Week 2: Pharmacogenomics

Question 1

Pharmacogenomics

Answer 1

the study of the effects of genetic differences among people and the impact that these differences have on the uptake, effectiveness, toxicity, and metabolism of drugs

Question 2

Pharmacogenetics

Answer 2

the study of the influence of hereditary factors on the response of individual organisms to drugs

Question 3

Genetic polymorphism

Answer 3

Multiple differences of a DNA sequence found in at least 1% of the population -occurs when differences in an allele or allele responsible for the variation is a common occurrence

Question 4

Poor metabolizers (PMs)

Answer 4

lack a working enzyme or decreased expression of an enzyme - exhibits decreased metabolism of drugs

Question 5

Intermediate metabolizers (IMs)

Answer 5

heterogeneous for one working, wild-type allele and one mutant allele (or two reduced-function alleles)

Question 6

What are the clinical implications for patients that are poor or intermediate metabolizers

Answer 6

• prodrugs will be metabolized slowly into active metabolite - may have accumulation of the prodrug
• active drug will be metabolized slowly into inactive metabolite
• potential for accumulation of the active drug
• patient requires lower dosage of medication

Question 7

Extensive metabolizers (EMs)

Answer 7

have two normally functioning alleles

Question 8

Ultrarapid metabolizers (UMs)

Answer 8

have more than one functioning copy of a certain enzyme

Question 9

What are the clinical implications for patients that are ultrarapid metabolizers?

Answer 9

• prodrugs will be rapidly metabolized into the active drug - no dosage adjustment is needed
• active drug is rapidly metabolized into inactive metabolites leading to potential therapeutic failure - patient requires higher dosage of an active drug

Question 10

Your patient is known to be an ultrarapid metabolizer. He is given Tylenol #3 following a back injury he got lifting boxes while moving. What is important to know about patients with this metabolic variance and Codeine?

Answer 10

UMs rapidly metabolize Codeine into morphine using the CYP2D6 enzyme following codeine administration, leading to a higher risk of toxicity- these patients will most likely not experience the analgesic effects of the drug at normal therapeutic doses, but could have toxic side effects such as respiratory depression

Question 11

If a patient is a poor metabolizer using the CYP2D6 enzyme, should Codeine be used for an analgesic?

Answer 11

No - because codeine is metabolized by the CYP2D6 enzyme, the metabolism of codeine into morphine is greatly reduced leading to insufficient pain relief