Antiepileptic medications

 

·         AEDs target (1) ion channels, (2) NT transporters, (3) NT metabolic enzymes

·         AEDs modify (1) bursting of neurons to decrease local synchronization and (2) inhibit spread of abnormal firing to distal sites

·         Mechanisms of action:

o        Modulation of voltage-gated ion channels

o        Enhancing synaptic inhibition

o        Inhibiting synaptic excitation

·         Modify the paroxysmal depolarizing shift – abnormal prolonged depolarization with repetitive spiking characteristic of neurons in epileptic cortical zones that are reflected as interictal discharges in the EEG.

 

Sodium channels

 

Voltage-gated calcium channels

 

GABA systems

 

Glutamate receptors

 

Drug

Dosing

Mechanism

Side effects

Interactions

Lorazepam

0.1mg/kg/dose

↑GABAAR opening frequency

Common: sedation, dizziness, CNS depression, paradoxical hyperactivity, dependence/withdrawal

N/A

Phenytoin

Load: 20mg/kg

Maint: 5mg/kg/d

 

Level 40-80 µM

Inh Na channel

(use-dependent)

Common: nystagmus, ataxia, gum hyperplasia, osteomalacia, facial coarsening, drowsiness, lymphadenopathy, hirsutism

Severe: Arrhythmias, Stevens-Johnson syndrome, fetal hydantoin syndrome, anticonvulsant hypersensitivity syndrome

Hepatic inducer

↑ by CBZ, TPM

Fosphenytoin

1.5x phenytoin

 

(see phenytoin)

 

Phenobarbital

Load: 20mg/kg

Maint: 5mg/kg/d

 

Level 80-180 µM

 

↑GABAAR opening time

Common: sedation, ↓BP, ataxia, ↓REM,  ↓IQ, ↓libido

Severe: SJS, anticonvulsant hypersensitivity syndrome, fetal hydantoin syndrome

Hepatic inducer

↑ by CBZ, TPM, VPA

Carbamazepine

15-20mg/kg/d

 

Level 17-42 µM

 

Inh Na channel

Inh adenosine receptors

Common: Blurred vision, nystagmus, dizziness, osteopenia, headache, ↑LFTs, ↓WBC, ↓Na

Severe: SJS, aplastic anemia, teratogenesis

Hepatic inducer

↑phenytoin levels

↑ by erythromycin, isoniazid, cimetidine, diltiazem, verapamil

Oxcarabazepine

10-50mg/kg/d

Inh Na channel

Mod VGCC

(see carbamazepine)

30% cross-rx for rash

↓OCP levels

Valproate

30-60mg/kg/d

 

Level 350-700 µM

 

Inh Na channel

T-type Ca channel

↑GABA turnover

Common: GI upset, weight gain, ↑LFTs, hair thinning, essential-like tremor, ↑NH3, osteopenia, PCOS, pancreatitis

Severe: Teratogen, NTDs, Reye-like syndrome, thrombocytopenia

Hepatic inhibitor

↑AEDs, ↓TCAs

↓ by CBZ, PHT, PB

↑ by ASA

 

Topiramate

6-8 mg/kg/d

Inh Na channel

Inh VGCC

Inh AMPA/KA

CAI

↑ GABAAR

Common: Anorexia, weight loss, cognitive slowing, nephrolithiasis, somnolence, metabolic acidosis, oligohydrosis, glaucoma

↓ TCAs, Li, risperidone

↓ by AEDs

 

Lamotrigine

1-10 mg/kg/d

Inh Na channel

Inh VGCC

Common: Dizzy, headache, ataxia, diplopia, worsen myoclonic seizures

Severe: rash, SJS

↓by AEDs, OCP

↑ by VPA

↓ VPA

Levetiracetam

60mg/kg/d

Inh VGCC

Mods GABA

Common: Anxiety, agitation, aggression, somnolence

N/A

Clobazam

0.5-1mg/kg/d

GABAAR opening frequency

Common: somnolence, ataxia, tolerance, dependence

↓ by enzyme inducers

Clonazepam

0.1-0.2mg/kg/d

GABAAR opening frequency

Common: somnolence, ataxia, hyperexcitability/agitation, tolerance, dependence

↓ by enzyme inducers

Gabapentin

20-50mg/kg/d (max 90mg/kg/d)

Inh VGCC

↑GABA turnover

Common: somnolence, weight gain

N/A

Vigabatrin

150mg/kg/d

Inh GABA-T

Common: Somnolence

Severe: Retinal toxicity

↓ PHT

Ethosuximide

20mg/kg/d

Inh T-type Ca channel

Inh Na channel

Common: Somnolence, weight gain

Severe: Aplastic anemia, SJS, SLE

↑PHT, ↓ VPA

↓ by enzyme inducers

Zonisamide

4-12mg/kg/d

Inh T-type Ca channel

Inh Na channel

Inh Glu effects

Common: dizzy, ataxia, anorexia

Severe: anhydrosis, SJS, sulfa allergy

↓ by enzyme inducers

Tiagabine

4mg/d (max 56)

GABA transporter

Common: somnolence, confusion, ataxia

↓ by enzyme inducers

Pregabalin

150-600mg (Adult)

VGCC

Common: weight gain

N/A

Felbamate

 

Inh Na channel

VGCC

GABAAR

NMDA/AMPA

Severe: aplastic anemia, hepatic failure

↓ CBZ, ↑ PHT, VPA

VGCC = voltage-gated calcium channel, Na channel = voltage gated sodium channel, CAI = carbonic anhydrase inhibitor, GABA-T = GABA transaminase

 

Anticonvulsant hypersensitivity syndrome

 

Updated: December 17, 2007

Disclaimer: These are personal study notes. No promises for accuracy or originality.