Pharmcogenomics

Question 1

Pharmacogenomics

Answer 1

Inherited variations in genes that determine a patient’s response to a drug

Question 2

What is the difference between dominant and recessive allele?

Answer 2

Dominant: one copy of the allele from one parent

Recessive: 2 copies, one from each parent

Question 3

DNA

Answer 3

2 long chains of nucleotides joined a twisted into a double helix

Question 4

Nucleotide

Answer 4

Bases consist of 2 purines (adenine and guanine) and 3 pyrimidines (thymine, cytosine, and uracil)

Question 5

Chromosome

Answer 5

Tightly packed structure within the cell nucleus of DNA and protein

Question 6

Gene

Answer 6

Specific sequence of nucleotides that code for a single protein

Question 7

Allele

Answer 7

Specific form of a gene (wild-type is most common)

Question 8

Genotype

Answer 8

Set of unique genes that determine a specific trait

2 identical (homozygous)
2 different (heterozygous)

Question 9

Phenotype

Answer 9

An observable trait (outward expression)

Question 10

Haplotype

Answer 10

A group of genes or DNA that are inherited together (linked)

Question 11

Polymorphism

Answer 11

An inherited variation of DNA seque3nce

Question 12

What is SNP

Answer 12

Most common genetic alteration when there is a change in a singe base pair

Question 13

What is poor metabolizer

Answer 13

Reduce or no enzymatic active → drug levels increse

Question 14

What is a normal metabolizer

Answer 14

Fully functional enzyme activity → expected drug response

Question 15

What is an ultra rapid or rapid metabolizer

Answer 15

Higher enzymatic activity → drug level decreases

Question 16

Abacavir gene

Answer 16

HLA-B*5701 → fatal hypersensitivity

Question 17

Allopurinol gene

Answer 17

HLA-B*5801 → SJS

Question 18

Antiseizure drugs gene? Presentation

Answer 18

Carbamazepine
Oxcarbazapine
Phenytoin
Fosphenytoin

HLA-B*1502 → SJS

All Asians must be tested before Tegretol and suggested testing in Trileptal, Optional in phenytoin and fosphenytoin

Question 19

Citalopram metabolism? Implications

Answer 19

CYP2C19

*2 and *3 are limited to 20 mg/day

Question 20

Clopidogrel metabolism? Implications?

Answer 20

CYP2C19

*2 and *3 consider alternatives

Question 21

Codeine metabolism? Implications?

Answer 21

CYP2D6 (ultra metabolizer)

Codeine → morphine → toxicity

Question 22

Warfarin metabolism? Implications?

Answer 22

CYP2C9*2 and *3
VRORC1

Increased bleeding → start with lower doses

Question 23

Trastuzumab testing? Implications

Answer 23

HER2

If negative, drug is ineffective

Question 24

Cetuximab testing implications

Answer 24

KRAS mutation (wild-type)

If positive don’t use

Question 25

Azothiopurine testing? Implications?

Answer 25

TPMT deficiency Low/absent → start at low dose or use alternative

Question 26

Capecitabine testing? Implications

Answer 26

DPD deficiency → severe toxicity

Question 27

Drugs to avoid with test is positive?

Answer 27

HLA-B KRAS mutation

Question 28

Drugs to avoid with test is negative?

Answer 28

HER2

Question 29

Drug where testing is strongly recommended? Testing?

Answer 29

Abacavir (HLA*5701) Aza (TPMT) Carbamazepine (HLA-B*1502) Cetuximab and other EGFR inhibitors (KRAS mutation) Trastuzamab (HER2)