Pharm 5 - Drug Metabolism

Question 1

What is the purpose of metabolism?

Answer 1

Converts lipophilic into polar derivates (polar derivates are readily excreted)

Question 2

Why should systemic-effect medicines have a low hepatic first pass?

Answer 2

Ensures most of the drug isn’t metabolised so there is enough to get inside the organ and produce desired effect

Question 3

What 3 reactions occur in phase 1 metabolism?

Answer 3

Oxidation / reduction / hydrolysis

Question 4

What main reactions occur in phase 2 metabolism?

Answer 4

Glucuronidation / acetylation / amino acid conjugation / methylation / sulphating / glutathione conjugation

Question 5

What does phase 2 metabolism do?

Answer 5

Makes drug water soluble by adding a polar group

Question 6

How is the Polarity of the drug affected after phase 1 metabolism?

Answer 6

Little change in polarity

Question 7

What else may phase 1 metabolism do?

Answer 7

Activate / inactivate chemicals

Question 8

Where is the point of attachment for phase 2 metabolism?

Answer 8

Functional groups

Question 9

How does oxidation and reduction and hydrolysis affect functional groups?

Answer 9

Oxidation / reduction = creates new functional groups

Hydrolysis exposes the functional groups

Question 10

Where is the cytochrome p450 enzyme system mainly found?

Answer 10

Liver endoplasmic reticulum

Question 11

What metabolic process is cytochrome p450 involved in?

Answer 11

Phase 1 oxidation reactions

Question 12

In oxidation by p450, what is the rate limiting step?

Answer 12

2nd reduction (step after stable Fe3+ forms)

Question 13

What does glutathione consist of?

Answer 13

Cysteine / glycine / glutamate

Question 14

What does flavin containing monooxygenase do?

Answer 14

Converts trimethylamine to amine oxide

Question 15

When does hydrolysis occur?

Answer 15

Whenever there is an ester or amide

Question 16

Does p450 use NADPH or NADH more commonly as a cofactor?

Answer 16

NADPH

Question 17

Conjugation in phase 2 reactions typically leads to an inactive conjugate. Name an exception

Answer 17

Morphine

Question 18

What do phase 2 reactions achieve?

Answer 18

Makes conjugate less lipid soluble = easier to excrete

Question 19

What defence reaction does phase 2 metabolism do against pathogens and toxins?

Answer 19

Glutathione conjugation

Question 20

Which phase 2 reaction occurs most often?

Answer 20

Glucuronidation

Question 21

Which cofactor does glucuronidation use?

Answer 21

UDGPA

Question 22

Which 3 elements can be acetylated in phase 2 metabolism?

Answer 22

N / O / S

Question 23

Which compound acts as the donor in methylation?

Answer 23

S-adenosyl methionine

Question 24

In paracetamol, which reaction happens first?

Answer 24

Phase 2 reactions

Question 25

What is the cofactor for oxidation?

Answer 25

Either CYP2E1 or CYP3A4