Pharmacogenetics

Question 1

Drug Response Phenotypes

Answer 1

Differences in:
- Metabolism
- Transport
- Drug Target

Question 2

Type of genetic variation

Answer 2

• Copy number variation
• Indel
• Single nucleotide polymorphism (SNP)

Question 3

Genetic variations in metabolism lead to

Answer 3

• Changes in bioavailability and/or clearance
• Can result in differences in response and/or toxicity

Question 4

Genetic variations in transport lead to

Answer 4

• Changes in bioavailability, biliary or renal elimination
• Changes in drug distribution and tissue uptake
• changes in response and/or toxicity

Question 5

Genetic variations in drug target lead to

Answer 5

Changes in concentration-response relationship

Question 6

Types of genetic variation

Answer 6

• Duplications/copy number variations (CNV)
• Indels
• Single nucleotide substitutions (SNPs)

Question 7

Duplications/copy number variations (CNV)

Answer 7

increase or decrease in function

Question 8

Indels

Answer 8

• usually decreased function, often frameshift

Question 9

insertions and deletions

Answer 9

genetic mutations that involve the insertion or deletion of one or more nucleotides (the building blocks of DNA) in a DNA sequence. These mutations can have significant effects on genes and their functions.

Question 10

Single nucleotide substitutions (SNPs)

Answer 10

usually decreased function (if any); most common variation

Question 11

Missense mutation

Answer 11

SNP causes amino acid substitution

Question 12

Nonsense mutation

Answer 12

SNP causes a premature stop codon, leading to a shortened, and likely nonfunctional, protein

Question 13

Silent mutation

Answer 13

SNP has no effect on amino acid

Question 14

Pharmacogenomics

Answer 14

you’re looking at the genetic material as a whole and how it affects drug’s response

Question 15

Pharmacogenetics

Answer 15

you’re taking into consideration only one gene and how it effects the response to drugs

Question 16

Deletion of an entire gene which encodes for CYP2D6

Answer 16

• Metabolism
• CNV

Question 17

A change which results in a premature stop codon, leading to a nonfunctional OATP1B1

Answer 17

• transport
• SNP

Question 18

A duplication of a gene which results in a high-functioning beta-adrenergic receptor

Answer 18

• drug target
• CNV

Question 19

An insertion which results in a frameshift of the gene that encodes for CYP2C9

Answer 19

• metabolism
• indel

Question 20

A mutation in a gene for OCT1 which results in one amino acid change from pro → lys

Answer 20

• transport
• SNP

Question 21

Deletion of an entire gene which
encodes for CYP3A4

CL, F, Efficacy, Toxicity

Answer 21

• Decrease clearance
• Increase Bioavailability
• Increase Efficacy
• Increase Toxicity

Question 22

Duplication of a gene which leads to an increased expression of the P-gp transporter

Answer 22

• Increase Clearance
• Decrease Bioavailability
• Decrease Efficacy
• Decrease Toxicity

Question 23

A mutation which renders the insulin receptor inactive

Answer 23

• No effect on Clearance
• No effect on Bioavailability
• Decrease Efficacy
• No effect on Toxicity

Question 24

Why are Pgx data important for pharmacists?

Answer 24

We need to consider ancestral genetic variations in drug dosing recommendations

Question 25

Explain to a health professional how CPIC guidelines could be applied to drug therapy decisions

Answer 25

• Clinicians would receive a patient’s genetic variability report whenever a drug needs to be ordered in order to be made aware and get ahead of efficacy/toxicity issues.
• The guidelines try to have clinicians understand HOW available genetic test results should be used to optimize drug therapy, NOT WHETHER tests should be ordered.
• The goal is to teach clinicians how to use a patient’s genotype to optimize drug therapy.