·
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.