PG & PK 2

Question 1

Phase I

Answer 1

Generates more polar compounds

Question 2

Phase II

Answer 2

Generates more conjugates

Question 3

Both Phase I and II

Answer 3

Increase water solubility

Question 4

Phase I Drug Metabolism Mechanisms?

Answer 4

Cytochrome P450
Azo/nitro reduction
Dehalogenation
Desulfuration
Ester/Peptide hydrolysis
Dealkylation, deamination

Question 5

What do CYP450s do?

Answer 5

Oxidize drugs making them polar by putting on a “OH” group

Question 6

Inducers of P450?

Answer 6

Increase activity

Question 7

Inhibitors of P450?

Answer 7

Decrease activity

Question 8

What do you need to now about P450 to be useful?

Answer 8

What P450 and are the affected by inhibitors or inducers

Question 9

What are the pharmacologically important CYPs?

Answer 9

CYP1-3

Question 10

CYP4 is mainly used for?

Answer 10

Lipid metabolism

Question 11

CYP2B6 and CYP2C19 do?

Answer 11

S-mephenytoin

Question 12

1A2 does?

Answer 12

Caffeine melatonin and theophylline

Question 13

2A6 does?

Answer 13

Coumarin Nicotine

Question 14

2B6 does?

Answer 14

Bupropion, efavirenz

Question 15

2C8 does?

Answer 15

Paclitaxel and pioglittazone

Question 16

2C9 does?

Answer 16

Tolbutamide
flurbiprofen
warfarin

Question 17

2C19 does?

Answer 17

omeprazole

Question 18

CYP3A4

Answer 18

Responsible for clearance of almost half of all drugs

Mainly in liver (1/3)Wide activity range

Question 19

What can’t you take with CYP3A4?

Answer 19

Grapefruit juice

Question 20

2C9*2 Races

Answer 20

10-14% White

3% Black

Question 21

2C9*3 Races

Answer 21

1-2% Asian
7-10% White
0.8% Black

Question 22

Hetero or homo makes a bigger difference with 2C9?

Answer 22

Homo –> poor metabolizers (basically no activity)

Question 23

2C19

Answer 23

S-mephenytoin

Question 24

Poor metabolizers of 2C19 races?

Answer 24

3. 9% black
4. 6 % asian
5. 8% white

Question 25

2C19*2 races

Answer 25

17% Black
30% Asian
15% White

Question 26

2C19*3 races

Answer 26

0.4% Black
5% Asian
0.04% White

Question 27

2D6

Answer 27

Highly polymorphic
Less than 2% in liver
White folks
Small change here makes a big difference bc it is a very important CYP

Question 28

2D6 is involved with what drugs?

Answer 28

Dextromethorphan, codein, hydrocodone, oxycodone, ethylmorphine
Tricyclic antidepressants
SSRI's
Antipsychotics
Deta-adrenergic antagonists
Anti-arrhythmics

Question 29

Fewer copies of a gene means?

Answer 29

Drug says in the body longer –> poor metabolizers