Seizures and Epilepsy Flashcards
what is an epileptic seizure
transient occurrence of signals or sx due to abnormal excessive and synchronous neuronal activity in the brain
3 points of an epilepsy diagnosis
at least 2 unprovoked seizures occurring >24hrs apart OR
1 unprovoked seizure and a probability of further seizures of at least 60% occuring over the next 10yrs
OR diagnosis of an epilepsy syndrome
what is epilepsy syndrome
sx complex with 1o feature of electroclinically characteristic epileptic seizures
epilepsy is considered resolved when
a pt is past the age in an age dependent epilepsy syndrome OR
pts who are seizure free for 10yrs, with no ASM in last 5yrs
describe simple seizure
no impairment of consciousness
may have motor, sensory, or autonomic sx
<60s
describe a complex partial seizure
Altered consciousness and behavioral arrest
Duration 1-2min with postictal confusion
Motor automatism (chewing or lip smacking)
Confused after, walking oddly but can’t respond
Altered consciousness and behavioral arrest
Duration 1-2min with postictal confusion
Motor automatism (chewing or lip smacking)
Confused after, walking oddly but can’t respond
complex partial seizure
No impairment of consciousness
Motor, sensory, or autonomic sx
<60s
Could still be awake, mostly facial twitching
simple seizure
how long do simple seizures last
<60s
how long do complex partial seizures last
1-2min with postictal confusion
what is a secondary generalized seizure
a focal seizure that becomes generalized
Loss of consciousness with hyperextension of body, followed by rhythmic full body contractions (tonic and clonic phases)
Duration 1-2min with postictal confusion, stupor, and headache
generalized tonic clonic seizure
how long do grand mal seizures last
1-2min
which of the following sees a loss/ alteration of consciousness
1. simple partial
2. complex partial
3. generalized tonic clonic
4. absence
5. myoclonic/ tonic
2,3,4
describe an absence seizure
sudden impairment of consciousness that starts in childhood
lasts 5-10s
how long do absence seizures last
5-10s
describe a myoclonic seizure
Sudden muscle contractions (jerks) w/out loss of consciousness
Jerks last milliseconds
describe a tonic seizure
Bilateral increased tone of limbs
Seconds to 1min
describe an atonic seizure
Sudden loss of muscle tone = limpness
Lasts for few seconds
Associated with epilepsy syndromes
what is a seizure related to the menstrual cycle called
catamenial epilepsy
how do you treat catamenial epilepsy
natural progesterones which are metabolized to allopregnanolone that has potent anticonvulsant actions
T or F: catamenial epilepsy can be treated with synthetic prostaglandins
F- natural only, synthetic are not metabolized the same way
list 3RF for seizures
Sleep dep, stress, drugs (rx and rec), alcohol abuse, photostimulation (flashing lights, rapidly changing images), hormonal changes
what is the most important piece for an epilepsy diagnosis
history from pt and witness
list 3 points of history you should ask about an epilepsy diagnosis
Presence or absence of aura
Circumstances surrounding/ could have precipitated seizure
Past hx of childhood epilepsy, childhood illnesses (ex- meningitis, encephalitis, febrile seizures)
Past hx of head injury, stroke, brain tumor, or any systemic conditions that might affect CNS (ex- cancer, electrolyte abnormalities)
Famhx of epilepsy
Hx of drug/ alcohol abuse
are physical exams helpful in epilepsy diagnosis?
usually no- but can still look for signs like tongue biting, incontinence, postictal confusion, and other neuro sx
what labs may be useful in diagnosing epilepsy
a comprehensive panel to look for precipitating factors like low glucose
are EEGs useful in epilepsy dx
maybe- can be used to confirm dx, but can be normal in 20% of pts
Can tell better if pt has a seizure during EEG
May be able to tell if pt has higher risk of seizure based on their normal waves
what type of imaging may be used in epilepsy dx
CT/MRI
what is the pathophys of epilepsy
Seizures = neuronal activity synched in an area of the brain
imbalance between excitatory and inhibitory mechs in the brain
in epilepsy, there is an increase of excitatory mechanisms like ______________ and a decrease in inhibitory mechs like ____________
increased glutamate receptors (NMDA, AMPA), sodium calcium influx
decreased GABA, voltage gated potassium channels
calcium dependent potassium channel
name the 8 broad spec ASMs
carbamazepine, clobazam, valproic acid/ divalproex, brivaracetam, levetiracetam, lamotrigine, topiramate
if on _____+ ________ lamotrigine needs to be titrated much slower
VA + lamotrigine,
T or F: ASMs only do symptomatic control and are not curative
T
name the 6 ASM that are sodium channel blockers
phenytoin, carbamazepine, lamotrigine, lacosamide, oxcarbazepine, eslicarbazepine
name 2 SV2A modulators
levetiracetam, brivaracetam
name the 4 GABA-A receptor gonists
clobazam, clonazepam, phenobarbital, primidone
which of the following is metabolized to which?
1. phenobarbital to primidone
2. primidone to phenobarbital
3. valproic acid to carbanazepine
4. valproic acid to divalproex
2
vigabatrin class
other GABA-A modulators
ethosuximide class
T type CCB
perampanel class
AMPA receptor blocker
what ASM are recommended for focal seizures
lamotrigine, levetriacetam, carbamazepine, phenytoin
what ASM are recommended for generalized tonic clonic seizures
levetiracetam, lamotrigine, VA/divalproex, carbamazepine, phenytoin
what ASM is recommended for absence seizures
ethosuxamide
what ASM are rec for myoclonic, tonic, and atonic seizures
VA/divalproex
most antiseizure meds have 100% bioavailability because
they must be very lipophilic to pass the BBB
which ASM has a lower bioavailability/ absorption? why?
gabapentin- saturable absorption rate
LD formula
LD = desired Css x Vd
what ASM must have free drug level corrected? how?
phenytoin- correct by calculating serum albumin
which ASM has saturable protein binding
VA
higher protein binding = ___ Vd
lower Vd
drugs levels are typically reported in
1. total drug conc
2. free/ unbound level
3. bound level
1
are presteady state levels ever helpful?
yes- can determine adequacy of dosage for ex- phenytoin
- if dropped a lot and not even at SS yet = need a higher dose
T or F: a LD gets you to SS immediately
kinda both- not true SS but gets you into the range
in a drug that is primarily metabolized, adjustments should be made on
liver function
in a drug that is primarily renally eliminated, adjustments should be made on
renal functio
name the 2 ASM with active metabolites + their active metabolites
Primidone → phenobarbital
Oxcarbazepine: → monohydroxymetabolite
how many half lives to get to SS
3-5
which ASM has saturable metabolism
phenytoin
which ASM has autoinduction of its own metabolism
carbamazepine
which of the following is a liver microsomal enzyme inhibitor
1. phenytoin
2. carbamazepine
3. topiramate
4. valproic acid
5. primidone
4
which of the following is NOT true about phenytoin
1. the powder of phenytoin sodium itself is ER = can crush and give as a long acting ASM
2. is highly protein bound
3. can NOT be given through an ET tube as bioavailability can decrease as much as 80%
4. difference between sodium salt and free acid form is not clinically significant and use 1:1 conversion
3- can be given through ET tube, hold feeds 1-2hrs before/ after
phenytoin RR
40-80umol/L or 10-20mg/L
what is the recommended LD for phenytoin
15-20mg/kg by TBW, dose div q2-4h
what is the target free phenytoin level
4-8umol/L
T or F: must always correct for pt’s albumin when calculating phenytoin dose, as the corrected and uncorrected will typically always make a clinical difference
F- correction only matters if the albumin is <30
phenytoin is a liver microsomal enzyme ______
inducer
phenytoin metabolism is ____ and follows _____ kinetics
saturable
michaelis-menten kinetics
Due to saturable kinetics of phenytoin, dose adjustments should not exceed _____mg/d
50-100
a patient has a phenytoin level that is <30 when the target is 40-80, how much should you adjust the dose? what if the level were >30?
level <30 = ↑ by 100, if lvl >30 = ↑50
only adjust if symptoms present
phenytoin half life is
22hrs
what is a prodrug for phenytoin
fosphenytoin
what is the conversion factor from fosphenytoin to phenytoin
1.5mg fosphenytoin sodium = 1mg phenytoin eq units
carbamazepine autoinduction decreases after
1-2mths
gabapentin has a saturable absorption rate, where bioavailability ____ with increases doses
decreases
what is divalproex sodium
a valproic acid/ sodium valproate coordinate compound
what is the conversion between divalproex and valorpic acid
1;1
how does VA saturable protein binding affect unbound fraction
at lower concs, unbound fraction is 7-10%, but as it increases, unbound becomes 15-20% - the increase in effect is not proportional to drug levels
which has the longer half life? primidone or phenobarb?
phenobarbital
what is the phenobarbital:primidone ratio in chronic dosing
1:1
which is found in higher concs, oxcarbazepine or MHD
MHD
list 3 conc dependent phenytoin AEs
ataxia, Nystagmus, dizziness, slurred speech, blurred vision, decreased mental status, confusion, coma
list 2 idiosyncratic phenytoin AEs
rash, blood dyscrasias
list one chronic phenytoin AE
Gingival hyperplasia, hirsutism, acne, coarsening of facial features, cog impairment
list 3 conc dependent VA AEs
GI upset, tremors, thrombocytopenia, CNS depression, increased LFT and serum ammonia
waht are 2 idiosyncratic VA SEs
acute hepatic failure, pancreatitis
what are 2 conc dependent carbamazepine AEs
Nausea, vomiting, decreased WBC, lethargy dizziness, drowsiness, blurred vision, diplopia`
what are 2 idiosyncratic carbamazepine AEs
Blood dyscrasias, rash
Must monitor CBC q6m then qyr- bone marrow may be depressed due to dyscrasias
SJS/RASH esp in HLA 1502 = must screen if sus
what are the 2 chronic AEs from phenobarbital
osteomalacia, mood changes
what is a chronic AE from carbanazepine
hyponatremia
what is a conc dependent AE of lacosamide
ECG and QT prolongation
what is an idiosyncratic AE of lamotrigine
Rash like SJS if titrated too quickly (must titrate up and down slowly)
what is an idiosyncratic AE of levetiracetam
Behavioural AEs, psychosis - 25% pts have hallucinations/ become another person
what is a chronic AE of vigabatrin
permanent vision loss- blidness
which causes more hyponatremia? carbamazepine or oxcarbazepine
oxcarbazepine
match the ASM to the AE
drugs: vigabatrin, phenytoin, lamotrigine, levetriacetam
SEs: SJS like rash ,behavioral changes, blindness, blood dyscrasias
vigabatrin = blindness
phenytoin = blood dyscrasias
lamotrigine = rash
levetriacetam = behavioural changes
osteomalacia: ASMs may increase risk of ____ and ________ turnover
bone loss and vit D turnover
which ASM are worse for osteomalacia?
older agents: phenytoin, carbamazepine, phenobarbital, VA
which ASM have a lower risk of osteomalacia?
newer agents have unknown/ no eff on bones
RF for ASM and osteomalacia
higher doses, longer durations, exposure to multiple ASM, enzyme inducing ASM
prevention of osteomalacia from ASM
regular bone density monitoring
Ca and vit D supplementation
what are sx of ASM hypersensitivity
Drug rash with eosinophilia and systemic sx (DRESS)
Sx: fever, rash, lymphadenopathy, eosinophilia, hepatosplenomegaly
which ASM are culprits for hypersensitivity
phenytoin, carbamazepine, phenobarbital, primidone
DRESS from ASM are attributed to ____________
arene oxide reactive metabolites
T or F: if you have a hypersensitivity to one of the below, you may trial a different one from the list
-phenytoin, carbamazepine, phenobarbital, primidone
F- do not, cross rxn 75%
most hypersensitivity ASM reactions occur within ______ of initiation
2mths
T or F: if a pt has already had a hypersensitivity rxn to an ASM, reinitiating is not recommended
T- Reinitiation of causative ASM can indue rxn immediately (<24h)
how to manage DRESS from ASM
Management: stop ASM, supportive tx, replace with valproic acid or levetiracetam for seizure control
3 general risks for ASM
osteomalacia, hypersensitivity rxn, suicidal behaviour
list 3 nonpharm management strategies for epilepsy
Avoid individual precipitants: sleep dep, drug abuse (cocaine, amphetamines), ↓ alcohol
Pt to consult pharmacist/ HCP when starting/ stopping any CAM products
Seizure precautions: driving restrictions, avoid heights, power tools, precautions when bathing, swimming, caring for young children
Ketogenic diet: deprive brain of glucose
Vagus nerve stimulation: electrical brain stim
Epilepsy surgery: remove pt of brain causing focalized seizures
Cannabis: currency being studied
when should you treat someone wiht seizures
pt has ≥ 2 unprovoked seizures or exp seizure provoked from some acquired cause like stroke, meningitis, brain injury
which ASM can be started with LD to target
phenytoin, phenobarbital, levetiracetam
slow titration is needed with carbamazepine to avoid
N/V, drowsiness
slow titration is needed with topiramate and lamotrigine to avoid ____ and _____ respectively
cognitive impairment
rash
slow titration is needed to gabapentin to avoid
CNS AEs
after ASM monotherapy fails. what should you do?
try 2-3 agents total - if that fails, add second agent
__% of epilepsy pts will need polypharmacy
30%
how to switch ASM
titrate up the new agent faster than titrating down the old agent (dose change q3-5 t1/2) - pref titrate to full dose before tapering the old agent
when might the old ASM dose need to be lowered a bit before the new one is increased
if both ASM have the same MOA and SEs
when to stop ASM
Consider if pt has been seizure free for ≥2yrs (nonacquired) or 6-12mths (acquired like stroke or meningitis)
seizure recurrence is highest in _______ after stopping ASM
1st yr
how to stop ASM is it was monotx
Slow taper (ex- ↓25% q2-4wks) for few mths
how to stop ASM if it was >1 med
taper separately and ↓ the most toxic/ least beneficial one first
what labs must be done at baseline before ASM initiation?
CBC, LFTs, lytes
when to repeat labs after ASM initiation?
4-8wks after, then qyr
may be done more often in symptomatic pts
what is a concern with ASM use in someone using oral birth control
ASM induces enzymes that metabolize OCs = decreased effectiveness of OCs
how to prevent pregnancy if on OCs and ASM
Use high dose E OCs (>50ug E)- not available in Canada
Use backup method of contraception
Consider non interacting ASMs
estrogen may decrease the concentration of __________ (an ASM)
lamotrigine
effect of seizures in first trimester on fetus
risk of malformations
effect of seizures on fetus in pregnancy
↑ risk of maternal and fetal hypoxia (esp tonic-clonic)
how does pregnancy alter the effectiveness of ASMs
Pregnancy ↓ ASM lvls esp in 3rd trimester
Measure SS before pregnancy and titrate accordingly - TDM rec to maintain lowest eff dose
T or F: Risk of malformations 2x with ASM, no ASM is completely safe but most can be used except for valproic acid
T
what is a concern with pregabalin in pregnancy
major birth defects in 1st trimester
if a patient was on topiramate to control seizures before, but is now pregnant, what should you do?
1. order baseline levels and monitor through pregnancy, continue topiramate
2. discontinue immediately
3. switch to valproic acid
4. switch to levetiracetam
1- If pt controlled on an agent before pregnancy = continue same agent (unless it’s valproic acid)
if a patient was on VA to control seizures before, but is now pregnant, what should you do?
1. order baseline levels and monitor through pregnancy, continue VA
2. discontinue immediately and switch to divalproex
3. DC and switch to another ASM that is not VA or pregabalin
4. discontinue VA immediately and monitor for seizures
3
what supplements should be started in pregnant women with seizures
folic acid 1mg, multivitamins
what is status epilepticus
Neurological emergency, can be convulsive or nonconvulsive
Continuous clinical or EEG seizure activity that lasts 5 or more minutes or recurrent seizures without return to baseline emong seizures
Neurological emergency, can be convulsive or nonconvulsive
Continuous clinical or EEG seizure activity that lasts 5 or more minutes or recurrent seizures without return to baseline emong seizures
status epilepticus
complications from status epilepticus includes
↑ brain activity and metabolic demand = CNS hypoxia and glycopenia
Overall mortality <30% in adults, <3% in peds
how to treat phase 1 status epilepticus
BZs: IV lorazepam, IM midazolam, IV diazepam- dose may be repeat, may need intubation from respiratory depression
how to treat phase 2 status epilepticus
Phenytoin 20mg/kg IV bolus, alt: valproic acid or levetiracetam (sim eff if used correctly)
2nd line if above didn’t work: phenobarbital LD
Maintenance dose to be continued
how to treat phase 3 status epilepticus
refractory status epilepticus = ICU
Requires intubation, admin of infusions of midazolam, propofol, and/or phenobarbital or pentobarbital
