pharmacogenomics

Question 1

Pharmacogenetics

Answer 1

Study of genetic causes of individual variations with drug response

Question 2

Pharmacogenomics

Answer 2

Study of genetic determinant of drug efficacy and toxicity

Question 3

Variation in response can be caused by

Answer 3

Difference in concentration at drug site-PK variability

Different response to same conc- PD variability

Question 3

Variation in response could be due to

Answer 3

Single nucleotide polymorphisms

insertions, deletions

Question 4

How do SNPs and indels cause these variations

Answer 4

By changing base sequence of DNA which may result in change in amino acid sequence
Enzymes, drug transporters,and receptors are made of proteins are made of proteins hence a change in protein can change how drug is metaboloised

Question 4

What is PK variability

Answer 4

Variability in the amount of drug delivered to receptor

Question 4

Some processes of PK

Answer 4

Metabolism process- converting drug o water soluble form

Enzymes- can convert inactive substances into active forms

Question 4

PK variability occurs because

Answer 4

Poor metabolizer
ultraRapid metabolizer
Enzyme deficiency
Drug transporter variability

Question 4

Drug metabolizing enzymes divided into

Answer 4

phase 1- enzymes that add or remove functional groups in a substrate through oxidation, reduction, hydrolysis

Phase 2- Enzymes that transfer moieties from co factor to substrate

Question 5

Most important phase 1 enzyme

Answer 5

cytochrome p450

Question 6

CYP genes are highly

Answer 6

Polymorphic which can produce abolished, reduced or enhanced enzyme activity

Question 7

Classification of 4 phenotypes due to level of CYP enzymes

Answer 7

Poor metabolizer - enzyme abolished
Intermediate- reduced
extensive- normal
ultrarapid-enhanced

Question 8

A poor metabolizer

Answer 8

Requires low dose so it doesnt accumulate in system

Question 9

A rapid metabolizer

Answer 9

Requires high doses so therapeutic effect can be met

Question 10

CYP polymorphisms mainly found in

Answer 10

CYP2D6
CYP2C9
CYP2C19

Question 11

Polymorphic phase one enzyme

Answer 11

plasma cholinesterase

Question 12

Clopidogrel is a

Answer 12

Prodrug

Question 13

Clopidogrel binds to

Answer 13

ADP receptor

Question 14

This enzyme helps metabolise clopidogrel

Answer 14

CYP2D19

Question 15

Loss of function alleles of CYP2C19

Answer 15

*2 and *3

Question 16

CYP2C19 loss of function alleles have been associated with

Answer 16

adverse ischemic events

Question 17

CYYP2C19 gain of function allele

Answer 17

CYP2C19*17

Question 18

Gain of function allele is thought to result in

Answer 18

higher cata;ytic activity
Decreased risk of ischemic events
Increased risk of bleeding

Question 19

Warfarin used for

Answer 19

Thromboembolism

prevents systemic embolism in people with atrial fibrillation

Question 20

Warfarin has a narrow

Answer 20

Therapeutic index

Question 21

Major enzyme that metabolizes warfarin

Answer 21

CYP2C9

VCORC1 gene, the target of warfarin

Question 22

Impairment of warfarin therapy by

Answer 22

Loss of function genes

Question 23

VKORCI MUTATION

Answer 23

warfarin tretment resistance

Adverse ischemic events

Question 24

Dabigatran etexilate is prodrug for

Answer 24

Dabigatran

Question 25

dabigatran is as effective as this for stroke prevention

Answer 25

Standard dose warfarin

Question 26

Decrease in Trough concentrations of dabigatran caused by

Answer 26

SNP in CES 1 gene

Question 27

CES 1 codes for

Answer 27

liver carboxylesterase 1 responsible for conversion of dabigatran etixilate to dabigatran