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7343 PK Test 3 > 7343 PK Test 3 > Flashcards

7343 PK Test 3 Flashcards

1
Q

antiarrythmics metabolized by what CYP?

A

2D6

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2
Q

fluoxetine and paroxetine metabolized by what CYP?

A

2D6

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3
Q

antipsychotics metabolized by what CYP?

A

2D6

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4
Q

metoprolol and carvedilol metabolized by what CYP?

A

2D6

not atenolol

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5
Q

codeine and tramadol metabolized by what CYP?

A

2D6

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6
Q

CYP2D6 metabolizes what % of drugs?

A

25-30

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7
Q

2D6 poor metabolizer genotype?

A

4/4 or 4/6

5-10% of whites
1% of asians

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8
Q

What % of whites are 2D6 UMs?

A

5%

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9
Q

duplication of gene metabolizer?

A

UM

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10
Q

2D6 PM have what symptoms with antipsychotics?

A

extrapyridimal

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11
Q

CYP2C9 poor metabolizer genotype?

A
  • 2, *3 in whites

* 5 only in blacks

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12
Q

What gene is key factor explaining dose variability of warfarin?

A

VKORC1

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13
Q

phenytoin is metabolized by what CYP?

A

2C9

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14
Q

warfarin is metabolized by what CYP?

A

2C9

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15
Q

NSAIDS (ibuprofen, diclofenac) are metabolized by what CYP?

A

2C9

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16
Q

ARBs are metabolized by what CYP?

A

2C9

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17
Q

glipizide, glyburide metabolized by what CYP?

A

2C9

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18
Q

CYP2C19 UM genotype?

A

*17

25% of whites

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19
Q

CYP2C19 PM genotype?

A

*2, *3

1-3% whites
13-23% asians

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20
Q

clopidogrel metabolized by what CYP?

A

2C19

prodrug

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21
Q

PPIs metabolized by what CYP?

A

2C19

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22
Q

diazepam is metabolized by what CYP?

A

2C19

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23
Q

citalopram, escitalopram metabolized by what CYP?

A

2C19

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24
Q

cyclophosphamide metabolized by what CYP?

A

2C19

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25
Q

bupropion metabolized by what CYP?

A

2B6

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26
Q

efavirenz metabolized by what CYP?

A

2B6

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27
Q

nevirapine metabolized by what CYP?

A

2B6

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28
Q

propofol metabolized by what CYP?

A

2B6

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29
Q

methadone metabolized by what CYP?

A

2B6

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30
Q

CYP2B6 PM genotype?

A

*6, *16

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31
Q

Which has higher conc. of nevirapine/efavirenz?

516GG or 516TT

A

516TT

PM genotype

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32
Q

CYP3A4 PM genotype?

A

*22

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33
Q

CYP3A4 UM genotype?

A

1B, Por28

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34
Q

CYP3A5 wild type genotype?

A

1/1 (normal expression)

80% african American
highest activity, highest dose requirement

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35
Q

CYP3A5 PM genotype?

A

3/3

85% whites
lowest activity, lowest dose requirement

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36
Q

caffeine, theophylline metabolized by what CYP?

A

1A2

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37
Q

clozapine, olanzapine metabolized by what CYP?

A

1A2

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38
Q

heterocyclic amines metabolized by what CYP?

A

1A2

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39
Q

What CYP is inducible by smoking 1PPD?

A

CYP1A2

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40
Q

What genes code for P-gp?

A

ABCB1, MDR1

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41
Q

What P-gp SNP is a silent mutation?

A

C3435T

TT less active (impaired efflux)

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42
Q

P-gp:

3435TT

more or less drug gets into blood?

A

more

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43
Q

P-gp:

3435CC or 3435CT

more or less drug gets into blood?

A

less

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44
Q

What CYP2C19 genotype is UM?

A

*17

white 25%

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45
Q

What CYP3A4 genotype is UM?

A

1B, Por28

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46
Q

What CYP3A5 genotype is UM?

A

1/1

80% african American

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47
Q

What CYP2D6 genotype is UM?

A

duplication of gene

white 5%

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48
Q

How is fosphenytoin dosed?

A

phenytoin sodium equivalents (PE)

1PE = 1mg phenytoin sodium = 1.5mg fosphenytoin sodium

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49
Q

Which dosage forms of phenytoin have salt factor (S) of 0.92?

A

capsules and injection

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50
Q

Which dosage forms of phenytoin have salt factor (S) of 1?

A

suspension and chewable tabs

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51
Q

Is phenytoin highly protein bound?

A

yes

90%

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52
Q

What CYPs metabolize phenytoin?

A

2C9 and 2C19

95% hepatic

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53
Q

Non-Linear PK of phenytoin:

enzyme induction has what effect on Vmax?

A

increased Vmax

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54
Q

Non-linear PK of phenytoin:

hepatic cirrhosis has what effect on Vmax?

A

decreased Vmax

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55
Q

Non-linear PK of phenytoin:

competitive inhibition has what effect on KM?

A

increased Km

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56
Q

Non-linear PK of phenytoin:

decreased plasma protein binding has what effect on Km?

A

decreased Km

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57
Q

Do children have different Vmax and Km than adults for phenytoin?

A

yes

58
Q

What is phenytoin adult Vmax and Km?

A

Vmax: 7 mg/kg/day
Km: 4mg/L

59
Q

Which is relatively water insoluble?

phenytoin or fosphenytoin?

A

phenytoin

fosphenytoin water soluble

60
Q

Phenytoin IV injections should not exceed what rate?

A

50mg/min

risk of hypotension

61
Q

fosphenytoin max IV infusion rate is what?

A

150mg PE/min

100mg PE fosphenytoin = 100mg phenytoin sodium

62
Q

Which has more rapid absorption?

phenytoin capsules or tabs

A

tabs

multiple doses/day required

capsules extended release

63
Q

What is bioavailability of oral phenytoin?

A

100%

64
Q

Phenytoin loading dose?

A

15-20mg/kg

1000mg/day

65
Q

phenytoin maintenance dose?

A

children: 5-10mg/kg/day
adults: 4-6mg/kg/day (300-400max/day)
older adults: 200 mg/day max

66
Q

What is the “magic” dose for phenytoin?

A

there is no magic dose

67
Q

nystagmus occurs with what phenytoin conc.?

A

> 20ug/mL

68
Q

ataxia occurs with what phenytoin conc.?

A

> 30ug/mL

69
Q

seizures occur with what phenytoin conc.?

A

> 50-60ug/mL

70
Q

phenytoin therapeutic range (total con.)?

A

10-20ug/mL

71
Q

phenytoin unbound therapeutic range?

A

1-2ug/mL

72
Q

Low albumin causes of increased unbound phenytoin:

A 
liver disease
pregnancy
burns
trauma
malnourishment

can cause unbound phenytoin to be as high as 30-40%

73
Q

endogenous compound displacement causes of increased unbound phenytoin:

A

hyperbilirubinemia
jaundice
liver disease

can cause unbound phenytoin to be as high as 30-40%

74
Q

exogenous compound displacement causes of increased unbound phenytoin?

A

warfarin
valproic acid
aspirin (over 2g/day)
NSAIDs

can cause unbound fraction to be as high as 30-40%

75
Q

Units of phenytoin loading dose?

A

mg

76
Q

Units of phenytoin maintenance dose?

A

mg/day

77
Q

warfarin inhibits what two natural anticoagulants?

A

proteins C and S

also inhibits activation of coagulation factors VII, IX, X, II

78
Q

S-warfarin is metabolized by what CYP?

A

2C9

79
Q

R-warfarin is metabolized by what CYP?

A

3A4, 2C19

80
Q

What % of warfarin is protein bound?

A

99%

81
Q

Which clotting factor has longest half-life?

A

II

60 hours

82
Q

When is peak effect of warfarin reached?

A

72-96hrs (3-4 days)

83
Q

Why does antibiotic use with warfarin cause increased bleeding risk?

A

gut flora produce vitamin K2. When these bacteria are killed there is less K2 production. Since warfarin inhibits activation of vit. K, the less there is present, the more effective warfarin is

84
Q

grapefruit

increase or decrease warfarin effect?

A

increase

“F’s and G’s” increase
fish oil, ginkgo, fenugreek, garlic, grapefruit

85
Q

St. John’s wort

increase or decrease warfarin effect?

A

decrease

CYP inducers decrease:
St. John’s wort
smoking
vitamin K

86
Q

affects warfarin sensitivity?

2C9 or VKORC1?

A

VKORC1

more prevalent in asians

87
Q

What CYP inducing antibiotic decreases warfarin effect?

A

rifampin

other CYP inducers that decrease:
barbiturates, carbamazepine, phenytoin

88
Q

barbiturates

increase or decrease warfarin effect?

A

decrease

89
Q

carbamazepine

increase or decrease warfarin effect?

A

decrease

90
Q

phenytoin

increase or decrease warfarin effect?

A

decrease

91
Q

SMX/TMP

increase or decrease warfarin effect?

A

increase

92
Q

metronidazole

increase or decrease warfarin effect?

A

increase

93
Q

fluoroquinolones

increase or decrease warfarin effect?

A

increase

94
Q

azole antifungals

increase or decrease warfarin effect?

A

increase

95
Q

amiodarone

increase or decrease warfarin effect?

A

increase

96
Q

levothyroxine

increase or decrease warfarin effect?

A

increase

97
Q

steroids

increase or decrease warfarin effect?

A

increase

98
Q

fenofibrate/gemfibrozil

increase or decrease warfarin effect?

A

increase

99
Q

warfarin:

INR goal for mechanical mitral valve?

A

2.5-3.5

2-3 for VTE TX and prevention, and bioprosthetic valves, aortic valves

100
Q

What is a standardized prothrombin time that represents what you’d expect from a healthy adult pt?

A

international normalized ratio (INR)

higher than 1 = bleeding risk
lower than 1 = clotting risk

101
Q

How often is warfarin monitored if pt stable for 6+ months?

A

q 8-12 weeks

102
Q

How often is warfarin monitored initially?

A

q 2-3 days until INR achieved

then q 1-2 weeks until INR achieved x 2, then q 4 weeks until INR stable for 2 readings

103
Q

Do you give vitamin K if pts’s INR is <10 and they aren’t bleeding?

A

no

104
Q

anticoagulant reversal:

contains clotting factors, protein C and S, and heparin

A

PCC (Kcentra)

105
Q

anticoagulant reversal:

promotes synthesis of clotting factors?

A

vitamin K

do not use IM (causes hematoma)

106
Q

What do you give if warfarin pt has INR 10+ with major bleeding?

A

PCC

with or without vitamin K

107
Q

aminoglycoside BBW for?

A

ototoxicity
nephrotoxicity
pregnancy

108
Q

What is aminoglycoside spectrum?

A

gram (-) only

can be used for synergy against gram (+)

109
Q

are aminoglycosides bactericidal or bacteriostatic?

A

bactericidal

110
Q

are aminoglycosides concentration or dose dependent?

A

concentration

peak:MIC

111
Q

AG extended interval optimizes ___ dependent killing.

A

concentration

higher doses with more time in between

reduces toxicity by using PAE

uses nomogram to determine intervals

112
Q

AG synergy uses what kind of dosing?

A

weight based

1mg/kg IV q8h
gentamicin trough < 2
max 3mg/kg/day

113
Q

What kind of dosing is used for plazomicin?

A

extended interval

114
Q

What is preferred AG dosing strategy?

A

extended interval

Unless:
pregnant, ascites, or other fluid abnormality, changing renal fxn, CrCl < 20, or hemodialysis

115
Q

Extended interval dose for tobramycin/gentamicin?

A

7mg/kg

116
Q

Extended interval dose for amikacin?

A

15mg/kg

don’t forget to divide amikacin level by 2 to plot on nomogram!!

117
Q

infusion time for plazomicin?

A

30mins

other Ads 1hr

118
Q

population data for AG Vd calculation?

A

0.25-0.35L/kg

119
Q

population data for AG Ke calculation?

A

0.00293(CrCl) + 0.014

120
Q

Cap CrCl at what # for AG calculations?

A

120ml/min

121
Q

What weight is used for vanc dosing?

A

TBW

122
Q

What parameter determines effectiveness of vanc?

A

bioavailability

AUC:MIC

123
Q

What is goal AUC24 for vanc?

A

400-600 with MIC of 1

124
Q

AEs of vanc?

A

red man syndrome
nephrotoxicity
ototoxicity

125
Q

What Vd is used for vanc dosing?

A

0.7-0.8L/kg

126
Q

MSSA bacteria developed what mutation to become MRSA?

A

MecA

127
Q

Vanc population PK loading dose?

A

20-35mg/kg

TBW

128
Q

VAnc population PK maintenance dose?

A

15-20mg/kg

q8-12hrs
TBW

129
Q

Vanc population PK Ke calculation?

A

0.00083(CrCl) + 0.0044

130
Q

Bayesian modeling Vanc monitoring:

Collect how many levels after 1st and 2nd dose?

A

2

131
Q

2 level PK approximation Vanc monitoring:

Collect how many levels after 4th dose?

A

2

don’t forget to add up AUCs to tao 24 hrs in calculation

132
Q

indications for hemodialysis in ESRD pts: AEIOU

A 
acidemia
electrolyte abnormalities
intoxication (methanol, lithium, aspirin)
overload
uremia
133
Q

Are SCr and BUN reliable in hemodialysis?

A

no

accumulate in dysfunction

134
Q

what is sieving coefficient ?

A

how well drug is dialyzed

0 = does not cross
1 = freely crosses
135
Q

Vanc in renal replacement therapy, focus on what?

A

pre-dialysis serum conc.

136
Q

What is goal vanc. conc. in RRT?

A

15-20mg/L

137
Q

When to take vanc level with RRT?

A

day of dialysis prior to HD

138
Q

What is max dose of vanc in RRT?

A

3g

use TBW

139
Q

Administer vanc before or after HD?

A

after

140
Q

AG in RRT:

re-dose when level is less than 1?

A

pulse dosing

141
Q

Use what weight for AG RRT?

ABW, IBW, TBW

A

IBW

traditional dosing only

7343 PK Test 3 (1 decks)

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