Chapter 7: Genetic & Genomic Considerations in Pharmacotherapeutics

Question 1

Pharmacogenomics

Answer 1

How genes affect a person’s response to drugs​

Provides safe drugs to patients​

Genomics education and competencies​

Biomarkers​

Used to genetic testing ​

Genetic variants that alter drug metabolism

Question 2

genetic variants that alter drug metabolism

Answer 2

done by altered drug metabolism

ex. P4502d6 genetic variants in the way tamoxifen (prevent breast cancer reoccurance) must work –women who have that gene there can’t activate that drug well, limit benefit for tx

ex. Plavix -genetic variants of CYP2C19 reduce benefits. With this variant need different anti-plt drug.

ex. European heritage -52% metabolism isoniazid slow, 48% metabolize it quickly –have to account for this differences bc you may see drug failure vs toxicity.

ex. 1 in 14 people have a form of cyp2d6 unable to convert codeine to morphine –won’t pain relieve in these people

Question 3

genetic and pharmacogeonmic testing

Answer 3

Genetic biomarkers​: Blood​, Saliva​, Urine​, Amniotic fluid​, Tissue​, Hair​

Genetic test kits

Question 4

barriers to pharmacogenomics

Answer 4

Lack of education​

Financial cost for testing

Question 5

others considerations for pharmacogenomics

Answer 5

Implications​ -Pt needs to be the final one to agree for testing , Takes a while for results

Ethics​ -Pt fear discrimination from insurance companies and employers and provides
GINA law ​-provides pt protection from discrimination from employers and insurance based on genetic info. Doesn’t apply to military health care, VA healthcare, indian healthcare, or for life or long term care insurance

Guidelines​ -CPIC ​

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Question 6

warfarin package insert

Answer 6

CYPTP2c9 and VKORC1 polymorphisms

the s-enantiomers of warfarin are mainly metabolized to 7-hydrooxywarfarin by CYP2C9, a polyorphic ezyme. the varient alleles, CYP2C92 amd CYP2c93, result is dereased in vitro CYP2C9 enzymatic 7-hydroxylation of s-warfarin. the frequencies of these alleles in causasians are approx 11% and 7% for CYP2C92 and CYP2C93

other CYP2C9 alleles asso with reduced enzymatic activity occur at lower frequencie, including 5,6, and *11 alleles in pop of african ancestory and *5, *9 and *11 in caucasians

warfarin reduces thr regeneration of vit K from vit K epoxide in the vit K cycle thru inhibtion of VKOR, a multiprotein enzyme complex. Certain single nucleotide polymorphisms in the VKOC1 gene have been asso with varible warfarin does requirement. VKORC1 andCYP2C9gene warients generally explainsthe alrgest proportion of known variability in wafarin dose requirements.

Question 7

genetic varents that ater drug targets

Answer 7

genetic variations can ater the structure of drug receptors and other target molecules and can thereby influence drg responses

Drug targets on normal cells
ADRB1
VKORC1

Drug targets on cancer cells and viruses
HER2
EGFR
CCR5

Genetic variants that alter immune responses to drugs
HLAs