Drug Metabolism Pt 2

Question 1

Put Mebabolism into 2 boxes

Answer 1

Phase 1 vs Phase 2

Question 2

Phase 1 = Functionalization Rxns

That means?

Answer 2

1. Introduce new polar functional groups
2. Replace existing functional groups
3. unmask existing polar groups and excrete them

Question 3

Phase 1 reaction include:

Answer 3

1. Oxidations (hydroxylations)
2. Reductions
3. Hydrolyses

Question 4

Oxidations (hydroxylations) = “new”

example:____

Answer 4

RH –> ROH

Question 5

Reductions = interconversion

example:____

Answer 5

C=O –> CH-OH (more polar)

Question 6

Hydrolyses = unmasking

example:____

Answer 6

R-COOCH3 –> RCOOH + CH3OH

Question 7

What is the purpose of phase 1 metabolism?

Answer 7

1. Enhance excretion by making a functional group more water soluble.
2. Prepare a drug molecule for Phase 2, as in add a functional “handle”

Question 8

Phase 2 = Conjugation Reactions

Conjugation occurs on:

Answer 8

1. Parent Drug
2. Phase 1 metabolite

Question 9

Conjugation in Phase 2 makes a drug/metabolite more water soluble, which enhances _____.

Examples of conjugation rxns:

Answer 9

excretion

• glucoronidation
• sulfate fomration

Question 10

Phase 1 and Phase 2 are complimentary.

They are not mutually _____.

Both Phases are available to ______.

Answer 10

exclusive

get rid of stuff.

Question 11

Site of Drug Metabolism.

Answer 11

Liver

Question 12

Liver is a big organ with a big job.

it performs:

Answer 12

1. Major xenobiotic metabolism
2. Major endobiotic metabolism
3. Presystem “First Pass Effect”

Question 13

The Presystemic First Pass Effect refers to

Answer 13

Enteral drug absorption leads to drug passing through portal vein to liver and the drug getting metabolized/destroyed before entering systemic circulation

Question 14

First Pass effect can be caused by

Answer 14

Liver metabolism or

GI mucosa metabolism

Question 15

Routes that overcome the first pass effect are:

Answer 15

1. Suppository
2. Intravenous
3. Transdermal patch
4. buccal
5. larger dose
6. insufflation (inhalation to lung)
7. Intrmuscular injection
8. Chemical modification to slow metabolism

Question 16

Foyes table 4.15 shows that

Answer 16

a limited number of drugs suffer 1st pass effect.

Rule of thumb: 10% of drugs get metabolized on first pass.

90% of drugs goes to systemic circulation.

Question 17

Another site of drug metabolism is the

Answer 17

GI Tract

Question 18

GI tract epithelium is very rich in _____ _____.

Which provide a significant contribution to ____.

Answer 18

drug-metabolizing enzymes.

oral bioavailability.

Question 19

Gut flora perform:

Answer 19

• reduction
• deconjugation
• enterohepatic recycling (EHC)

Question 20

Enterohepatic recycling can be used to:

Answer 20

Recycle bile salts.

Reabsorb excreted drugs.

Question 21

EHC of a drug means:

Answer 21

Phase 2 metabolism conjugates the active drug (>500MW) with a sugar, excrete. Then gut flora eat the sugar, and the drug returns to circulation, where it is conjugated again by the liver, and a loop reaction repeats the process.

Question 22

Other organs of drug metabolism include

Answer 22

Kidney, lungs, brain, any organ really.