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Therapeutics > Therapeutic Drug Monitoring > Flashcards

Therapeutic Drug Monitoring Flashcards

1
Q

Drug response variability occurs due to:

A

1) Pharmacokinetics: Variation in absorption, distribution, metabolism or excretion

2) Pharmacodynamics: Variation at/or beyond tissue receptors or other macromolecular drug targets

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2
Q

What is the continuous variable that must be monitored when dosing?

A

Biological response;

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3
Q

What is the biological response to a drug closely linked to?

A

Desired therapeutic outcome of a drug

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4
Q

Drug monitoring is needed to reduce the risk of:

A

A clinical event (stroke, heart attack, pulmonary
embolism, etc.).

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5
Q

What biological response is monitored when taking antihypertensive drugs?

A

Blood pressure

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6
Q

What biological response is monitored when taking statins?

A

Serum cholesterol

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7
Q

What biological response is monitored when taking Warfarin?

A

International Normalized Ratio (INR)

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8
Q

Is there always a continuous variable to monitor?

A

No

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9
Q

How can you identify pharmacokinetic variability?

A

By measuring drug concentrations in plasma or serum

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10
Q

Measuring drug concentrations in plasma or serum may usefully guide:

A

Dose adjustment

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11
Q

What is therapeutic drug
monitoring?

A

Measuring drug concentrations in plasma or serum in order to guide dose adjustment.

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12
Q

Measurements of drug concentrations in plasma are most useful when:

A

1) There is a direct relationship between plasma concentration and pharmacological or toxic effect, and a therapeutic range has been established. (Different dose = bad)

2) Drug effect can NOT readily be assessed quantitatively by clinical observation.

3) Inter-individual variability in plasma drug concentrations from the same dose is large

4) Narrow/low therapeutic index

5) Polypharmacy with anticipation of serious interactions

6) When drug “isn’t working”: “Apparent resistance” to the action of a drug needs an explanation. (when non-compliance is suspected)

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13
Q

Which drugs have an established therapeutic range that shouldn’t be messed around with?

A

1) Drugs that act via active metabolites
2) Drugs with irreversible actions

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14
Q

What could restrict the usefulness of plasma
concentrations measurement?

A

Tolerance

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15
Q

Which drug has a very high inter-individual variability?

A

Phenytoin

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16
Q

Low therapeutic index means:

A

Ratio of toxic concentration/effective concentration is < 4

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17
Q

What is a non-pharmacological reason for therapeutic
drug monitoring?

A

Clinical toxicology purposes (Poisoning)

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18
Q

Drug concentration at the site of action is related to:

A

Drug effect

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19
Q

Drug effect should be proportional to:

A

Plasma drug concentration

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20
Q

A constant tissue to plasma drug concentration ratio only occurs during:

A

The terminal β-phase of
elimination

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21
Q

When does the plasma concentration NOT reflect the concentration at the site of action accurately?

A

Early on in the dosing interval (If you JUST gave the patient his meds, for example)

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22
Q

When should the therapeutic drug monitoring measurements be made?

A

When distribution of the drug has been completed.

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23
Q

What thing is CRITICAL for the therapeutic drug monitoring measurement to be useful?

A

Timing of blood sampling

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24
Q

Should you do routine or random blood sampling when therapeutic drug monitoring?

A

NO

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25
Q

When is blood sampling useful?

A

When the drug concentration reaches a steady-state

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26
Q

When is a blood sample taken if you are repeatedly dosing a patient?

A

Just before the next dose to assess the ‘trough’ concentration

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27
Q

What is the trough concentration?

A

The concentration of drug in the blood immediately before the next dose is administered

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28
Q

What is the peak concentration?

A

Highest level of a medication in the blood

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29
Q

How is the peak concentration determined?

A

By taking a blood sample after distribution has been completed

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30
Q

Advice on the interpretation of information obtained by measurement of serum drug
concentration should be obtained from:

A

A local therapeutic drug-monitoring service (clinical pharmacology and/or clinical pharmacy departments)

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31
Q

Plasma drug concentrations must always be interpreted in the context of:

A

The patient’s clinical state

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32
Q

WHAT DONT WE LIKE WHEN BLOOD SAMPLING?

A

RANDOM MEANINGLESS BLOOD SAMPLING

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33
Q

What is the optimum sampling time for Digoxin?

A

1) Trough
OR
2) >8 hours post-dose

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34
Q

Time to steady state for Digoxin?

A

7-10 days

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35
Q

What is the optimum sampling time for Lithium?

A

> 12h post-dose

36
Q

Time to steady state for Lithium?

A

3-7 days

37
Q

What is the optimum sampling time for Clozapine?

A

Trough

38
Q

Time to steady state for Clozapine?

A

5-7 days

39
Q

What is the target clozapine/norclozapine ratio for Clozapine?

A

1.3

40
Q

What are the aminoglycoside antibiotics?

A

1) Gentamicin
2) Amikacin
3) Tobramycin
4) Neomycin
5) Streptomycin

41
Q

What is the optimum sampling time for aminoglycoside abx?

A

1) Peak: 1hr post-dose (30-60)
2) Trough

42
Q

What is extended-interval aminoglycoside therapy?

A

Aminoglycoside abx given once daily

43
Q

Time to steady state for aminoglycoside antibiotics?

A

10-15hrs with normal renal function

44
Q

What is the optimum sampling time for Vancomycin?

A

1) Peak: 1hr post-dose (30-60min)
2) Trough

45
Q

Time to steady state for Vancomycin?

A

20-35hrs with normal renal function

46
Q

Teicoplanin is an antibiotic used against:

A

Gram-positive bacteria

47
Q

What is the optimum sampling time for Teicoplanin?

A

Trough

48
Q

Time to steady state for Teicoplanin?

A

14 days or more

49
Q

Phenytoin has ___(linear/non-linear) pharmacokinetics?

A

Non-linear pharmacokinetics

50
Q

Non-linear pharmacokinetics means:

A

Dose-dependent

51
Q

What can affect the pharmacokinetics of Phenytoin?

A

Concurrent renal or hepatic disease

52
Q

What can affect the distribution of Phenytoin?

A

Pregnancy

53
Q

Which lab value is necessary for
appropriate interpretation of Phenytoin concentration?

A

Serum albumin concentration

54
Q

What is the optimum sampling time for Phenytoin/Fosphenytoin?

A

1) If steady state: Any (long half-life)
2) If short-term (Fosphenytoin): Trough

55
Q

Time to steady state for Phenytoin/Fosphenytoin?

A

2-6 days

56
Q

What is the optimum sampling time for Carbamazepine?

A

Trough

57
Q

Time to steady state for Carbamazepine?

A

2-6 days

58
Q

What is the optimum sampling time for Ethosuximide?

A

Trough

59
Q

Time to steady state for Ethosuximide?

A

5-15 days

60
Q

What is the optimum sampling time for Lamotrigine?

A

Trough

61
Q

Time to steady state for Lamotrigine?

A

5-7 days

62
Q

What is the elimination half-life of Lamotrigine?

A

20-35hrs

63
Q

Is the elimination half-life of Lamotrigine longer or shorter in children?

A

Shorter

64
Q

What is the elimination half-life of Lamotrigine when given with enzyme inducers?

A

15hrs

65
Q

What is the elimination half-life of Lamotrigine when given with Valproate?

A

60hrs

66
Q

What is the optimum sampling time for Valproate?

A

Trough

67
Q

Time to steady state for Valproate?

A

3-7 days

68
Q

Protein binding for valproate is normally:

A

95%

69
Q

If you increase the dose of valproate, protein binding will become:

A

80%

70
Q

What is the optimum sampling time for Zonisamide?

A

1) Any (long half-life)
2) Trough (advised)

71
Q

Time to steady state for Zonisamide?

A

2 weeks

72
Q

Plasma concentration of Methotrexate is an important predictor of:

A

Toxicity

73
Q

What should be given with Methotrexate to avoid toxicity?

A

Folinic acid

74
Q

What is the optimum sampling time for Methotrexate?

A

24, 48, and 72hrs post high-dose therapy

75
Q

Time to steady state for Methotrexate?

A

1-2 days of chronic low dosing

76
Q

What are some immunosuppressants?

A

1) Cyclosporine
2) Sirolimus
3) Tacrolimus
4) Mycophenolate

77
Q

What is a common problem in children taking Cyclosporine?

A

Compliance

78
Q

Deterioration in post-transplant renal function in patients taking Cyclosporine can reflect either:

A

1) Graft rejection due to
inadequate cyclosporine concentration
2) Toxicity from excessive concentrations

79
Q

Sirolimus use should be monitored, especially when:

A

1) Used with Cyclosporine
2) There is hepatic impairment
3) During or after treatment with inducers or inhibitors of drug metabolism

80
Q

What is the optimum sampling time for Cyclosporine?

A

1) Trough
2) 2hrs post-dose

81
Q

Time to steady state for Cyclosporine?

A

2-6 days

82
Q

What is the optimum sampling time for Sirolimus?

A

Trough

83
Q

Time to steady state for Sirolimus?

A

5-7 days

84
Q

What is the optimum sampling time for Tacrolimus?

A

Trough

85
Q

Time to steady state for Tacrolimus?

A

2-5 days

86
Q

What is the optimum sampling time for Mycophenolate?

A

Trough

Therapeutics (23 decks)

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