Pharmacology of Antiseizure Drugs Flashcards
What drugs are GABA receptor agonists?
benzodiazepines
What drugs inhibit GABA reuptake?
tiagabine
What drugs target GABA metabolism?
valproic acid and vigabatrin
Describe the GABA channel/receptor
Cl- permeable inotropic receptor, inhibitory= influx of Cl- to increase membrane polarization
What is the MOA of Phenobarbital?
prolongs Cl- channel opening in presence of GABA by binding to an allosteric site
What is the MOA of benzodiazepines?
requires initial activity of GABA for their activity then increases the frequency of channel opening
What drugs are benzodiazepines?
-diazepam
-clobazam
-clonazepam
-clorazepate
-lorazepam
What is the MOA of Tiagabine?
inhibits GABA transporter to decrease glial and presynaptic neuronal uptake of the inhibitory GABA
What is the MOA of Valproic Acid?
-potentiates effects of GABA by enhancing the activity of glutamic acid decarboxylase which converts glutamate to GABA
-inhibits metabolism of GABA
-mimics actions of GABA at postsynaptic receptor sites
What are the adverse effects of Valproic Acid?
alopecia and weight gain with chronic use
What is the MOA of Vigabatrin?
structural analog of GABA, irreversible inhibition of GABA transaminase “suicide inhibitor”, duration of action is based on synthesis of GABA-T (~5 days)
What is the MOA of Carbamazepine (Tegretol)?
inhibits voltage gated Na+ channels (binds alpha subunit)= maintains Na+ channels in activated state= inhibits generation of action potential
What are the indications of Carbamazepine (Tegretol)?
-partial seizures
-generalized tonic seizures
-mixed seizure patterns
What are the adverse effects of Carbamazepine (Tegretol)?
Stevens-Johnson Syndrome (SJS)/toxic epidermal necrolysis (TEN) increased risk for HLA-B 1502 allele
What is the MOA of Phenytoin sodium (Dilantin)?
block voltage gated Na+ channels in the inactive state (slow rate of recovery)
What are the adverse effects of Phenytoin (Dilantin)?
-SJS/TEN *increased risk for HLA-B 1502 allele
-gingival hyperplasia
-hirsutism
What is the MOA of Lacosamide?
Na+ channel inhibitor, selectively binds to fast inactivated Na+ channels
What is the MOA of Lamotrigine?
Na+ channel inhibitor, neuronal voltage-gated Na+ channels and blocks the release of glutamate through the stabilization of the presynaptic membrane
What is the MOA of Zonisamide?
multiple MOA but primary MOA is inhibition of neuronal voltage-gated Na+ channels= prolongs Na+ channel inactivation and stabilizes the cell membrane
What is the MOA of Cenobamate?
-reduces repetitive neuronal firing by inhibiting voltage-gated Na+ channels
-positive allosteric modulator of GABA ion channel
What are the indications of Cenobamate?
partial onset seizures in adults
What is the MOA of Gabapentin?
bind to alpha2omega subunit of P/Q type voltage gated Ca2+ channels in the neuronal synapse and reduce Ca2+ entry into neurons, which may inhibit synaptic release of excitatory neurotransmitters such as glutamate
What is the MOA of Ethosuximide?
inhibit low voltage activated T-type Ca2+ channels in the thalamocortical neurons
What is the indication of Ethosuximide?
1st line for generalized absence seizures
What is the MOA of Levetiracetam?
binds SV2A (important for normal synaptic function), reducing synaptic vesicle cycling which decreases synaptic transmission which may modulate neurotransmitter release
What is the MOA of Topiramate?
multiple MOA but primarily antagonist at the AMPA/kainite subtype of glutamate receptor
What is the MOA of Perampanel?
noncompetitive antagonist of the AMPA glutamate receptor
What is the MOA of Felbamate?
antagonist at the strychine-insensitive glycine recognition site of the NMDA receptor-ionophore complex= raises the seizure threshold
