These MCQs relate to the process of drug metabolism in the liver, the major enzymes involved in the processing of drugs and how age and individual variation in patients affect this process. Good Luck!

Peer Reviewed by Jonathan Loomes-Vrdoljak on 23 October 2019

Hepatic drug metabolism

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Question 1

Define first pass metabolism

A
When a drug is processed by the liver before entering the systemic circulation
B
When a drug is processed by the intestines and enters the hepatic portal system
C
When a drug is processed by the intestines and enters the systemic circulation
D
When a drug is processed by the stomach and enters the small intestine
Question 2

What effect would portal hypertension have on the serum concentration of an orally administered drug (assuming it does not to need to undergo hepatic drug metabolism to be rendered active)?

A
Reduced concentration of the drug in the systemic circulation
B
Increased concentration of the drug in the systemic circulation
C
The drug would not reach the blood due to high pressure of the blood portal system
D
Serum concentrations of the drug are unaltered in portal hypertension
Question 2 Explanation: 
Damage or pathology of the liver can cause a decrease in diameter of the efferent veins inside the liver and thus cause back up of the hepatic portal vein. This means that there is a reduced amount of unprocessed drug entering the liver to undergo metabolism and alteration, and therefore an increased concentration in the systemic circulation (due to porto systemic anastomoses). Loss of the liver’s ability to alter the drug can also lead to reduced renal excretion of the drug
Question 3

What are the four main phases of drug metabolism?

A
Absorption, alteration, excretion, effect
B
Absorption, transport, distribution, excretion
C
Absorption, distribution, metabolism, excretion
D
Distribution, transport, alteration, conjugation
Question 4

Adding a glucuronyl group using a conjugation reaction occurs at which stage?

A
Phase I
B
Phase II
C
Phase II
D
Phase IV
Question 4 Explanation: 
Conjugation is a phase II reaction where a large molecule is added to a functional group. The purpose of phase II reactions is to render a drug inactive or increase its polarity.
Question 5
What is the most likely effect of methylation on a drug?
A
Renders the drug acidic
B
Renders the drug active
C
Renders the drug inactive
D
Renders the drug more polar
Question 5 Explanation: 
Methylation is an example of a conjugation reaction that occurs in phase II. The purpose of phase II reactions is to render a drug inactive or increase its polarity. A methyl group is composed of 1 carbon and 3 hydrogen molecules, and is thus a non-polar molecule. Methylation aids in rendering a drug inactive.
Question 6

What are the requirements of cytochrome P450 enzymes to complete oxidation reactions?

A
Molecular oxygen, NADPH+, NADPH cytochrome P450 reductase, protons
B
Molecular oxygen, NADPH+, NADPH cytochrome P450 reductase
C
Water, NADPH+, NADPH cytochrome P450 reductase
D
NADPH+, NADPH cytochrome P450 reductase, protons
Question 7

A de novo mutation caused a loss of function in the gene that encodes for a CYP3A isoform. Metabolism of which of the following is affected?

A
Caffeine
B
Atorvastatin
C
Alcohol
D
Aspirin
Question 8

What are the 3 main reactions that occur during phase I metabolism?

A
Hydrogenation, oxidation, reduction
B
Oxidation, reduction, hydrolysis
C
epoxidation, polymerisation, hydrolysis
D
condensation, elimination, oxidation
Question 8 Explanation: 
The purpose of phase I reactions is to render a drug more polar and to prepare it for conjugation reactions in phase II.
Question 9

Which of the following is not part of a phase III reaction?

A
Release into the circulation for renal excretion
B
Release into bile for elimination in faeces
C
Membrane bound transport carriers remove hydrophilic metabolites from hepatocytes
D
Bound to haemoglobin to be excreted by the lungs
Question 10

When prescribing for a neonate, the dosage must be altered due to:

A
Increased drug metabolism due to the presence of a high concentration of liver enzymes in the blood stream
B
Immature hepatocytes and renal podocytes
C
Inability of the neonate to swallow the drug
D
Inability of the neonate to produce bile salts
Question 11

An elderly patient is prescribed ketamine at the standard dose for a 25 year old adult. Why is this a problem?

A
Because elderly individuals do not make the enzymes to metabolise the drug
B
Reduced blood flow to the liver and kidneys results in decreased drug metabolism and renal excretion respectively, therefore systemic concentration of the drug will be higher than normal
C
They have difficulty swallowing the drug
D
Administration of ramipril is difficult so compliance is reduced
Question 12

Which of the following is not an example of a drug that is metabolised by CYP3A?

A
Calcium channel blockers
B
Antihistamines
C
Contraception
D
Osmotic laxatives
Question 13

A patient is on contraception and reveals to you that they are taking St. John’s wort. What is the issue with this?

A
St. John’s wort is a cytochrome p450A inhibitor. It will thus require you to prescribe a lower dose of the drug to avoid build up of toxic levels in the blood stream
B
St. John’s wort is a cytochrome p450A inducer and thus require you to prescribe a higher dose of the drug to reach therapeutic levels.
C
There is no issue, this is a herbal supplement and does not have an impact on drug metabolism
D
The drug increases albumin levels and thus decreases drug bioavailability, requiring you to prescribe a higher dose of the drug to reach therapeutic levels.
Question 14

Genetic polymorphisms in the population can result in different phenotypes of cytochrome P450 enzymes. Your patient has a “ poor metaboliser” allele. What is the fate of a drug that is normally inactivated by the enzyme encoding this gene?

A
Decreased concentration of the drug in the blood stream at a normal dose
B
Increased concentration of the drug in the blood stream at a normal dose
C
Partial decrease in concentration of the drug in the blood stream at a normal dose
D
The drug does not reach the bloodstream as it is inactivated by stomach acid
Question 14 Explanation: 
In the general population there is individual variation of the cytochrome P450 enzyme. These genetic polymorphisms can sometimes result in enhancement or reduction in drug metabolism. Genes that cause cytochrome P450 reduction can result in an increased level of drug in the blood as the enzymes involved in the metabolism have reduced reaction rate and thus take longer to process the same amount of drug as a normal metaboliser.
Question 15

Your patient has a genetic mutation in one of their cytochrome P450 enzymes resulting in them becoming a rapid metaboliser. What is the fate of a pro-drug that is normally activated by CYP metabolism?

A
Increased concentration of the drug in the blood stream at a normal dose and rapid onset
B
Increased concentration of the drug in the blood stream at a normal dose and slow onset
C
Decreased concentration of the drug in the blood stream at a normal dose and rapid onset
D
Decreased concentration of the drug in the blood stream at a normal dose and slow onset
Question 16

Drug metabolism disruption in liver disease can occur in part due to the liver’s decreased access to the drug (portal hypertension) and the liver’s decreased metabolic capabilities. What is another consequence of liver damage on drug availability?

A
The liver cannot produce bile
B
The liver cannot produce red blood cells
C
The liver cannot produce albumin
D
The liver cannot synthesise cholesterol to sequester hydrophobic drugs
Question 16 Explanation: 
Normally blood proteins like albumin bind to drugs in the bloodstream, reducing the concentration of free drug in the blood that is available to have an effect on its effectors. If the liver is damaged, it is not able to produce as these drug binding proteins (like albumin), resulting in an increased bio availability of the drug in the bloodstream.
Question 17

You have prescribed a normal dose of warfarin to a patient with liver disease. What should be your concern?

A
That the dose you administered is too high. Liver disease results in reduced albumin concentration in the blood stream increasing the bioavailability of warfarin
B
The dose you administered is too high. Liver disease results in increased albumin concentration in the blood stream increasing the bioavailability of warfarin
C
That the dose you administered is too low. Liver disease results in reduced conversion of warfarin into its active form
D
Warfarin is one of the drugs that are not impacted by liver disease. The normal dose can be followed.
Question 18

Which of the following is not a CYP3A inducer?

A
Carbamazepine
B
St. John’s wort
C
Rifampicin
D
Furosemide
Question 19
Which of the following is not a way in which doctors can reduce drug interactions?
A
Full medication history
B
Having a good understanding of cytochrome P450 metabolism
C
Using the BNF
D
Prescribing more herbal remedies
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