Carbamazepine: mechanism
Binds to neuronal sodium channels to reduce sustained high-frequency repetitive firing of action potentials
Carbamazepine: indication
Partial and secondarily generalized seizures
Carbamazepine: dose
Start 400 mg/day in 2 divided doses
Maximum 1,600 mg/day
Several long-acting forms available
Carbamazepine: side effects
- Dose-related
- Drowsiness, dizziness, ataxia, dyskinesias, and visual disturbance
- Rare: Severe idiosyncratic hematologic reactions of agranulocytosis and aplastic anemia
- Induces CYP-450 isoenzyme
- Consider screening for HLA-B*1502 allele in Asians as this is associated wtih marked increase in skin rash.
Ethosuximide: mechanism
Decreases the bursting of thalamocortical neurons responsible for generation of 3 Hz spike-and-wave discharges via reduction of low threshold (T-type) calcium channel currents
Ethosuximide: indications
Absence seizures
Ethosuximide: dose
500 mg in 2 divided doses
May increase to 1,500 mg/day
Ethosuximide: side effects
- Common: nausea, vomiting, weight loss, diarrhea, abdominal pain, constipation
- Serious: blood dyscrasias
Fosphenytoin: dose
Loading dose of 15-20 mg phenytoin equivalents/kg
Can be administered in 100-150 mg PE/min
Fosphenytoin: side effects
Risk of hypotension and cardiac dysfunction lower than for phenytoin
Phenobarbital: mechanism
- Enhancement of GABA-mediated inhibitory synaptic transmission
- Voltage-regulated calcium ion channels
- Reduces glutamate-mediated excitation
Phenobarbital: indication
All seizures except absences
Phenobarbital: dose
1.5-4 mg/kg/day in daily doses
IV available
Phenobarbital: side effects
- Common: sedation, drowsiness, hyperactivity, irritability, and insomnia
- Rare: cognitive impairment, depression, movement disorders, megaloblastic anemia, osteoporosis, connective tissue disorders, teratogenicity, and exacerbation of porphyria
- Induces CP-450 isoenzyme, resulting in drug-drug interactions
Phenytoin: mechanism
- Rate-dependent inhibition of sodium channels
- Calmodulin and cyclic nucleotide 2nd messenger systems
- Inhibition of voltage-dependent neurotransmitter release at the synapse
Phenytoin: indications
- Partial-onset seizures and generalized tonic-clonic seizures
- Limited efficacy in absence, myoclonic, or atonic seizures
Phenytoin: dose
Start 200-300 mg in 3 divided doses
Increase until maintenance dose reached (300-400 mg daily)
Loading dose of 1,000 mg may be given in 3 divided dose in 2 hour intervals or by IV
Phenytoin: side effects
- Common: nystagmus, blurred vision, ataxia, slurred speech, gingival hypertrophy, hirsutism
- Long-term use: osteoporosis, peripheral neuropathy, cerebellar atrophy, gum hypertrophy
- Serious: purple glove syndrome
Phenytoin: metabolism
Metabolized by CYP-450 system
Excretion by urine and feces
Conversion from 1st-order to Zero-order kinetics at levels in middle of average therapeutic range
Induces CYP-450, resulting in multiple interactions with other medications
Valproate: mechanism
- Increased rate of GABA turnover
- Reduction of NMDA glutamate receptor-mediated excitation
- Inhibit sustained repetitive firing of neurons with blockage of voltage-dependent sodium channels
Valproate: indications
Complex partial seizures, generalized, absence seizures
Also effective for headache and mood stabilization
Valproate: dose
15 mg/kg a day in divided doses with weekly dose increases of 5-10 mg/kg
IV available
Long-acting form available
Valproate: side effects
- Common: drowsiness, tremor, nausea, vomiting, hair loss, weigh gain, tremor
- Serious: hepatotoxicity, hemorrhagic pancreatitis
Felbamate: mechanism
Interaction with NMDA receptors, resulting in decreased excitatory amino acid neurotransmission
