Pharmacology

Question 1

What’s the purpose of phase I biotransformation?

Answer 1

Make the metabolite more polar

Question 2

What reactions constitute phase i biotransformation?

Answer 2

Reduction, oxidation, hydrolysis

Question 3

Name 5 classes of phase i enzymes

Answer 3

monooxygenases,
oxidases,
dehydrogenases,
reductases,
hydrolases

Question 4

To which class of phase I enzymes do P450s belong?

Answer 4

Monooxygenases

Question 5

Who discovered P450 and when?

Answer 5

Omura and Sato, 1962.

Question 6

Where are CYPs in a cell?R

Answer 6

RER

Question 7

Which three CYPs can metabolize acetaminophen to NAPQI?

Answer 7

2E1, 3A4, 1A2

Question 8

How many genes have to be identical within the same CYP family?

Answer 8

40% (e.g. CYP1)

Question 9

How many genes have to be identical within the same CYP subfamily?

Answer 9

55% (e.g. CYP1A)

Question 10

What are individual members of the CYPs called?

Answer 10

Isoforms (e.g. CYP1A2)

Question 11

Which enzyme metabolizes caffeine (and clozapine, theophylline, aromatic amines, and aflatoxins)?

Answer 11

CYP1A2. It’s in the liver.

Question 12

Where’s CYP2E1 expressed?

Answer 12

Liver, kidney, Lung

Question 13

What does the pregnane x receptor do?

Answer 13

Upregulate enzymes when toxic metabolites detected

Question 14

Where does CYP3A4 exist?

Answer 14

Liver, small intestine

Question 15

Where are monoamine oxidases found?

Answer 15

Mainly in the CNS

Question 16

What is a general class of substrates for monoamine oxidases?

Answer 16

Neurotransmitters. See: epinephrine, norepinephrine, dopamine, serotonin

Question 17

What are 3 examples of reduction reactions?

Answer 17

Nitro reduction, dehalogenation, carbonyl reduction

Question 18

Name 5 phase II biotransformation reactions

Answer 18

Glucuronidation, sulfation, glutathione addition, acetylation, methylation

Question 19

What’s a necessary co-substrate for glucuronidation?

Answer 19

UDP-glucuronic acid

Question 20

What’s a necessary co-substrate for sulfonation?

Answer 20

PAPS

Question 21

What’s a necessary co-substrate for acetylation?

Answer 21

Acetyl-CoA. Catalyzed by N-acetyltransferases (NAT1/2)

Question 22

What’s a necessary co-substrate for methylation?

Answer 22

SAM

Question 23

How is morphine metabolized?

Answer 23

UGT metabolizes it into morphine-3-glucuronide

Question 24

How is codeine metabolized?

Answer 24

CYP2D6 turns it into morphine.

Question 25

How is heroin metabolized?

Answer 25

Undergoes hydrolyzation to become morphine

Question 26

How is diazepam metabolized?

Answer 26

Glucuronidation

Question 27

How is bilirubin metabolized?

Answer 27

Glucuronidation

Question 28

How is acetaminophone metabolized?

Answer 28

Glucuronidation, sulfonation, CYP metabolism

Question 29

What’s Gilbert’s syndrome?

Answer 29

low levels of promoter for UGT, leading to low levels of the enzyme. occasional bouts of jaundice

Question 30

What’s crigler-najjar syndrome?

Answer 30

UGT code is scrambled, leading to catastrophic effects in bilirubin removal.

Question 31

What compounds typically undergo sulfonation?

Answer 31

Phenols and occasionally alcohols

Question 32

What compounds typically undergo glutathione conjugation?

Answer 32

Ones with an electrophilic centre

Question 33

What conjugates NAPQI?

Answer 33

Glutathione conjugation

Question 34

What does acetylation target?

Answer 34

Aromatic amines, hydrazine

Question 35

What groups are involved in methylation?

Answer 35

Phenols, catechols, aliphatic/aromatic amines, N-heterocyclics, sulfhydryl

Question 36

Name 3 polymorphic CYPs

Answer 36

2C9, 2C19, 2D6

Question 37

What does grapefruit juice inhibit?

Answer 37

CYP3A4

Question 38

What does smoking induce?

Answer 38

CYP2A1

Question 39

What does alcohol induce?

Answer 39

CYP2E1

Question 40

What does St.John’s wort induce?

Answer 40

CYP3A4

Question 41

What can be given to induce UGT and clear bilirubin more effectively?

Answer 41

phenobarbital