Quiz 2

If a drug has very low clearance and a very large volume of distribution, and the fraction of
unbound drug (fub) doubles due to hepatic disease, how would the dose rate likely need to be
adjusted to maintain a constant free plasma drug concentration?
The dose rate should be halved
The dose rate should be adjusted only if the drug is highly lipophilic
The dose rate should be doubled
No dose rate adjustment is needed for a drug with very low clearance and very large volume of
distribution

Which of the following factors may affect the fraction of drug bound to plasma proteins?
Disease states such as hypoalbuminemia
Co-administration with other drugs competing for the same plasma protein
Non-linear protein binding, when the binding process undergoes saturation
All the indicated factors affect the fraction of drug bound to plasma proteins

If a drug has very high clearance and very small volume of distribution, and the fraction of
unbound drug (fub) doubles due to a hepatic disease, how would the dose rate likely need to be
adjusted to maintain a constant free plasma drug concentration?
The dose rate should be doubled
The dose rate should be halved
No dose rate adjustment is needed for a drug with very high clearance and very small volume of
distribution
The necessity for a dose rate adjustment will depend on the polarity of the drug

Which types of drugs does albumin preferentially bind to?

Basic drugs
Acidic drugs
Highly lipophilic drugs
Neutral drugs

Which of the following statements is correct for a drug with a very low clearance?
The clearance will likely not be affected by changes in the fraction of unbound drug (fub)
If the fraction of unbound drug (fub) increases, the clearance will decrease proportionally
If the fraction of unbound drug (fub) increases, the clearance will increase proportionally
None of the provided answers is correct

Which fraction of the total drug in the body can be considered the "biologically active" portion?
It depends on whether the drug has a large or small volume of distribution
The unbound fraction
The fraction that is bound to plasma proteins
The entire amount of drug in the body is biologically active, independently from the extent of its binding
Chlorpromazine (shown below) is a basic drug. As such, which plasma protein class is it most likely
to bind?

Lipoproteins
α1-Acid Glycoprotein (AAG)
Albumin
Chorpromazine binds to all the plasma proteins with the same affinity

Which of the following statements is correct for a drug with a very low volume of distribution
(Vss)?
The volume of distribution will likely not be affected by changes in the fraction of unbound drug (fub)
If the fraction of unbound drug (fub) increases, the volume of distribution will decrease proportionally
None of the provided answers is correct
If the fraction of unbound drug (fub) increases, the volume of distribution will increase proportionally

Which of the following statements is correct for drugs with linear plasma protein binding?
The drug will likely not bind to plasma proteins at all
All the drug present in the blood is bound to plasma proteins
The fraction of total drug bound to plasma protein will always vary with plasma drug concentration
At equilibrium, the fraction of total drug bound to plasma proteins is constant

Which of the following processes is influenced by a drug's extent of protein binding?

All the indicated processes
Excretion
Pharmacologic and Toxic effects
Metabolism

If a drug has a high hepatic extraction ratio (E)

the first pass effect will be substantial, so the bioavailability will be low
the first pass effect will be negligible, so the bioavailability will be low
the first pass effect will be substantial, so the bioavailability will be high
the first pass effect will be negligible, so the bioavailability will be high
What is the intrinsic clearance (Cl'int) of a drug?
An alternative definition of clearance
A property that is highly dependent on the hepatic blood flow
The ability of the liver to metabolize endogenous compounds
The innate ability of the liver to metabolize the drug when no limitations or barriers (e.g. given by the
blood flow) exist

What types of chemical reactions does the Phase I metabolism include?

All the indicated reactions are part of Phase I metabolism
Oxidation
Reduction
Hydrolysis

If the concentration of a drug in the blood entering the liver (Cin) is 400 mg/L, and the
concentration in the blood exiting the liver(Cout) is 20 mg/L, what is the hepatic Extraction ratio
(E) of the drug?
0.95
0.05
1.0
It cannot be calculated without knowing the hepatic blood flow (Q)

Simvastatin is a substrate of the CYP3A4 enzyme. What is the likely consequence of the
coadministration of Simvastatin with Clarithromycin, which is an inhibitor of CYP3A4?
Reduction of Simvastatin metabolism leading to reduced plasma Simvastatin concentration
Increased of Simvastatin metabolism leading to increased plasma Simvastatin concentration
Reduction of Simvastatin metabolism leading to increased plasma Simvastatin concentration
Increase of Simvastatin metabolism leading to increased plasma Simvastatin concentration

What happens when an inactive prodrug that is metabolysed by the CYP3A4 enzyme is
coadministered with a CYP3A4 inducer?
The plasma concentration of the active drug will remain unchanged
The plasma concentration of the active drug will increase
The plasma concentration of the active drug will decrease
The plasma concentration of the active drug will increase only if the drug has an extremely low volume
of distribution

Which of the following actions is recommended when prescribing a new drug for a patient with
possible hepatic dysfunction?
All the indicated actions are recommended
Checking how much of the drug's elimination depends on hepatic metabolism
Determining the degree of hepatic impairment
Determining whether the patient is already taking any drug that could interact with the new drug being
prescribed (e.g. inhibitor or inductor of the specific enzyme that metabolises the new drug)
If the clearance of a drug is decreased, for example because of a particular disease state, what
happens to the drug's half-life?
It remains unchanged
We cannot say it without knowing the drug's volume of distribution
It decreases proportionally
It increases proportionally

Which of the following is a correct definition of clearance?

The amount of drug removed from the body per unit time
The time needed to remove the drug from one liter of blood
The amount of plasma from which a substance is completely removed per unit time
The time needed to remove 100% of the drug from plasma

Knowing that the hepatic blood flow (QH) is 1.5 L/min, what is the hepatic clearance (ClH) of a
drug whose hepatic extraction ratio (E) is 0.2?
7.5 L/min
0.3 L/min ClH = QH * E
0.13 L/min
0.3 L/h

What is the rationale behind the "forced diuresis" used to detoxify a patient from a drug that is
reabsorbed in the distal tubule of the kidney?
Increasing the diuresis "dilutes" the drug in the urine, and the resulting lower concentration creates a less
"steep" gradient driving reabsorption from urine to blood
The ionized drug is trapped in the urine
The unionized drug is trapped in the urine
Increasing the diuresis increases the drug's concentration in urine, and this creates a less "steep" gradient
driving reabsorption from urine to blood

During the process of blood ultrafiltration occurring in the glomerulus of the kidney, which fraction
of the drug will be eliminated from the blood?
The fraction unbound to plasma proteins
The fraction which is bound to plasma protein
Both fractions of the drug, bound and unbound to plasma protein
Only the ionized fraction

During the process of passive reabsorption of a drug, occurring in the distal tubules of the kidney,
which fraction of the drug is reabsorbed from the kidney back to the blood?
The unionized fraction
The ionized fraction
The positively charged fraction
The negatively charged fraction
Question 4
0 / 1 pts
Which of the following is a component of renal clearance?
Correct Answer
All the indicated components are part of the renal clearance
You Answered
Clearance by secretion
Clearance by reabsorption
Clearance by filtration

Question 5
1 / 1 pts
If a drug has a very low fraction excreted unchanged in the urine (Fe) and a patient has severe renal
failure, would a dose adjustment likely be necessary?
Correct!
No, because being Fe low the drug's clearance will mainly rely on hepatic metabolism
No, because being Fe low the drug's clearance will mainly rely on renal excretion
Yes, because being Fe low the drug's clearance will mainly rely on hepatic metabolism
Yes, because being Fe low the drug's clearance will mainly rely on renal excretion

Question 6
1 / 1 pts
Which of the following factors influences the process of glomerular filtration of a drug?
Correct!
All the indicated factors
Molecular size
Plasma protein binding
Renal blood flow (QR)

Question 7
0 / 1 pts
If 70% of a drug is bound to plasma proteins (fub = 0.7), and the glomerular filtration rate (GRF) is 125
mL/min, what will the clearance by filtration (Clfilt) be?
Correct Answer
87.5 mL/min
You Answered
178.6 mL/min
Clfilt = fub * GFR
0.0056 mL/min
87.5 L/h

Question 8
0 / 1 pts
If the fraction excreted unchanged (Fe) of a drug is very close to 1
Correct Answer
the drug's clearance will be mostly renal
You Answered
the drug 's clearance will be mostly hepatic
the drug's clearance will depend on both liver and kidneys equally
the drug's clearance will be highly impacted by hepatic diseases

Question 9
1 / 1 pts
If the total renal clearance of a drug is 0.2 mL/min, and its clearance by filtration (calculated by
multiplying fub * GFR) is 15 mL/min, which process will be predominant in determining the renal
clearance?
Correct!
Reabsorption
Secretion
Filtration
Reabsorption and Secretion will be equally important

Question 10
0 / 1 pts
An important characteristic of drug's active secretion, occurring in the proximal tubule of the kidney, is
that
Correct Answer
it is an energy dependent process
You Answered
it only transports drug following a concentration gradient, from a high concentration compartment to a
low concentration compartment
it only occurs for cationic drugs
it only occurs for anionic drugs