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PK > Final > Flashcards

Final Flashcards

1
Q

In pharmacodynamics, is the change in drug effect usually proportional to the change in drug dose or concentration?

A

No
-Drug concentrations often must reach certain threshold to exert pharmacologic effect, but provide diminishing returns at higher concentrations (toxicity)

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2
Q

Narrow therapeutic index drugs

A

Drugs in which small changes in dose may lead to therapeutic failure or toxicities.
Little separation between therapeutic and toxic doses
Subject to therapeutic drug monitoring based on PK/PD parameters.

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3
Q

Intersubject variability in narrow therapeutic index drugs

A

Low to moderate

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4
Q

Narrow therapeutic index drugs examples

A

Digoxin, warfarin, lithium, phenytoin, TAC/CSA, theophylline, most anti-infectives (aminoglycosides and Vanc)

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5
Q

Minimum inhibitory concentration (MIC)

A

Lowest antimicrobial concentration that prevents visible growth of a standard inoculum of organism after 24 hours of incubation under standard conditions.

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6
Q

Antibiotics with time dependent killing

A

Penicillins, cephalosporins, carbapenems, vanc, oxazolidinones, macrolides

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7
Q

Which Abx with time-dependent killing should you optimize time above MIC (time >MIC)

A

Penicillin
Cephalosporin
Carbapenem

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8
Q

Which Abx with time-dependent killing should you optimize AUC over MIC ratio?

A

Vanc
Oxazolidinones
Macrolides

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9
Q

Optimizing time over MIC (T>MIC)

A

Extending duration of infusion (continuous infusions) decreases peak concentrations, but extends time over MIC
In a continuous infusion T>MIC is about 100%

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10
Q

Area under the curve

A

Measure of the extent of exposure to a drug, taking into account clearance from the body.

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11
Q

Which antibiotics have concentration dependent killing?

A

Aminoglycosides
Lipopeptides
Lipoglycopeptides
FQs

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12
Q

Which antibiotics with concentration dependent killing should you optimize the peak/MIC ratio?

A

Aminoglycosides

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13
Q

Which antibiotics with concentration dependent killing should you optimize the AUC/MIC?

A

Lipoglycopeptides
Lipopeptides
FQs

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14
Q

PK parameters of vancomycin

A 
Abs- IV- complete; oral-poor
Vd- 0.7L/kg
Metabolism: >90% unchanged
Elimination: >90% urine
Protein binding- 55% protein bound
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15
Q

Serum concentration monitoring for Vanc

A

Trough concentrations:
10-15mcg/mL for UTI, skin/soft tissue infections
15-20mcg/mL for other infections
AUC/MIC >400

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16
Q

Vanc dosing loading dose

A

20-35mg/kg as a single dose (max 3000mg)
Consider in critically ill patients, patients receiving renal replacement therapy
Rapidly achieves targeted vanc concentration but does NOT lead to faster time to steady state.
Doses are based on ACTUAL body weight.

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17
Q

Renal replacement and the PK of vancomycin

A

Renal failure- reduced elimination of vanc
Hemodialysis- generally give a loading dose and maintenance dose after dialysis.
CRRT- give vanc every 12-24 hours

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18
Q

Limitations of the Ryback Nomogram for Vanc dosing

A

Only for adults with weight 50kg-110kg
Only for CrCl 40-110mL/min
Not validated in unstable conditions

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19
Q

AUC monitoring of Vanc

A

AUC/MIC is a PK/PD parameter that predicts clinical cure rate for severe MSSA and MRSA infections.
AUC/MIC >400 is the best way to ensure positive clinical outcomes
AUC/MIC <600 reduces toxicities

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20
Q

Aminoglycosides PK parameters

A

Abs- complete IV/IM
Distribution- highly hydrophilic, minimal penetration to CSF and ocular tissues
Metabolism/elimination- Primary unchanged, Eliminated in urine
Protein binding <30%

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21
Q

Aminoglycosides conventional dosing

A

Only used for synergistic dosing with beta-lactam in endocarditis.
1mg/kg IV Q 8 hrs
Goal peak: 3-5mg/L
Goal trough: <1mg/L

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22
Q

Aminoglycosides extended dosing interval

A 
Most patients with serious gram negative infections are treated this way
Gentamicin/tobramycin: 5-7mg/kg IV Q24 H
Peak: 15-30mg/dL
Goal trough <0.5mg/L
Drug free interval of 4-10 hours
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23
Q

Advantages of extended interval dosing

A

Optimization of PD parameters (Cmax/MIC)
QD dosing
Comparable cure rates
SImilar AE

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24
Q

Disease states affecting the PK/PD of aminoglycosides

A

Obesity
Renal dysfunction
Hemodialysis

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25
Q

Monitoring conventional dosing of aminoglycosides

A

Serum peak and trough concentrations at steady state (typically around 4-5 dose)
Peak: drawn 30-60 minutes after completion of aminoglycoside infusion (goal 3-5)
Trough- drawn 30 minutes prior to the next dose (goal <1)

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26
Q

Age and warfarin

A

Increasing age has been associated with an increase response to the effects of warfarin. People need lower doses of warfarin as they age.

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27
Q

Gender and warfarin

A

Men need higher warfarin doses than women

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28
Q

Weight and warfarin

A

Weight effects warfarin requirements in men.

Increasing BW= increasing warfarin dose

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29
Q

Warfarin drug interactions

A 
Amiodarone
Quinolones
Macrolides 
Metronidazole
Bactrim
Azole antifungals
30
Q

Comorbidities that affect warfarin

A

HF
Thyroid disorder
Liver disease
Diarrhea

31
Q

You need _____ warfarin in hyperthyroidism?

A

Less

32
Q

What are the factors that affect warfarin requirements?

A

Age, sex, DDI, diet, weight, smoking, alcohol, comorbidities, genetics

33
Q

Affect on warfarin: Acute exacerbation of HF

A

Decreases the metabolism of warfarin due to congestion in the liver

34
Q

Thyroid disease affects…..

A

Metabolism of clotting factors

One of the main AE of amiodarone is hyperthyroidism

35
Q

Pharmacogenomics and warfarin dose

A

Genetics, age, and BW account for up to 50% of variability in daily dosing requirements

36
Q

Genotype

A

Particular genetic pattern seen in the DNA of an individual

37
Q

Polymorphism

A

A difference in DNA sequence among individuals, groups, or populations
Can differ in a single nucleotide (SNP)

38
Q

Wild type

A

The form of the gene that occurs most frequently

39
Q

SNPs affecting warfarin

A

CYP4F2
GGCX
CALU

40
Q

CYP4F2 SNP affect on warfarin

A

Metabolizes vitamin K and takes it out of the cycle.
More sensitive to warfarin
A vitamin K oxidase

41
Q

GGCX SNP affect on warfarin

A

involves a carboxylation of Vitamin K dependent proteins

42
Q

CALU SNP affect on warfarin

A

A calcium binding protein that binds GGCX and inhibits the Vitamin K cycle
A single SNP associated with higher warfarin doses in AA and egyptians

43
Q

Warfarin metabolism

A

CYP2C9

44
Q

CYP2C9 polymorphisms in warfarin

A

CYP2C91- wild type
CYP2c92= leads to reduced enzymatic activity, less ability to metabolize S-warfarin, more sensitive to warfarin. Prolongs t1/2.
CYP2C9*3- can be homozygous or heterozygous. Results in a reduction in enzyme activity

45
Q

What do CYP2C9 SNPs mean?

A

Patient will require lower warfarin doses (most pronounced in *3 homozygous patients)
Pt will take longer to reach SS
Higher risk of bleeding, higher INR

46
Q

VKORC1 SNPs

A

Occur in promoter region of gene
Grouped into haplotypes (H)
H1 and H2= group A- require lower warfarin doses
H7, H8, and H9= group B- require higher warfarin doses

47
Q

VKORC1 SNPs what does it mean?

A

Patients with the group A haplocyte have less enzyme present and group B have more.
The require lower and higher doses of warfarin respectively.

48
Q

Should you genotype test for warfarin dosing?

A

Conflicting evidence supports, but is likely not cost effective
It may be considered

49
Q

Which polymorphism results in approx. 80% reduction in CYP2C9 activity?

A

CYP2C9 *3/3

50
Q

What SNP is associated with higher warfarin requirements?

A

VKORC1 B haplotype

51
Q

DOAC DDI

A

CYP3A4 and/or Pgp inducers decrease serum DOAC levels and increase thrombotic risk
CYP3A4 and/or Pgp inhibitors increase serum DOAC levels and increase bleeding risk

52
Q

Which DOAC do you use in the presence of an inducer?

A

None, avoid all DOACs

53
Q

Which DOAC to avoid in the presence of a Pgp inhibitor?

A

Dabigatran and Edoxaban

54
Q

Which DOAC to avoid in the presence of Pgp and strong CYP3A4 inhibitors?

A

Apixaban, Rivaroxaban

55
Q

Monitoring of dabigatran

A

aPTT

56
Q

Monitoring of apixaban, rivaroxaban, edoxaban

A

Anti-Xa levels

57
Q

When do you monitor DOACs?

A 
Patient undergoing urgent surgical procedures
CKD dialysis
Drug interactions
Severely obese patients
Assessment of pt adherence
58
Q

Which DOAC has the greatest renal elimination?

A

Dabigatran

59
Q

Which clotting assay is best to measure exposure to apixaban?

A

Anti-Xa

60
Q

Which clotting assay is best to measure exposure to dabigatran?

A

Ptt

61
Q

What are the substrates for rivaroxaban?

A

Pgp and 3A4

62
Q

Factors influencing PK of heparin

A 
Age
Gender
Body weight
Thromboembolic disease
Smoking
Hepatic function
Renal function
63
Q

AT is a 52 year old who is admitted to the hospital for acute DVT. She weighs 152 pounds and all labs are normal. What is appropriate dose of heparin at 25000units/250mL

A

5600 at 13ml/hr

64
Q

When do you check PTT for UFH

A

6 hours

65
Q

What is the therapeutic anti-Xa peak level for enoxaparin 80mg SQ Q12H? Pt weighs 172 pounds

A

0.5-1units/mL

66
Q

Drug therapy options for cancer treatment?

A

Chemotherapy
Immunotherapy
Targeted therapy
Other

67
Q

What is one of the big toxicities we see with chemotherapy?

A

Because it targets rapidly dividing cells, it destroys cells in the GI tract. Diarrhea is common.

68
Q

Classic chemotherapy

A

Cell cycle dependent- schedule dependent

Cell cycle independent- concentration dependent

69
Q

Are cancer cells different than healthy cells?

A

Yes

They have driver mutations that cause uncontrolled cell growth

70
Q

What do we target in anticancer therapy?

A

The pathways, not necessarily the direct mutation

71
Q

The higher the dose you give, the ______ the cell kill

A

Higher until the point where there is no more benefit

PK (1 decks)

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