Antiepileptic Drugs Flashcards
general goal of antiepilpetics
*reduce the ability of neurons to fire action potentials at a high rate and reduce neuronal synchronization
4 main mechanisms of action of antiepilpetics
- modulate voltage-gated sodium, calcium, or potassium channels
- enhance fast GABA-mediated synaptic inhibition (MORE inhibition)
- reduce fast glutamate-mediated excitation (LESS excitation)
- modify synaptic release process
antiepileptics that target voltage-gated SODIUM channels
-carbamezepine
-phenytoin
-lamotrigine
-lacosamide
antiepileptics that target voltage-gated CALCIUM channels
ethosuximide
antiepileptics that enhance GABA inhibition by targeting GABA receptors
-phenobarbital
-benzodiazepines
antiepileptics that enhance GABA inhibition by targeting GAT-1 GABA transporter
tiagabine
antiepileptics that enhance GABA inhibition by targeting GABA transaminase
vigabatrin
antiepileptics that target SV2A to inhibit glutamate release
levetiracetam
antiepileptics that target alpha-2-delta to inhibit glutamate release
-gabapentin
-pregabalin
narrow-spectrum antiepileptic agents
*specific for a given seizure type (usually focal)
*these can exacerbate certain generalized onset seizures
broad-spectrum antiepileptics
effective in focal and generalized seizures
carbamazepine - target & seizure type
*target: blocks voltage-gated sodium channels
*SZ type: narrow (focal)
phenytoin - target & seizure type
*target: blocks voltage-gated sodium channels
*SZ type: narrow (focal; gen. tonic-clonic)
lamotrigine - target & seizure type
*target: blocks voltage-gated sodium channels
*SZ type: broad
lacosamide - target & seizure type
*target: blocks voltage-gated sodium channels
*SZ type: narrow (focal)
ethosuximide - target & seizure type
*target: blocks voltage-gated CALCIUM channels (T-type calcium channels)
*SZ type: narrow (ABSENCE)
phenobarbital - target & seizure type
*target: GABA receptors (enhancing GABA inhibition)
*SZ type: narrow (focal)
benzodiazepines - target & seizure type
*target: GABA receptors (enhancing GABA inhibition)
*SZ type: broad (for status epilepticus)
tiagabine - target & seizure type
*target: GAT-1 GABA transporter (enhancing GABA inhibition)
*SZ type: narrow (focal)
levetiracetam - target & seizure type
*target: SV2A (inhibits glutamate release)
*SZ type: broad
gabapentin & pregabalin - target & seizure type
*target: alpha-2-delta (inhibits glutamate release)
*SZ type: narrow; used more for other things (neuropathic pain, restless leg syndrome, anxiety)
valproate - uses
*SZ type: broad (generalized tonic-clonic)
*used for many other things, like mood stabilization in bipolar disease and to prevent migraines
topiramate - seizure type
*SZ type: broad
phenytoin - testable pearls
*zero-order metabolism
*highly bound to albumin
*ADEs: hirsutism, nystagmus, gingival hyperplasia
*tons of drug interactions
carbamazepine - testable pearls
*induces its own metabolism
*ADEs: agranulocytosis (leukopenia), teratogenic, SIADH
*tons of drug interactions
lacosamide - testable pearls
*minimal drug interactions
gabapentin and pregabalin - testable pearls
*do NOT act via GABA
*instead, act via alpha-2-delta to inhibit glutamate release
levetiracetam - testable pearls
*NO LIVER METABOLISM
*few drug interactions
valproate - testable pearls
*teratogenic
*causes hepatotoxicity
topiramate & zonisamide - testable pearls
*cause cognitive impairment & weight loss
*metabolic acidosis via CA inhibition
antiepileptic drugs associated with Stephens-Johnson Syndrome
*lamotrigine
*carbamazepine
which antiepileptics INDUCE CYP450 enzymes
*carbamazepine
*phenytoin
*phenobarbital
which antiepileptics INHIBIT CYP450 enzymes
*valproate
which 2 antiepileptics have minimal drug interactions
*levetiracetam
*lacosamide
treatment of status epilepticus
- give benzodiazepine (usually IV lorazepam)
- follow immediately with IV loading dose of either:
-fosphenytoin
-valproate
-levetiracetam
what symptoms do all antiepileptic drugs cause
*dizziness
*fatigue
*ataxia
*diplopia
phenytoin - adverse drug effects
1. hirsutism: (excess hair, often around mouth and chin)
2. nystagmus
3. gingival hyperplasia
carbamazepine - adverse drug effects
*agranulocytosis (leukopenia)
*Stephens-Johnson syndrome
*teratogenic in first trimester
*SIADH (too much ADH secretion)
which antiepileptic med is used for absence seizures
ethosuximide
elimination of levetiracetam (Keppra)
NO liver metabolism:
*two-thirds excreted unchanged in urine
*one-third metabolized in the blood
phenobarbital - adverse drug effects
*severe sedation
*cardiac depression and hypotension in high doses
*drug interactions
