Lecture 6

Question 1

What is a Phase 1 Reaction?

Answer 1

it introduces a polar functional group into the xenobiotic (foreign) molecule

-OH, -COOH, -NH2, -SH

Question 2

Which enzyme does most of the Phase 1 reactions?

Answer 2

CYP450

Question 3

Heme molecules allows what?

Answer 3

It allows the oxygen to come in and oxidize our drug

Question 4

_________ convert the relatively lipid-soluble xenobiotics to water-soluble (hydrophilic) compounds that can be excreted

Answer 4

Metabolic Reactions

Question 5

Metabolism leads to compounds that are generally what?

Answer 5

Pharmacologically less active and relatively nontoxic
(also regarded as the detoxification process)

Question 6

what is a prodrug?

Answer 6

Administers an inactive form of the drug and becomes active when it enters the body

Question 7

what is the main purpose of phase 1 rxn?

Answer 7

to introduce a polar functional group into the xenobiotic molecule (-OH, -COOH, _NH2, -SH)

Question 8

What type of reactions are considered phase 1?

Answer 8

-oxidations
-reductions
-hydrolysis

Question 9

Aromatic Methyl Oxidation

Answer 9

Question 10

Dehydration

Answer 10

Question 11

4 types of Privileged positions

Answer 11

-Adjacent to a heteroatom-containing functional groups (S,O,N)
-Benzylic position
-Allylic Position
-Highly Substituted- C-H bonds (so a carbon with 3 R groups and a hydrogen)

Question 12

Oxidative Dealkylation

Answer 12

you basically lose and akyl group (-CH3) and it attaches a hydrogen

Works on Primary, secondary, and Tertiary Groups

Question 13

For Oxidative Dealkylation there are two different metabolic pathways

Answer 13

Oxidation & Dealkylation

Question 14

Deamination

Answer 14

Only works on Primary and Secondary Amines
Converts the amine to either a ketone or aldehyde

Question 15

N-Oxidation

Answer 15

N-oxidation transforms a basic amino group into a neutral motif, so a neutral group is not ionizable

this is a tertiary amine, so N-oxide

Question 16

O & S dealkylations occurs in similar fashion to N dealkylations

Answer 16

Question 17

What are Phase 2 (Conjugation) reactions?

Answer 17

typically attaches the polar and ionizable groups to the phase 1 metabolites or the xenobiotics containing the necessary polar functional groups to form water-soluble conjugated products devoid of activity

Question 18

Phase 2: The Glutathione conjugation

Answer 18

Main purpose is to protect the body against the chemically reactive metabolites/xenobiotics

ex: acetaminophen

Question 19

Phase 2: Acetylation

Answer 19

does not increase water solubility significantly

Question 20

Phase 2: Methylation

Answer 20

does not lead to polar/water soluble metabolites except when a quaternary ammonium derivative is formed