epilepsy - dr krysiak

2 hours

what is epilepsy?

neurologic condition in which a pt is prone to recurrent and unpredictable epileptic seizures

T/F all patients that have a seizure will be diagnosed with epilepsy

FALSE

all pts with epilepsy have seizures, but NOT all pts with a seizure will have epilepsy

what are the 2 most common triggers?

hyperventilation

photo stimulation (flashing lights)

what drugs can lower the seizure threshold in high doses and renal impairment?

carbapenems (imipenem)

lithium

meperidine

PCN

quinolones

theophylline

what other drugs can lower the seizure threshold?

clozapine

bupropion

tramadol

varenicline

what causes epilepsy?

neuronal hyperexcitability + hypersynchronization

hyperexcitability can happen because of an imbalance between _________

glutamate (excitatory) and GABA (inhibitory)

what are the 3 key features when classifying epilepsy?

where seizures start in the brain

level of awareness during seizure

other seizure featurs: nonmotor and motor symptoms

_______ seizures start on one side of the brain, have asymmetrical motor manifestation, may have aura, and may/may not have loss of consciousness

a. focal

b. generalized

c. unknown

a.

________ seizures start bilaterally, sudden interruption of activities, loss of awareness or consciousness

a. focal

b. generalized

c. unknown

b.

differentiate between focal seizures and generalized seizures

	focal	generalized
sides	unilateral	bilateral
motor signs	asymmetrical	both sides
nonmotor signs	autonomic: flushing, sweating, piloerection behavior arrest: pausing, freezing, activity arrest cognitive: language problems, thinking problems emotion: fear, depression, joy, anger sensory: numbness, tingling, vertigo	sudden arrest of behavior blank stare with brief upward rotation of eye lasting 2-30 seconds eyelid jerks

how does ILAE define epilepsy?

≥ 2 unprovoked seizures > 24 hours apart

or

1 unprovoked seizure and probability of further seizures (high risk features)

what high risk features can classify someone with epilepsy after 1 seizure?

abnormal brain imaging

epileptiform activity on EEG

relevant family history

neurological deficit

prior brain injury or structural lesion

T/F there are NO diagnostic laboratory tests for epilepsy

TRUE

serum prolactin levels are elevated after convulsions, but need to get within 10-20 minutes of seizure

what is the gold standard for diagnosis of epilepsy?

who is it reserved for?

gold standard: video EEG

reserved for pts unresponsive to meds or difficult to characterize

list the goals of treatment of epilepsy

sustained seizure freedom

matching seizure disorder with appropriate ASM

minimizing ADRs

optimizing pts quality of life

monotherapy when possible

rational cost-effective decisions

_______ unprovoked seizures should be started on AED

2 or more

what is a major reason that seizures are not controlled?

lack of adherence

is there a target serum level for AEDs?

NO

just titrate up until they are seizure free

what should you do if the first monotherapy is ineffective?

add a second AED (different MOA)

taper off the first one

what should you do if the second AED is ineffective?

polytherapy

if someone is “medication-resistant”, what are some nonpharm tx options?

ketogenic diet

vagus nerve stimulation (VNA)

surgery

list the sodium channel blockers

carbamazepine

lamotrigine

phenytoin

oxcarbazepine

list the calcium channel blockers

ethosuximide

gabapentin

list the GABA enhancers

benzodiazepines

tiagabine

phenobarbital

vigabatrin

list the glutamate inhibitors

levetiracetam

valproate

what drug is a potent inducer of CYP3A4 and an auto-inducer?

carbamazepine

what drug has a boxed warning for increased risk of SJS/TEN with HLA-B*1502 allele in Asian population?

carbamazepine

oxcarbazepine is an inhibitor of _______ and inducer of ________

inhibitor of CYP2C19

inducer of CYP3A4

what’s important about the pharmacokinetics of phenytoin?

Michaelis-Menten kinetics —> saturates metabolizing enzymes at higher doses

since 90% total phenytoin is protein bound, what lab value do we need to look out for with regards to phenytoin levels?

albumin

if low (<3.5 g/dL), then total phenytoin levels will be falsely low or normal

the boxed warning for phenytoin IV administration rate should not exceed _______

50 mg/min

what are the long term ADRs of phenytoin?

hirsutism

gingival hyperplasia

hepatotoxicity

what is the prodrug of phenytoin?

what is it’s advantage compared to phenytoin?

fosphenytoin

LOWER risk of purple-glove syndrome

when do you use a lower starting dose of lamotrigine XR (blue box)?

pts taking valproate

when do you use a higher starting dose of lamotrigine XR (green box)?

pts taking inducers (carbamazepine, phenytoin, phenobarbital, or primidone)

NOT taking valproate

what does lamotrigine have a boxed warning for?

serious skin reactions: SJS/TEN

higher risk: higher dosing, quick dose escalation, used with valproic acid

what is the drug of choice for absence seizures?

ethosuximide

what is the boxed warning for benzodiazepines (clonazepam, clobazam)?

concurrent use with opioids may result in profound sedation, respiratory depression, and death

valproic acid/valproate is an inhibitor of ______

CYP2C9

what are the boxed warnings associated with valproic acid/valproate?

hepatic failure

fetal harm

pancreatitis

what drug prolongs PR interval, leading to an increased risk of arrhythmias, requiring an ECG prior to use?

lacosamide

topiramate is a weak inhibitor of _______ and inducer of ______

weak inhibitor of CYP2C19

inducer of CYP3A4

what is contraindicated with Trokendi XR (topiramate)?

alcohol use 6 hours before/after dose

what is contraindicated with zonisamide?

hypersensitivity to sulfa

what are the boxed warnings for felbamate (felbatol)?

hepatic failure

aplastic anemia

(within 68-354 days of therapy)

what drug requires informed consent to be signed by pt and prescriber prior to dispensing?

felbamate (felbatol)

what drug is a prodrug that undergoes hydrolysis to S-licarbazepine and is a major metabolite of oxcarbazepine?

eslicarbazepine (aptiom)

what drug requires a REMS program because of the risk of vision loss?

vigabatrin (sabril)

what AEDs may potentially precipitate or aggravate generalized onset tonic-clonic seizure types?

carbamazepine

phenytoin

what AEDs may potentially precipitate or aggravate children with absence seizures or JME?

carbamazepine

gabapentin

oxcarbazepine

phenytoin

tiagabine

vigabatrin

T/F the efficacy of newer AEDs is considered less than that of older AEDs

FALSE

comparable

what drugs require SLOW titration?

lamotrigine

topiramate

clobazam

phenobarbital

how does ILAE define drug resistance in epilepsy?

failure of adequate trials of 2 tolerated and appropriately chosen and used ASD schedules to achieve sustained seizure freedom

what are common ADRs for AEDs as a class?

CNS effects

suicidal ideation

hypersensitivity reactions

osteoporosis

how can you manage CNS effects from AEDs?

titrate slowly

avoid polytherapy

when is the risk higher for hypersensitivity reactions?

during first 2 months of usage

HLA-B*1502 allele

hypersensitivity reactions are associated with ____________

aromatic anticonvulsants

-carbamazepine

-ethosuximide

-lamotrigine

-oxcarbazepine

-phenobarbital

-phenytoin

-primidone

list pt counseling points

can cause suicidal thoughts or actions

do NOT stop taking this med without consulting your healthcare provider

can impair judgment, thinking, and coordination

avoid drugs that can lower seizure threshold

avoid st john’s wort with all anticonvulsants

use caution with different generic substitutions

when can you consider withdrawing AEDs?

seizure free period of 2-5 years

history of a single type of focal seizure or primary generalized seizure

normal neurologic exam and normal IQ

EEG that has normalized with tx

should you discontinue AEDs abruptly?

NO

DO IT GRADUALLY

what is the drug of choice for focal onset seizures in elderly?

lamotrigine

what do we need to consider in elderly pts?

more sensitive to neurocognitive effects —> titrate SLOWLY

requires lower serum concentrations

what meds decrease efficacy of oral contraceptives?

carbamazepine

topiramate

oxcarbazepine

rufinamide

lamotrigine

clobazam

felbamate

what meds do NOT affect oral contraceptives?

valproic acid

benzodiazepines

gabapentin

levetiracetam

tiagabine

zonisamide

lacosamide

when should folic acid be supplemented?

any woman of childbearing age taking an AED

pregnant women

during pregnancy, what drugs have increased clearance and should monitor plasma levels prior to, during pregnancy, and postpartum?

lamotrigine

carbamazepine

phenytoin

levetiracetam

what AEDs cause fetal harm?

carbamazepine

valproic acid

lacosamide

topiramate

what drug has the highest risk of major congenital malformations in pregnancy?

valproic acid

what drug has a high association with cleft palate?

topiramate