Liver and drug metabolism

Question 1

What are the main functions of the liver?

Answer 1

Secretion of bile
Synthesis and storage of many nutrients e.g. vitamins, lipids and glycogen
Breakdown of old RBCs
Synthesis of plasma proteins

Question 2

The liver is involved in the metabolic elimination of what?

Answer 2

Alcohol
Nitrogenous waste
Foreign chemicals (xenobiotics)

Question 3

Elimination of waste takes place via excretion in the ____

Answer 3

bile

Question 4

Liver has a dual blood supply from the portal ____ and the hepatic _____

Answer 4

vein

artery

Question 5

On entering the liver, blood drains into the hepatic ________

Answer 5

sinusoids

Question 6

What are sinusoids lined up by?

Answer 6

fenestrated endothelium

Question 7

Hepatocytes represent roughly 70-80% of liver mass. True or false?

Answer 7

True

Question 8

How are hepatocytes separated from the sinusoids?

Answer 8

The space of Disse

Question 9

What are Kupffer cells?

Answer 9

Specialised macrophages

Question 10

Metabolites are more hydrophilic and polar than the parent drug and are renally excreted. True or false?

Answer 10

True

Question 11

What is clearance?

Answer 11

The volume that is cleared of drug per unit time

Question 12

What are the factors that affect hepatic clearance?

Answer 12

Drug’s affinity to drug metabolising enzymes
Amount of enzymes per gram of liver
Size of the liver (influenced by age)

Question 13

Is clearance or half life more representative of elimination of a drug?

Answer 13

Clearance

Question 14

Why is clearance the favoured parameter for elimination compared to half life of drug?

Answer 14

Because half life is influenced by both clearance and volume of distribution - vd makes it not a pure estimate of what clearance is

Question 15

Extensive first pass metabolism in the liver can reduce bioavailability of orally administered drugs. True or false?

Answer 15

True

Question 16

No drugs can be eliminated unchanged via biliary excretion. True or false?

Answer 16

False - some drugs can be e.g. rosuvastatin

Question 17

Inhibition of metabolic enzymes in the liver/intestine reduces the risk of DDIs. True or false?

Answer 17

Fasle - it is the most common form of DDIs

Question 18

What are the roles of transporters in the liver?

Answer 18

Uptake transporters e.g OATP1B1

Efflux transporters e.g. BCRP

Question 19

What is enterohepatic recirculation?

Answer 19

The liver releases the drug into the bile duct, which empties into the small intestine. Drug is then reabsorbed and goes to the portal vein and back to the liver

Question 20

Bile salts and bilirubin undergo ________ recirculation

Answer 20

enterohepatic

Question 21

Bile release is a continuous process. True or false?

Answer 21

False - it is not a continuous process but happens in bursts

Question 22

What is liver cirrhosis caused by?

Answer 22

excessive intake of alcohol

Question 23

There is a decrease in _________ and _________ in liver cirrhosis

Answer 23

liver volume

blood flow

Question 24

hepatic clearance of many drugs is increased in liver cirrhosis. True or false?

Answer 24

False - reduced

Question 25

GFR is often impaired in patients with liver cirrhosis. True or false?

Answer 25

True

Question 26

Liver cirrhosis is reversible if you stop drinking alcohol/ True or false?

Answer 26

False - irreversible in late stage - transplant is only option