antiepileptics Flashcards
paroxysmal depolarization shift (PDS)
membrane potential doesn’t return rapidly to normal
prolonged Ca2+ dependent depolarization
results in several Na+ mediated APs
followed by long period of hyperpolarization
feed-forward inhibition
inhibits over-activation (prevents spike)
feedback inhibition
excites interneurons to prevent neighboring neurons from firing (prevent spread of seizure)
interictal period
“inhibitory surround”
abnormal activity is confined to seizure focus by afterhyperpolarization
CNS excitation
Glu, Asp
inward Na+ and Ca2+
CNS inhibition
GABA
inward Cl-
outward K+
inhibit Na+ channel
focal, status epilepticus
modulate gating mechanism (fast)
bind inactivated subunits (slow)
inhibit Ca2+ channel
all except LG
T-type (absence) - decrease slow depolarization
N/L-type - decrease excitatory NT
GABA-A receptor agonist
myoclonic, GL, status epilepticus
barbiturates MOA
status epilepticus
increase duration of Cl- channel opening
benzodiazepines MOA
increase affinity of GABA for receptor
GABA uptake inhibitors
adjunct for focal seizures
tiagabine
inhibit GABA transporter
focal
GABA transaminase inhibitors
adjunct for seizures
vigabatrin
inhibit degradation of GABA by GABA transaminase
broad spectrum
SV2A ligands
adjunct for seizures
release GABA
levetiracetam
inhibits vesicular release of Glu
broad-spectrum:
myoclonic (adjunctive)
Glu antagonist
focal, generalized
block NMDA/AMPA receptors
selection of AED
1) seizure type
2) epilepsy syndrome
3) pharmacokinetic profile
4) adverse effects
acute, dose-related SE
neurologic/psychiatric
GI
weight change
appetite change
acute, serious SE
renal stones, anhydrosis, acute closed angle glaucoma, hyponatremia, leukopenia, thrombocytopenia
idiosynchratic SE
rash/exfoliation
Stevens-Johnson Syndrome
hematologic damage
chronic SE
osteoporosis (vit D deficiency) teratogenesis (folate deficiency) altered CT metabolism/growth neuropathy cerebellar degeneration sexual dysfunction
strong inducers
increase clearance
decrease concentration
