-
phenytoin and fosphenytoin
- blocks Voltage gated Na+ channels (and VG Ca2+ channels)
- drug of choice for initial therapy of epilepsy (oral)
- - partial simple, partial complex, tonic-clonic seizures, emergency rx of status epilepticus (IV)
- NOT used for absence seizures
- liver metabolized - can cause saturation at high dosage, enhances P450
- phenytoin metabolism stimulated by carbamazepine
- phosphenytoin is prodrug, can be given IM
- adverse effect: gingival hyperplasia, megaloblastic anemia, teratogenic
-
carbamazepine
- blocks Voltage gated Na+ channels
- drug of choice for partial simple, partial complex, and tonic-clonic seizures
- other use: trigeminal neuralgia, bipolar disorder
- admin: oral, slow absorbed, highly lipid soluble
- metabolized by hepatic P450 enzymes, induces P450 enzymes which increases its own metabolism during chronic administration
- adverse effect:
hepatotoxicity, teratogenic
-
valproic acid
- blocks VG sodium and calcium channels
- facilitates GABAergic synaptic transmission
- drug of choice for myoclonic seizures
- second line (due to hepatotoxicity) for TC and absence seizures
- oral - rapidly absorbed, high level of plasma protein binding
- metabolized by liver P450
- Divalproex is combination sodium valproate and valproic acid (improve GI tolerance)
- adverse effect: hepatotoxicity, thrombocytopenia, teratogenic
-
ethosuximide
- blocks VG T-type calcium channels in thalamic neurons (suppressed rhythmic activity)
- drug of choice in absence seizures
- oral - well absorbed, NOT bound to plasma proteins
- long half life
- 75% metabolized by hepatic enzymes, 25% excreted unchanged
-
phenobarbital and primidone
- barbiturates - facilitates activation of GABA receptors to increase inhibitory tone
- treat simple partial and recurrent TC seizures, as well as febrile seizures in children
- combined with carbamazepine and phenytoin to allow for smaller doses
- other use: rx anxiety
- oral: well absorbed, freely penetrates brain
- 75% inactivated by hepatic microsomal system
- metabolite of primidone is phenobarbital
- adverse effect: megaloblastic anemia, teratogenic
-
diazepam and lorazepam
- benzodiazepine - potentiate activation of GABA receptors
- drug of choice for acute status-elipticus, (clonazepam) treats myoclonic and absence seizures
- other use: anxiety drug of choice
- tolerance can develop after 1-6 mo
-
lamotrigine
- blocks voltage gated sodium channels, also inhibits glutamate release
- used to treat simple partial, complex partial, and generalized TC seizures
- metabolized by liver
- drug interactions: half life decreased by enzyme-inducing drugs (carbamazepine, phenytoin) and increased by valproic acid
-
gabapentin
- blocks calcium channels (binding to α2-δ subunit) and release of glutamate, enhances GABAergic synaptic transmission
- used in simple or complex partial seizures and generalized TC
- not metabolized, doesn't induce hepatic enzymes
- not bound to plasma proteins
- short half life
- eliminated by kidneys
- negligible drug interactions
-
pregabalin
- blocks calcium channels (binding to α2-δ subunit) and release of glutamate
- used in simple or complex partial seizures
- adverse effect: thrombocytopenia
-
topiramate
- blocks sodium channels, increase activity of postsynaptic GABAa receptors
- used in simple or complex partial seizures and generalized TC
-
levetiracetam
- modifies glutamate and GABA release via binding to synaptic protein SV2A
- broad spectrum for partial and generalized seizures (TC, MC)
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