Chemical Pathways of Drug Metabolism Phase I and II

Question 1

What type of metabolism occurs before the drug reaches systemic circulation?

Answer 1

Pre-systemic metabolism

Question 2

What is the most commonly seen metabolizing enzyme in the blood?

Answer 2

Esterases

Question 3

What are the two major classifications of drug metabolism?

Answer 3

Hepatic and extra-hepatic

Question 4

What are the two common sites of pre-systemic metabolism?

Answer 4

GI tract and liver

Question 5

Which CYP enzyme is the major one found in the GI?

Answer 5

CYP3A4

Question 6

Which CYP enzymes are polymorphic?

Answer 6

All to a certain degree

Question 7

Where can esterases be found?

Answer 7

Blood, liver, GI tract

Question 8

Which phase II enzymes are polymorphic?

Answer 8

UGTs largely, TPMT, NAT1, NAT2, GSTs (M,T,P,A)

Question 9

Where is enzyme CYP2E1 most commonly expressed?

Answer 9

Lungs

Question 10

Major con of CYP2E1?

Answer 10

Metabolizes procarcinogens in the body

Question 11

What factor largely affects how much of an enzyme each individual expresses?

Answer 11

Genetic factors

Question 12

Which enzyme shows increased activity due to inflammation?

Answer 12

CYP2E1

Question 13

Which 2 CYP enzymes are commonly affected by a deleted gene mutation?

Answer 13

CYP2D6 and CYP2C19

Question 14

The expression of which 5 CYP enzymes can be either be increased or decreased by polymorphism?

Answer 14

CYP2D6, CYP2C19, CYP2C8, CYP2B6 and CYP2A6

Question 15

What is the main purpose of metabolism?

Answer 15

Make the drug more water solubility, making excretion possible

Question 16

What is the primary method of excretion for Phase I metabolic waste?

Answer 16

Urine

Question 17

What is the primary method of excretion for Phase II metabolic waste?

Answer 17

Feces

Question 18

True or false: Non-polar conjugates are commonly excreted in the urine

Answer 18

False. Non-polar conjugates are commonly excreted in the feces, and polar metabolites in the urine

Question 19

In what case may a drug directly undergo Phase II metabolism?

Answer 19

The drug already contains a functional group (biological marker) identifying it should undergo Phase II metabolism

Question 20

Exceptions to the Phase II metabolism rule

Answer 20

Methylation and acetylation. Decrease water solubility

Question 21

What is the major Phase I reaction?

Answer 21

Oxidation

Question 22

Which of the following is not a Phase I reaction?
.Oxidation
.Methylation
.Hydrolysis
.Reduction

Answer 22

Methylation

Question 23

What non-CYP enzyme is highly responsible for oxidation reactions?

Answer 23

Monoamine oxidase (MAO)

Question 24

What is the most common Phase II reaction?

Answer 24

Glucuronidation

Question 25

True or false: 95% of oxidation reactions are catalyzed by CYP enzymes

Answer 25

True

Question 26

Which enzyme converts codeine to morphine?

Answer 26

CYP2D6

Question 27

True or false: If morphine is administered, it will undergo Phase I metabolism

Answer 27

False. Morphine undergoes Phase II metabolism. If codeine is administered, it undergoes Phase I metabolism and is converted to morphine

Question 28

True or false: Deamination of a terminal amine forms a ketone

Answer 28

False. It forms a carboxylic acid

Question 29

True or false: Deamination of a penultimate amine forms a ketone

Answer 29

True

Question 30

True or false: Formation of both ketones and carboxylic acids after metabolism will increase water solubility

Answer 30

False. Formation of ketones decreases water solubility

Question 31

What are the 3 Phase I reactions from most to least occurence?

Answer 31

Oxidation, hydrolysis, reduction

Question 32

Which two enzymes are highly responsible for hydrolysis?

Answer 32

Esterases and amidases

Question 33

True or false: Amidases and esterases are both highly suited for drug metabolism

Answer 33

False. Amidases are mostly suited for protein and peptide metabolism

Question 34

Glucuronidation at the carboxylic acid group, or _____________, is the least common form of glucuronidation

Answer 34

Acylglucuronidation

Question 35

True or false: GSSG is the active form of glutathione because it has a free thiol group

Answer 35

False. GSH is the active form

Question 36

True or false: Glutathione undergoes conjugation in the presence of enzymes or nucleophiles (electron donating groups)

Answer 36

True

Question 37

What is the most commonly seen type of amino acid conjugation?

Answer 37

Glycine conjugation

Question 38

Glycine conjugation is the major metabolic route for xenobiotic ________ _______

Answer 38

Carboxylic acids

Question 39

Why should newborns not receive anything containing benzoic acid preservatives?

Answer 39

Their glycine conjugation pathway is underdeveloped, therefore, preparations containing preservatives can lead to toxicity

Question 40

Why are methylation and acetylation considered Phase II reactions?

Answer 40

These processes add on functional groups (conjugate), despite decreasing water solubility

Question 41

``` Imipramine can undergo all metabolic transformations except: Oxidative Deamination Oxidative N-Dealkylation Hydrolysis Aromatic Oxidation Glucuronide conjugation ```

Answer 41

Hydrolysis

Question 42

``` Which of the following structural features must be present in an organic compound for it to undergo amino acid conjugation? Amines Alcohols Epoxides Esters Carboxylic acids ```

Answer 42

Carboxylic acids

Question 43

Highly lipophilic amine containing compounds undergo N-dealkylation at an (inc/dec) rate

Answer 43

Increased