Pharmacogenomics

Question 1

What are adverse drug reactions?

Answer 1

Negative/undesirable effects of drug treatment.

Question 2

What contributes towards differential responses to medications?

Answer 2

Pharmacogenomic, demographic factors, clinical factors, dosing factors, other factors.

Question 3

How does ancestry impart ADR?

Answer 3

Ancestry; genetic factors and environmental factors.

Question 4

What are two examples of ethnic effects on ADR?

Answer 4

1. Black people increased risk of heart failure from hydralazine.
2. East asian descent alcohol metabolism.

Question 5

How do sex differences contribute to ADR?

Answer 5

Women are underrepresented in drug trials, although physiologically different.

Question 6

How does age impact ADR?

Answer 6

Drug metabolism and elimination is less efficent in extremes, changes in body composition as well as polypharmacy.

Changes in gene expressions for CYPS

Question 7

What age group is GFR lower in?

Answer 7

Elderly and neonates.

Question 8

What is a regulatory variation?

Answer 8

Mutation on regulatory site, causes increased for decreased expression.

Question 9

What is coding variation?

Answer 9

Mutation in coding site: SNP or translocations.

Question 10

What are splice-site variations?

Answer 10

Mutations at splice sites; create or abolish acceptor/donor sites.

Question 11

What is expression quantitative loci?

Answer 11

Variations causing changes in downstream (cis) genes or genes elsewhere (trans)

Question 12

What is the key determinant to a drug response?

Answer 12

Genetics

Question 13

What is precision health?

Answer 13

Taking genetic and non-genetic factors into account during prescription and administration

Question 14

What is CYP2D6?

Answer 14

Pharmacogene that is a metabolizing enzyme, has MANY polymorphisms.

Question 15

What must be done before the administration of codeine to pregnant/nursing women?

Answer 15

Test for CYP2D6 polymorphisms.

Question 16

What is the result of CYP2D6 duplication?

Answer 16

Ultra fast metabolism

Question 17

What is the result of CYP2D6 deletion?

Answer 17

Ultra slow metabolism

Question 18

How many individuals will carry clinically relevant pharmacogenomic variants?

Answer 18

97%

Question 19

What are important clinical considerations for pharmacogenomic biomarkers and clinical implementation?

Answer 19

Results must be replicated

There must be robust ADR phenotyping when obtaining clinical data

The risk of ADR must be clinically relevant

Question 20

What are clinical practice guidelines?

Answer 20

CPIC; standardize peer-reviewed consortium that grades evidence and clinical reccommendation

Question 21

What is the survival rate of childhood cancer?

Answer 21

80%

Question 22

What is cisplatin-induced hearing loss?

Answer 22

Hearing loss due to treatment of solid tumors, affects language and social development and causes permanent bilateral hearing loss.

Question 23

What is the risk of cisplatin-induced hearing loss?

Answer 23

40-60%

Question 24

What was discovered to be a pharmacogene causing cisplatin-induced hearing loss?

Answer 24

TCERG1L

Question 25

How does TCERG1L interact with cisplatin?

Answer 25

Linked to pro-inflammatory cisplatin toxicity.

Question 26

What is the adverse effect associated with chemotherapy?

Answer 26

Myelosuppression

Question 27

What is thiopurine used in the treatment of?

Answer 27

Cancer and autoimmune diseases

Question 28

What is the mechanism of thiopurine?

Answer 28

Purine antagonist (inhibits synthesis); cytotoxic.

Question 29

What is the ADR of mercaptopurine (6-MP)?

Answer 29

Hematological toxicity

Question 30

What pharmacogene does 6-MP interact with?

Answer 30

TPMT and NUDT15 gene.

Question 31

What is the TPMT gene?

Answer 31

Catabolized thiopurines.

Question 32

What is the NUDT gene?

Answer 32

Metabolizes cytotoxic thioguanine nucleotides.