GN 1.5.2

Question 1

Define pharmacogenomics.

Answer 1

Development of NEW DRUGS based on INCREASING KNOWLEDGE of all genes in the human genome

Question 2

What was the lesson the three patients treated with the same drug dosage (antileukemia, antihypertensive, oral anticoagulant)?

Answer 2

The three levels of effect (hyperactive, desired response, and hypoactive)

Question 3

What the four major cytochromes involved in drug metabolism?

Answer 3

CYP3A4, CYP2D6, CYP2C19, CYP2C9

Question 4

For a drug to be effective, a drug or toxicant must: (4 pharmacokinetic principles)

Answer 4

1) Reach target
2) Be in active form
3) Sufficient Concentration
4) Sufficient period of time

Question 5

In pharmacology, what are the three desires for the clinical decision?

Answer 5

Right drug, right dose, right patient

Question 6

In regards to metabolism of debrisoquine, most humans are? Less are? The least are?

Answer 6

Most: Extensive metabolizers
Less: Poor metabolizers (hint: LOF mutations more prevalent)
Least: Hyperactive metabolizers (GOF mutations rare)

Question 7

What are the two main studies of pharmacology?

Answer 7

Pharmacokinetics and pharmacodynamics

Question 8

What is significant about primiquine?

Answer 8

In the 1940s, AA soldiers had a different response to the drug than white soldiers (1st observed racial inheritance of drug-related metabolism)

Question 9

What is the process by which an environmental influence can increase/decrease the expression of drug metabolizing enzymes?

Answer 9

Induction

Question 10

In the FDA table of pharmacogenomic biomarkers of drug labels, there are 160 issues listed w/ 74 coming from drug metabolizing enzymes. Many of the drug metabolizing polymorphisms occur in what family of enzymes?

Answer 10

CYP

Question 11

Where are the CYPs most active?

Answer 11

Liver

Question 12

Increasing expression of drug metabolizing enzymes leads to what result on concentration of the drug?

Answer 12

Decrease concentration, faster elimination

Question 13

What is pharmacokinetics?

Answer 13

What patient does to the drug (dose leading to amount of drug at active site)

Question 14

What is a haplotype?

Answer 14

A haplotype is a group of genes within an organism that was inherited together from a single parent

Question 15

Why in Brazil (and increasingly more places around the world) is ethnicity no longer a good predictor of genetic predispositions?

Answer 15

Lack of Population Isolation

Question 16

The antihypertensive medication, debrisoquine, is metabolized by what CYP?

Answer 16

CYP2D6

Question 17

What is pharmacodynamics

Answer 17

What the drug does to the patient (the effects/mechanism of the drug)

Question 18

Define pharmacogenetics.

Answer 18

Study of heritability in drug responses

Question 19

In the case of the patient taking erythromycin in addition to terfenidine, why is the metabolism of terfenidine effected?

Answer 19

In this specific case, erythromycin inhibits CYP3A4 that is used to metabolize terfenidine.

Drugs can compete for/inhibit drug metabolizing enzymes

Question 20

What super family of membrane bound proteins plays a key role in drug metabolism?

Answer 20

CYP family

Question 21

Getting the right form to the right place in right amount. Requires the balance of what 4 biological mechanisms.

Answer 21

A - Absorption
D - Distribution
M - Metabolism
E - Excretion

Question 22

What is the expression of most variants of CYP2D6?

Answer 22

Diminished or no activity