Seizure

Question 1

Phenytoin

Answer 1

• Mechanism: Use-dependent effect on Na channels (holds inactivation gate closed longer to lengthen refractory period), inhibits repetitive action potentials
• Dose-dependent; dependent upon drug formulation; highly protein bound. Despite broad therapeutic range, dose required varies by individual.
• Use: generalized tonic-clonic seizures and partial seizures–NOT absence seizures. IV for status epilepticus (fosphenytoin).
• Side effects: 1) Dose-dependent/CNS: nausea, anorexia, apathy, sedation, ataxia, nystagmus. 2) Dose-independent/idiosyncratic: gingival hyperplasia, hirsuitism, teratogenicity–fetal hydantoin syndrome, rash.

Question 2

Carbamazepine

Answer 2

• Mechanism: similar to phenytoin; blocks Na channels.
• Use: drug of choice for partial seizures; CONTRAINDICATED in absence.
• Toxicity: dose-related. Includes diplopia, ataxia, GI upset, drowsiness, rare blood dyscrasias, terotogen (increased risk of spina bifida)
• DOC for pregnant women; risk is less than with other drugs.

Question 3

Oxycarbazepine

Answer 3

• New analog of carbazepine.

- Less likely to cause CNS side effects.

Question 4

Ethosuximide

Answer 4

• Mechanism: Reduce low-threshold T-type Ca currents in thalamus
• Not protein bound.
• Side effects: Gastric distress (so dose twice daily), lethargy and fatigue
• Use: absence seizures

Question 5

Valproic Acid

Answer 5

• Mechanism: Blocks repetitive neuronal firing, may reduce T-type Ca currents, increases GABA contractions
• Bound to plasma protein (competes with phenytoin)
• Use: absence, absence+tonic-clonic, tonic-clonic+partial, myoclonic
• Side effects: GI upset, weight gain, hair loss, hepatotoxicity, teratogenicity (spina bifida)

Question 6

Felbamate

Answer 6

• antagonist at glycine-modulator site on the NMDA receptor antagonist
• Use: partial seizures that are refractory to other agents
• Side effects: aplastic anemia and hepatic failure

Question 7

Gabapentin

Answer 7

• GABA structural analog, but not a GABA agonist!
• Use: adjunct therapy for partial seuizures with/without secondary generalized tonic-clonic seizures
• Not metabolized, no protein binding
• Also used for neuropathic pain and ALS

Question 8

Pregabalin

Answer 8

• Similar to gabapentin but more potent
• May interact with alpha-2-delta subunit of voltage-gated Ca channels–>reduces NT release
• Use: partial seizures, neuropathic pain for peripheral neuropathy, postherpetic neuralgia, fibromyalgia.

Question 9

Lamotrigine

Answer 9

• Blocks repetitive action potentials, may block Na channels
• Use: partial, generalized tonic-clonic, absence
• Approved for bipolar disorder
• Side effects: serious rash/Stevens-Johnsons

Question 10

Topiramate

Answer 10

• Mechanism: inhibits excitatatory transmission by blocking activation of kainate/AMPA subtype of glutamate receptor. May also block Na channels.
• Blocks spread of seizures rather than raising seizure threshold
• Use: add-on therapy for partial seizures in adults and migraine prevention
• Side effects: fatigue, nausea, confusion

Question 11

Tiagabine

Answer 11

• Mechanism: inhibits GABA transporter GAT-1, blocking GABA reuptake
• Use: Add-on for complex and simple partial seizures
• Side effects: dizziness, tremor, somnolence

Question 12

Levetiracetam

Answer 12

• Use: adjunct therapy for partial seizures, myoclonic seizures, primary generalized tonic-clonic.
• Mechanism unknown
• Side effects: somnolence, asthenia, dizziness

Question 13

Zonisamide

Answer 13

• Mechanism: Na and Ca channels; reduces voltage-dependent inward current (T type). Stops seizure spread and suppresses focus.
• CNS Side effects: ataxia, anorexia, nervousness, fatigue, speech impairment
• Use: adjunctive treatment for partial seizures in adults

Question 14

Vigabatrin

Answer 14

• Irreversible inhibitor of GABA metabolism (GABA-transaminase inhibitor)
• Possible permanent effects on vision
• Use: adjunctive treatment of refractory complex partial seizures and infantile spasm