Phenobarbital

Phenytoin

Carbamazepine

Valproate, Divalproex

Ethosuximide

Benzodiazepines (diazepam, lorazepam, clonazepam)

2nd Generation Anticonvulsants

Felbamate

Lamotrigine

Gabapentin

Pregabalin

Topiramate

Tiagabine

Levetiracetam

Zonisamide

Lacosamide

Rufinamide

Phenobarbital

-mechanism

-primary use

-side effects

Mechanism:

- enhances GABA effects via ↑ Cl channel opening time

- ↓ Ca²⁺ channel activity → ↓ excitatory neurotransmitter release

Primary Use:

- generalized tonic-clonic seizures

Side effects:

- enzyme induction → reduced plasma levels of many drugs

- cognitive deficits in children, cleft palates

Phenytoin

-mechanism

-primary use

-side effects

-notes

Mechanism:

- enhanced sodium channel inactivation

Primary use:

- generalized and partial seizures

Side effects:

- within therapeutic levels:

   ~ gingival hyperplasia

   ~ folate deficiency

   ~ hypertrichosis

   ~ cystic acne

- out of therapeutic levels:

   ~ nystagmus, ataxia, deminished cognitive function

   ~ enzyme induction, protein displacement

   ~ thrombocytopenia

   ~ lupus-like syndrome

   ~ fetal anticonvulsant syndrome

Notes:

- contraindicated in absence seizures

Carbamazepine

-mechanism

-primary use

-side effects

-notes

Mechanism:

- prolonged recovery of voltage-gated Na channels

Primary use:

- partial seizures

- generalized tonic-clonic seizures

- trigeminal neuralgia

Side effects:

- N&V

- diplopia

- leukopenia

- thrombocytopenia

- enzyme induction

- neural tube defects

Notes:

- autoinduction

- oxycarbazepine is analog of CBZ that is not metabolized to epoxide

Valproate

Divalproex

-mechanism

-primary use

-side effects

-notes

Mechanism:

- prolonged recovery of voltage-gated Na-channels

- inhibits T-type Ca-channels

- inhibits GABA metabolism and reuptake

- stimulates GABA synthetic enzymes

- ↑ Na-channel inactivation and ↑ [GABA] (net effects)

Primary Use:

- most major seizure types including absence

Side effects:

- weight gain

- hepatotoxicity

- thrombocytopenia

- enzyme inhibition

- fetal anticonvulsant syndrome

- neural tube defects

- metabolic defects

Notes:

- caution in patients with diabetes mellitus or gout

Ethosuximide

-mechanism

-primary use

-side effects

Mechanism:

- blockade of T-type Ca-channels

Primary use:

- absence seizures

Side effects:

- drowsiness

- GI effects

- mood changes

Benzodiazepines

(Diazepam, lorazepam, clonazepam)

-mechanism

-primary use

-side effects

Mechanism:

- enhanced GABA binding → increased frequency of Cl channel openings

Primary use:

- Status epilepticus and EtOH WD (diazepam and lorazepam)

- akinetic and myoclonic seizures, Lennox-Gastaut (clonazepam)

Side effects:

- drowsiness

- abuse

- tolerance

Lamotrigine

-mechanism

-primary use

-side effects

-notes

Mechanism:

- inhibits sustained repetitive firing of Na-channels

Primary use:

- adjunctive for complex partial seizures

Side effects:

- Stevens-Johnson syndrome

Notes:

- interacts with valproate to increase risk of S-J syndrome

Gabapentin

-mechanism

-primary use

-side effects

Mechanism:

- binds to α₂δ subunit of Ca-channel and decreases Ca2+ influx

Primary use:

- adjunctive for complex partial seizures

Pregabalin

-mechanism

-primary use

Topiramate

-mechanism

-primary use

-side effects

-notes

Mechanism:

- inhibition of Na-channels

Primary use:

- complex, partial

- generalized tonic-clonic seizures

- Lennox-Gestaut

Side effects:

- renal calculi

- oligohydrosis

- glaucoma

Notes:

- also used for migraine prophylaxis

Levetiracetam

-mechanism

-primary use

Mechanism:

- binds selectively to SV2A (synaptic vesicle protein)

- may modify release of glutamate and GABA

Primary use:

- adjunctive for complex partial seizures

Zonisamide

-mechanism

-primary use

-side effects

Mechanism:

- inhibits T-type Ca-channels

Primary use:

- adjunctive for complex partial seizures

Side effects:

- renal calculi

- oligohydrosis

- rash

Gabapentin

Pregabalin

Lamotrigine

Tiagabine

Levetiracetam

Zonisamide

Lacosamide

Phenytoin

Carbamazepine

Divalproex

Lamotrigine

Zonisamide

Divalproex

Zonisamide

Benzodiazepines

Barbituates

Gabapentin

Divalproex

Phenobarbital

Topiramate

Levetiracetam

Oxcarbazepine

-mechanism

-primary use

-side effects

-notes

Mechanism:

- prolonged recovery of voltage gated Na-channels

Primary use:

- partial seizures

Side effects:

- SJS

- N&V

- diplopia

- hyponatremia is worse than carbamazepine

Notes:

- reduces blood concentration of oral contraceptives