Anticonvulsants Flashcards
anticonvulsant possible MOAs
- enhancement of inhibition (GABA)
- inhibition of excitation (glutamate or aspartate)
- modulation of voltage-dependent ion channels in propagating AP
all SLOW NT transmission
Anticonvulsants: Na channel blockers
- phenytoin
- carbamazepine (and oxcarbazepine)
Anticonvulsants: Ca channel blockers
- ethosuximide
- gabapentin
Anticonvulsants: GABA modulators
- benzodiazepines (diazepam, lorazepam, midazolam)
- barbiturates (phenobarbital)
Anticonvulsants: “other”
valproic acid
lamotrigine
levetiracetam
main toxicities of anticonvulsants
CNS (simple sedation to ataxia)
GI (nausea, vomiting, diarrhea)
Dermatologic (rash)
Bone marrow suppression
Drug interactions (possibly CYP450)
Dose titration
Suicide
Pregnancy
Phenytoin
MOA?
Side effects?
-binds to voltage-dependent Na channels
-Zero-order kinetics (elimination is by a set amount/unit time, clearance system can be saturated.)
^monitor plasma levels
-CYP450 clearance
Side effects:
- gingival hyperplasia
- hirsutism (female w/ male hair pattern)
- reduced folate levels
Carbamazepine
MOA?
Side effects?
- binds to voltage-dependent Na channels
- CYP450 clearance
Side effects:
- CNS (drowsy, dizzy, ataxia, nystagmus)
- GI (nausea, vomiting, diarrhea)
- RASHES (asian)
- Hyponatremia (ADH release)
- BONE MARROW SUPPRESSION (agranulocytosis)
- monitor plasma levels
- monitor active metabolite (10,11 epoxide)
ethosuximide
MOA?
Side effects?
- interferes w/ T-type Ca channels
- used for absence seizures
Side effects:
-sleep disturbances, nausea, vomiting
benzodiazepines
GABA facilitators. Increase frequency of Cl- channel opening only w/ GABA present –> CNS depression
Side effects:
sedation, cognitive impairment, ataxia
barbiturates
Increase duration of Cl- channel opening, don’t need GABA present –> CNS depression
higher risk of OD
T/F benzo-like drugs (zolpidem, zalepon, eszopiclone) are used as anticonvulsants.
FALSE.
Used for sleep.
possible mechanisms of GABA modulating meds
- mimic GABA/improve effects (benzos/barbs)
- reduce reuptake into neurons/glia
- inc GABA production
- reduce GABA metabolism (valproic acid)
valproic acid
MOA?
- interferes w/ Na channels
- blocks T-type Ca channels
- increases GABA levels (inhibits breakdown)
valproic acid
Clearance?
Side effects?
-CYP450 clearance
Side effects:
- weight gain
- HEPATOTOXICITY, PANCREATITIS, thrombocytopenia
- NEURAL TUBE DEFECTS
- monitor plasma levels
- LFTs
Gabapentin
MOA?
Side effects?
- interferes w/ P/Q type Ca channels
- RENAL clearance (few drug interactions)
- well-tolerated but INFREQUENTLY USED FOR SEIZURES bc not as efficacious
lamotrigine
MOA?
Side effects?
- interferes w/ Na channels
- more direct interference w/ glutamate and aspartate (drug binds to postsynaptic AMPA receptors)
- prominent CNS side effects, some GI
- RASHES –> risk of Stevens-Johnson Syndrome (slow taper introduction reduces risk)
- linear kinetics, well-tolerated (don’t need to monitor)
levetiracetam
MOA?
- suppresses synaptic vesicle protein SV2A
- -> reduce release of excitatory NT –> CNS depression
- FREQUENTLY USED for seizures
- good oral bioavailibility
- RENAL clearance
- well-tolerated, good efficacy
(looks like gabapentin, but more efficacious)
therapeutic considerations for anticonvulsants
- dose titration to therapeutic effect (slowly introduce, don’t want to intro seizure)
- monitor plasma levels
- monotherapy preferred (max dose of drug first. stop drop before moving on to next)
anticonvulsants:
common themes for OLDER agents
- phenytoin
- carbamazepine
- valproic acid
- phenobarbital
- narrow therapeutic margins
- HEPATIC metabolism/protein binding
- drug interactions
- good experience
anticonvulsants:
common themes for NEWER agents
- gabapentin
- lamotrigine
- levetiracetam
- wider therapeutic margins
- RENAL clearance
- few drug interactions
- improved tolerability
- narrow indications
Pt on lamotrigine presents w/ rash on most of upper trunk and arms. What do you do?
Even if mild rash, discontinue lamotrigine b/c rash can progress in unpredictable manner.
Tx for status epilepticus seizures
BENZOS (via IV)
diazepam, lorazepam, midazolam
If unsure of seizure type, which tx?
Valproic acid (multiple mechanisms)
Despite good efficacy of benzos for partial or generalized tonic-clonic seizures, why are these drugs not usually used?
They would work but would cause tolerance (would need higher and higher doses)
Oxcarbazepine
carbamazepine derivative
less side effects compared to carbamazepine, doesn’t get metabolized to 10,11-epoxide
