Seizure Drugs Flashcards
Phenytoin
Indications
MOA
PK
Tox
Indications: any focal, and primary generalized tonic-clonic
MOA: Na+ channel blocker
PK: 90% bound, hepatic elim (1st order [low] 0th [therapeutic], induces CYPs and UGT
Tox: hirsutism, gingival hyperplasia, decreased serum [folate, thyroxine, vitamin K], megaloblastic anemia, rash/SJS, teratogen
Carbamazepine
Indications
MOA
PK
Tox
Indications: all focal, primary generalized tonic-clonic
MOA: slows rate of recovery of Na+ channels
PK: 75% bound, active metabolite is epoxide, t1/2 falls due to induction of hepatic enzymes (autoinduction).
Tox: hyponateemia, leukopenia, aplastic anemia+agranulocytosis, teratogen, rash/SJS especially with HLA allele B*1502
Valproate
Indications
MOA
PK
Tox
Indications: ALL. Good for photosensitive epilepsy and juvenile myoclonic epilepsy. Best for men with generalized epilepsy.
MOA: Na+ channel inhibition, inhibition of T-type Ca++, increased GABA production and decreased GABA metabolism
PK: highly bound, but fx bound reduces as total [valproate] is increased. Hepatically metabolized via UGT and b-ox. Crosses placenta and higher binding in fetal compartment. INHIBITS cyps.
Tox: carbapenem antibiotics reduce [valproate]. Valproate can displace other ASDs from albumin. Transient GI symptoms. Temp alopecia. FULMINANT HEPATITIS. Acute pancreatitis/hyperammonemia. Teratogenic–> spina bifida
Lamictal
Indications
MOA
PK
Tox
Indications: all but myoclonic. Only good for conversion to monotherapy. Good for childbearing women.
MOA: Na+ channel inhibition, inhibits synaptic release of glutamate, inhibits voltage gated Ca++ channels.
PK: no induction of CYPs. Coadministration with valproate can double [valproate] while coadmin with phenytoin can reduce [lamictal].
Tox: rash/SJS. OCs can reduce effectiveness of drug.
Ethosuximide
Indications
MOA
Tox
Indications: absence seizures
MOA: inhibits T-type Ca++–> reducing pacemaker current that underlies thalamic rhythm.
Tox: leukopenia, thrombocytopenia, pancytopenia, aplastic anemia, SJS/rash, GI upset
Phenobarbital
Indications
MOA
PK
Tox
Indications: every kind + status
MOA: binds GABA-a to prolong Cl- channel opening
PK: good oral absorption, prodrug, metabolized by CYPs, CYP/UGT inducer
Tox: hyperactivity in children, rash, megaloblastic anemia, CNS/cardiac depression
Clonazepam and Clobazepam
Indications
MOA
Indications: Lennox, myoclonic, atonic, absence
MOA: bind GABA-A and increases frequency of Cl- channel opening
Diazepam and Lorazepam
Indications
Indications: 1st line tx for status, intermittent use for control of seizure clusters
Tigabine
Indications
MOA
PK
Tox
Indications: adjunct for partial
MOA:
PK
Tox
Vigabatrin
Indications: monotherapy for infantile spasms, adjunct for complex partial
MOA: inhibits breakdown of GABA by targeting GABA transaminase
Tox: retinal toxicity, permanent visual field loss
Gabapentin
Indications
MOA
Indications: adjunct for partial and secondarily generalized
MOA: selective inhibition of voltage-gated Ca++ channels containing alpha2delta1 subunit
Levetiracetam
Indications
MOA
Tox
Indications: adjunct for partial, Lennox, and primary gen tonic-clonic
MOA: binding synaptic vesicle protein 2A. Renally cleared.
Perampanel
Indications
MOA
Tox
Indications: adjunct for adult partial seizures and gen tonic-clonic. Monotherapy for partial.
MOA: binds AMPA receptor, non-competitive antagonist of glutamate
Tox: black box warning for life-threatening psychiatric and behavioral adverse rxns
