Just a phase: Metabolism of xenobiotics by the liver

Question 1

What are xenobitoics?

Answer 1

They are substances foreign to the host

Question 2

Xenobiotics accumulate in different body tissues. TRUE OR FALSE?

Answer 2

TRUE

Question 3

Many xenobiotics are non polar and lipophilic. TRUE OR FALSE?

Answer 3

TRUE

Question 4

Xenobiotics require modifications to make them polar and water soluble and easier to excrete. TRUE OR FALSE?

Answer 4

TRUE

Question 5

Metabolism may terminate the action of xenobiotics. TRUE OR FALSE?

Answer 5

FALSE

Question 6

Several routes of metabolism may exist for xenobiotics. TRUE OR FALSE?

Answer 6

TRUE

Question 7

Active absorption of molecules does not occur via transport protein. TRUE OR FALSE?

Answer 7

FALSE

Question 8

If xenobiotics is small ion it can cross the membrane via aqueous channels. TRUE OR FALSE?

Answer 8

TRUE

Question 9

List the factors that affect absorption

Answer 9

• lipohilicity vs hydrophobicity
• relative concentrations on either side of the membrane
• The ionisation of xenobiotic
• Particle size

Question 10

List the factors that affect distribution

Answer 10

• Drug lipophilicity
• Lipoidality of tissue
• Blood flow through tissue
• Mass of the tissue
• Plasma/tissue concentration gradient

Question 11

Drug action differs between men and women. TRUE OF FALSE?

Answer 11

TRUE

Question 12

Define metabolism

Answer 12

It is the chemical modification of xenobiotics with overall goal of ridding the body of the substance

Question 13

Where does metabolism mainly occur?

Answer 13

In the liver

Question 14

During first pass effect there is an extensive chemical transformation of lipophilic or heavy compounds. TRUE OR FALSE?

Answer 14

TRUE

Question 15

List the effects the metabolite may have

Answer 15

• May have equal activity to xenobiotic/drug
• No or reduced activity
• Increased activity (prodrugs)
• Toxicity not observed in the parent molecule

Question 16

What is elimination?

Answer 16

The main process by which the body eliminated unwanted substances

Question 17

Name the most common routes of elimination

Answer 17

• renal
• biliary
• exhalation
• perspiration

Question 18

What type of filtration allows drugs to pass through urine?

Answer 18

Glomerular

Question 19

What kind of secretion provides an active carrier process for anion and cations?

Answer 19

Tubular secretion

Question 20

Volatile agents cannot be excreted via the lungs. TRUE OR FALSE?

Answer 20

FALSE

Question 21

Where can glucuronic acid conjugate be excreted?

Answer 21

In bile

Question 22

Phase 1 metabolic reactions create functional groups that place xenobiotics in a correct chemical state to be acted upon at phase 2. TRUE OR FALSE?

Answer 22

TRUE

Question 23

The majority of phase 1 reactions in hepatic microsomes employ cytochrome P450 (CYP) enzymes .TRUE OR FALSE?

Answer 23

TRUE

Question 24

What are cytochrome P450 (cyp) enzymes?

Answer 24

They are large group of enzymes encoded for by the P450 gene superfamily

Question 25

CYPs have substrate and reaction specificity. TRUE OR FALSE?

Answer 25

TRUE

Question 26

Which CYP metabolises 50% of therapeutic drugs?

Answer 26

CYP3A4

Question 27

Genetic polymorphisms lead to individual metabolic profiles which can impact on chemotherapy of disease . TRUE OR FALSE?

Answer 27

TRUE

Question 28

Where are reductive reactions catalysed?

Answer 28

Within the liver

Question 29

What do reductive reactions require?

Answer 29

NADPH

Question 30

What inhibits reductive reactions?

Answer 30

Oxygen

Question 31

How does phase 2 metabolism occur?

Answer 31

It occurs through the action of a diverse group of enzymes performing a range of different reactions

Question 32

What is usually involved in conjugation in phase 2 metabolism?

Answer 32

A high energy co-factor, resulting in water soluble product which can be readily excreted

Question 33

What is the major pathway in phase 2 metabolism?

Answer 33

Major route is conjugation with a-D-glucuronic acid

Question 34

What intermediate is required in conjugation?

Answer 34

UDP-glucuronic acid

Question 35

What is the major pathway for phenols?

Answer 35

Sulfation

Question 36

What intermediate is required for sulfation?

Answer 36

PAPS

Question 37

Sulfation is a competing pathway with glucuronidation. TRUE OR FALSE?

Answer 37

TRUE

Question 38

Glucuronidation is predominates at high substrate. TRUE OR FALSE?

Answer 38

TRUE

Question 39

Sulfation prdominates at low substrate. TRUE OR FALSE?

Answer 39

TRUE

Question 40

There is relatively more PAPS in cell cytosol compared to UDPGA. TRUE OR FALSE?

Answer 40

FALSE

Question 41

What intermediate does Methylation require?

Answer 41

SAM

Question 42

Acetylation requires acetyl CoA, TRUE OR FALSE?

Answer 42

TRUE

Question 43

Where does acetylation occur?

Answer 43

In kupffer cells in the liver

Question 44

In AA conjugation, substrate is activated by the attachment of AMP. TRUE OR FALSE?

Answer 44

TRUE

Question 45

what occurs during AA conjugation?

Answer 45

- Substrate is activate by attachment of AMP - AMP is then replaced with S-CoA - Conjugation with endogenous AAs then occurs

Question 46

Glutathione substrates are highly electrophiic compounds. TRUE OR FALSE?

Answer 46

TRUE

Question 47

Glutathione conjugates are excreted in bile or via | kidney. TRUE OR FALSE?

Answer 47

TRUE