking, which lasts for 3 to 5 seconds.

Absence:

CLASSIFICATION OF SEIZURES
GENERALIZED
This seizure has a very distinct three-per-second spike

Myoclonic: These seizures consist of short episodes of muscle

and wave discharge seen on electroencephalogram.

Febrile Seizures Young children may develop seizures with illness

contractions that may reoccur for several minutes. They generally occur after wakening and exhibit as brief jerks of the limbs. accompanied by high fever. It consists of generalized tonic-clonic convulsions of short duration and do not necessarily lead to diagnosis of epilepsy.

CLASSIFICATION OF SEIZURES
GENERALIZED

Status Epilepticus:
Two or more seizures recur without recovery of full

consciousness between them. These maybe partial or primary generalized, convulsive or nonconvulsive. It is life-threatening and requires emergency treatment.

Blockade of voltage-gated channels (Na+ or Ca2+) Enhancement of inhibitory GABAergic impulses, or interference with excitatory glutamate transmission. The antiepilepsy drugs suppress seizures but do not cure or prevent epilepsy.

Choice of drug treatment is based on the classification of the seizures being treated, patient specific variables(age, comorbid medical conditions, lifestyle, and other preferences), and characteristics of the drug, including cost and interactions with other medications. The toxicities of the agent and characteristics of the patient are major considerations in drug selection.

In newly diagnosed patients, monotherapy is instituted with a single agent until seizures are controlled or toxicity occurs. If seizures are not controlled with the first drug, monotherapy with an alternate antiepileptic drug(s), or vagal nerve stimulation should be considered.

BENZODIAZEPINES

Mechanism of Action: It binds to GABA inhibitory receptors to reduce firing rate.

Indications:
Diazepam and lorazepam are most often used as an adjunctive therapy for myoclonic as well as for partial and generalized tonic-clonic seizures. Lorazepam has a shorter pharmacokinetic half-life but stays in the brain longer than diazepam. Diazepam is available for rectal administration to avoid or interrupt prolonged generalized tonic-clonic seizures or clusters.

CARBAMAZEPINE

Mechanism of Action: Blocks Na+ channels. Indications: Treatment of partial seizures. Secondarily generalized tonic-clonic seizures. Trigeminal neuralgia and in bipolar disease. It is absorbed slowly and erratically following oral administration and may vary from generic to generic. It should not be prescribed for patients with absence seizures beacause it may cause an increase in seizures.

CARBAMAZEPINE

Adverse Effects: Hyponatremia Drowsiness Fatigue Dizziness Blurred vision Drug use has been associated with Stevens-Johnson Syndrome. Blood dyscrasias: neutropenia, leukopenia, thrombocytopenia, pancytopenia, and anemias.

DIVALPROEX

Mechanism of Action: Sodium channel blockade Blockade of GABA transaminase Action at the T-type calcium channels. Indications: Treatment of partial and primary generalized epilepsies.

Valproate is bound to albumin which can cause significant interaction with other highly protein bound drugs.

DIVALPROEX

Adverse effects: Weight gain Easy bruising Nausea Tremor Hair loss GI upset Liver damage Alopecia sedation

Hepatic failure Pancreatitis Teratogenic effects

ETHOSUXIMIDE

Mechanism of Action: Blocks Ca2+ channels. Indications: Treat only primary generalized absence seizures.

This is very narrow spectrum.

ETHOSUXIMIDE

Adverse effects: Drowsiness Hyperactivity Nausea Sedation GI upset Weight gain Lethargy SLE Rash Blood dyscrasias can occur; periodic CBCs should be done. Abrupt discontinuance of drug may causes seizures.

FELBAMATE

Mechanism of Action: Blocks voltage-dependent Na channels Competes with the glycine-coagonist binding site on the N-methyl-D-aspartate (NMDA) glutamate receptor. Blocks Ca channels Potentiation of GABA actions. Indications: Use in refractory epilepsies(Lennox-Gastaut Syndrome)

FELBAMATE

Adverse effects: Insomia Dizziness Headache Ataxia Weight gain Irritability Aplastic anemia Hepatic failure Broad spectrum of antiseizure activity.

GABAPENTIN
Mechanism

of Action:

Unknown.
Indications:

Adjunct therapy for partial seizures. Treatment of postherpetic neuralgia.

It

does not bind to plasma proteins and is excreted unchanged through the kidneys.

GABAPENTIN

Adverse Effects: Mid drowsiness Dizziness Ataxia Weight gain Diarrhea Few drug interactions. One-hundred percent renal elimination.

LAMOTRIGINE

Mechanism of Action: Blocks Na channels. High voltage-dependent Ca channels. Indications: Treatment of partial seizures, generalized seizures, typical absence seizures, and the Lennox-Gastaut syndrome. The half-life of lamotrigine(24-35 hours) is decreased by enzyme-inducing drugs(carbamazepine&phenytoin) and increased by greater than 50percent with addition of valproate.

LAMOTRIGINE

Adverse Effects: Nausea Drowsiness Dizziness Headache Diplopia Rash(Stevens-Johnson Syndrome potentially lifethreatening). Broad spectrum of antiseizure activity.

LEVETIRACETAM

Mechanism of Action: Unkown. Indications: Adjunct therapy of partial onset seizures, myoclonic seizures, and primarily generalized tonic-clonic seizures in adults and children.

The drug is well absorbed orally, and excretion is urinary, with most of the drug (66%) being unchanged.

LEVETIRACETAM

Adverse Effects: Sedation Dizziness Headache Anorexia Fatigue Infections Behavioral symptoms Few drug interactions. Broad spectrum of antiseizure activity.

OXCARBAZEPINE

Mechanism of Action: Blocks Na+ channels.

Indications: Treatment of partial onset seizures in adults and children.

OXCARBAZEPINE

Adverse Effects: Nausea Rash Hyponatreamia Headache Sedation Dizziness Vertigo Ataxia diplopia

PHENYTOIN&FOSPHENYTOIN

Mechanism of Action: Blocks Na+ channels. Indications: PHENYTOIN; Treatment of partial seizures and genralized tonicclonic seizures andd status epilepticus. The drug is 90% bound to plasma albumin. FOSPHENYTOIN Is a prodrug Is rapidly converted to phenytoin in the blood, providing high levels of phenytoin within minutes. Is the drug of choice and standard of care for IV&IM administration.

FOSPHENYTOIN

Adverse effects: Gingival hyperplasia Confusion Slurred speech Double vision Ataxia Sedation Dizziness Hirsutism Primary treatment for status epilepticus

PREGABALIN

Mechanism of Action: Binds to a2-d site, an auxiliary subunit of voltagegated Ca channels in the CNS, inhibiting excitatory neurotransmitter release.

Indications: Treatment of partial onset seizures, neuropathic pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, and fibromyalgia.

PREGABALIN
Adverse

effects:

Weight gain Somnolence Dizziness Headache Diplopia Ataxia

One

hundred percent renal elimination.

PRIMIDONE

Mechanism of Action: GABA receptor Has 2 active metabolites, phenobarbital and phenylethylmalonamide. Indications: Use in refractory epilepsy.

PRIMIDONE

Adverse Effects: Sedation Lethargy Behavioral changes Ataxia Hyperactivity nausea

TIAGABINE

Mechanism of Action: GABA receptor. Indications: Use in partial onset epilepsy.

TIAGABINE

Adverse Effects: Sedation Weight gain Fatigue Headache Tremor Dizziness Anorexia Multiple drug interactions.

TOPIRAMATE

Mechanism of Action: Blocks voltage-dependent Na channels. It is a carbonic anhydrase inhibitor May act at glutamate(NMDA) sites. Indications: Use in partial and primary generalized epilepsies. Also, treatment of migraine.

TOPIRAMATE

Adverse Effects: Paresthesia Weight loss Nervousness Depression Anorexia Anxiety Tremor Cognitive complaints Headache Oligohidrosis Few drug interactions.

ZONISAMIDE

Mechanism of Action: Blockade of both voltage-gated Na channels and T-type Ca currents.

Indications: Use in patients with partial epilepsy.

ZONISAMIDE

Adverse Effects: Nausea Anorexia Ataxia Confusion Difficulty concentrating Sedation Paresthesia Oligohidrosis

 It requires surgical implant of a small pulse generation

with a battery and a lead wire for stimulus. The device is implanted and lead wires wrapped around the patients vagal nerve. This device and treatment were approved in 1997.
Indications: Treatment of partial onset seizures

Treatment of depression