Epilepsy Meds Flashcards
What is the neuronal basis for epilepsy?
over-excitation
increased glutamate and aspartate
decreased inhibitory GABA
Generally, what do epilepsy drugs do?
suppress excitatory (glutamate)
enhance inhibitory (GABA)
The faster neurons fire in epilepsy, ___________
the faster meds can block the receptors to reduce activity
What drugs prolong fast inactivation of Na ion channels?
Stop/decrease APs by binding inside open gate:
Carbamazepine (azepines) Lamotrigine Phenytoin Topiramate Valproic acid Lacosamide (amides)
What drug enhances slow inactivation of Na channels?
Lacosamide
–> doesn’t need activation gate of receptor open to work like other meds (can work with minimal open sodium channels)
What drugs block AMPA receptor on postsynaptic membrane so glutamate can’t activate it, thus decreasing APs/firing?
AMPA receptor antagonists:
topiramate
perampanel
What drug prolongs fast inactivation of Na channel (blocks it), blocks glutamate binding of AMPA receptor (antagonist), and increases frequency of GABA receptor transmission?
topiramate
What drug prevents binding of glutamate to NMDA receptor on postsynaptic membrane?
NMDA receptor antagonist:
Felbamate
T-type calcium channels are the hallmark of what seizure?
petit mal (absence)
inhibition of these channels decrease seizures
What drug inhibits T-type calcium channels and is only used for petit mal/absence seizures?
ethosuximide
What drug can block T-type calcium channel and sodium channels (prolong fast inactivation)?
Zonisamide
What drugs block synaptic vesicle SV2A (prevent glutamate from binding to presynaptic cleft, decreases release)?
levetiracetam
brivaracetam
What drugs block alpha 2 delta subunit of T-type calcium channels?
Gabapentin
Pregabalin
-both have GABA in name
What drug OPENS KCNQ potassium channels (pre and post) to hyperpolarize (stop AP) and stimulates GABA receptors in high doses?
Ezogabine
How does post-synaptic GABA transmission work?
when GABA receptor unoccupied–> inactive chloride channel
When GABA binds to its receptor–> chloride channel opens–> hyperpolarizes membrane to blunt AP
INHIBITORY
What is the significance of presynaptic GABA meds?
glutamate makes GABA, so meds increase conversion
meds that inhibit GABA metabolism (via GABA-T and SSD) or transport back to presynaptic neuron (via GAT-1) so there is more of it to inhibit neurons
What drug blocks GAT-1 (reuptake of GABA)?
tiagabine
What drug blocks GABA-T (metabolizes GABA)?
Valproic acid
Vigabatrin
–>viGABATrin
What drugs increase glutamic acid decarboxylase to produce more GABA?
valproic acid
gabapentin
pregabalin
What drugs block the alpha-2-delta subunit of T-type calcium channels (decrease excitation) AND increase glutamic acid decarboxylase (produce more GABA)?
gabapentin
pregabalin
What drug blocks SSD (stops metabolism of GABA)?
valproic acid
What drugs enhance post-synaptic GABA transmission?
Barbiturates (phenobarbital/primidone)
Benzodiazapines (lorazepam, diazepam, clonazepam, clobazam)
Topiramate
How do benzodiazepines work in seizures?
bind to distinct site–> potentiate GABA binding–> chloride channels open with greater frequency
need GABA present to work
How to barbiturates work in seizures?
bind to distinct site on GABA and increase DURATION of chloride channel opening
don’t need GABA to work (high doses lethal c/t benzos)
What 2 drugs are broad spectrum in treating seizures with 3 MOAs?
topiramate
valproic acid
What drug treats rare, severe forms of epilepsy?
cannabidiol
only can be used in combo with other antiepileptic drugs
What are the broad warnings for all antiepileptic meds?
abrupt withdrawal or stopping of meds increases risk of status epilepticus
suicidal ideation more likely
Phenytoin
zero order, saturable
induces CYP450
gingival hyperplasia
hypocalcemia–> bone issues
What drugs induce CYP450–> Vitamin D catabolism–> bone issues?
phenytoin
carbamazepine
phenobarbital
valproic acid
Carbamazepine
auto-induction (loss of efficacy, recurrent seizures)
inducer CYP450
leukopenia/neutropenia/thrombocytopenia
–> bone marrow suppression
What is an analogue of carbamazepine that is less-potent CYP450 inducer (less bone marrow suppression) and doesn’t have a toxic intermediate metabolite?
oxcarbazepine
Phenobarbital
fatality risk (high doses d/t not dependent on GABA for rxn)
inducer CYP450
CNS depressant (how overdose with other depressants)
Vigabatrin
permanent vision loss
can only prescribe with REMS program
Antiepileptic drugs and oral contraceptives
oral contraceptives metabolized by CYP450
since antiepileptics (some) are inducers, more is cleared –> increased risk for failure and unplanned pregnancy
Antiepileptic drugs and warfarin
increase clearance of warfarin (d/t induction of CYP450)–> less anticoag–> increase risk for clot
Antiepileptic drugs and HIV meds
increase clearance of HIV meds via induction of CYP450–> increased risk for HIV replication
What drugs inhibit conjugation of drugs by UGT–> accumulation of parent drug
valporic acid
lamotrigine
What drugs induce conjugation of UGT–> reduce parent drug?
phenytoin
carbamazepine
phenobarbital
especially when given with valproic acid
How do new drugs get around CYP450 system?
renal clearance
renal insufficiency requires dose adjustments (elderly especially)
Treat status epilepticus
give benzodiazepine
–> lorazepam IV classic
fosphenytoin IV
OR
levetiracetam
