Metabolism/Pharmacogenetics

Question 1

Important sites for metabolsim

Answer 1

lining of gut, liver, kidneys and lungs

Question 2

What are prodrugs

Answer 2

drugs activated following metabolism

Question 3

Examples of prodrugs

Answer 3

codeine, enalapril, simvastatin, sacubitril

Question 4

Effects of metabolism (4)

Answer 4

Loss of pharmacological activity
Decrease in activity
Increase in activity (prodrug)
Production of toxic metabolites

Question 5

Individual drugs can be metabolised by more than one enzyme (T/F)

Answer 5

T

Question 6

How many phases does drug metabolism have

Answer 6

2

Question 7

Phase 1

Answer 7

Oxidation
Reduction
Hydrolysis

Question 8

What is the purpose of phase 1 meatbolsim

Answer 8

Increases the polarity of the compound and provides an active site for phase 2

Question 9

Cytochrome P450

Answer 9

Family of enzymes critical for the metabolism of drugs

Question 10

Cytochrome P450

Answer 10

Family of enzymes critical for the metabolism of drugs

Question 11

CYP3A4

Answer 11

Found in gut and responsible for the pre-systemic metabolism of several drugs- methadone,diazepam, Simvastatin, CCBs

Question 12

CYP2D6

Answer 12

Responsible for the metabolism of anti-depressants, anti-psychotics and conversion of codeine to morphine

Question 13

CYP1A2

Answer 13

Induced by cigarette smoke and is important in the metabolism ofntheophylline

Question 14

Phase 2

Answer 14

Glucuronidation (glucuronide acts as a conjugation molecule and binds to a substrate) which increases water solubility and enhances excretion of metabolised compound

Question 15

Factors that affect metabolism (8)

Answer 15

Herbal/natural drugs
Genetics
Hepatic blood flow
Liver disease
Age
Sex
Ethnicity
Pregnancy

Question 16

Grapefruit_____effects of____ by inhibiting CYP3A

Answer 16

increases and felodipine

Question 17

CYP2D6 has ____ nucleotide pleomorphisms

Answer 17

70

Question 18

CYP2C9 has_____ allelic variants known

Answer 18

2

Question 19

CYP2C19 has _____ allelic variants known

Answer 19

8

Question 20

Enzymes that exhibit genetic variations (6)

Answer 20

Pseudocholinesterase
N-Acetyletransferase
CYP2D6
CYP2C19
TMPT
Dihydropyrimidine

Question 21

Women don’t metabolise drugs faster than men (T/F)

Answer 21

F they do

Question 22

Production of toxic metabolites can lead to___

Answer 22

Direct toxicity
Carcinogenesis
Teratogenesis

Question 23

Example of activation of prodrug

Answer 23

Terfenadine ___> Fexofenadine

Question 24

Drug substrate for CYP1A2

Answer 24

Theophylline

Question 25

Drug substrate for CYP2D6

Answer 25

Coedine

Question 26

Drug substrate for CYP3A4

Answer 26

Cyclosporine

Question 27

CYP2D6 can be induced by

Answer 27

Cigarette smoke

Question 28

Drugs and Food stuffs that inhibit drug metabolising enzymes

Answer 28

``` Cimetidine Erythromycin Clarithromycin Ketoconazole CCBs Grapefruit ```

Question 29

CCBs

Answer 29

Calcium Channel Blockers- medications to decrease blood pressure in patients with hypertension

Question 30

Grapefruit Juice_____ Felodipine Oral Availibility by ____

Answer 30

increases | decreasing intestinal CYP3A protein expression

Question 31

Four phenotype subpopulations of metabolisers

Answer 31

Poor metabolisers Intermediate metabolisers Extensive metabolisers Ultrarapid metabolisers

Question 32

How many nucleotide polymorphisms are known

Answer 32

70

Question 33

CYP2CP metabolises ___ commonly used drugs which include

Answer 33

Warfarin and Phenytoin

Question 34

A poor metaboliser will need a ___ dose and an ultrarapid metaboliser will need a ____ dose

Answer 34

Lower and higher