Epilepsy Flashcards by Sara Bojarski

transient alteration of behavior, sensation, and/or consciousness due to disordered, synchronous, and rhythmic firing of neurons in the brain

seizure

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disorder characterized by recurrent epileptic seizures

epilepsy

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seizure localized to part of one cerebral hemisphere

focal onset/partial

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seizure involving both hemispheres widely from the outset, generally associated with impaired awareness

generalized onset

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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

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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

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pathophysiologic changes during a seizure

abnormal ion channel activity
decreased inhib neuron activity
increased excit neuron activity
rhythmic & repetitive neuron discharge

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if you need to use polytherapy for ASMs, the 2nd med should have…

a different MOA

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common AEs of ALL ASMs

CNS depression
fatigue, dizziness, unsteadiness, ataxia, diplopia, memory & thinking problems

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what are the 1st generation ASMs (7)

carbamazepine
clonazepam
ethosuximide
phenobarbital
phenytoin
primidone
valproate

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what are the 2nd generation ASMs (8)

felbamate
gabapentin
lamotrigine
levetiracetam
oxcarbazepine
tiagabine
topiramate
zonisamide

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what are the 3rd generation ASMs (7)

brivaracetam (briviact)
cenobamate (xcopri)
eslicarbazepine (aptiom)
lacosamide (vimpat)
perampanel (fycompa)
pregabalin (lyrica)
vigabatrin (sabril)

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which ASMs are Na channel blockers/modulators (7)

carbamazepine, oxcarbazepine, eslicarbazepine
cenobamate
lacosamide
lamotrigine
phenytoin

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which ASMs are Ca channel modulators (3)

ethosuximide
gabapentin
pregabalin

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which ASMs are GABA modulators (3)

valproate
tiagabine
vigabatrin

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which ASMs are GABA receptor agonists (3)

clonazepam, phenobarbital, primidone
ALL 1ST GEN

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which ASMs are glutamate blockers (2)

felbamate
parampanel

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which ASMs are SV2A modulators (2)

levetiracetam, brivaracetam

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which ASMs are highly protein bound (6)

carbamazepine, clonazepam, valproate, phenytoin, tiagabine, perampanel

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which 2nd gen ASMs have high renal elimination (4)

felbamate, gabapentin, levetiracetam, topiramate

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which 3rd gen ASMs have high renal elimination (4)

eslicarbazepine, lacosamide, pregabalin, vigabatrin

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which ASMs have multiple MOAs (2)

topiramate and zonisamide

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which seizure can carbamazepine NOT BE USED for? why?

absence
may worsen b/c of epoxide metabolite

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which ASMs have a narrow therapeutic index (3)

carbamazepine
ethosuximide
phenytoin

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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

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

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