Variability due to genetic differences

Question 1

Define pharmacogenomics

Answer 1

(PGx) Is defined as the variations of DNA and RNA characteristics as related to drug response

Question 2

Define pharmacogenetics

Answer 2

(PGt) A subset of PGx defined as the influence of variations in DNA sequence on drug response

Question 3

How much predictable variability to drug response is their

Answer 3

50%- due to genetic and environmental factors

Question 4

CYP3A5

Relevant drug and drug response variability due to genetic differences

Answer 4

Tacrolimus, used as an immunosuppressant.
Some genotypes have a 2 fold increased clearance while others are non-expressers. 80% of caucasian are non-expressers vs. 25% African descent

Question 5

N-acetyl-transferase acetylation

Relevant drug and drug response variability due to genetic differences

Answer 5

Procainamide (anti-arrhythmic) and isoniazid
NAT genotype, associated with the enzyme.
Ethnicity with low clearance caucasian (50%), african (30%), asian (10%)

Question 6

UDP-glucuronosyl-transferase glucuronidation

Answer 6

Hereditary hyperbilirubinaemia (gilberts syndrome) due to deficiency of this enzyme.
Also a anti cancer drug irinotecan has an active metabolite which is eliminated by glucuronidation when this doesn't occur neutropenia and diarrhoea occur. There is a genotype which is a predictor of who will get toxicity

Question 7

Alcohol/acetaldehyde dehydrogenase

Answer 7

Increased or decreased activity in this enzyme changes your metabolism of alcohol.
Decrease in the enzyme causes increased acetaldehyde. 50-80% of asians have this causing flushing.

Question 8

Gene mutations changing warfarin sensitivity

Answer 8

VKORC1 mutation causes reduced vitamin k recycling causing lower vitamin K1 and increased sensitivity to the action of warfarin

Others where binding of warfarin does not occur so higher concentrations needed