, Question 1
A drug undergoes extensive first-pass metabolism by CYP3A4 in the gut wall
and liver. If the same total daily dose is administered intravenously instead of
orally, which parameter is most directly altered, and how does this change the
steady-state concentration?
A. Volume of distribution decreases, lowering steady-state concentration.
B. Bioavailability increases, raising steady-state concentration
proportionally.
C. Clearance increases, lowering steady-state concentration.
D. Half-life decreases, raising steady-state concentration.
Correct Answer: B - Bioavailability increases, raising steady-state
concentration proportionally.
RATIONALE
First-pass metabolism reduces oral bioavailability (F); IV
administration bypasses this, increasing F toward 1 and proportionally
raising Css = (F-Dose)/(CL-). Volume of distribution and clearance are
independent of route, so A and C are incorrect; half-life is a function
of Vd and CL, not route, making D incorrect.
Question 2
A patient carrying two reduced-function alleles for CYP2C19 is started on
clopidogrel. Which mechanistic consequence best explains the anticipated
therapeutic failure, and what is the most appropriate management?
A. Clopidogrel is a prodrug requiring CYP2C19 activation; consider
prasugrel or ticagrelor.
B. Clopidogrel is active and CYP2C19 inactivates it; reduce the dose to
avoid toxicity.
C. CYP2C19 poor metabolism increases active metabolite; monitor for
bleeding.
D. CYP2C19 genotype does not affect clopidogrel; no change is needed.
Page 2
,Correct Answer: A - Clopidogrel is a prodrug requiring
CYP2C19 activation; consider prasugrel or ticagrelor.
RATIONALE
Clopidogrel is a prodrug bioactivated by CYP2C19; poor metabolizers
form less active metabolite and have reduced antiplatelet effect, so
alternative P2Y12 inhibitors are recommended per CPIC. Options B,
C, and D misstate the metabolic pathway or ignore established
pharmacogenomic evidence.
Question 3
Which statement most accurately distinguishes a drug's potency from its
efficacy?
A. Potency is the maximal response; efficacy is the dose required to
produce it.
B. Potency is the dose required to produce a given effect; efficacy is the
maximal response achievable.
C. Both terms describe the same property and are interchangeable.
D. Potency determines therapeutic index; efficacy determines
bioavailability.
Correct Answer: B - Potency is the dose required to produce a
given effect; efficacy is the maximal response achievable.
RATIONALE
Potency refers to the amount of drug needed to produce a given effect
(related to EC50/ED50), whereas efficacy is the maximal effect a drug
can produce. A reverses the definitions; C is false; D confuses
unrelated concepts, as therapeutic index reflects safety and
bioavailability reflects absorption.
Page 3
, Question 4
A patient with cirrhosis (Child-Pugh C) is prescribed a drug that is highly
protein-bound and hepatically cleared. Which pharmacokinetic alteration is
most likely, and what is the safest initial approach?
A. Increased albumin binding reduces free drug; give standard dose.
B. Decreased hepatic clearance and hypoalbuminemia increase free drug;
reduce dose and monitor.
C. Renal clearance compensates fully; no adjustment is needed.
D. Hepatic blood flow increases, raising clearance; increase dose.
Correct Answer: B - Decreased hepatic clearance and
hypoalbuminemia increase free drug; reduce dose and monitor.
RATIONALE
Cirrhosis reduces hepatic metabolism and albumin, increasing the free
fraction of highly bound drugs, so lower initial doses with close
monitoring are prudent. A and D incorrectly predict increased binding
or clearance; C ignores the primary hepatic elimination pathway.
Question 5
A patient on warfarin is started on rifampin. Which mechanism best explains
the expected change in INR, and what monitoring action is indicated?
A. Rifampin inhibits CYP2C9, raising INR; reduce warfarin dose.
B. Rifampin induces CYP2C9 and CYP3A4, lowering INR; increase
monitoring and anticipate dose adjustment.
C. Rifampin displaces warfarin from albumin, raising INR; no change
needed.
D. Rifampin has no effect on warfarin; continue current regimen.
Correct Answer: B - Rifampin induces CYP2C9 and CYP3A4,
lowering INR; increase monitoring and anticipate dose
adjustment.
Page 4
A drug undergoes extensive first-pass metabolism by CYP3A4 in the gut wall
and liver. If the same total daily dose is administered intravenously instead of
orally, which parameter is most directly altered, and how does this change the
steady-state concentration?
A. Volume of distribution decreases, lowering steady-state concentration.
B. Bioavailability increases, raising steady-state concentration
proportionally.
C. Clearance increases, lowering steady-state concentration.
D. Half-life decreases, raising steady-state concentration.
Correct Answer: B - Bioavailability increases, raising steady-state
concentration proportionally.
RATIONALE
First-pass metabolism reduces oral bioavailability (F); IV
administration bypasses this, increasing F toward 1 and proportionally
raising Css = (F-Dose)/(CL-). Volume of distribution and clearance are
independent of route, so A and C are incorrect; half-life is a function
of Vd and CL, not route, making D incorrect.
Question 2
A patient carrying two reduced-function alleles for CYP2C19 is started on
clopidogrel. Which mechanistic consequence best explains the anticipated
therapeutic failure, and what is the most appropriate management?
A. Clopidogrel is a prodrug requiring CYP2C19 activation; consider
prasugrel or ticagrelor.
B. Clopidogrel is active and CYP2C19 inactivates it; reduce the dose to
avoid toxicity.
C. CYP2C19 poor metabolism increases active metabolite; monitor for
bleeding.
D. CYP2C19 genotype does not affect clopidogrel; no change is needed.
Page 2
,Correct Answer: A - Clopidogrel is a prodrug requiring
CYP2C19 activation; consider prasugrel or ticagrelor.
RATIONALE
Clopidogrel is a prodrug bioactivated by CYP2C19; poor metabolizers
form less active metabolite and have reduced antiplatelet effect, so
alternative P2Y12 inhibitors are recommended per CPIC. Options B,
C, and D misstate the metabolic pathway or ignore established
pharmacogenomic evidence.
Question 3
Which statement most accurately distinguishes a drug's potency from its
efficacy?
A. Potency is the maximal response; efficacy is the dose required to
produce it.
B. Potency is the dose required to produce a given effect; efficacy is the
maximal response achievable.
C. Both terms describe the same property and are interchangeable.
D. Potency determines therapeutic index; efficacy determines
bioavailability.
Correct Answer: B - Potency is the dose required to produce a
given effect; efficacy is the maximal response achievable.
RATIONALE
Potency refers to the amount of drug needed to produce a given effect
(related to EC50/ED50), whereas efficacy is the maximal effect a drug
can produce. A reverses the definitions; C is false; D confuses
unrelated concepts, as therapeutic index reflects safety and
bioavailability reflects absorption.
Page 3
, Question 4
A patient with cirrhosis (Child-Pugh C) is prescribed a drug that is highly
protein-bound and hepatically cleared. Which pharmacokinetic alteration is
most likely, and what is the safest initial approach?
A. Increased albumin binding reduces free drug; give standard dose.
B. Decreased hepatic clearance and hypoalbuminemia increase free drug;
reduce dose and monitor.
C. Renal clearance compensates fully; no adjustment is needed.
D. Hepatic blood flow increases, raising clearance; increase dose.
Correct Answer: B - Decreased hepatic clearance and
hypoalbuminemia increase free drug; reduce dose and monitor.
RATIONALE
Cirrhosis reduces hepatic metabolism and albumin, increasing the free
fraction of highly bound drugs, so lower initial doses with close
monitoring are prudent. A and D incorrectly predict increased binding
or clearance; C ignores the primary hepatic elimination pathway.
Question 5
A patient on warfarin is started on rifampin. Which mechanism best explains
the expected change in INR, and what monitoring action is indicated?
A. Rifampin inhibits CYP2C9, raising INR; reduce warfarin dose.
B. Rifampin induces CYP2C9 and CYP3A4, lowering INR; increase
monitoring and anticipate dose adjustment.
C. Rifampin displaces warfarin from albumin, raising INR; no change
needed.
D. Rifampin has no effect on warfarin; continue current regimen.
Correct Answer: B - Rifampin induces CYP2C9 and CYP3A4,
lowering INR; increase monitoring and anticipate dose
adjustment.
Page 4
