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601 - Exam 2 > 4.11 - Pharmacogenomics > Flashcards

4.11 - Pharmacogenomics Flashcards

1
Q

Define pharmacogenomics

A

Study of the impact of genetic polymorphisms on drug response
- To personalize/individualize drug therapy

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2
Q

What does pharmacogenomics promise?

A

The possibility that knowledge of a patient’s DNA sequence could be used to enhance pharmacotherapy

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3
Q

___ are the most common gene variations associated w/ drug response

A

SNPs

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4
Q

Where can gene modifications occur?

A
  • In the gene
  • In the promoters
  • Enhancers
  • Splice sites
  • Sites that control gene transcription or mRNA stability
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5
Q

What types of variations are associated with pharmacokinetics?

A
  • Variation in enzymes of drug metabolism
  • Variation in transporters
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6
Q

What genetic variations are associated w/ pharmacodynamics?

A

Variation in drug targets

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7
Q

Pharmacodynamic and pharmacokinetic interactions have a ___ effect

A

Polygenic

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8
Q

Genetic variation in ___ affects HLA polymorphism

A

Immune system function

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9
Q

What are phase 1 and 2 of pharmacokinetics?

A
  • Phase 1 = oxidation/reduction enzymes
  • Phase 2 = conjugation enzymes
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10
Q

CYP2D6 converts codeine to

A

Morphine

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11
Q

In CYP2D6, ___ function is associated with increased toxicity

A

Increased

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12
Q

IN CYP2D6, decreased function is associated w/ ___

A

Decreased analgesia

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13
Q

Reduced function in thiopurine S-methyltransferase (TPMT) is associated w/

A

Increased thiopurine (azathioprine, 6-mercaptopurine, 6-thioguanine) toxicity

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14
Q

In CYP2D6, ultra-rapid metabolizer phenotype has what dosing recommendation?

A
  • Alternative analgesic
  • Increased formation of morphine following codeine admin leads to higher risk of toxicity
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15
Q

In CYP2D6, ___ metabolizer phenotype has a standard dosing rate

A

Extensive metabolizer phenotype

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16
Q

In CYP2D6, which metabolizer phenotype should you monitor closely for lack of analgesic response due to reduced morphine formation?

A

Intermediate metabolizer phenotype

17
Q

In CYP2D6, Poor metabolizer phenotype has what dosing recommendation?

A
  • Alternative analgesic
  • Reduce morphine formation following codeine administration
  • Avoid high doses
18
Q

CYP2C9 has what affected drug?

A

Warfarin

19
Q

Thiopurine S-methyltransferase has what affected drugs?

A

Azathioprine, mercaptopurine, and thioguanine

20
Q

CYP2D6 has what affected drugs?

A

Antidepressents
beta-adrenergic antagonists
Codeine
Debrisoquine
Dextromethorphan

21
Q

Genetic differences in ___ genes can dramatically alter drug disposition and response

A

Transporter

22
Q

Example of an organic anion transporter (OATP)1B1 encoded by the SLCO1B1 gene, that’s responsible for the hepatic uptake of many drugs

A

Statins

23
Q

Statins ___ cholesterol levels

A

decrease

24
Q

Examples of pharmacodynamics variation in drug targets

A
  • beta2-adrenergic receptor
  • some asthma patients don’t respond to 5-lipoxygenase inhibitor Zileuton
25
Q

Why is it difficult to predict warfarin an ideal dosing?

A

Genetic variations in both the drug receptor and drug metabolism

26
Q

Which 2 drugs undergo polymorphism that can affect patient response to warfarin?

A

CYP4F2 and CYP2C9

27
Q

Polymorphism in ___ leads to warfarin resistance or warfarin sensitivity phenotype

A

VKORC1

28
Q

Severe hypersensitivity reaction associated w/ the HLA-B*5701 allele in HIV patients taking ___

A

Abacavir

29
Q

What is abacavir?

A

A reverse transcriptase inhibitor

30
Q

Predrug testing for ___ nearly eliminates hypersensitivity reaction w/ abacavir

A

HLA-B*5701

31
Q

Genome-Wide Association Study (GWAS)

A

Analysis of complete genomes of a population of individuals w/ regard to the frequency of association of specific allelic variations w/ a specific phenotype

32
Q

SNPs analysis through GWAS can be used to predict ___

A

Predict patients who will have altered metabolism of statins, increasing the frequency of statin-induced myopathy

601 - Exam 2 (11 decks)

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