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PK > Exam 3 > Flashcards

Exam 3 Flashcards

1
Q

Phenytoin classification

A

Hydantoin anticonvulsant

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2
Q

Phenytoin indication

A

Grand mal and temporal lobe seizures

Prophylaxis for neurosurgery

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3
Q

Fosphenytoin indications

A

Tonic-clonic seizures

Prophylaxis of neurosurgery

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4
Q

Fosphenytoin route of administration

A

Only parenteral

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5
Q

Phenytoin concentration related SE

A

Nystagmus

Depression of the CNS

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6
Q

Nystagmus

A

Rapid involuntary movement of the eye

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7
Q

Safety/tolerability issues that may occur with chronic phenytoin treatment

A 
Hypertrichosis
Coarsened facial features
Folate deficiency
Glucose intolerance
Gingival hyperplasia
Vit D deficiency
Osteomalacia
Peripheral neuropathy
SLE
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8
Q

Phenytoin bound therapeutic range

A

10-20

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9
Q

Phenytoin % bound to plasma

A

90 (primarily albumin)

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10
Q

Phenytoin unbound therapeutic range

A

1-2

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11
Q

When is unbound phenytoin monitoring reserved for?

A

Hypoalbuminemia

Displacement from albumin

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12
Q

Phenytoin acid salt factor

A

1

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13
Q

Phenytoin sodium salt factor

A

0.92

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14
Q

Phenytoin Pediatric formulations

A

Oral suspension
Chewable tablet
S=1, phenytoin acid

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15
Q

Phenytoin sodium formulations

A

Oral capsule
Injectable
S=.92

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16
Q

Phenytoin sodium max recommended infusion rate

A

50 mg/min in adults
0.5 mg/kg/min for neonates
1 mg/kg/min for older children

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17
Q

Fosphenytoin salt factor

A

0.92

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18
Q

Fosphenytoin formulations

A

injectable

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19
Q

Fosphenytoin max recommended infusion rate

A

150 mg/min in adults

ALWAYS MONITOR CARDIAC RATES

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20
Q

F for oral phenytoin

A

100%

Reduced in neonates and patients receiving nasogastric feedings (separate by 1-2 hours on either side)

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21
Q

Phenytoin is (hydrophilic/lipophilic)

A

Lipophilic

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22
Q

Enzyme metabolism of phenytoin

A

2C9 - 90%

2C19 - 10%

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23
Q

Phenytoin kinetics

A

Behaves according to Michaelis-Menten kinetics

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24
Q

Phenytoin clearance

A

Hepatic - 95%

Renal - 5%

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25
Q

Reason for phenytoin/fosphenytoin LD

A

An urgent need to achieve therapeutic concentrations

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26
Q

Phenytoin IV LD monitoring

A

check level 12 hours after completion of LD

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27
Q

Phenytoin oral LD monitoring

A

Check level 24 hours after the last oral LD

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28
Q

Phenytoin MD monitoring

A

Collect sample 5-8 days after initiation of MD

Collect as a trough sample prior to next scheduled dose

29
Q

Phenytoin chronic therapy monitoring

A

Monitor every 3-12 months as a trough

30
Q

How do we monitor phenytoin?

A

Total phenytoin concentrations

31
Q

How does protein binding affect phenytoin concentrations

A

Can change total phenytoin concentrations, but have little effect on unbound concentrations

32
Q

Two causes of altered phenytoin binding

A

Hypoalbuminemia

ESRD

33
Q

How to measure phenytoin concentrations in patients with hypoalbuminemia and ESRD

A

Corrected phenytoin concentration

34
Q

Diseases that cause hypoalbuminemia

A 
Liver disease
Nephrotic syndrome
Pregnancy
Cystic Fibrosis
Burns
Trauma
Malnourishment
Elderly
35
Q

What effect does phenytoin have on CYP450 systems

A

Inhibitor and inducer

36
Q

Phenytoin decreases concentrations of these antiepileptics

A 
Carbamazepine
Felbamate
Lamictal
Phenobarbital
Primidone
Tiagabine
Topiramate
Zonisamide
Ethosuximide
37
Q

Antiepileptics that decrease phenytoin concentrations

A

Carbamazepine
Phenobarbital
Primidone

38
Q

Antiepileptics that increase phenytoin concentrations

A

Felbamate
Oxcarbazepine
Valproic acid

39
Q

Indications of Valproic Acid

A

Treatment of partial and generalized seizures

Absence, tonic-clonic, myoclonic

40
Q

Phenytoin drug interactions

A 
Theophylline
Warfarin
Corticosteroids
CsA
Methadone
41
Q

Theophylline effect on phenytoin

A

Clearance increased by 45%

42
Q

Warfarin effect on phenytoin

A

Reports of biphasic reaction

An increase in activity, with subsequent decrease in hypoprothrombinemic effect

43
Q

Corticosteroids effect on phenytoin

A

Reported 45% decrease in serum concentrations of dexamethasone, methylprednisolone, and prednisone

44
Q

CsA effect on phenytoin

A

Dual mechanism: increased metabolism and reduced absorption, potential increased risk of organ rejection

45
Q

Methadone effect on phenytoin

A

Increased metabolism can induce methadone withdrawal

46
Q

Valproic acid forms

A

VPA
Na Valproate
Divalproate sodium

47
Q

Valproic acid formulations

A 
IV
Syrup
Soft capsule
Enteric coated capsule
ER tablets
Sprinkle capsule
48
Q

VPA ADR

A 
GI: N/V, anorexia
Concentration-dependent:
-Ataxia, sedation, lethargy, tiredness, thrombocytopenia
-Tremor at concentrations > 100
-Stupor or coma at concentrations > 175
49
Q

VPA therapeutic range

A

Total: 50-100

Approximate unbound therapeutic range is: 2.5-10

50
Q

VPA half-life

A

12-18 hours

51
Q

VPA % protein bound

A

90-95%

52
Q

VPA and enzyme systems

A

VPA is a potent inhibitor of multiple drug-metabolizing enzyme systems

53
Q

VPA on phenytoin clearance

A

Decreased phenytoin clearance

54
Q

Uses of MTX

A

Leukemias
Lymphomas
RA
Severe psoriasis

55
Q

Absorption of MTX

A

F = 100% for doses < 30mg/m2

56
Q

Distribution of MTX

A

50% bound to plasma proteins

Vd = 0.5-0.5 L/kg

57
Q

MTX metabolism

A

Small amount of active metabolites, including 7-hydroxymethotrexate

58
Q

MTX elimination

A 
80-90% unchanged in urine
T1/2 alpha - 2-3 hours
T1/2 beta - 10 hours
With decreased urine pH, MTX can precipitate and cause nephrotoxicity
Hydration is essential
59
Q

MTX toxicities

A

Hematologic: Myelosuppression, thrombocytopenia
Other: Mucositis, renal toxicity, N/V, rash

60
Q

Goal MTX concentration

A

< 0.1 micromolar 48 hours following initiation of therapy

61
Q

Busulfan uses

A

Leukemia, conditioning regimen for hematopoietic stem cell transplant
IV and oral
NTI

62
Q

Busulfan absorption

A

Rapid and complete

F = 70-100%

63
Q

Busulfan distribution

A

32% bound to plasma proteins
47% binding to RBC
Vd = 1 L/kg

64
Q

Busulfan metabolism

A

Hepatic

Glutatione conjugation followed by oxidation

65
Q

Busulfan elimination

A

Urine: 25-60% metabolites, < 2% unchanged drug

T1/2 = 2.5 hours

66
Q

MTX rescue medications

A

Leucovorin

Glucarpidase

67
Q

Leucovorin

A

Restores folate stores needed for purine/pyrimidine synthesis
Works by competitive cellular uptake
Given with HD MTX regimens to help prevent toxicities

68
Q

Glucarpidase

A

Converts MTX to inactive metabolites
Indicated when MTX concentration is in toxic range, specifically for patients with impaired renal function
Leucovorin should not be administered within 2 hours of glucarpidase because it is a substrate

69
Q

MTX ss concentration equation

A

Css = Ro / CLmtx

PK (6 decks)

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