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Clinical PK Exam 3 > Antiepileptic Drug > Flashcards

Antiepileptic Drug Flashcards

1
Q

What is phenytoin indicated for

A
  • tonic-clonic (grand mal) seizures
  • psychomotor seizures
  • prophylaxis for seizures
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2
Q

what can Fosphenytoin be used as

A

short term substitute for oral phenytoin

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3
Q

what is Fosphenytoin

A

ester prodrug of phenytoin

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4
Q

when is Fosphenytoin converted

A

converted to phenytoin in vivo by circulating esterates (about 15 minutes)

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5
Q

what is Fosphenytoin indicated for

A
  1. tonic-clonic seizures

2. prophylaxis of seizure following neurosurgery

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6
Q

what dosage form does phenytoin acid come in

A
  • oral suspension

- chewable tablet

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7
Q

what dose strength does the oral suspension of phenytoin acid come in

A

125 mg/5 ml

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8
Q

what dose strength does phenytoin acid chewable tablet come in

A

50mg

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9
Q

what is the salt factor of phenytoin acid

A

1

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10
Q

what dosage form does phenytoin sodium come in

A
  1. oral capsule

2. injection

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11
Q

what dose strength does the oral capsule of phenytoin sodium come in

A
  • 30 mg ER
  • 100 mg ER
  • 200 mg ER
  • 300 mg ER
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12
Q

what is the salt factor of phenytoin sodium

A

0.92

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13
Q

If a patient is taking > 300 mg of phenytoin sodium what has to happen

A

it has to be divided into two or three doses

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14
Q

what dosage form does fosphenytoin come in

A

injection

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15
Q

what is the dose strength of fosphenytoin

A

equivalent to 50mg phenytoin sodium/ml

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16
Q

what is the salt factor of fosphenytoin

A

0.92

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17
Q

what is important about phenytoin acid oral suspension

A

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

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18
Q

what is the max infusion rate for phenytoin sodium in adults

A

50 mg/min due to propylene glycol in formulation

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19
Q

what is the max infusion rate of phenytoin sodium in neonates

A

0.5 mg/kg/min

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20
Q

what is the max infusion rate of phenytoin sodium in children

A

1 mg/kg/min

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21
Q

what is the max infusion rate of fosphenytoin

A

150 mg/min

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22
Q

why are max infusion rates important

A

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

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23
Q

what is the NC law behind phenytoin

A

phenytoin must be refilled using the same product by the same manufacturer unless BOTH prescriber and patient give DOCUMENTED consent for the change

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24
Q

Are phenytoin and fosphenytoin narrow therapeutic index drugs

A

yes

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25
Q

what is the therapeutic concentration based on

A

total phenytoin concentration 10-20 mg/L

26
Q

how much of phenytoin is bound to albumin

A

90%

27
Q

how much of phenytoin is unbound

A

10%

28
Q

what is the unbound or free therapeutic range

A

1-2 mg/L

29
Q

what equation do you use when albumin < 4.4 g/dL and CrCl > 25 mL/min

A

C(corrected) = C(reported)/ [ 0.2 * albumin (g/dL)] + 0.1

30
Q

What equation do you use when albumin is low or normal and ESRD on dialysis

A

C(corrected) = C(reported)/ [ 0.1 * albumin (g/dL)] + 0.1

31
Q

What are common concentration related safety/tolerability issues of phenytoin

A
  1. Nystagmus rapid involuntary movement of the eye
  2. Depression of CNS can range from mild sedation to confusion and ultimately to coma with sufficiently high phenytoin levels
32
Q

what are the most common long term adverse effects of phenytoin

A
  1. hypertrichosis (excessive hair everywhere on the body)
  2. Folate deficiency (lack of folic acid in the body)
  3. gingival hyperplasia (overgrowth of gum tissue around the teeth)
33
Q

How long should phenytoin be separated given via feeding tube

A

2 hours before and after phenytoin dose

34
Q

is phenytoin linear or non linear

A

non linear

35
Q

Does time to peak concentration increase or decrease with increasing dose

A

increase

36
Q

If there is an increase in dose what happens to clearance

A

a decrease

37
Q

If there is a lower dose will this reach peak concentration quicker or slower

A

quicker

38
Q

what is apparent Vd of phenytoin related to?

A

body size

39
Q

What is the apparent Vd in neonates (< 28 days) and infants (> 28 days and < 1 year)

A

1 (+/-) 0.3 L/kg

40
Q

What is the Vd of children (>1yr), adults, and geriatrics

A

0.65 (+/-) 0.2 L/kg

41
Q

what is the Vd of obese patients

A

0.65 (L/kg) * [(IBW) + 1.33 * (TBW-IBW)]

42
Q

where is phenytoin primarily eliminated by

A

hepatic metabolism (95%)

43
Q

what percent is CYP 2C9 responsible for metabolism of phenytoin

A

90%

44
Q

what percent is CYP 2C19 responsible for metabolism of phenytoin

A

10%

45
Q

what will individuals with 2C9 poor metabolizer phenotype have

A

reduced phenytoin clearance and higher concentrations

46
Q

what effects does phenytoin have on other antiepileptics

A

decreased concentrations of carbamazepine, lamotrigine, phenobarbital

47
Q

what effects does antiepileptics have on phenytoin

A
  • Decreased phenytoin concentrations: carbamazepine, phenobarbital, primidone
  • Increased phenytoin concentrations: oxcarbazepine, valproic acid (increases free phenytoin levels)
48
Q

What effect does phenytoin have on theophylline

A

theophylline clearance increased by 45%

49
Q

what effect does phenytoin have on warfarin

A

reports of biphasic reaction; initial increase in warfarin with subsequent decrease in effect

50
Q

what effect does phenytoin have on steroids

A

reported 45% decrease in concentration of dexamethasone, methylprednisolone and prednisone

51
Q

what effect does phenytoin have on cyclosporine

A

increased metabolism and reduced absorption –> increased risk of organ rejection

52
Q

what effect does phenytoin have on methadone

A

increased metabolism of methadone, may induce methadone withdrawal

53
Q

is clearance a constant value in the michaelis menten kinetics?

A

no but changes with circulating phenytoin concentrations

54
Q

To get Vmax what two things do you multiply together

A

vmax on chart and weight

55
Q

What is the only kinetic parameter needed to calculate a loading dose for phenytoin or fosphenytoin

A

Vd

56
Q

If there is a IV LD when should it be checked?

A

1-2 hours after LD is complete

57
Q

if there is an oral LD when should the last oral LD be checked

A

24 hours

58
Q

when initiating maintenance therapy, when should a sample be collected

A

5-8 days after maintenance therapy begins

59
Q

If patient is on chronic therapy for phenytoin when should monitoring take place

A
  • every 3-12 months as a trough sample
  • document concentrations associated with seizure control
  • ensures concentrations are maintained
60
Q

If there is evidence of acute toxicity what should happen

A
  • draw a level ASAP
  • document concentration of level associated with adverse events
  • provide important information for dose adjustment or wash out period
61
Q

what are other reasons for monitoring collect sample at time of admission

A
  • suspected non compliance

- break through seizures

Clinical PK Exam 3 (5 decks)

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