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
Define first pass metabolism
When a drug is processed by the liver before entering the systemic circulation
When a drug is processed by the intestines and enters the hepatic portal system
When a drug is processed by the intestines and enters the systemic circulation
When a drug is processed by the stomach and enters the small intestine
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)?
Reduced concentration of the drug in the systemic circulation
Increased concentration of the drug in the systemic circulation
The drug would not reach the blood due to high pressure of the blood portal system
Serum concentrations of the drug are unaltered in portal hypertension
What are the four main phases of drug metabolism?
Absorption, alteration, excretion, effect
Absorption, transport, distribution, excretion
Absorption, distribution, metabolism, excretion
Distribution, transport, alteration, conjugation
Adding a glucuronyl group using a conjugation reaction occurs at which stage?
Renders the drug acidic
Renders the drug active
Renders the drug inactive
Renders the drug more polar
What are the requirements of cytochrome P450 enzymes to complete oxidation reactions?
Molecular oxygen, NADPH+, NADPH cytochrome P450 reductase, protons
Molecular oxygen, NADPH+, NADPH cytochrome P450 reductase
Water, NADPH+, NADPH cytochrome P450 reductase
NADPH+, NADPH cytochrome P450 reductase, protons
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?
What are the 3 main reactions that occur during phase I metabolism?
Hydrogenation, oxidation, reduction
Oxidation, reduction, hydrolysis
epoxidation, polymerisation, hydrolysis
condensation, elimination, oxidation
Which of the following is not part of a phase III reaction?
Release into the circulation for renal excretion
Release into bile for elimination in faeces
Membrane bound transport carriers remove hydrophilic metabolites from hepatocytes
Bound to haemoglobin to be excreted by the lungs
When prescribing for a neonate, the dosage must be altered due to:
Increased drug metabolism due to the presence of a high concentration of liver enzymes in the blood stream
Immature hepatocytes and renal podocytes
Inability of the neonate to swallow the drug
Inability of the neonate to produce bile salts
An elderly patient is prescribed ketamine at the standard dose for a 25 year old adult. Why is this a problem?
Because elderly individuals do not make the enzymes to metabolise the drug
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
They have difficulty swallowing the drug
Administration of ramipril is difficult so compliance is reduced
Which of the following is not an example of a drug that is metabolised by CYP3A?
Calcium channel blockers
A patient is on contraception and reveals to you that they are taking St. John’s wort. What is the issue with this?
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
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.
There is no issue, this is a herbal supplement and does not have an impact on drug metabolism
The drug increases albumin levels and thus decreases drug bioavailability, requiring you to prescribe a higher dose of the drug to reach therapeutic levels.
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?
Decreased concentration of the drug in the blood stream at a normal dose
Increased concentration of the drug in the blood stream at a normal dose
Partial decrease in concentration of the drug in the blood stream at a normal dose
The drug does not reach the bloodstream as it is inactivated by stomach acid
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?
Increased concentration of the drug in the blood stream at a normal dose and rapid onset
Increased concentration of the drug in the blood stream at a normal dose and slow onset
Decreased concentration of the drug in the blood stream at a normal dose and rapid onset
Decreased concentration of the drug in the blood stream at a normal dose and slow onset
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?
The liver cannot produce bile
The liver cannot produce red blood cells
The liver cannot produce albumin
The liver cannot synthesise cholesterol to sequester hydrophobic drugs
You have prescribed a normal dose of warfarin to a patient with liver disease. What should be your concern?
That the dose you administered is too high. Liver disease results in reduced albumin concentration in the blood stream increasing the bioavailability of warfarin
The dose you administered is too high. Liver disease results in increased albumin concentration in the blood stream increasing the bioavailability of warfarin
That the dose you administered is too low. Liver disease results in reduced conversion of warfarin into its active form
Warfarin is one of the drugs that are not impacted by liver disease. The normal dose can be followed.
Which of the following is not a CYP3A inducer?
St. John’s wort
Full medication history
Having a good understanding of cytochrome P450 metabolism
Using the BNF
Prescribing more herbal remedies