seizures

Question 1

what is the definition of a seizure

Answer 1

a SYMPTOM of disturbed electrical activity in the brain

Question 2

what is the bimodal distribution of first seizure occurrence

Answer 2

newborn infants & young children; patients >65 years

Question 3

what is epilepsy

Answer 3

a chronic disorder of recurrent, unprovoked seizures

Question 4

what are some characteristics that increase seizure risk

Answer 4

genetic mutations
patient with cerebral palsy, head injury, stroke, etc
MEDICATIONS
hormonal changes in pregnancy, etc

Question 5

what medications increase seizure risk

Answer 5

-subtherapeutic AED levels
-withdrawal CNS depressants (alcohol, benzos, opioids, barbiturates, baclofen)
-antibiotics: PCN, cephs, cipro, carbapenems
-others (bupropion, SSRI, TCA overdose, etc etc)

Question 6

what are some classifications of seizures

Answer 6

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

Question 7

describe partial (focal) seizures

Answer 7

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

Question 8

describe generalized seizures

Answer 8

bilaterally symmetrical without local onset
loss of consciousness
6 types: absence, myoclonic, clonic, tonic, tonic-clonic, atonic

Question 9

describe what the different types of generalized seizures look like

Answer 9

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

Question 10

T/F: febrile seizures require daily antiepileptic therapy

Answer 10

FALSE

Question 11

clinical pearls for TBI

Answer 11

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

Question 12

who should be treated with AEDs?

Answer 12

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

Question 13

how to discontinue AEDs?

Answer 13

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

Question 14

considerations for seizures in the elderly population

Answer 14

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

Question 15

considerations for seizures in the neonate/infant population

Answer 15

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

Question 16

considerations for seizures in females

Answer 16

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

Question 17

considerations for seizures in pregnancy

Answer 17

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

Question 18

considerations for hormonal contraception and seizures

Answer 18

women taking enzyme-inducing AEDs should use an alternative method of contraception
often recommend a preparation with at least 50 mcg estrogen

Question 19

which of the big 4 older AEDs are inhibitors/inducers

Answer 19

inducers: carbamazepine, phenytoin, phenobarbital
inhibitor: valproic acid

Question 20

what are the advantages of the newer AEDs

Answer 20

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)

Question 21

what is the FDA alert about AEDs

Answer 21

increased suicidality

Question 22

phenytoin dosing

Answer 22

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

Question 23

therapeutic range for phenytoin

Answer 23

trough 10-20 mg/L
Free 1-2 mg/L

obtained 2-3 weeks after initiation or change of dose

Question 24

maintenance dosage increase ranges for phenytoin

Answer 24

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

Question 25

extra phenytoin loading dose to achieve desired serum levels

Answer 25

IV dose (mg/kg)= (Cdesired-Cactual) x 0.7 PO dose add extra 10%

Question 26

correction for hypoalbuminemia

Answer 26

C corrected= C observed/[0.2(alb + 0.1)]

Question 27

correction for renal failure CrCL<10

Answer 27

C corrected= C observed/[0.1(alb + 0.1)]

Question 28

side effects of phenytoin

Answer 28

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

Question 29

pharmacokinetic considerations for phenytoin

Answer 29

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

Question 30

carbamazepine dosing

Answer 30

start at 200 mg BID weekly increase by 200 mg/day usual dose is 800-1200 mg/day given in 2-4 divided doses

Question 31

carbamazepine therapeutic range

Answer 31

4-12

Question 32

carbamazepine side effects

Answer 32

concentration dependent: nystagmus, ataxia, blurred vision, diplopia, vomiting, sedation, dizziness independent: leukopenia: hold drug if WBC<2500 and ANC<1000

Question 33

serious clinical pearl for carbamazepine

Answer 33

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

Question 34

pharmacokinetic considerations for carbamazepine

Answer 34

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

Question 35

valproic acid dosing

Answer 35

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

Question 36

valproic acid therapeutic range

Answer 36

50-100

Question 37

valproic acid side effects

Answer 37

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)

Question 38

valproic acid PK considerations

Answer 38

many drug interactions increases carbamazepine, lamotrigine, phenytoin, phenobarbital

Question 39

phenobarbital dosing

Answer 39

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

Question 40

phenobarbital therapeutic level

Answer 40

15-40

Question 41

phenobarbital side effects

Answer 41

concentration dependent: sedation, respiratory depression, hypotension independent: hypersensitivity, hyperactivity, altered concentration, altered learning, depression

Question 42

clinical pearls for fosphenytoin

Answer 42

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)

Question 43

clobazam pearls

Answer 43

benzodiazepine (CIV) adjunct treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients 2 years+ somnolence/sedation, avoid abrupt withdrawal, pregnancy C

Question 44

ethosuximibe pearls

Answer 44

first line for absence seizures TDM required: therapeutic level is 40-100

Question 45

ezogabine pearls

Answer 45

adjunct for partial seizures QT interval prolongation within 3 hours of admin (monitor) REMS program for urinary retention

Question 46

felbamate pearls

Answer 46

reserved for patient not responding to other AEDs side effects include aplastic anemia, acute liver failure: patient or guardian must sign consent form

Question 47

gabapentin pearls

Answer 47

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

Question 48

lacosamide pearls

Answer 48

adjunct treatment of partial seizures CV prolongation of PR interval: caution in conductance problems must dispense each Rx with med guide

Question 49

lamotrigine pearls

Answer 49

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)

Question 50

levetiracetam pearls

Answer 50

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

Question 51

oxcarbazepine pearls

Answer 51

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)

Question 52

rufinamide pearls

Answer 52

adjunct for generalized seizures of Lennox-Gastaut syndrome ADEs QT shortening contraindicated in familial short QT syndrome

Question 53

tiagabine pearls

Answer 53

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)

Question 54

topiramate pearls

Answer 54

first line AED for partial seizure migraine prophylaxis ADEs are CNS effects (word finding problems, slurred speech, confusion, etc) and kidney stones (stay hydrated)

Question 55

vigabatrin pearls

Answer 55

black box warning, REMS for permanent vision loss in infants, children, adults (blind as a bat)

Question 56

zonisamide pearls

Answer 56

ADEs include idiosyncratic severe skin rash, SJS (d/c immediately) advantage is long half life= once daily dosing

Question 57

pearls of medical marijuana in seizures

Answer 57

potential drug interactions: induced by carbamazepine and phenytoin, inhibited by ketoconazole epilepsy is an approved indication in PA

Question 58

folic acid supplementation in pregnancy and other pearls

Answer 58

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

Question 59

definition of status epilepticus

Answer 59

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

Question 60

treatment for wernicke's encephalopathy

Answer 60

thiamine 50-100 mg IV

Question 61

first line agent for status epilepticus

Answer 61

benzodiazepines (LORAZEPAM) generally 1-2 doses will stop seizures within 2-3 minutes

Question 62

option for seizures if there is no IV access

Answer 62

diazepam gel for rectal delivery intranasal diazepam (6+) or midazolam (12+)

Question 63

second to third line agents for status epilepticus

Answer 63

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)