Antiepileptic Drug Flashcards
What is phenytoin indicated for
- tonic-clonic (grand mal) seizures
- psychomotor seizures
- prophylaxis for seizures
what can Fosphenytoin be used as
short term substitute for oral phenytoin
what is Fosphenytoin
ester prodrug of phenytoin
when is Fosphenytoin converted
converted to phenytoin in vivo by circulating esterates (about 15 minutes)
what is Fosphenytoin indicated for
- tonic-clonic seizures
2. prophylaxis of seizure following neurosurgery
what dosage form does phenytoin acid come in
- oral suspension
- chewable tablet
what dose strength does the oral suspension of phenytoin acid come in
125 mg/5 ml
what dose strength does phenytoin acid chewable tablet come in
50mg
what is the salt factor of phenytoin acid
1
what dosage form does phenytoin sodium come in
- oral capsule
2. injection
what dose strength does the oral capsule of phenytoin sodium come in
- 30 mg ER
- 100 mg ER
- 200 mg ER
- 300 mg ER
what is the salt factor of phenytoin sodium
0.92
If a patient is taking > 300 mg of phenytoin sodium what has to happen
it has to be divided into two or three doses
what dosage form does fosphenytoin come in
injection
what is the dose strength of fosphenytoin
equivalent to 50mg phenytoin sodium/ml
what is the salt factor of fosphenytoin
0.92
what is important about phenytoin acid oral suspension
Has to be shaken well to avoid dilution of early doses and concentration of later doses. Pharmacist should shake stock bottle well prior to dispensing to ensure suspension is uniform in strength
what is the max infusion rate for phenytoin sodium in adults
50 mg/min due to propylene glycol in formulation
what is the max infusion rate of phenytoin sodium in neonates
0.5 mg/kg/min
what is the max infusion rate of phenytoin sodium in children
1 mg/kg/min
what is the max infusion rate of fosphenytoin
150 mg/min
why are max infusion rates important
phenytoin can cause cardiac depressant effects such as bradycardia, hypotension, and EKG changes. All patients should have CV monitoring when IV phenytoin products are given
what is the NC law behind phenytoin
phenytoin must be refilled using the same product by the same manufacturer unless BOTH prescriber and patient give DOCUMENTED consent for the change
Are phenytoin and fosphenytoin narrow therapeutic index drugs
yes
what is the therapeutic concentration based on
total phenytoin concentration 10-20 mg/L
how much of phenytoin is bound to albumin
90%
how much of phenytoin is unbound
10%
what is the unbound or free therapeutic range
1-2 mg/L
what equation do you use when albumin < 4.4 g/dL and CrCl > 25 mL/min
C(corrected) = C(reported)/ [ 0.2 * albumin (g/dL)] + 0.1
What equation do you use when albumin is low or normal and ESRD on dialysis
C(corrected) = C(reported)/ [ 0.1 * albumin (g/dL)] + 0.1
What are common concentration related safety/tolerability issues of phenytoin
- Nystagmus rapid involuntary movement of the eye
- Depression of CNS can range from mild sedation to confusion and ultimately to coma with sufficiently high phenytoin levels
what are the most common long term adverse effects of phenytoin
- hypertrichosis (excessive hair everywhere on the body)
- Folate deficiency (lack of folic acid in the body)
- gingival hyperplasia (overgrowth of gum tissue around the teeth)
How long should phenytoin be separated given via feeding tube
2 hours before and after phenytoin dose
is phenytoin linear or non linear
non linear
Does time to peak concentration increase or decrease with increasing dose
increase
If there is an increase in dose what happens to clearance
a decrease
If there is a lower dose will this reach peak concentration quicker or slower
quicker
what is apparent Vd of phenytoin related to?
body size
What is the apparent Vd in neonates (< 28 days) and infants (> 28 days and < 1 year)
1 (+/-) 0.3 L/kg
What is the Vd of children (>1yr), adults, and geriatrics
0.65 (+/-) 0.2 L/kg
what is the Vd of obese patients
0.65 (L/kg) * [(IBW) + 1.33 * (TBW-IBW)]
where is phenytoin primarily eliminated by
hepatic metabolism (95%)
what percent is CYP 2C9 responsible for metabolism of phenytoin
90%
what percent is CYP 2C19 responsible for metabolism of phenytoin
10%
what will individuals with 2C9 poor metabolizer phenotype have
reduced phenytoin clearance and higher concentrations
what effects does phenytoin have on other antiepileptics
decreased concentrations of carbamazepine, lamotrigine, phenobarbital
what effects does antiepileptics have on phenytoin
- Decreased phenytoin concentrations: carbamazepine, phenobarbital, primidone
- Increased phenytoin concentrations: oxcarbazepine, valproic acid (increases free phenytoin levels)
What effect does phenytoin have on theophylline
theophylline clearance increased by 45%
what effect does phenytoin have on warfarin
reports of biphasic reaction; initial increase in warfarin with subsequent decrease in effect
what effect does phenytoin have on steroids
reported 45% decrease in concentration of dexamethasone, methylprednisolone and prednisone
what effect does phenytoin have on cyclosporine
increased metabolism and reduced absorption –> increased risk of organ rejection
what effect does phenytoin have on methadone
increased metabolism of methadone, may induce methadone withdrawal
is clearance a constant value in the michaelis menten kinetics?
no but changes with circulating phenytoin concentrations
To get Vmax what two things do you multiply together
vmax on chart and weight
What is the only kinetic parameter needed to calculate a loading dose for phenytoin or fosphenytoin
Vd
If there is a IV LD when should it be checked?
1-2 hours after LD is complete
if there is an oral LD when should the last oral LD be checked
24 hours
when initiating maintenance therapy, when should a sample be collected
5-8 days after maintenance therapy begins
If patient is on chronic therapy for phenytoin when should monitoring take place
- every 3-12 months as a trough sample
- document concentrations associated with seizure control
- ensures concentrations are maintained
If there is evidence of acute toxicity what should happen
- draw a level ASAP
- document concentration of level associated with adverse events
- provide important information for dose adjustment or wash out period
what are other reasons for monitoring collect sample at time of admission
- suspected non compliance
- break through seizures
