seizures Flashcards
what is the definition of a seizure
a SYMPTOM of disturbed electrical activity in the brain
what is the bimodal distribution of first seizure occurrence
newborn infants & young children; patients >65 years
what is epilepsy
a chronic disorder of recurrent, unprovoked seizures
what are some characteristics that increase seizure risk
genetic mutations
patient with cerebral palsy, head injury, stroke, etc
MEDICATIONS
hormonal changes in pregnancy, etc
what medications increase seizure risk
-subtherapeutic AED levels
-withdrawal CNS depressants (alcohol, benzos, opioids, barbiturates, baclofen)
-antibiotics: PCN, cephs, cipro, carbapenems
-others (bupropion, SSRI, TCA overdose, etc etc)
what are some classifications of seizures
partial (focal): begins in one hemisphere & results in asymmetric motor manifestation
generalized: clinical manifestations that indicate involvement of both hemispheres
idiopathic: no identifiable cause; presumably genetic
secondary: infection, fever, intracranial event, toxin, metabolic
describe partial (focal) seizures
may manifest as changes in motor function, sensory symptoms, automatisms (sets of brief unconscious behaviors like lip smacking)
simple partial seizure: without loss of consciousness
complex partial seizure: with loss of consciousness
describe generalized seizures
bilaterally symmetrical without local onset
loss of consciousness
6 types: absence, myoclonic, clonic, tonic, tonic-clonic, atonic
describe what the different types of generalized seizures look like
absence: interruption of activities; blank stare (young kids)
myoclonic: brief shock-like contractions
clonic: rhythmic contractions
tonic: contract into rigid position
tonic-clonic: contraction followed by rigidity (patient may moan, cry, bite tongue, cyanosis)
atonic: sudden loss of muscle tone (head drop, limb drop, slumps to ground)– wear protective head gear
T/F: febrile seizures require daily antiepileptic therapy
FALSE
clinical pearls for TBI
early seizures occur within 7 days of TBI (late seizures represent epilepsy)
more severe injury is higher risk for late seizures
prophylaxis with antiepileptic drugs is used to prevent early post-traumatic seizures
who should be treated with AEDs?
not usually after the first seizure
start after the second seizure generally
also treat when patients present with status epilepticus or multiple seizures within a single day
how to discontinue AEDs?
may be considered by a neurologist after 2-4 years seizure free
gradual tapering reduces risk of provoking a seizure: taper at 25% of the dose monthly
considerations for seizures in the elderly population
think about drug interactions: many AEDs are CYP3A4 inducers/inhibitors
hypoalbuminemia is common in the elderly: some AEDs are bound to albumin which makes monitoring difficult
body mass changes, renal function, etc
considerations for seizures in the neonate/infant population
increased ratio of total body water to fat
decrease in albumin
newborns: decreased renal elimination/hepatic function
past 2-3 years: greater hepatic activity than adults so require higher AED doses
considerations for seizures in females
estrogen is seizure activating; progesterone is seizure protecting
high seizure vulnerability before/during period, at ovulation
peri-menopausal period can be associated with worsening seizure
considerations for seizures in pregnancy
25% of women have increased seizures during pregnancy
congenital malformation thought to be due to folate insufficiency associated with AEDs: prevent with adequate folate intake
considerations for hormonal contraception and seizures
women taking enzyme-inducing AEDs should use an alternative method of contraception
often recommend a preparation with at least 50 mcg estrogen
which of the big 4 older AEDs are inhibitors/inducers
inducers: carbamazepine, phenytoin, phenobarbital
inhibitor: valproic acid
what are the advantages of the newer AEDs
lower side effects, little or no need for serum monitoring, once or twice daily dosing for some, fewer drug interactions, all are pregnancy category C (vs D for older)
what is the FDA alert about AEDs
increased suicidality
phenytoin dosing
loading: 15-20 mg/kg IV at rate <50 mg/min (or <25 mg/min in hemodynamic instability) or 20 mg/kg PO divided by 3 and administered q2-4h
maintenance: 5-6 mg/kg/day in 1-2 divided doses
therapeutic range for phenytoin
trough 10-20 mg/L
Free 1-2 mg/L
obtained 2-3 weeks after initiation or change of dose
maintenance dosage increase ranges for phenytoin
increase by 100 mg/day if phenytoin <7
increase by 50 mg/day if phenytoin 7-12
increase by 30 mg/day if phenytoin >12
extra phenytoin loading dose to achieve desired serum levels
IV dose (mg/kg)= (Cdesired-Cactual) x 0.7
PO dose add extra 10%
correction for hypoalbuminemia
C corrected= C observed/[0.2(alb + 0.1)]
correction for renal failure CrCL<10
C corrected= C observed/[0.1(alb + 0.1)]
side effects of phenytoin
concentration dependent: lethargy, fatigue, blurred vision, dizzy, etc
independent: hypertrichosis, gingival hypertrophy, thickening of facial features, osteomalacia, folate deficiency, hypersensitivity
purple glove syndrome w/ IV
pharmacokinetic considerations for phenytoin
hold tube feeds 1-2 hours before & after phenytoin administration. can’t substitute– different salt products are not the same.
90% bound to albumin (free phenytoin causes therapeutic effect) so low albumin increases free drug conc.
obesity increases Vd; use AdjBW if obese
carbamazepine dosing
start at 200 mg BID
weekly increase by 200 mg/day
usual dose is 800-1200 mg/day given in 2-4 divided doses
carbamazepine therapeutic range
4-12
carbamazepine side effects
concentration dependent: nystagmus, ataxia, blurred vision, diplopia, vomiting, sedation, dizziness
independent: leukopenia: hold drug if WBC<2500 and ANC<1000
serious clinical pearl for carbamazepine
do not treat patients with carbamazepine if they test positive for HLA-B*1502 allele (present in patients with Asian ancestry): strong correlation with serious dermatologic reactions including SJS
pharmacokinetic considerations for carbamazepine
auto-inducer: max autoinduction is 2-4 weeks after initiation or dose change; re-adjust dose at 3-4 weeks
many drug interactions; macrolides decrease carbamazepine metabolism causing toxicity
carbamazepine can cause subtherapeutic INR w/ warfarin
valproic acid dosing
loading dose 15-20 mg/kg IV
maintenance dose initially 10-15 mg/kg/day in 2-3 divided doses
weekly increase 10 mg/kg/day and target 30-60 mg/kg/day in 2-3 divided doses
valproic acid therapeutic range
50-100
valproic acid side effects
dose dependent: GI complaints (minimized w/ enteric coated form or food), alopecia, thrombocytopenia, platelet dysfunction
independent: hepatotoxicity: unpredictable/fatal, most common in young children <2, on polytherapy, within first 6-12 months of therapy (check LFTs if patients complain of n/v, lethargy, anorexia, edema)
valproic acid PK considerations
many drug interactions
increases carbamazepine, lamotrigine, phenytoin, phenobarbital
phenobarbital dosing
loading: 15-20 mg/kg IV
avoid rapid administration > 60 mg/min due to hypotension, caution if hemodynamically unstable
maintenance 1-3 mg/kg/day in 2-3 divided doses
phenobarbital therapeutic level
15-40
phenobarbital side effects
concentration dependent: sedation, respiratory depression, hypotension
independent: hypersensitivity, hyperactivity, altered concentration, altered learning, depression
clinical pearls for fosphenytoin
phenytoin prodrug dosed by phenytoin equivalents (PE) with loading dose 10-20 mg/kg PE
benefits over phenytoin: less infusion reactions, administration (peripheral IV, can give IM if no IV access)
clobazam pearls
benzodiazepine (CIV)
adjunct treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients 2 years+
somnolence/sedation, avoid abrupt withdrawal, pregnancy C
ethosuximibe pearls
first line for absence seizures
TDM required: therapeutic level is 40-100
ezogabine pearls
adjunct for partial seizures
QT interval prolongation within 3 hours of admin (monitor)
REMS program for urinary retention
felbamate pearls
reserved for patient not responding to other AEDs
side effects include aplastic anemia, acute liver failure: patient or guardian must sign consent form
gabapentin pearls
second line for partial seizures +/- generalizations
highly used for off label indications (neuropathic pain, migraines, bipolar)
can accumulate in renal disease so have to adjust dose
lacosamide pearls
adjunct treatment of partial seizures
CV
prolongation of PR interval: caution in conductance problems
must dispense each Rx with med guide
lamotrigine pearls
interaction with valproic acid increases the serum concentration by 200%; inducers like phenytoin/carbamazepine accelerate metabolism
rash due to stevens johnson syndrome: high initial dose, concurrent valproic acid use, rapid escalation (use low dose and slow titration to avoid SJS)
levetiracetam pearls
100% bioavailable after PO administration (1:1 IV:PO)
no induction/inhibition hepatic interactions (basically only drug with no interactions)
overall best safety profile and minimal ADEs
oxcarbazepine pearls
not a prodrug of carbamazepine, but structurally related. potentially first line for primary generalized convulsive seizures. no auto induction but still an enzyme inducer (less potent than carbamazepine or phenytoin)
25-30% carbamazepine cross-sensitivity with rash
hyponatremia in 2.5%
when transitioning from carbamazepine: CBZ dose per day x 1.5= OXC dose/day (you can’t just switch on same dose)
rufinamide pearls
adjunct for generalized seizures of Lennox-Gastaut syndrome
ADEs QT shortening
contraindicated in familial short QT syndrome
tiagabine pearls
2nd line for partial seizures in patients who failed initial therapy
no inhibition or induction of hepatic enzymes
CYP3A4 substrate (phenytoin, carbamazepine, and phenobarbital decrease serum concentration)
topiramate pearls
first line AED for partial seizure
migraine prophylaxis
ADEs are CNS effects (word finding problems, slurred speech, confusion, etc) and kidney stones (stay hydrated)
vigabatrin pearls
black box warning, REMS for permanent vision loss in infants, children, adults
(blind as a bat)
zonisamide pearls
ADEs include idiosyncratic severe skin rash, SJS (d/c immediately)
advantage is long half life= once daily dosing
pearls of medical marijuana in seizures
potential drug interactions: induced by carbamazepine and phenytoin, inhibited by ketoconazole
epilepsy is an approved indication in PA
folic acid supplementation in pregnancy and other pearls
use 0.4 mg/day
take the best drug for seizure type and monotherapy if possible; avoid valproic acid monotherapy or polytherapy in the first trimester if possible
definition of status epilepticus
a neuro emergency that can cause brain damage, death
at least 5 minutes of continuous seizures
or at least 2 discrete seizures between which there is incomplete recovery of consciousness
treatment for wernicke’s encephalopathy
thiamine 50-100 mg IV
first line agent for status epilepticus
benzodiazepines (LORAZEPAM)
generally 1-2 doses will stop seizures within 2-3 minutes
option for seizures if there is no IV access
diazepam gel for rectal delivery
intranasal diazepam (6+) or midazolam (12+)
second to third line agents for status epilepticus
2nd line: phenytoin or fosphenytoin IV if unresponsive to lorazepam
3rd line: phenobarbital or valproic acid
refractory status epilepticus: search for the actual cause, intubate patient, propofol, continuous IV infusion of midazolam or pentobarbital (get norepi ready since causes hypotension)
