Epilepsy Flashcards
transient alteration of behavior, sensation, and/or consciousness due to disordered, synchronous, and rhythmic firing of neurons in the brain
seizure
disorder characterized by recurrent epileptic seizures
epilepsy
seizure localized to part of one cerebral hemisphere
focal onset/partial
seizure involving both hemispheres widely from the outset, generally associated with impaired awareness
generalized onset
generalized onset seizure characterized by sudden loss of consciousness, tonic phase followed by a clonic phase, interrupted respirations, tongue biting, headache, confusion
generalized tonic-clonic or grand mal
generalized onset seizure characterized by altered consciousness, staring with occasional eye blinking, brief twitching of the body/eyelids, enuresis
non-motor
petit mal or absence
pathophysiologic changes during a seizure
abnormal ion channel activity
decreased inhib neuron activity
increased excit neuron activity
rhythmic & repetitive neuron discharge
if you need to use polytherapy for ASMs, the 2nd med should have…
a different MOA
common AEs of ALL ASMs
CNS depression
fatigue, dizziness, unsteadiness, ataxia, diplopia, memory & thinking problems
what are the 1st generation ASMs (7)
- carbamazepine
- clonazepam
- ethosuximide
- phenobarbital
- phenytoin
- primidone
- valproate
what are the 2nd generation ASMs (8)
- felbamate
- gabapentin
- lamotrigine
- levetiracetam
- oxcarbazepine
- tiagabine
- topiramate
- zonisamide
what are the 3rd generation ASMs (7)
- brivaracetam (briviact)
- cenobamate (xcopri)
- eslicarbazepine (aptiom)
- lacosamide (vimpat)
- perampanel (fycompa)
- pregabalin (lyrica)
- vigabatrin (sabril)
which ASMs are Na channel blockers/modulators (7)
carbamazepine, oxcarbazepine, eslicarbazepine
cenobamate
lacosamide
lamotrigine
phenytoin
which ASMs are Ca channel modulators (3)
ethosuximide
gabapentin
pregabalin
which ASMs are GABA modulators (3)
valproate
tiagabine
vigabatrin
which ASMs are GABA receptor agonists (3)
clonazepam, phenobarbital, primidone
ALL 1ST GEN
which ASMs are glutamate blockers (2)
felbamate
parampanel
which ASMs are SV2A modulators (2)
levetiracetam, brivaracetam
which ASMs are highly protein bound (6)
carbamazepine, clonazepam, valproate, phenytoin, tiagabine, perampanel
which 2nd gen ASMs have high renal elimination (4)
felbamate, gabapentin, levetiracetam, topiramate
which 3rd gen ASMs have high renal elimination (4)
eslicarbazepine, lacosamide, pregabalin, vigabatrin
which ASMs have multiple MOAs (2)
topiramate and zonisamide
which seizure can carbamazepine NOT BE USED for? why?
absence
may worsen b/c of epoxide metabolite
which ASMs have a narrow therapeutic index (3)
carbamazepine
ethosuximide
phenytoin
carbamazepine induces
1A2, 2B6, 2C9, 2C19, 3A4
GT
ITSELF!!!!- AUTOINDUCER
carbamazepine is a substrate of
3A4
AEs of carbamazepine
hyponatremia due to SIADH
elevated LFTs
teratogenic
BBW for carbamazepine w/ increased risk depending on genetics
SJS/TEN
CIs for carbamazepine
bone marrow suppression, MAOIs, nefazodone, 3A4 sub NNRTIs
clonazepam 1/2 life is very?
it is a substrate of?
very long t1/2
3A4 substrate
AEs of clonazepam
pronounced sedation, paradoxical agitation, tolerance, withdrawal symptoms
clonazepam has a BBW for use with which drug class
opiates
this 1st gen ASM is choice for ABSENCE seizures only (may worsen other types)
ethosuximide
ethosuximide is a substrate of
3A4 & 2E1
ethosuximide AEs
GI related
phenobarbital & primidone induce
3A4, 2C9, 2C19. 1A2
GT
phenobarbital & primidone are substrates of
3A4 & 2C19
half life of phenobarbital/primidone?
very long t1/2
AE of phenobarbital
CNS depression/sedation
BBW for phenobarbital
risk of overdose with opioids
dependence
phenobarbital is contraindicated for? why?
respiratory disease w/ evidence of dyspnea or obstruction
due to AE of respiratory depression
what type of metabolism does phenytoin follow
saturable Michaelis-Menten
phenytoin induces
3A, 2C, GT
phenytoin is a substrate of
2C9, 2C19
common AEs of phenytoin
gingival hyperplasia
teratogenic
serious AEs of phenytoin (rare)
SJS/TEN
blood dyscrasia
purple glove syndrome (severe inj site rxn)
BBW for phenytoin when given IV
hypotension & arrhythmias
prodrug converted to phenobarbital & PEMA
primidone
DDI with valproate that may increase its metabolism
oral contraceptives
valproate inhibits
2C9, GT epoxide hydrolase
valproate is a substrate of
UGT hepatic metabolism
common AEs of valproate
tremor, weight gain, alopecia/hair text changes, nail disorders, hormone changes, osteoporosis.
serious AEs of valproate??
leads to CI in??
hyperammonenia & encephalopathy, thrombocytopenia
CI in hepatic disease, urea cycle disorders
BBW of valproate
hepatotoxicity, teratogenicity, mitochondrial disease, pancreatitis
should valproate be used in WOCBP if avoidable?
no- teratogen
felbamate induces
3A4
felbamate inhibits
2C19
felbamate is a substrate of
3A4 and 2E1
BBW of felbamate
leads to CI in
irreversible fatal aplastic anemia
hepatic failure
CI in hx of blood dyscrasia or hepatic dysfunction
felbamate is only used
for severe refractory cases
gabapentin & pregabalin are labeled for use as??
primarily used for??
ADJUNCT for focal onset
used for other indications such as neuropathy
how is lamotrigine dosed and why??
slow titration to mitigate the risk of TEN
which drugs require dose titration adjustments for lamotrigine
valproate, carbamazepine, phenobarbital/primidone, phenytoin
all 1st gens
which drugs may decrease lamotrigine levels
estrogen OCs
BBW for lamotrigine
SJS/TEN
increased risk with valproate or rapid dose escalation
in general, when lamotrigine is titrated with valproate, the dose is increased at a ____ rate than normal, and the maintenance dose is ___
slower, lower
in general, when lamotrigine is titrated with carbamazepine, phenytoin, phenobarb/primidone, the dose is increased at a ___ rate than normal, and the maintenance dose is ___
faster, higher
AEs of levetiracetam
mood related
irritability, anger, agitation, depression (can worsen pre-existing psych)
2nd gen & 3rd gen ASMs that are analogues of carbamazepine??
they do not produce what metabolite??
2nd- oxcarbazepine
3rd- eslicarbazepine
NO epoxide metabolite
oxcarbazepine induces
3A4/3A5
GT
oxcarbazepine inhibits
2C19
rare but serious AEs for oxcarbazepine
agranulocytosis
SJS/TEN
tiagabine is a substrate of
3A4/1A2/2D6/2C19
when is tiagabine used?
due to what AEs?
used for refractory epilepsy
serious AEs: new onset seizures, status epilepticus, exacerbation of EEG abnormalities
topiramate induces
3A
topiramate inhibits
2C19
AEs of topiramate
notable cognitive impairment, bilateral paresthesias, weight loss, hyperhidrosis, kidney stones
zonisamide is a substrate of
3A4
AEs of zonisamide
notable cognitive impairment, weight loss, hyperhidrosis, kidney stones
main benefit of zonisamide
ease of adherence- once daily dose
3rd gen ASMs that is an analog of levetiracetam
brivaracetam (Briviact)
brivaracetam inhibits
2C19, GT
brivaracetam is a substrate of
2C19
AEs of brivaracetam
mood & behavioral
better tolerated than levetiracetam
dosing of cenobamate (xcopri)?
why is this done?
titrated no more quickly than Q2W
due to risk of dress
cenobamate induces
2B6/2C/3A4
cenobamate inhibits
2B6/2C19/3A
cenobamate is a substrate of
UGT2B7/B7
2E1/2A6/2B6/2C19/3A4/3A5
BBW for cenobamate
psychiatric, behavioral, mood, or personality changes which may be life threatening
eslicarbazepine induces
GT
eslicarbazepine inhibits
2C19
AEs of eslicarbazepine (Aptiom)
tremor, hyponatremia due to SIADH, rash, likely teratogenic
serious AEs of eslicarbazepine
SJS, DRESS, angioedema, cardiac effects, hepatotoxicity, blood dyscrasia
benefit of eslicarbazepine
good for adherence- dosed once daily
lacosamide inhibits
2C19
lacosamide is a substrate of
2C19/2C9/3A4
AEs of lacosamide (vimpat)
GI effects
serious AEs of lacosamide
cardiac arrhythmias, syncope, DRESS, neutropenia, anemia
perampanel induces
3A4/3A5/2B6, GT
perampanel inhibits
3A4/3A5/2C8, GT
perampanel is a substrate of
3A4/3A5/1A2/2B6
AEs of perampanel (fycompa)??
1 of them leads to what BBW??
mood related, weight gain
BBW- aggression, hostility, irritability, anger, homicidal ideation
AEs of pregabalin
cognitive impairment, edema, weight gain
potential for misuse with opiates
vigabatrin induces
2C9
AEs of vigabatrin
pronounced CNS depressive effects, weight gain, edema, peripheral neuropathy, neuropsychiatric effects, vision loss
vigabatrin is used when??
why??
reserved for refractory cases
AE for risk of aggravating absence & myoclonic seizures & vision loss
BBW w/ REMs for vigabatrin
progressive & permanent vision loss
misc ASMs used for LGS or refractory epilepsies off label (3)
epidiolex
clobazam
rufinamide
misc ASMs used for DRAVET SYNDROME or refractory epilepsies off label (2)
epidiolex
stiripentol
3 rescue therapies to stop a cluster of seizures
diazepam rectal gel, nasal spray (diastat, valtoco)
midazolam nasal spray (nayzilam)
3 nonpharm options for seizures
keto diet
vagus nerve stimulator
surgery
children may be more susceptible to what AEs?
neuropsychiatric
dosing method for children
weight based with higher mg/kg than adults
caution in older adults for…
cognitive AEs
PKPD changes- renal, hepatic, hypoalbuminemia
which ASMs can be used for migraine (3)
topiramate, valproate, zonisamide
which ASMs can be used for bipolar disorder (4)
lamotrigine, valproate, carbamazepine, oxcarbazepine
which populations have higher risk of HLA-B*1502 gene??
what does that put them at risk for
Asian populations
increased risk of SJS/TEN
which ASMs recommend genetic testing for the HLA-B*1502 gene
carbamazepine + both analogs
phenytoin
lamotrigine
which 2 ASMs are preferred in pregnancy
levetiracetam and lamotrigine
which 3 ASMs are teratogens
valproic acid, carbamazepine, topiramate (among others)
all WOCBP should supplement what?
what should women in 8th month of pregnancy supplement if on enzyme inducing AEDs?
WOCBP- folic acid
8 month pregnancy- vitamin K
which ASMs can decrease effectiveness of OCs (8)
oxcarbazepine/carbamazepine
primidone/phenobarb
phenytoin
topiramate
felbamate
parampanel