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 M

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 M

 

↑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 M

 

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 M

 

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.