applied pharmacokinetics in neurologic disease (Dr. Nguyen)

carbamazepine, phenytoin, valproic acid is what generation of anti seizures

first generation

lamotrigine and levetiracetam is what generation of antiseizure

second generation

which antiseizure comes in IV formulations

phenytoin

fosphenytoin

levetiracetam

what is the brand name for phenytoin

dilantin

what is the brand name for fosphenytoin

cerebryx

what is the brand name for levetiracetam

keppra

phenytoin 20mg/kg (max 1500mg) is what kind of dose

IV loading dose

fosphenytoin 20PE/kg (max 1500mg) is what dose

IV loading dose

levetiracetam 60mg/kg ( max 4500mg) is what dose

IV loading dose

Phenytoin 300mg PO qhs is what dose

PO maintenance dose

does fosphenytoin have oral dose

no

Phenytoin IV will precipitate out of solution in 1-2 hours, must use within 1 hour

true

fosphenytoin is dosed as phenytoin equivalent (PE) to make dosing interchangeable with phenytoin

true

for phenytoin and fosphenytoin.

Serious but rare side effects can occur with fast IV administration of phenytoin and fosphenytoin

true

purple glove syndrome can happen with what drug due to extravasation by propylene glycol

phenytoin

severe hypotension and life threatening cardiac arrythmias occurs with what drug due to the structure of phenytoin + addition of propylene glycol

phenytoin

severe hypotension and life threatening cardiac arrhythmias still occurs with fosphenytoin due to structure of fosphernytoin even though there is no propylene glycol

true

to prevent these serious ADEs what administration of phenytoin and fosphentoin is required

slow IV administration

for phenytoin: rate of IV administration not to exceed what in slow IV administration

50mg/min

fosphenytoin: rate of IV administration not to exceed what in slow IV administration

150mg/min

some hospitals also require close BP monitoring and ECG monitoring during IV administration of phenytoin and fosphenytoin

true

phenytoin administered with tube feeds reduces the absorption of phenytoin in the gut

true

must stop tube feeds ~ 2 hours prior and ~2 hours after phenytoin administration

true

Therapeutic drug monitoring is required for anti seizure with narrow therapeutic window which are

first generation

therepeutic for phenytoin/fosphenytoin

total: 10-20mg/L

free: 1-2mg/L

what is the therapeutic drug monitoring for valproate

50-100mg/L

distribution of antiseizures for phenytoin is what

90%

in normal individuals, phenytoin is what percent protein bound

90%

only free phenytoin is pharmacologically active

true

in patients with low protein status there is less <90% protein binding for phenytoin

true

what is the phenytoin protein binding total phenytoin in the blood

10-20mg/L

what are the broad spectrum inducers

carbamezepine

phenytoin

what are the broad spectrum inhibitors

valproic acid

inducers increase enzyme activity ; decrease efficacy

true

inhibitors decrease enzyme activity'

true

handful of antiseizure are really eliminated and require dose adjustment in patient with renal disease (levetiractem)

true

non-linear Michaelis menten elimination kinetics, occurs when any ADME process is dependent on enzyme having a definite capacity and subjected to saturation

true

elimination rate of phenytoin decreases at higher doses

true

at that point, small change in dose can lead to large increase in phenytoin levels

true a

a typical phenytoin dose is what

300mg daily

IV carbamazepine is only approve as replacement for patients already on what

PO carbamazepine

which is a rate but serious Adverse effect with rapid IV administration

purple glove syndrome (phenytoin)

non-linear —> elimination rate decreases at higher dose

true

small change in high dose can lead to large increases in phenytoin levels

true