NR565 ADVANCED PHARMACOLOGY FUNDAMENTALS
MIDTERM EXAM REVIEW 2026/2027 | 130 Q&A Highly Rated
Question Bank | Chamberlain College | Pass Guaranteed - A+
Graded
Unit 1: Pharmacokinetics & Pharmacodynamics (15 Questions)
Q1: A 68-year-old male with chronic kidney disease (eGFR 28 mL/min/1.73m²) is
prescribed metformin 1000 mg twice daily for newly diagnosed type 2 diabetes. His
serum creatinine is 2.4 mg/dL. Which pharmacokinetic principle most directly
contraindicates this prescribing decision?
A. Decreased hepatic first-pass metabolism in elderly patients increases metformin
bioavailability
B. Renal impairment significantly reduces metformin clearance, increasing risk of lactic
acidosis [CORRECT]
C. Metformin undergoes extensive cytochrome P450 3A4 metabolism, which is
impaired in CKD
D. Reduced plasma protein binding in renal disease increases metformin free fraction
Correct Answer: B
Rationale: Metformin is eliminated unchanged by renal tubular secretion with
approximately 90% renal clearance. In CKD Stage 4 (eGFR <30), metformin
accumulation occurs due to reduced renal clearance, significantly increasing the risk of
lactic acidosis. The FDA has established a contraindication for metformin when eGFR
,<30 mL/min/1.73m². Option A is incorrect because metformin undergoes minimal
hepatic metabolism (<5%). Option C is incorrect because metformin is not metabolized
by CYP450 enzymes. Option D is incorrect because metformin is not protein-bound
(100% free fraction), so changes in protein binding do not affect its pharmacokinetics.
Q2: A 45-year-old female presents with atrial fibrillation. Her provider considers
prescribing warfarin. Genetic testing reveals she is CYP2C9 *1/*3 and VKORC1
-1639A/A. Which pharmacogenomic principle applies?
A. She will require higher warfarin doses due to rapid CYP2C9 metabolism
B. She is at increased risk of bleeding and requires significantly lower initial doses
[CORRECT]
C. The VKORC1 variant increases warfarin resistance requiring dose escalation
D. CYP2C9 *3 variant increases vitamin K epoxide reductase activity
Correct Answer: B
Rationale: The CYP2C9 *3 allele reduces S-warfarin metabolism (30-50% reduction in
clearance), while the VKORC1 -1639A/A genotype indicates high sensitivity to warfarin
due to decreased VKORC1 expression. This combination predicts a 50-60% reduction in
warfarin dose requirement and significantly increased bleeding risk. Option A is
incorrect because *3 is a reduced-function allele. Option C is incorrect because
-1639A/A indicates sensitivity, not resistance. Option D is incorrect because CYP2C9
variants affect warfarin metabolism, not VKORC1 enzyme activity.
,Q3: A patient receiving digoxin 0.25 mg daily develops toxicity (nausea, visual
disturbances, ventricular arrhythmias). Concurrent medications include furosemide 40
mg BID and spironolactone 25 mg daily. Which pharmacokinetic interaction is most
responsible?
A. Furosemide inhibits P-glycoprotein-mediated renal digoxin secretion
B. Spironolactone competes for digoxin assay, causing falsely elevated levels
C. Hypokalemia from furosemide increases digoxin tissue binding and toxicity
[CORRECT]
D. Spironolactone inhibits CYP3A4-mediated digoxin hepatic metabolism
Correct Answer: C
Rationale: Digoxin toxicity is potentiated by hypokalemia because potassium and
digoxin compete for binding to the Na+/K+-ATPase pump. Furosemide-induced
potassium depletion increases digoxin binding to cardiac tissue, enhancing its
pharmacodynamic effects and toxicity. While spironolactone can interfere with digoxin
immunoassays (Option B), this does not cause true toxicity. Option A is incorrect
because furosemide does not significantly inhibit P-gp. Option D is incorrect because
digoxin undergoes minimal hepatic metabolism.
Q4: A 55-year-old male with hepatic cirrhosis (Child-Pugh Class C) requires analgesia for
acute pain. Which opioid requires the most significant dose reduction due to altered
pharmacokinetics?
A. Morphine
, B. Oxycodone
C. Fentanyl
D. Meperidine [CORRECT]
Correct Answer: D
Rationale: Meperidine undergoes extensive hepatic metabolism via N-demethylation to
normeperidine, a neurotoxic metabolite that accumulates in hepatic impairment,
causing seizures. In severe liver disease, meperidine clearance is reduced by 50% and
its half-life doubles. While morphine (Option A) has increased oral bioavailability due to
reduced first-pass metabolism, it is safer than meperidine. Oxycodone (Option B)
requires monitoring but is less problematic. Fentanyl (Option C) is metabolized by
CYP3A4 but has a large safety margin in acute use.
Q5: A patient receiving phenytoin 300 mg daily has a measured serum level of 8
mcg/mL (therapeutic range 10-20 mcg/mL). The prescriber increases the dose to 400
mg daily. Two weeks later, the level is 22 mcg/mL. Which pharmacokinetic principle
explains this disproportionate increase?
A. Phenytoin exhibits first-order kinetics at therapeutic concentrations
B. CYP2C9 and CYP2C19 metabolism becomes saturated at higher concentrations,
converting to zero-order kinetics [CORRECT]
C. Increased dose inhibits P-glycoprotein efflux from the brain
D. Higher doses increase phenytoin protein binding, reducing free drug clearance
MIDTERM EXAM REVIEW 2026/2027 | 130 Q&A Highly Rated
Question Bank | Chamberlain College | Pass Guaranteed - A+
Graded
Unit 1: Pharmacokinetics & Pharmacodynamics (15 Questions)
Q1: A 68-year-old male with chronic kidney disease (eGFR 28 mL/min/1.73m²) is
prescribed metformin 1000 mg twice daily for newly diagnosed type 2 diabetes. His
serum creatinine is 2.4 mg/dL. Which pharmacokinetic principle most directly
contraindicates this prescribing decision?
A. Decreased hepatic first-pass metabolism in elderly patients increases metformin
bioavailability
B. Renal impairment significantly reduces metformin clearance, increasing risk of lactic
acidosis [CORRECT]
C. Metformin undergoes extensive cytochrome P450 3A4 metabolism, which is
impaired in CKD
D. Reduced plasma protein binding in renal disease increases metformin free fraction
Correct Answer: B
Rationale: Metformin is eliminated unchanged by renal tubular secretion with
approximately 90% renal clearance. In CKD Stage 4 (eGFR <30), metformin
accumulation occurs due to reduced renal clearance, significantly increasing the risk of
lactic acidosis. The FDA has established a contraindication for metformin when eGFR
,<30 mL/min/1.73m². Option A is incorrect because metformin undergoes minimal
hepatic metabolism (<5%). Option C is incorrect because metformin is not metabolized
by CYP450 enzymes. Option D is incorrect because metformin is not protein-bound
(100% free fraction), so changes in protein binding do not affect its pharmacokinetics.
Q2: A 45-year-old female presents with atrial fibrillation. Her provider considers
prescribing warfarin. Genetic testing reveals she is CYP2C9 *1/*3 and VKORC1
-1639A/A. Which pharmacogenomic principle applies?
A. She will require higher warfarin doses due to rapid CYP2C9 metabolism
B. She is at increased risk of bleeding and requires significantly lower initial doses
[CORRECT]
C. The VKORC1 variant increases warfarin resistance requiring dose escalation
D. CYP2C9 *3 variant increases vitamin K epoxide reductase activity
Correct Answer: B
Rationale: The CYP2C9 *3 allele reduces S-warfarin metabolism (30-50% reduction in
clearance), while the VKORC1 -1639A/A genotype indicates high sensitivity to warfarin
due to decreased VKORC1 expression. This combination predicts a 50-60% reduction in
warfarin dose requirement and significantly increased bleeding risk. Option A is
incorrect because *3 is a reduced-function allele. Option C is incorrect because
-1639A/A indicates sensitivity, not resistance. Option D is incorrect because CYP2C9
variants affect warfarin metabolism, not VKORC1 enzyme activity.
,Q3: A patient receiving digoxin 0.25 mg daily develops toxicity (nausea, visual
disturbances, ventricular arrhythmias). Concurrent medications include furosemide 40
mg BID and spironolactone 25 mg daily. Which pharmacokinetic interaction is most
responsible?
A. Furosemide inhibits P-glycoprotein-mediated renal digoxin secretion
B. Spironolactone competes for digoxin assay, causing falsely elevated levels
C. Hypokalemia from furosemide increases digoxin tissue binding and toxicity
[CORRECT]
D. Spironolactone inhibits CYP3A4-mediated digoxin hepatic metabolism
Correct Answer: C
Rationale: Digoxin toxicity is potentiated by hypokalemia because potassium and
digoxin compete for binding to the Na+/K+-ATPase pump. Furosemide-induced
potassium depletion increases digoxin binding to cardiac tissue, enhancing its
pharmacodynamic effects and toxicity. While spironolactone can interfere with digoxin
immunoassays (Option B), this does not cause true toxicity. Option A is incorrect
because furosemide does not significantly inhibit P-gp. Option D is incorrect because
digoxin undergoes minimal hepatic metabolism.
Q4: A 55-year-old male with hepatic cirrhosis (Child-Pugh Class C) requires analgesia for
acute pain. Which opioid requires the most significant dose reduction due to altered
pharmacokinetics?
A. Morphine
, B. Oxycodone
C. Fentanyl
D. Meperidine [CORRECT]
Correct Answer: D
Rationale: Meperidine undergoes extensive hepatic metabolism via N-demethylation to
normeperidine, a neurotoxic metabolite that accumulates in hepatic impairment,
causing seizures. In severe liver disease, meperidine clearance is reduced by 50% and
its half-life doubles. While morphine (Option A) has increased oral bioavailability due to
reduced first-pass metabolism, it is safer than meperidine. Oxycodone (Option B)
requires monitoring but is less problematic. Fentanyl (Option C) is metabolized by
CYP3A4 but has a large safety margin in acute use.
Q5: A patient receiving phenytoin 300 mg daily has a measured serum level of 8
mcg/mL (therapeutic range 10-20 mcg/mL). The prescriber increases the dose to 400
mg daily. Two weeks later, the level is 22 mcg/mL. Which pharmacokinetic principle
explains this disproportionate increase?
A. Phenytoin exhibits first-order kinetics at therapeutic concentrations
B. CYP2C9 and CYP2C19 metabolism becomes saturated at higher concentrations,
converting to zero-order kinetics [CORRECT]
C. Increased dose inhibits P-glycoprotein efflux from the brain
D. Higher doses increase phenytoin protein binding, reducing free drug clearance
