Phase 1 and Phase 2 Rxns and pharmacogenomics

Question 1

Phase 1 rxns

Answer 1

focused on adding or unmasking polar groups such as (OH, NH2) If a molecule has a methoxyl group, it will remove it leaving the hydroxyl.

Question 2

P1 rxns can either be

Answer 2

oxidation or Hydrolysis reduction

Question 3

P1 rxns will generate products that are either

Answer 3

electrophiles or nucleophiles

Question 4

For a phase 2 reaction, the nucleophiles generated from phase 1 reaction will undergo

Answer 4

sulfonation
acetylation
glucuronidation

Question 5

For a phase 2 reaction, the electrophiles generated from phase 1 reaction will undergo

Answer 5

Glutathione conjugation

Question 6

Cytoplasm is a - environment

Answer 6

Reducing

Question 7

Exception to P1—>P2

Answer 7

Ionizide undergoes acetylation and then hydrolysis

Question 8

Ethanol and nicotine usually

Answer 8

speed up the metabolism of other drugs

Question 9

Ethanol is given for methanol poisoning, why?

Answer 9

Ethanol induces stimulation of liver enzymes in order to get rid and metabolize the methanol.

Question 10

Molecule in grapefruit juice

Answer 10

furanocoumarin

Question 11

Tylenol can undergo

Answer 11

Glucuronidation or sulfonation

Question 12

A class of enzymes known as ? will ? Tylenol.

Answer 12

Monooxygenase hydroxylation. This will oxidize Tylenol. And can be a harmful electrophile.

Question 13

Molecule given for Tylenol overdose

Answer 13

N-Acetylcysteine – This has a very potent sulfhydryl group to react with the potent electrophile. Must be given early so that it does not interact with other molecules.

Question 14

How to smartly use drug metabolizing enzymes and issues that may arise.

Answer 14

First pass effect may result in the molecules becoming inactive. Design a molecule that will be activated as metabolism goes on.

Question 15

Tamoxifen is used to treat breast cancer , tamoxifen is a

Answer 15

prodrug, and endoxifen is the pharmacologically active drug.

Question 16

This is a highly polymorphic cytochrome

Answer 16

CYP2D6

Question 17

Codeine is a prodrug used an an analgensic, broken down by

Answer 17

CYP2D6

Question 18

1. Ultrarapid
2. Extensive
3. Intermediate metabolizer
4. Poor metabolizer

Answer 18

1. more than two copies of functional allele
2. two functional alleles
3. one reduced and one nonfunctional
4. no functional alleles

Question 19

Hawaii lawsuit enzyme and drug

Answer 19

Clopidogrel and CYP2C19 (<15%)

Clopidogrel and SR26334 (> 85%)

Question 20

Used in treatment of colorectal cancer

Answer 20

Fluorouracil -Enzyme is DPD-Dihydropyrimidine Dehydrogenase

Question 21

Example of using first pass effect to advantage

Answer 21

Loratadine metabolized to Descarboethoxyloratadine

Question 22

More alpha-2 receptors means

Answer 22

more likely to develop nicotine addiction

Question 23

Four focuses on drug metabolism

Answer 23

1. Genetic variations in enzymes
2. ” “ “”” transporters
3. ””””” immune system function
4. polygenic effects

Question 24

Codeine is

Answer 24

lipophilic and can cause opioids to pass through the breast milk and target breathing center of the brain.

Question 25

If metabolism is ultra rapid to clopidogrel this can cause

Answer 25

increased bleeding

Question 26

Irinotekan

Answer 26

used to treat colorectal cancer. To rid of this molecule, polar groups must be attached. You accumulate higher concentrations of metabolites. Slow metabolism leads to toxicity. Enzyme is UGT1A1

Question 27

Mediterranean populations should not eat broad beans because

Answer 27

G6PD deficiency leads to lower levels of NADPH leading to a person being unable to deal with certain molecules that cause oxidative stress on erythrocytes and may result in hemolysis. For this same reason, Rasburicase can increase uric acid. Rasburicase breaks down uric acid to either allatonin(non toxic) or hydrogen peroxide (oxidative stress).

Question 28

statins work to

Answer 28

lower cholesterol

Question 29

Metabolism of statins

Answer 29

transported to hepatocytes via transporters If a patients transporters are not effective then an increase in concentration will cause potential myotrophy.

Question 30

Transporter associated with statins

Answer 30

OATp1B1

Question 31

Very susceptible to a certain class of drugs that contain sulfonamides

Answer 31

Polymorphism in Human Leukocyte antigen results in Stevens-Johnson Syndrome

Question 32

Used in the treatment of epilepsy, people in East Asia may have sensitivity to these drugs.

Answer 32

Carbamazepine

Question 33

Warfarin is an anticoagulant developed from natural products

Answer 33

Cumurin

Question 34

Enzymes involved in warfarin metabolism

Answer 34

CYP2C9 and VKORC1