Pharmacogenomics

Question 1

pharmacogenomics

Answer 1

• the study of how an individual’s genetic inheritance affects the manner in which they respond to drugs
• goal= greater efficacy and safety

Question 2

diagnostic goals of pharmacogenomics

Answer 2

-identify genomic, genetic, and proteomic data

Question 3

therapeutic goals

Answer 3

• predict and avoid adverse drug reations

- increase probability for positive clinical outcomes (medicine selection, dosage regimen, and targeted therapy)

Question 4

four general areas of pharmacogenomics

Answer 4

• avoiding adverse drug reactions
• identifying causes of disease
• designing clinical trials
• treating specific diseases

Question 5

general rule: number of individuals plotted against maintenance dose for a given drug will show a _____ distribution

Answer 5

-bell shaped

Question 6

a lot of genetic disorders are due to ______

Answer 6

protein folding defects

Question 7

too much of the drug can cause….

Answer 7

• side effects that are an extension of the therapy but bad at high doses (i.e. morphine =analgesic but at too high = decr respiration)
• can cause the drug to interact with more tissues besides the target

Question 8

people with different genetic makeup have ______ at different concentrations

Answer 8

peaks of medications

Question 9

CYP3A4

Answer 9

metabolizes about 50% of drugs and isn’t polymorphic
-contraindication: grapefruit juice has polyphenolic compounds like flavonoids and furanocoumarins which inhibit CYP3A4 and possibly others and it affects many drugs

Question 10

CYP2C9

Answer 10

metabolizes about 15% of drugs and is polymorphic so drugs metabolized by these enzyme need to be monitored more because there is more variability

• about 40% of ppl are heterozygotes and 1% are homozygotes
• warfarin is metabolized by it

Question 11

CYP2D6

Answer 11

metabolizes about 25% of drugs and is polymorphic so drugs metabolized by these enzyme need to be monitored more because there is more variability

• metabolizes tricyclic antidepressants, anti-arrhythmic drugs, Beta-blockers, and neuroleptics
• deficiency can have diverse consequences

Question 12

CYP2C19

Answer 12

• phase I enzyme that metabolizes about 5% of all drugs
• Incidence of heterozygotes: 24% whites, 33% of blacks, and 54% of Asians
• 1% homozygotes (two coppies of CYP2C19*2 = inactive)
• Clopidogrel (Plavix) = prodrug converted to active metabolite

Question 13

N-Acetyltransferase (NAT2)

Answer 13

• phase II enzyme found in the liver
• inactivating polymorphisms - inefficient conjugation= slow acetylator phenotype
• drug associated ADRs = isoniazid (is an antibiotic that can cause peripheral neuropathy), hydralazine (is an antihypertensive that can cause lupus erythematosus), and sulfonamides (is an antimicrobial that can cause hypersensitivity reactions)

Question 14

vitamin K epoxide reductase (VKORC1)

Answer 14

• involved in clotting process
• target of warfarin- biochemically characterized
• polymorphisms= 25% of variability

Question 15

pharmacodynamic variability

Answer 15

drug variability due to polymorphisms/mutations at the site of drug action

Question 16

pharmogenomic therapeutics based on recombinant proteins

Answer 16

• genes encoding hormones have been identified along with their proteins so could give that instead of hormone replacment
• delivery is an issue

Question 17

pharmacogenomics and designing clinical trials: most important for ______ (which disease?)

Answer 17

cancer because of variety of different gene mutations that can cause the same cancers- if you can target the right mutation, there is a better likelihood that it would work

Question 18

It is important to perform clinical trials with a lower _______ ______

Answer 18

tolerable dose