Snapshot A 6-year-old boy presents with brief periods of unresponsiveness. He is accompanied by his mother, who states that these episodes last approximately 15 seconds and occur multiple times a day. Associated symptoms include perioral automatisms. The mother has noticed that in moments of anger or hyperventilation, the patient's symptoms surface. Physical examination is completely normal. EEG shows spike and wave pattern at 3 Hz. The boy is started on ethosuximide. (Absence seizures) General Properties of Anticonvulsants Antiepileptic drugs (AED) can be separated by mechanism of action (MOA) affecting voltage-gated Na+ channels affecting Ca2+ channels affecting GABA activity Choice of AED is dependent on seizure type, patient, and side-effect profile Affecting Voltage-Gated Na+ Channels Phenytoin uses parital (simple and complex) generalized (tonic-clonic) prophylaxis for status epilepticus mechanism blocks voltage-gated Na+ channels stops seizure propogation kinetics induction of P450 can increase vitamin D metabolism zero-order kinetics with saturation of degradative liver enzymes toxicity nystagmus/ataxia/diplopia initially managed by decreasing the dose or altering the treatment schedule sedation/CNS depression SLE-like syndrome gingival hyperplasia peripheral neuropathy osteopenia megaloblastic anemia (↓ folate absorption) tetratogenic fetal hydantoin syndrome cleft lip and palate notes fosphenytoin for parenteral use Carbamazepine uses partial (simple and complex) generalized (tonic-clonic) mechanism ↑ refractory period of voltage-gated Na+ channels likely binds to the inactivated state, inhibiting action potential generation kinetics induction of P450 reduces its own levels toxicity diplopia/ataxia agranulocytosis aplastic anemia hepatotoxicity SIADH Stevens-Johnson syndrome teratogenic cleft lip and palate spina bifida notes first-line for trigeminal neuralgia also used for bipolar disorders Lamotrigine uses partial (simple and complex) generalized (tonic-clonic) absence mechanism blocks voltage-gated Na+ channels and glutamate receptors toxicity Stevens-Johnson syndrome Affecting Calcium Channels Ethosuximide uses generalized (absence) mechanism blocks thalamic T-type Ca2+ channels toxicity GI distress fatigue headache Stevens-Johnson syndrome Affecting GABA Activity Phenobarbital uses partial (simple and complex) in pregnant women and children generalized (tonic-clonic) in pregnant women and children mechanism ↑ GABAA action kinetics induction of P450 tolerance/dependence toxicity sedation Benzodiazepines uses acute treatment for status epilepticus alcohol withdrawal syndrome mechanism ↑ GABAA action notes also used for seizures of eclampsia 1st-line is MgSO4 Tiagabine uses partial (simple and complex) mechanism inhibition of GABA reuptake Vigabatrin uses partial (simple and complex) mechanism irreversible inhibition of GABA transaminase Multiple Mechanism of Action Valproic acid uses partial (simple and complex) generalized (tonic-clonic and absence) mechanism ↑ refractory period of voltage-gated Na+ channels ↑ GABA concentration via inhibition of GABA transaminase inhibition of thalamic T-type Ca2+ channels toxicity pancreatitis hepatoxicity accumulation of toxic metabolite tetratogenic neural tube defects tremor notes first-line for myoclonic seizures also used for migraines Topiramate uses partial (simple and complex) generalized (tonic-clonic) migraine prophylaxis mechanism blocks voltage-gated Na+ channels ↑ GABA action toxicity sedation/mental dulling renal stones weight loss Other Levetiracetam uses partial (simple and complex) complex (tonic-clonic) mechanism unknown Gabepentin uses partial (simple and complex) mechanims inhibit volate-gated Ca2+ channel via α2δ subunit structurally similar to GABA toxicity sedation ataxia notes also used for peripheral neuropathy/neuropathic pain