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I&I WC1 > Clinical Pharmacology I - Pharmacogenetics > Flashcards

Clinical Pharmacology I - Pharmacogenetics Flashcards

1
Q

Which factors influence the dose of a drug that a patient receives?

A
  • Absorption
  • Metabolism
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2
Q

What is pharmacogenetics?

A

DNA analysis to explain/predict the response of a patient to drug therapy

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3
Q

Which factors affect the blood concentration and therefore the effect of a drug? (2)

A
  • Receptors
  • Effectors
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4
Q

Which path do drugs travel through the body?

A

Ingestion → intestine → blood → liver → blood → urine

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5
Q

What determines the liver metabolizing capacity?

A

Cytochrome P450 enzymes

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6
Q

How many percent of all hospitalizations are due to Adverse Drug Reactions?

A

5-7%

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7
Q

What defines the therapeutic window?

A

Range of doses at which the drug is effective in producing the desired therapeutic effect while minimizing adverse effects.

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8
Q

Which CYP enzymes are mainly involved in metabolizing drugs? (4)

A
  • CYP3A4
  • CYP2D6
  • CYP2C9
  • CYP2C19
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9
Q

What kind of drugs are metabolized by CYP3A4?

A
  • Oncology drugs
  • Psychiatric drugs
  • Cyclosporin, tacrolimus
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10
Q

What kind of drugs are metabolized by CYP2D6?

A
  • Anti-depressives
  • Antipsychotics
  • Beta-blockers
  • Tamoxifen
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11
Q

What kind of drugs are metabolized by CYP2C9?

A

Anti-coagulation drugs

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12
Q

What kind of drugs are metabolized by CYP2C19?

A
  • Anti-depressives
  • Clopidogrel
  • Proton pump inhibitors
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13
Q

Which types of metabolizers exist? (4)

A
  • Ultrarapid metabolizer (UM)
  • Normal metabolizer (NM)
  • Intermediate metabolizer (IM)
  • Poor metabolizer (PM)
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14
Q

What does an Ultra-Rapid metabolizer have genome-wise?

A

An extra copy of CYP2D6

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15
Q

Which CYP2D6 variant alleles are most abundant in the African American population?

A
  • 2850C>T
  • 1023C>T
  • Gene duplication
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16
Q

Which CYP2D6 variant alleles are most abundant in the Caucasian population?

A
  • 2850C>T
  • 1846G>A, 100C>T
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17
Q

What could be a probable reason for the increase of CYP2D6 gene duplication when you travel further down the South (towards Africa)?

A

Diet changes, probably has detoxifying purposes

18
Q

You are seeing a patient that complains that the antidepressivum nortripyline you prescribed him 3 months ago, does not have any affect. What could be the possible causes of this? (2)

A
  • Non-compliance
  • CYP2D6 ultra rapid metabolism
19
Q

What could be the cause of (severe) side-effects?

A

Poor metabolizing

20
Q

What are the dosing guidelines for metoprolol?

A

UM: 250% of standard dose
IM: 50% of standard dose
PM: 25% of standard dose

21
Q

Which CYP enzyme metabolizes tramadol?

A

CYP2D6

22
Q

Which CYP enzyme inactivates antidepressants such as imipramine and metoprolol?

A

CYP2D6?

23
Q

Name two immunosuppressants that play a role in pharmacogenetics

A
  • 6-Mercaptopurine
  • Azathioprine
24
Q

How many percent of the population is deficient in CYP2D6?

A

5-10%

25
Q

Which kind of therapies can benefit the most from CYP2D6 genotyping?

A

Antidepressant therapy

26
Q

How many percent of the population is an intermediate metabolizer of TPMT?

A

11%

27
Q

What is the dosing guideline for an intermediate metabolizer of TPMT?

A

50% of the standard dose

28
Q

Which treatment can benefit form TMPT genotyping?

A

Azathioprine treatment

29
Q

Which patients material can you obtain to perform a genetic analysis on?

A
  • EDTA blood
  • Cheekswab
30
Q

Name an anti-coagulation drug which is being metabolized by CYP2C19?

A

Clopidogrel

31
Q

Which enzyme inactivates voriconazol?

A

CYP2C19

32
Q

What are the most important inactive alleles of CYP2C19?

A

*2, *3

33
Q

What is the most hyperactive allele of CYP2C19?

A

*17

34
Q

How many percent of the caucasian population is an ultra-rapid metabolizer of CYP2C19 and which mutation is most common?

A

6%, 1717

35
Q

What can be said about the metabolism and trough concentrations of voriconazol in ultra-rapid and rapid metabolizers?

A
  • Increased metabolism
  • Low trough concentrations
36
Q

What can be said about the metabolism and trough concentrations of voriconazol in poor metabolizers?

A
  • Reduced metabolism
  • High trough concentrations
37
Q

True or False: “The risk of getting adverse side effects is highest when you are a poor metabolizer of voriconazole.”

A

True. Caused by high trough concentrations

38
Q

Which CYP enzymes metabolize tacrolimus?

A

CYP3A4 and CYP3A5

39
Q

What can be said about the CYP3A5 expression between individuals?

A

It varies
- Caucasians: 80% non-expresser
- Africans: 30% non-expresser

40
Q

How do you adjust the tacrolimus dose for CYP3A5 expressers?

A

Significantly increase it

41
Q

Why do you have to increase the tacrolimus dose for CYP3A5 expressers?

A
  • CYP3A5 inactivates tacrolimus
  • Most individuals (80%) are a CYP3A5 non-expresser
42
Q
A

I&I WC1 (25 decks)

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