Drug Metabolism

Question 1

What is cometabolism?

Answer 1

enzymes that are present to metabolize endogenous material also metabolize exogenous material

Question 2

What are the Phase I reactions?

Answer 2

oxidation and hydrolysis

Question 3

What are the Phase II reactions?

Answer 3

SAGGMeth: sulfation, acetylation, glucuronidatin, glutathionation, methylation

Question 4

What does CYP stand for and what is its function?

Answer 4

CYP: 450 monooxygenase system
requires cosubstrate of NADPH reductase
does oxidation

Question 5

What is the Phase I metabolism of benzodiazepines?

Answer 5

allopathic hydroxylation (oxidation) by CYP3A4

Question 6

What is the Phase I metabolism of propranolol (beta blockers)?

Answer 6

aromatic hydroxylation (oxidation) by CYP2D6

Question 7

What is the Phase I metabolism of cimetidine?

Answer 7

histidine H2 receptor competitive inhibitor

metabolized by S-oxidation by CYP

Question 8

What is the effect of cimetidine on CYPs?

Answer 8

inhibits all CYPs except CYP2E1

Question 9

What is the Phase I metabolism of diphenhydramine (Benadryl)?

Answer 9

treats mild allergic reactions through competitive inhibition of H1 receptor
metabolized by N-oxidation by CYPs

Question 10

What is the Phase I metabolism of caffeine and theophylline?

Answer 10

adenosine receptor antagonists

n-dealkylation by CYPs

Question 11

What is the Phase I metabolism of ethanol?

Answer 11

dehydrogenase (alcohol then aldehyde)

Question 12

What is the Phase I metabolism of succinylcholine?

Answer 12

two molecules of acetylcholine, blocks ACh from binding

hydrolyzed by acetylcholinerase

Question 13

What is the Phase II metabolism of albuterol?

Answer 13

used to treat asthma by stimulating B2 receptor

sulfation inactivates it

Question 14

What is the Phase II metabolism of acetaminophen?

Answer 14

sulfation and glucoronidation metabolize it to a non-toxic metabolite

Question 15

What is the Phase II metabolism of benzodiazepines?

Answer 15

glucoronidation (main inactivation pathway)

Question 16

What is the function of glutathione?

Answer 16

protects cells from electrophiles/epoxides decreasing DNA damage

Question 17

What leads to toxic metabolism of acetominophen?

Answer 17

Phase I metabolism by CYP2E1 and CYP3A4 leads to reactive toxic intermediate of NAPQI

Question 18

How can toxic intermediates of acetaminophen be detoxified?

Answer 18

through glutathionation, but if GSH is depleted then liver cell death occurs

Question 19

How does ethanol consumption affect acetaminophen metabolism?

Answer 19

ethanol induces CYP2E1 which causes more acetaminophen to be metabolized into toxic intermediates

Question 20

Which CYP has the most polymorphisms?

Answer 20

CYP2D6

Question 21

What drugs are metabolized by CYP2D6?

Answer 21

beta blockers (like metoprolol) and opioids (codeine and hydrocodone) and other CNS drugs

Question 22

What drugs are metabolized by CYP2C19?

Answer 22

benzodiazepines, -prazoles (proton pump inhibitors)

Question 23

What drugs are metabolized by CYP2C9?

Answer 23

warfarin, NSAIDs (ibuprofen, celecoxib)

Question 24

What drugs are metabolized by CYP2E1?

Answer 24

ethanol, acetominophen

Question 25

What drugs are metabolized by CYP1A2?

Answer 25

caffeine, theophylline

induced by many environmental pollutants