Pharmacogenomics

Question 1

ADME

Answer 1

Absorption, distribution, metabolism, excretion

Pharmacokinetic elements that determine how drug works

Question 2

Transporters

Answer 2

Transport drug into or out of the body or cells

Question 3

Phase I

Answer 3

Chemical modification of drug
Part of metabolism
Enables excretion

Question 4

Phase II

Answer 4

Conjugation reactions of drug
Part of metabolism
Enables excretion

Question 5

5 ways that polymorphisms affect drugs

Answer 5

1. Increasing/decreasing drug transport in and out of cells
2. Increasing/decreasing metabolism
3. Changes in binding to cellular target
4. Increasing/decreasing risk of toxicity or side effects
5. Increasing/decreasing efficacy

Question 6

CYP2D6 and codeine/morphine metabolism

Answer 6

Converts codeine (prodrug with no analgesic activity) into morphine (metabolite with analgesic activity)
5-10% of Caucasians have deletion that causes decreased metabolism ( conversion is reduced, resulting in no pain relief)
Duplication causes increased metabolism (conversion is increased, resulting in adverse effects)

Question 7

UGT2B7 and codeine/morphine metabolism

Answer 7

Converts morphine into morphine-6-glucuronide (active metabolite)
Those homozygous for UGT2B7*2 allele have higher M6G to morphine ratios
Leads to increased codeine effects

Question 8

Warfarin

Answer 8

Anticoagulant
Inhibits vitamin K cycle (vitamin K epoxide reductase complex subunit 1: converts precursor forms of clotting factors into active forms)

Question 9

Narrow therapeutic index

Answer 9

Small change in systemic concentration of drug may lead to significant changes in pharmacodynamic response

Question 10

CYP2C9 and warfarin

Answer 10

Variants of CYP2C9 (metabolizes warfarin) cause reduced coagulation
These patients need less warfarin than average

Question 11

Polymorphism of VKORC1 and warfarin

Answer 11

A allele of VKORC1 causes reduced coagulation
AA patients need less warfarin than average
G allele of VKORC1 causes increased coagulation
GG patients need more warfarin than average