Pharmacogenetics and Pharmacogenomics- Lecture 50 Flashcards

1
Q

Define pharmacogenetics.

A

study of drug responses in relation to genetic variation in specific candidate genes

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2
Q

Define pharmacogenomics.

A

study of drug response in relation to genetic variation in the entire genome

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3
Q

What are ADME genes?

A

genes that are involved in the absorption, distribution, metabolism, or excretion of a drug
influence pharmacokinetic aspects of drug metabolism

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4
Q

What are the two pharmacokinetic phases?

A
phase 1 (oxidation, reduction, hydrolysis)
phase 2 (conjucation by a variety of biotransformation processes - acetylation, glucoronidation, sulfation, methylation)
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5
Q

Describe the genotype nomenclature for the P450 system.

A
CYP2C19*2
(CYP) - superfamily
(2)- family
(C)- subfamily
(19)- isoform
(*2)- allele
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6
Q

Describe the phenotype nomenclature for the P450 system.

A

Extensive (normal) metabolizers- 1* and 1*
Intermediate metabolizers- 1* and 2*
Poor metabolizers- 2* and 2*
(where 2* can be any loss of function mutation)

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7
Q

Provide examples of genes involved in metabolism of common medications.

A

VKORC1
CYP2C19
CYP2D6

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8
Q

What genes are associated with metabolism of clopidogrel?

A

inactive prodrug to active drug
CYP2C19 codes for enzymes aiding in processing of this in the liver (once the 15% is imported after the bottleneck)
loss of function mutations result in reduced efficiency and decreased likelihood to benefit from this treatment

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9
Q

What genes are associated with the metabolism of codeine?

A

metabolized to morphine via enzymes coded for by the CYP2D6 gene
gain of function mutations (resulting in UM) –> concerns for toxicity
loss of function mutations (resulting in PM) –> concerns for reduced efficacy

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10
Q

What genes are associated with the metabolism of TCAs and SSRIs?

A

both CYP2D6 (UM mutatants concern for toxicity) and CYP2C19

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11
Q

What are the challenges for implementation of PGx in clinic?

A

genotype/phenotype relationships are not always clear cut
cost (reimbursement is sporadic)
need for fast results
post-testing counseling

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