Pharmacogenomics

Question 1

What is pharmacogenomics?

Answer 1

How genetics affects response to drugs

Question 2

In the normal curve, what groups are on the far left?

Answer 2

Poor Metabolizers

Excellent Responders

Question 3

In the normal curve, what groups are in the middle?

Answer 3

Good Metabolizers

Normal Responders

Question 4

In the the normal curve, what groups are on the far right?

Answer 4

Ultra Metabolizers

Poor Responders

Question 5

Mutation

Answer 5

It is an alteration of DNA sequence that is present only rarely in the population

Question 6

Polymorphism

Answer 6

It is an alteration of DNA sequence that is present commonly in the population (>1% of the population)
- difference between mutation and polymorphism lies only in the frequency of occurrence

Question 7

What is a SNP?

Answer 7

Single Nucleotide Polymorphism (SNP) - a polymorphism due to a change in a single nucleotide

Question 8

ADR

Answer 8

Adverse Drug Reaction

Question 9

What are the two genetic factors that affect an individuals response to a drug?

Answer 9

• Drug Metabolism Enzymes

- Drug Receptor Enzymes

Question 10

What part of metabolism is CYP2D6 a part of and what types of drugs does it affect?

Answer 10

Phase I Enzyme

Debrisoquine and sparteine

Anti-depressants (Tricyclics)
Anti-arrhythmics,
Beta-blockers
Neuroleptics

Question 11

What part of metabolism is CYP2C9 a part of and what types of drugs does it affect?

Answer 11

Phase I Enzyme

Warfarin - mutations can cause danger for excessive bleeding

Tolbutamide
Phenytoin
Nonsteroidal anti-inflammatories

Question 12

What do mutations in VKORC1 affect?

Answer 12

Warfarin as it is a key warfarin drug target

Question 13

What part of metabolism is CYP2C19 a part of and what types of drugs does it affect?

Answer 13

Phase I Enzyme

Clopidogrel (Plavix) - prodrug converted to active metabolite and patients with CYP2C19 are unresponsive to clopidogrel

Question 14

What part of metabolism is N-Acetyltransferase 2 a part of and what types of drugs does it affect?

Answer 14

Phase II Enzyme

There is a slow acetylator phenotype that causes poor conjugation leading to the danger of increased toxicity.

Question 15

Directly hereditary diseases

Answer 15

Diseases whose origin is in the genome itself.

Examples:

Huntington’s Chorea (autosomal dominant) 
Cystic fibrosis (autosomal recessive)

Question 16

Environmentally dependent diseases

Answer 16

Have a genetic disease that is influenced by genetic factors that will increase a person’s susceptibility to diseases if they are exposed to the proper environments.

Examples:

Type II diabetes mellitus
Parkinson’s disease
Hypertension – 50 different genes
Alzheimer’s disease (late-onset; Cholesterol genes – ApoE) 
Cancer

Question 17

What are pharmacogenomic therapies and what are examples of them?

Answer 17

Hormones can now be routinely synthesized in the laboratory in mass production – recombinant protein hormones used as therapeutic agents.

Example: Epogen (erythropoietin) - used to treat chronic kidney failure on dialysis

Question 18

How can pharmacogenomics be useful in clinical trials?

Answer 18

Use pharmacogenetic data to determine who would be good responders

Question 19

What population responds well to hydralazine?

Answer 19

African Americans

Question 20

PCR

Answer 20

Polymerase Chain Reaction

-Used for DNA amplification

Question 21

FISH

Answer 21

Fluorescent in situ Hybridization

-Identify gene location on chromosome

Question 22

How was Her2-Neu used to individualize cancer treatment?

Answer 22

Patients with Her2 amplification are treated with Herceptin (trastuzumab)

Question 23

How is Bcr-Abl used to individualize leukemia treatment?

Answer 23

Gleevec (imatinib) - inhibits Bcr-Abl tyrosine kinase and is used on patients with abnormal karyotype showing a chromosomal rearrangement due to a translocation
designated t(9;22)