Gneomics

Question 1

What is pharmacogneomics?

Answer 1

• examing inherited varitations in genes that determine the drug response a patient has

Question 2

What are dominant and recessive traits?

Answer 2

• Dominant: makes “dominant” phenotype and patient must have ONE
• Recessive: make “recessive” phenotype and patient must have TWO

Question 3

What is the definition of Deoxyribonucleic Acid (DNA)?

Answer 3

• Genetic information from both parnets that is present as two long chains of nucleotides that makes a double helix
• Main component of a chromosome

Question 4

What is the definition of nucleotides?

Answer 4

• Subunit of DNA and RNA containing a nitrogen base, 5 carbon sugar, and a phosphate group
• Adenine & Guanine (Purines) and Thymine & Cytosine (Pyrimidines)

Question 5

What is the definition of chromosomes?

Answer 5

• Tightly packed structuce within the cells nucleus
• Human cells contain 23 pairs

Question 6

What is the definition of gene?

Answer 6

• sequence of nucloetides taht code a single protein

Question 7

What is the definition of allele?

Answer 7

• Form of a gene
• Wild type us the most commonly occuring allele

Question 8

What is the definition of genotype?

Answer 8

• set of unique genes that determine a specific trait

Question 9

What is the definition of Genotype?

Answer 9

• Unique genes that determines a specific trait
• Two identical alleles make up homozygous genotypes and two different alleles make up heterozygous genotypes

Question 10

What is the definition of phenotype?

Answer 10

• the observed trait (what you phyiscally see)

Question 11

What is the definition of polymorphorism?

Answer 11

• Inherited variation in the DNA

Question 12

What is a SNP within the CYP enzymes?

Answer 12

• Causes enzyme activity or production to increase or decrease which will increased or decresed the drug metabolism

Question 13

What are the 5 classifications of CYP enzyme variations?

Answer 13

• Ultrarapid Metabolizer (UM)
• Rapid Metabolizer (RM)
• Normal Metabolizer (NM)
• Intermediate Metabolizer (IM)
• Poor Metabolizer (PM)

Question 14

What is important to know about Poor Metabolizers?

Answer 14

• NO enzyme activity
• Will increase drug levels (patient my need to avoid drugs or lower doses)

Question 15

What is important to know about Ultrarapid Metabolizers?

Answer 15

• Higer enzyme activity
• May cause drug levels to decrease faster

Question 16

What test should be done for Abacavir?

Answer 16

• HLA-B * 5701

Question 17

What is the significane/population for the abacavir test and what is the action/result for it?

Answer 17

• If postive do not use
• Test ALL before starting = fatal hypersenistivity reactions have happened

Question 18

What test should be done for Allopurinol?

Answer 18

• HLA-B * 5801

Question 19

What is the significane/population for the allopurinol test and what is the action/result for it?

Answer 19

• If Positive, do not use
• Positive test have lead to SJS; DC at first signsq

Question 20

What test should be done for Carbamazeipine, Oxcarbazepine, Phenytion, Fosphenytion?

Answer 20

• HLA-B * 1502

Question 21

What is the significane/population for the Carbamazepine, Oxcarbazepine, Phenytion, Fosphenytion test and what is the action/result for it?

Answer 21

• if positive do not use
• More commonly in asain populations; increased risk of SJS or TEN; test ALL before starting

Question 22

What test should be done for citalproam?

Answer 22

• CYP 2C19

Question 23

What is the significane/population for the citalopram test and what is the action/result for it?

Answer 23

• 2C19 * 1 allele are fully functioning
• 2C19 * 2 & * 3 are PM so they are at an increased risk of QTc Prolongation (limit to 20mg/day)

Question 24

What test should be done for clopidogrel?

Answer 24

• CYP 2C19

Question 25

What is the **significane/population** for the **clopidogrel test** and what is the **action/result** for it?

Answer 25

- Clopidogrel is a **prodrug** and needs to be convert by 2C19 - 2C19 * 2 & * 3 are **Poor metabolizers** and have increased cardio events (**consider alternatives**)

Question 26

What test should be done for **codeine**?

Answer 26

- CYP **2D6**

Question 27

What is the **significane/population** for the **codeine test** and what is the **action/result** for it?

Answer 27

- Codeine is a **prodrug** and needs to be converts by 2D6 - **Ultrarapid Metabolizers** are at increased risk of **overdosing** (DO NOT USE if UM or PM)

Question 28

What test should be done for **warfarn**?

Answer 28

- CYP **2C9 * 2 & * 3** - **VKORC1**

Question 29

What is the **significane/population** for the **Warfarin test** and what is the **action/result** for it?

Answer 29

- **Increased bleeding** risks with (2C9 *** 2 & * 3** and **VKORC1 G > A**) [lower the dose]

Question 30

What test should be done for **Trastuzumab**?

Answer 30

- HER2

Question 31

What is the **significane/population** for the **trastuzumab test** and what is the **action/result** for it?

Answer 31

- This requires **overexpression** of HER2 of it to work (**-** HER2 = drug not effective)

Question 32

What test should be done for **Cetuximab**?

Answer 32

- KRAS

Question 33

What is the **significane/population** for the **cetuximab test** and what is the **action/result** for it?

Answer 33

- Only those that are **KRAS -** should get these medicaitons - if **positive** DO NOT use

Question 34

what test should be done for **Azathioprine**

Answer 34

- Thiopurine methyltransferase (TPMT)

Question 35

What is the **significane/population** for the **azathiopurine test** and what is the **action/result** for it?

Answer 35

- **low/absent** TPMT activity Increases the risk of **myelosuppression** - If TPMT is **low/absent** start with a very low dose or alternatives

Question 36

what test should be done for **Capecitabine or 5-FU**?

Answer 36

- DPD Deficiency

Question 37

What is the **significane/population** for the **Capecitabine or 5-FU test** and what is the **action/result** for it?

Answer 37

- DPD deficiency **increases** the risk of toxicity (if **+** do NOT use)