Lecture 4- principles of drug individualizing

Question 1

Define Gene

Answer 1

segment of DNA that contains information for encoding a protein

Question 2

Define SNPs

Answer 2

single nucleotide polymorphism

Question 3

Define alleles

Answer 3

different DNA sequences at a locus

Question 4

Define genotypes

Answer 4

pair of alleles at a particular locus

Question 5

Define phenotypes

Answer 5

the observable property of an organism; a trait such as height, weight, medical condition, etc.

Question 6

Define Haplotype

Answer 6

a set of DNA variations, or polymorphisms, that tend to be inherited together

Question 7

MDR1

Answer 7

for digosin (reduce dose if have MDR1 because have higher drug plasma level)

Question 8

3 factors affecting patient drug response

Answer 8

1. Environment: diet, lifestyle, socioeconomics, others
2. Biology: age, sex, others
3. Genetics

Question 9

EM

Answer 9

normal metabolism (homozygous for the 2 “normal” alleles)

Question 10

PM

Answer 10

poor metabolizer (homozygous w/two variant alleles)

Question 11

IM

Answer 11

intermediate metabolizer (heterozygous)

Question 12

UM

Answer 12

ultra-rapid metabolizer (gene duplication/multiplication)

Question 13

systemic approach to genetic variations

Answer 13

identify genetic variation
determine who is impacted
identify how relevant to drug
determine how relevant to disease

Question 14

goals of pharmacogenomics

Answer 14

4 rights
To Enhance drug efficacy and Reduce drug toxicity

Question 15

Initial Dose

Answer 15

based on medical need and factors that will alter the PK or PD of drug (i.e. warfarin)

Question 16

Phase I

Answer 16

oxidation
hydroxylation
reduction
hydrolysis

(P450 CYPs)

Question 17

Phase II

Answer 17

conjugation:
- glucuronidation
- acetylation
- methylation
- glutathione conjugation
- sulphation

Question 18

Maintenance Dose

Answer 18

adjust the maintenance dose by X% up or down based on INR: caution about factors that will alter the PK and PD of drug (i.e. warfarin)

Question 19

Warfarin mechanism

Answer 19

Warfarin blocks VKOR enzyme that reduces Vit. K in order to coagulate.. therefore working as an anticoagulant

Question 20

Irinotecan

Answer 20

UGT1A1*28
neutropenia (reduce neutrophil count?)

Question 21

Codeine (prodrug for morphine)

Answer 21

CYP2D6 enzyme to activate it to morphine, but not actually morphine so no analgesic
PM: No analgesic effect
UM: respiratory depression

Question 22

Clopidogrel (prodrug)

Answer 22

if CYP2C19 low then..
PM: No drug activity cause not activated