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260 Cards in this Set
- Front
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|
nonpharm tx
--- diet --- ---- --- stimulation |
ketogenic
surgery vagus nerve stimulation |
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reasons for sx
|
dx: epilepsy
failure of drug trials electroclinical syndrome |
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enzyme inducing --- increase the metabolism of sex hormones
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AEDs
so need another contraceptive or alternate form of bc |
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--- epilepsy is a pattern o f seizre exacerbation just before and during menstrual flow
|
catamenial
|
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|
t/f
seizures increase during pregnancy |
f
increase or decrease |
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1st line pharm tx for patial
|
carbamazepine
lamotrigne valproic acid oxcarbazepine |
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|
alternate drugs for partial:
|
gabapentin
topiramate levetiracetam zonisamide tiagabine primidone phenobarbital |
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inducers:
|
phenytoin
topiramate oxcarbezapine carbezapine |
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1st line generalized seizures
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valproic acid
ethosuximide |
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not inducers:
|
valproic acid
bzd gabapentin levotyroceium |
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1st line absence generalized seizures
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valproic acid
ethosuximide |
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alternate absence
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lamotrigine
levetiracetam |
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myoclonic gen seizures 1 st line
|
valproic acid
clonazepam |
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myoclonic gen seizures alter meds
|
lamotrignine
topiramate felbamate zonisamide levetiracetam |
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|
tonic-clonic 1st line drugs
|
phenytoin
carbamazepine valproic acid |
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tonic-clinic alternate drugs
|
lamotrigne
topiramate phenobarbital primidone oxcarbazepine levetiracetam |
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t/f
carbamazepine has 1ST pass metabolism |
f
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what can increase bioavailability of carbamazepine
|
food
|
|
|
how much carbamazepine metabolized by the liver
|
98-99%
|
|
|
which med has autoinduction?
do to this what occurs |
carbamazepine
initial conc may fall despite continued tx |
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|
conc dependent ae of carbamazepine:
|
diplopia
dizziness drowsiness nausea unsteadiness lethargy |
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|
idiosyncratic ae of carbazepine
|
blood dyscrasias
rash |
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|
chronic se of carbamazepine
|
hyponatremia
|
|
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carbamzepine has di w/
----- increase metabolite drugs that inhibit ------ may potentially increase carbamazepine levels carbamazepine may interact w/ other drug by ----- their metabolism |
valproic acid
3Aa4 inducing |
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|
initial dose of carbamazepine
|
400 mg/day
|
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|
usual max daily dose of carbamazepine
|
400-2400 mg
|
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|
Cl of carbamazepine increases w/ ---
|
time
|
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doses of carb may be started at 1/3 - 1/4 of --- dose and increases q -- to --- weeks
|
maintenance
2-3 weeks |
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|
carb is given --- x day
|
2-4
|
|
|
what formulations of carba provided fewer peak and trough fluctuations
so can improve compliance and se |
controlled and sustained release
|
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|
target serum conc of carba
|
0.4 - 14 mcg/mL
|
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|
ethosuximide metabolised by:
how: |
liver
hydroxylation |
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|
ethosuximide has active/inactive metabolites
|
inactive
|
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|
ethosuximide:
metabolism induced by ------- |
carbamazepine. . . so decrease conc
|
|
|
ethosuximide has a complex interaction w/ ---- -----
|
valproic acid
but need to be near saturation for this to occur |
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|
conc dependent ae of ethosuximide
|
ataxia
drowsiness GI distress unsteadiness hiccups n/v |
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|
idosyncratic ae of ethosuximide
|
blood dyscrasias
rash |
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|
chronic se of ethosuximide
|
behavior changes
ha |
|
|
when dosing ethosuximide what's required
|
loading dose
|
|
|
usu initial dose of ethosuximide:
max dose? |
initial dose: 500 mg/day
max daily dose: 500 - 2000 mg |
|
|
how long do you titrate ethosuximide for
to what maintenance dose |
1-2 weeks
main dose: 20mg/kg/day (conc of 50mcg/ml) |
|
|
target serum conc range of ethosuximide
|
40-80 mcg/ml
|
|
|
felbamate is --- and -- absorbed
|
rapidly
well |
|
|
t/f
felbamate absorption is affected by food and antacids |
f
unaffected |
|
|
felbamate is metabolized by -----
|
liver
40-50% hydroxylation and conjugation |
|
|
if not metobolized by felbamate what occurs
|
remainder excreted unchanged in urine
|
|
|
t/f
felbamate is a commonly rxed drug |
f
not! due to se |
|
|
conc ae of felbamate
|
anorexia
n/v insomnia ha |
|
|
idosyndratic ae of felbamate
|
aplastic anemia
acute hepatic failure (why felbamate no commonly used) |
|
|
chronic ae of felbamte
|
not established
|
|
|
who are felbamate given to
|
limited to pts who are refractor to other meds
|
|
|
felbamate increases ss conc of
|
valproic acid
|
|
|
felbamate decreases ss conc of
|
carbamazepine
|
|
|
felbamate conc is decreased by
|
carbamazepine
phenytoin |
|
|
tx range of felbamate
|
not established
dosed to clinical response |
|
|
monotx
initial dose: |
1200 mg/day
increase dose by 600 mg q 2 weeks |
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|
max dise if felbamate
|
3600 mg/day
|
|
|
felbamate is used. . .
|
when other AEDs not working
|
|
|
t/f
gabapentin affected by food |
f
|
|
|
gabapentins has dose ---- biovailability
|
dependent
varies among patients |
|
|
gabapentin is eliminated ?
|
by the kidneys
|
|
|
w/ gabapentin, impaired renal fx need
|
dose adjustment
|
|
|
gabapentin absorbed by an ---- process
|
active
saturated at higher doses |
|
|
what drugs will interact w/ gabapentin
|
di not likely to occur, cuz gabapentin does not induce or inhibit liver enzymes
|
|
|
as you increase the dose of gabapentin what decreases?
|
bioavailability
so separate doses to maintain bioavailability |
|
|
gabapentin conc dependent ae
|
dizziness
fatigue somnolence ataxia |
|
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gabapentin idiosyndratic ae
|
pedal edema
|
|
|
gabapentin choric se
|
weight gain
|
|
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gabapentin used for --- seizures or when --- --- needed
|
partial
additinal med needed |
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|
when can gabapentin used as monotx
|
less severe or new onset partial
|
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|
initial dose of gaba
|
300 mg q hs the first day
increase to 900 mg/day over 3 days |
|
|
t/f
gaba should be titrated slowly |
f
faster titration has been well tolerated |
|
|
mainten of gaba
|
1800-2400 mg/day
higher doses have been used safely (5,000 - 10,000) |
|
|
dose of gaba for hemodialysis pts
|
initial dose 300-400 mg
give 200-300 mg following q 4 hrs of hemodialysis |
|
|
gaba also used for
|
chronic pain
|
|
|
if CrCL is >60 what's the dose of gaba?
30 - 60? 15 - 30? < 15? |
> 60: normal dose
30 - 60: less than 300 mg 15 - 30: 300 mg < 15: < 300 mg /day |
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|
lamotrigine is -- and -- absorbed
|
completely
rapidly (bioavailability: 98%) |
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|
t/f
lamotrignine absorption is not altered by food |
t
|
|
|
lamotrignine is metabolied by
|
UGT1A4
|
|
|
renal elinamtion of lamotrignine is < -- %
|
10
|
|
|
t1/2 of lamotrig:
|
24- 29 hrs in adults (monotx)
|
|
|
who has higher Cl of lamotrig
|
kids
elderly |
|
|
how is the t1/2 of lamo prolonged?
decreased |
prolonged: renal failure
reduced: homodialysis ( to 13 hrs) |
|
|
conc dependent ae of lamo
|
diplopia
dizziness unsteadiness ha |
|
|
idiosyncratic ae of lamo
|
rash
watch for steven johnson's start low and go slow |
|
|
chronic se of lamo
|
no establised
|
|
|
to prevent getting a rash in lamo what do you do
|
start low and go slow
|
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|
di of lamotrig:
|
decreased
does not inhibit or induce liver enzymes |
|
|
lamotrig has a low potential for PK/PD
|
PK interactions
|
|
|
what can reduce the t1/2 of lamo
|
carbamazepine
phenobarbital primidone phenytoin |
|
|
what may reduce conc of lamotrig
|
oral contraceptives
|
|
|
what can inhibit Cl of lamotrigine
|
valproic acid
max inhibition occurs at valproic acid doses of 500 mg/day so increased levels of lamo |
|
|
tx dose of lamo
|
not establised
|
|
|
initial dose of lamo
|
if not on vpa: 25 - 50 mg/day
on vpa: 25 mg qod |
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|
usu max daily dose of lamo
|
not on vpa: 300- 500 mg
on vpa: 100- 150 mg |
|
|
what can affect pk of lamo
|
hepatic disease
|
|
|
w/ lamo and hepatic disease
enzyme inducer: |
50 mg for 1-2 weeks
weeks 3-4: 50 mg bid maintain dose: 800 mg bid |
|
|
w/ lamo and hep disease
enzyme inhibitor: |
25 mg qod for 1-2 weeks
weeks 3-4: 25 mg q day max dose: 200 mg divided |
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|
oxcarb is a ---
|
prodrug of carbameza
|
|
|
oxcar is extensively metabolized by
|
noninducable cytosolic ketoreductase
|
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what is oxcarb rapidly converte to
|
MHD
|
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|
t/f
oxcarb absorbed completely |
t
|
|
|
oxcarb elimnated by
|
kidneys
|
|
|
t1/2 of MHD is
|
9.3 + 1.8
|
|
|
oxcarb is 67% ---
|
protein bound
(MHD is 35 - 40 %) |
|
|
which has more se and di
carb or oxycarb |
carb
but they have same efficacy |
|
|
ae of oxycarb:
conc dependent |
sedation
dizziness ataxia nausea |
|
|
idiosyncratic ae of oxycarb
|
rash
|
|
|
chronic se of oxcarb
|
hyponatremial
more in oxycarb than carb |
|
|
oxcarb decreases bioavailability of
|
ethinyl estradiol
levonorgestrel so alternate form of bc or need to talk to md |
|
|
dose of oxcar greater than 1200 mg can lead to elevated -- levels
|
phenytoin by 40%
inhibition of cyp450 2c19 |
|
|
oxcarb can lower --- levels
|
lamotrigine
induction of ugt isoenzymes |
|
|
oxcarb
enzyme inducing drugs increase clearance of ----- |
MHD
the active metabolite |
|
|
initial dose of oxcarb:
|
300 mg qd or bid
|
|
|
titrate oxcarb:
|
600 mg/week
|
|
|
max dose of oxcarb
|
2400 mg/day
|
|
|
target serum conc of oxcarb
|
12-30 mcg/ml
|
|
|
what requires dose adjustment w/ oxcarb
|
renal impairment
|
|
|
when switching from carb to oxycarb waht hte dose
|
oxcarb are 1.5 x greater than carba
|
|
|
phenobarbital absorbed -- and ---
|
completely
rapidly (regardless of route) |
|
|
protein binding of pheno
|
50%
|
|
|
phenobarb:
long/short t1/2 |
very long
|
|
|
what can affect metabolism of phenobarb
|
liver enzyme altering drugs
|
|
|
what can affect renal excretion of phenobarb
|
diuretics and urinatry alkalinizers
|
|
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pheno is the doc for --- seizures
|
neonatal
|
|
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what type of seizures do you use phenobarbital
|
generalized
|
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|
conc dependent ae of phenobarb
|
ataxia
hyperactivity ha unsteadinesss sedation depression |
|
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what can be chronic w/ phenobarbital
|
sedation
|
|
|
idiosyn ae of pheno
|
blood dyscrasias
rash |
|
|
chronic se of pheno
|
behavior/mood changes
connective tissue disorders intellectual blunting metabolic bone disease sedation |
|
|
pheno may increase elimation of any drug metabolized by -- or ---- mediated metabolism
|
CYP
UGT |
|
|
what inhibits pheno metabolism
|
valproic acid
phenytoin felbamate cimetidine chloramphenicol |
|
|
--- increases metabolism of pheno
|
ethanol
|
|
|
why can pheno be given q day
|
long t1/2
|
|
|
what can minimize cns effects of pheno
|
dosing at hs
|
|
|
how long does it take to reach ss of pheno
|
3-4 wks
|
|
|
ld of pheno
|
10-20 mg/kg
|
|
|
initial dose of pheno
|
1-3 mg/kg/day
|
|
|
max dose of pheno
|
180-300 mg
|
|
|
adjusted conc for pheno =
|
measured total conc divided by ((0.2 x albumin) + 0.1)
|
|
|
target conc for pheno
|
10-40 mcg/ml
|
|
|
pheno used for
|
refractory status epilepticus
|
|
|
highly protein bound:
|
90%
|
|
|
phenytoin competes for -- binding sites w/ other highly protein binding sites
|
protein
|
|
|
what must you know about pt to properly determin serum pheny conc
|
albumin levels
|
|
|
t/f
ok to give phenytoin w/ food |
f
absorption may be altered |
|
|
what will alter protein bindind of pheny
|
renal insufficiency
|
|
|
what is pheny metabolized by
|
cyp 2c9 and 2c19
|
|
|
pheny has --- metabolism
|
saturable
not linear |
|
|
phenytoin is 1st line in --- and ---- but not ---
|
generalized and partial
not absence |
|
|
if you decrease the dose of phenytoin what will occur
|
not decrease phenytoin. . . might increase
|
|
|
what conc dependent ae is transient for pheny
|
lethargy
|
|
|
conc dependent ae of pheny
|
ataxia
nystagmus behav chages lethargy dizziness fatigue ha incoordination sedation cognitive impairment visual blurring |
|
|
idiosyn ae of pheny
|
blood dyscrasias
rash immunologic rxn |
|
|
why is dental hygine necessary for phenytoin
|
gingival hyperplasia
|
|
|
chronic se of phenytoin
|
behavior changes
cerebellar syndrome connective tissue changes |
|
|
pheny induces
|
cyp p450
ugt isoenzymes |
|
|
pheny decreases absorption of --- ---
|
folic acid
|
|
|
--- --- enchances clearance of phenytoin
|
folic acid
|
|
|
replacement of folice acid w/ pheny can result in --- -----
|
loss of efficacy
so it's a balancing act |
|
|
pheny available in --- dosage forms
|
4
liquid, capsule, parental, tablets |
|
|
t/f
ok to switch btw dosage forms of phenytoin |
f
can lead to changes in phenytoin conc |
|
|
prodrug for phenytoin
|
fosphenytoin
|
|
|
fosphenytoin can be given rapidly by which routes
|
IM
IV |
|
|
which is better tolerated phenytoin or fosphen
|
fospheny
|
|
|
initial dose of of fosphen
|
5-7 mg/kg/day
|
|
|
max daily dose of phenytoin
|
500- 600 mg
|
|
|
which has less phlebitis phenytin or fospheny
|
fosphenytoin
|
|
|
target serum level of pheny
|
10-20 mcg/ml
unbound: 1-2 mch/ml |
|
|
how should fospheny and pheny be given
d5w or ns |
NS
|
|
|
100 mg fospheny = -- mg of phenytoin
|
100 mg
|
|
|
fospheny ld
|
15-20mg iv or po
but should be divided due to nausea |
|
|
adult initial dose of fospheny:
|
5-7 mg/kg
|
|
|
kid initial dose of fospheny:
|
6-15 mg/kg/day divided
|
|
|
tiagabine given for --- seizures
|
partial
|
|
|
tiagbine given -- and --- completely
|
quickly
completely |
|
|
tiagabine --- by liver by cyp 3a4
|
oxidized
|
|
|
----- eliminate tiagabine much faster than adults
|
children
|
|
|
who will have a higher conc of tiagabine
|
pt w/ hepatic impairment
|
|
|
t/f
renal dysfx does not affect PK of tiagabine |
t
|
|
|
conc dependent ae of tiagabine
|
dizziness
fatigu difficulties concentrating nervousness tremor blurred vision depression weakness |
|
|
idiosyn ae of tiagabine
|
spike-wave stupor psychosis
|
|
|
chronic se of tiagabine
|
not established
|
|
|
what will increase tiagabine cl
|
carbamazepine
phenytoin |
|
|
food decreases ----, but not --- of absorption of tiagabine
|
rate
extent |
|
|
what will displace tiagabine from proteins
|
naproxen
salicylates valproate |
|
|
minimal effective dose of tiagabine for adults
|
30 mg/day
|
|
|
initial dose of tiagabine
|
4 mg/day
|
|
|
tiagabine titrated by adding -- to --- to the daily dose each week
|
4-8 mg
up to 56 mg/day |
|
|
slow titration is necessary to decrease adverse --- effects
|
CNS
|
|
|
t/f
there's significant protein biding of topiramate |
f
|
|
|
80% of topiramate is excreted via
|
renal
|
|
|
metabolism of topiramate increased by 50% when given w/ enzyme inducing ---
|
AEDs
|
|
|
conc dependent topiramate ae
|
difficulty conc (more than others )
psychomotor slowing speech or language problems somnolence dizziness fatigue ha |
|
|
idiosyn ae of topiramate
|
metabolic acidosis
acute angle glaucoma oligohidrosis |
|
|
chronic se of topiramate
|
kidney stones (hx of; drink fluids)
weight loss |
|
|
oral cl of ----- will increase when topiramate is added
|
digoxin
|
|
|
topiramate may increase levels of ---
|
phenytoin
( topiramate inhibits cyp2c19) |
|
|
topiramate increases cl of --- ----
|
ethinyl estradiol
(doses less than 200mg/day are unlikely to affect oral contra. PK) |
|
|
what will increase topiramate
|
carbamazepine
phenytoin |
|
|
to decrease ae of topiramate what do u do
|
TITRATE SLOWLY
|
|
|
initial dose of topiramate
|
12.5 - 50 mg/day
|
|
|
increase topiramate dose by -- to --- q week
|
12.5 to 50 mg/day
|
|
|
max daily dose of topiramate
|
200 - 1000 mg
start low and go slow w/ topiramate |
|
|
valproic acid has --- protein binding
|
saturable
|
|
|
ae of valproic acid
|
weight gain
pancreatitis hepatoxicity thrombocytopenia |
|
|
valproic acid is an inhbitor of --- --- and -- ---
|
cyp 450
epoxide hydrolase |
|
|
valproic acid inhibits --- ----
|
ugt isozyme
|
|
|
tx range of valproic acid
|
50-100 mg/ml
(maybe higher) |
|
|
dose of valproic acid
|
15-45 mg/kg/day divided in 2-4 doses
|
|
|
depakote to depakote er requrires an increase/decrease of total daily dose of 8-20%
|
increase
|
|
|
when do you avoid zonisamide
|
pts w/ sulfa allergies
|
|
|
ae of zonisamide
|
renal calculi
|
|
|
dose of zonisamide
|
100-600 mg daily
initiate 100 mg and increase q 2 weeks by 100 mg |
|
|
zonisamide used for ---- and ---- seizures
|
partial
generalized |
|
|
pregabalin r/t to ---
|
gabapentin
|
|
|
pregabalin is schedule ---
|
5
|
|
|
pregabalin is an adjunct for --- seizures
|
partial
|
|
|
pregabalin increases ---
decrease --- increase --- --- -- |
increases gaba
decreases calcium increases glutamic acid |
|
|
adjust pregabalin dose w/ pt's w/
|
renal insufficiency
|
|
|
initial dose of pregabalin
max dose |
initial: 150 mg/day
max: 600 mg/day in 2-3 doses |
|
|
ae of pregabalin
|
drowsiness
dizziness blurred vision myoclonic jerks (dose dependent) peripheral edema weight gain ha |
|
|
lacosamide adjunct for -- seizures
|
partial
|
|
|
dosage forms of lacosamide
|
oral
IV |
|
|
oral and iv formulations has ---% bioavailability
|
100%
|
|
|
lacosamide has -- significant protein binding
|
NO
|
|
|
lacosamide is a -- substrate
|
2C19
|
|
|
95% of lacosamide excreted in
|
the urine
|
|
|
lacosamide AUC increases in -- and --- impairment
|
renal
hepatic |
|
|
lacosamide dose
|
50 mg bid
increase by 100 mg/day |
|
|
mainten dose of lacosamide
|
200-400 mg/day
|
|
|
equivalence of lacosamide po and iv doses
|
po = iv
|
|
|
how long to give lacosamide
|
over 30-60 min
|
|
|
lacosamide: mild to mod --- impairment
|
hepatic
max dose 30 mmg/day |
|
|
crcl </= 30 dose of lacosamide
|
300 mg/day
|
|
|
hemodialysis give --- % of lacosamide dose after a 4 hr tx
|
50
adjust renal dose |
|
|
ae of lacosamide
|
dizziness
ataxia n/v (why pt usu d/c meds) |
|
|
di of lacosamide
drugs that prolong --- ----- potent 2c19 ------ |
QT interval (erythromycin)
inhibitors (increase lacosamide, e.g, fluconazole) |
|
|
rufinamide used for
|
lennox gastaut syndrome
adjunct tx > 3 yrs old |
|
|
rufinamide should be dosed w/ ---
|
meals
|
|
|
what inibits metabolism of rufinamide
|
valproic acid
|
|
|
rufinamide is a mild --- inducer
|
cyp 3a4
|
|
|
most common ae of rufinamide
|
somnolence
nausea |
|
|
dose of rufinamide
rapid/slow titration kids : adults |
rapid
kids: 10mg/kg/day, titrate 10mg/kg/day qod adults: 400-800 mg/day; increase 320 mg qod |
|
|
t/f
ok to crush rufinamide and serve w/ food |
t
|
|
|
rufinamide tabs are ---
|
scored
and expensive |
|
|
tx of status epilepticus
|
abc's
pt safety lorazepam (preferred) or diazepam phenytoin/fosphen, phenobarb, valporic: IV general anesthesia or pentobarbital coma |
|
|
when aed changes
|
inadequate efficacy
ae not tolerated |
|
|
how to do change aed
|
gradually introduec new agent to appropriate dose
then gradually decrease old dose |
|
|
how to add a new aed
|
add new and titrate up slowly to appropriate dose
then titrate down the other med |
|
|
t/f
there may be a change in seizre control during change |
t
think about driving |
|
|
to stop aed pt is seizure free for -- yrs
|
2-5 yrs
|
|
|
to stop aed the pt should have ---- seizure type of -- or ---gtc
|
single
partial primary |
|
|
ok to stop aeds w/ complete seizure control w/in -- yr
|
one
|
|
|
stop aed for seizures after - but before ----
|
2
35 |
|
|
stop aed w/ normal ---, --- - and ---
|
eeg
neuro exam IQ |
|
|
stop aed w/ -----
|
polypharmacy
reduce/discontinue drug less appropriate for seizure type first |
|
|
d/c aed's poor prognosis
|
high freq of seizure
multi episodes of status epilepticus combo seizure types development of abdnormal mental fxing |
|
|
aed withdrawal not recommended for
|
juvenile myclonic epilepsy
absence w/ clonic-tonic-clonic seizures clonico tonic clonic seizures |
|
|
if relapse after dcing:
|
restart aed
full control might not be immediate |
