1. recurrent seizures. 

2. seizures - abnormal discharge of cerebral neurons

3. convulsions - abnormal discharge of motor neurons

4. seizures may be Focal or Generalized.

5. can be one hemisphere or both hemispheres which will cause loss of consciousness

1. Loss of GABA function

2. Increased excitatory Glutamate transmission

1. Inhibition of Na+ or Ca++ channels

2. Increased GABA 

3. Decreased Glutamate

1. Pentylenetetrazol test --> for Generalized seizures, especially Absence

2. Maximal Electroshock (MES) test --> for partial seizures

1. Phenytoin (Dilantin) & Fosphenytoin

2. Carbamazepine (Tegretol)

3. Lamotrigine (Lamictal)

Phenytoin (Dilantin)

&

Fosphenytoin (prodrug for status epilepticus and more soluble)

1. metabolized by CYP450

2. FOK at lower concentrations and ZOK at higher concetrations - monitor plasma Rx levels

3. MOA - stabilizes inactivated state of voltage gated Na+ channels causing decreased repetitive firing. Use dependent block

4. Use - DOC for tonic Clonic. Status epilepticus, partial seizures, cardiac arrhythmias.

5. SE - Ataxia, Nystagmus, Gingival hyperplasia, Hirsutism, hypersensitivity, Teratogenic. May increase risk of suicide

6. Rx interaction - induces CYP3A4 and causes dicumarol to be metabolized faster. 

Cimetadine, Valproic acid inhibits metabolism.

PB & Carbamazepine increases metabolism.

1. MOA - similar to Phenytoin

2. Use - DOC in combo w/ Phenytoin for severe cases. Trigeminal neuralgia, Manic episodes in bipolar disorder. Partial and tonic clonic

3. SE - aplastic anemia (rare but serious), diplopia and ataxia. SJS (10x higher in asians so do a genetic test), Teratogenic

4. Rx interaction - induction of microsomal enzymes. cimetidine decreases metabolism. PB and Phenytoin increases metabolism.

1. metabolized by glucuronidation

2. MOA - similar to phenytoin

2. USE - broad spectrum, partial, tonic clonic, absence, myoclonic

3. SE - somnolence, diploplia, allergic rash (life threatening in 2% of pediatric patients.

4. Rx interaction - carbamaxepine, PB, phenytoin increase metabolism. Valproic Acid decreases metabolism.

1. Ethosuximide (Zarontin)

2. Valproic Acid (Depakene, Depakote, generic)

1. metabolized by hydroxylation & conjugation

2. MOA - Asynchronizes T-type calcium channels. Hyperpolarization of the thalamic relay neurons causes burst firing of Ca++ channels

3. Use - DOC for Absence in children

4. SE - Gastric Distress

1. conjugated in liver. excreted in urine & feces

2. MOA - unknown. Increase GABA

3. Use - 2nd choice for Absence in adults. DOC for myoclonus. Broad spectrum. Lennox-gestault, manic bipolor episodes, prophylaxis of migraine

4. SE - NV, anorexia, Hepatotoxicity (young children on polytherapy)

-Teratogenic

5. Rx interxn - decrease metabolism of PB, Lamo, Etho

- Carba & Pheny increase metabolism

- Monitor serum Levels

1. Gabapentin

2. BZDs:

a. Diazepam

b. Lorazepam

c. Clonazepam

3. Phenobarbital

1. MOA - unknown, increase GABA, decrease Glutamate

2. Use - Add on for partial seizures & tonic clonic. Neuropathic pain. Fibromyalgia.

3. SE - CNS ataxia, somnolence.

1. MOA - increase GABA inhibitory activity

2. Use - DOC for status epilepticus

3. SE - Dizziness, Ataxia, drowsiness

1. Use - (intermediated acting) longer acting than diazepam 

2. status epilepticus

1. Use - long acting for Absence

2. SE - sedation

1. metabolized by liver microsomal enzymes

2. MOA - unknown. increase GABA mediated Cl- influx --> membrane hperpolarization & increase surround inhibition. Decrease Glutamate.

3. Use - tonic clonic and partial seizures. used alone or with phenytoin or carbamazebine. Febrile seizures in infants.

4. SE - most common (drowsiness, sedation). Cognitive impairment. Nystagmus.

1. Topiramate

2. Tiagabine

3. Levetiracetam

4. Zonisamide

1. MOA - blocks Na+ channels. Increase GABA mediated inhibition. Decrease excitatory action of kainate on glutamate AMPA receptors

2. Use - partial and tonic clonic. Migraine prophylaxis.

3. SE - dizziness, cognitive impairment, weight loss

1. metabolized by CYP3A4

2. MOA - GABA reuptake inhibitor (inhibits GAT-1). 

3. Use - partial seizures

4. SE - CNS (dizziness, nervousness, difficulty concentrating)

1. 2/3 excreted unchanged in urine.

2. MOA - unknown

3. Use - partial & generalized tonic clonic seizures

4. SE - Somnolence, fatigue, dizziness, incoordination

1. sulfa derivative

2. MOA - unclear. may block Na+ channels and increase GABA mediated inhibition

3. Use - partial & generalized tonic clonic seizures

4. SE - dizziness, SJS, ataxia, hyperthermia in kids

Miscellaneous AntiEpileptic Drugs

Felbamate

1. MOA - blocks Na+ channels, blocks glycine co-activation of NMDA glutamate R, blocks Ca++ channels

2. Use - broad spectrum for refractory cases of partial seizures and lennox-gestault syndrome

3. SE - aplastic anemia & acute hepatitis