,NSG 533 Exam 2 - Advanced Pharmacology -
Wilkes University - (2026–2027) actual (PDF)
1. A 72-year-old man with atrial fibrillation is on warfarin 5 mg daily with a therapeutic INR of 2.4. He is
started on amiodarone for rhythm control. Two weeks later, his INR is 4.8 without bleeding. Which
pharmacokinetic mechanism best explains this interaction?
A) Amiodarone induces CYP3A4, increasing warfarin clearance
B) Amiodarone displaces warfarin from albumin binding sites
C) Amiodarone inhibits CYP2C9 and CYP1A2, reducing warfarin metabolism
D) Amiodarone increases warfarin renal excretion
Correct Answer: Amiodarone inhibits CYP2C9 and CYP1A2, reducing warfarin metabolism
Rationale: Amiodarone is a potent inhibitor of CYP2C9 and CYP1A2, the primary enzymes metabolizing
S-warfarin and R-warfarin. This inhibition reduces warfarin clearance, leading to elevated INR and
increased bleeding risk. Amiodarone does not induce metabolism, significantly displace warfarin from
albumin, or affect renal excretion.
2. A patient with epilepsy is started on phenytoin. The nurse practitioner knows that phenytoin exhibits
capacity-limited metabolism. Which clinical implication is most important?
A) The drug follows first-order kinetics at all therapeutic concentrations
B) Renal impairment requires major dose reductions
C) Small dose increases can produce disproportionately large increases in plasma concentration
D) Steady state is reached within 24 hours of initiation
Correct Answer: Small dose increases can produce disproportionately large increases in plasma
concentration
Rationale: Phenytoin follows zero-order (capacity-limited) kinetics at therapeutic concentrations. Once
metabolic enzymes are saturated, small dose increases cause disproportionately large concentration
increases and toxicity risk. It does not follow first-order kinetics at therapeutic levels, is not primarily
renally cleared, and has a long half-life with steady state taking 7–10 days.
3. A 58-year-old woman with depression is found to be a CYP2D6 poor metabolizer by
pharmacogenomic testing. She is prescribed tramadol 50 mg every 6 hours for chronic back pain. Which
outcome is most likely?
A) Enhanced analgesic effect due to increased active metabolite formation
,B) Reduced analgesic effect because tramadol requires CYP2D6 conversion to O-desmethyltramadol
C) Increased risk of serotonin syndrome due to impaired metabolism
D) Decreased risk of constipation due to reduced opioid receptor activation
Correct Answer: Reduced analgesic effect because tramadol requires CYP2D6 conversion to O-
desmethyltramadol
Rationale: Tramadol is a prodrug requiring CYP2D6-mediated O-demethylation to its active metabolite,
O-desmethyltramadol. Poor metabolizers have reduced conversion and diminished analgesia. Serotonin
syndrome risk is not the primary issue, and constipation is not significantly altered.
4. A patient with end-stage renal disease (eGFR 8 mL/min) is prescribed gentamicin for sepsis. The
pharmacist recommends extended-interval dosing (e.g., 5 mg/kg every 24–36 hours) rather than
traditional divided doses. Which pharmacokinetic rationale supports this approach?
A) Gentamicin is primarily hepatically metabolized, so renal impairment does not affect dosing
B) Extended-interval dosing exploits the concentration-dependent killing and post-antibiotic effect of
aminoglycosides
C) Traditional divided doses are more effective in renal impairment
D) Extended-interval dosing reduces the peak concentration to minimize nephrotoxicity
Correct Answer: Extended-interval dosing exploits the concentration-dependent killing and post-
antibiotic effect of aminoglycosides
Rationale: Aminoglycosides exhibit concentration-dependent killing and a post-antibiotic effect, making
high peak concentrations more effective. Extended-interval dosing achieves higher peaks while allowing
drug-free intervals to reduce toxicity. Gentamicin is renally excreted, not hepatically metabolized, and
requires dose adjustment in renal impairment.
5. A patient is started on a medication that is a high-extraction-ratio drug with significant first-pass
metabolism. Which route of administration would most effectively bypass first-pass metabolism to
achieve higher systemic bioavailability?
A) Oral
B) Sublingual
C) Intravenous
D) Intramuscular
Correct Answer: Sublingual
, Rationale: The sublingual route allows direct absorption into the systemic circulation via the rich venous
network under the tongue, bypassing the portal circulation and hepatic first-pass metabolism. Oral
administration undergoes extensive first-pass metabolism. Intravenous administration also bypasses
first-pass but is invasive; sublingual is the least invasive non-oral route that effectively bypasses first-
pass.
6. A drug has a volume of distribution (Vd) of 500 L. Which statement best describes the clinical
significance of this Vd?
A) The drug is primarily confined to the plasma compartment
B) The drug is highly protein-bound
C) The drug is extensively distributed into tissues
D) The drug has a short elimination half-life
Correct Answer: The drug is extensively distributed into tissues
Rationale: A Vd of 500 L far exceeds total body water (~42 L), indicating extensive tissue distribution.
Drugs with large Vd are sequestered in tissues, have long half-lives, and are not easily removed by
hemodialysis. Highly protein-bound drugs typically have small Vd, as they are largely confined to the
vascular compartment.
7. A patient with hypertension is started on a beta-blocker. Which receptor subtype is primarily
responsible for the drug's negative chronotropic effect on the heart?
A) Beta-1
B) Beta-2
C) Alpha-1
D) Alpha-2
Correct Answer: Beta-1
Rationale: Beta-1 receptors are predominant in the heart, where their stimulation increases heart rate
(chronotropy) and contractility. Beta-1 blockade produces negative chronotropic and inotropic effects.
Beta-2 receptors mediate bronchodilation and vasodilation. Alpha-1 and alpha-2 receptors are
adrenergic but are not primarily responsible for cardiac chronotropy.
8. A patient is prescribed a cholinergic agonist for postoperative ileus. Which receptor subtype mediates
the desired increase in gastrointestinal motility?
A) Nicotinic
Wilkes University - (2026–2027) actual (PDF)
1. A 72-year-old man with atrial fibrillation is on warfarin 5 mg daily with a therapeutic INR of 2.4. He is
started on amiodarone for rhythm control. Two weeks later, his INR is 4.8 without bleeding. Which
pharmacokinetic mechanism best explains this interaction?
A) Amiodarone induces CYP3A4, increasing warfarin clearance
B) Amiodarone displaces warfarin from albumin binding sites
C) Amiodarone inhibits CYP2C9 and CYP1A2, reducing warfarin metabolism
D) Amiodarone increases warfarin renal excretion
Correct Answer: Amiodarone inhibits CYP2C9 and CYP1A2, reducing warfarin metabolism
Rationale: Amiodarone is a potent inhibitor of CYP2C9 and CYP1A2, the primary enzymes metabolizing
S-warfarin and R-warfarin. This inhibition reduces warfarin clearance, leading to elevated INR and
increased bleeding risk. Amiodarone does not induce metabolism, significantly displace warfarin from
albumin, or affect renal excretion.
2. A patient with epilepsy is started on phenytoin. The nurse practitioner knows that phenytoin exhibits
capacity-limited metabolism. Which clinical implication is most important?
A) The drug follows first-order kinetics at all therapeutic concentrations
B) Renal impairment requires major dose reductions
C) Small dose increases can produce disproportionately large increases in plasma concentration
D) Steady state is reached within 24 hours of initiation
Correct Answer: Small dose increases can produce disproportionately large increases in plasma
concentration
Rationale: Phenytoin follows zero-order (capacity-limited) kinetics at therapeutic concentrations. Once
metabolic enzymes are saturated, small dose increases cause disproportionately large concentration
increases and toxicity risk. It does not follow first-order kinetics at therapeutic levels, is not primarily
renally cleared, and has a long half-life with steady state taking 7–10 days.
3. A 58-year-old woman with depression is found to be a CYP2D6 poor metabolizer by
pharmacogenomic testing. She is prescribed tramadol 50 mg every 6 hours for chronic back pain. Which
outcome is most likely?
A) Enhanced analgesic effect due to increased active metabolite formation
,B) Reduced analgesic effect because tramadol requires CYP2D6 conversion to O-desmethyltramadol
C) Increased risk of serotonin syndrome due to impaired metabolism
D) Decreased risk of constipation due to reduced opioid receptor activation
Correct Answer: Reduced analgesic effect because tramadol requires CYP2D6 conversion to O-
desmethyltramadol
Rationale: Tramadol is a prodrug requiring CYP2D6-mediated O-demethylation to its active metabolite,
O-desmethyltramadol. Poor metabolizers have reduced conversion and diminished analgesia. Serotonin
syndrome risk is not the primary issue, and constipation is not significantly altered.
4. A patient with end-stage renal disease (eGFR 8 mL/min) is prescribed gentamicin for sepsis. The
pharmacist recommends extended-interval dosing (e.g., 5 mg/kg every 24–36 hours) rather than
traditional divided doses. Which pharmacokinetic rationale supports this approach?
A) Gentamicin is primarily hepatically metabolized, so renal impairment does not affect dosing
B) Extended-interval dosing exploits the concentration-dependent killing and post-antibiotic effect of
aminoglycosides
C) Traditional divided doses are more effective in renal impairment
D) Extended-interval dosing reduces the peak concentration to minimize nephrotoxicity
Correct Answer: Extended-interval dosing exploits the concentration-dependent killing and post-
antibiotic effect of aminoglycosides
Rationale: Aminoglycosides exhibit concentration-dependent killing and a post-antibiotic effect, making
high peak concentrations more effective. Extended-interval dosing achieves higher peaks while allowing
drug-free intervals to reduce toxicity. Gentamicin is renally excreted, not hepatically metabolized, and
requires dose adjustment in renal impairment.
5. A patient is started on a medication that is a high-extraction-ratio drug with significant first-pass
metabolism. Which route of administration would most effectively bypass first-pass metabolism to
achieve higher systemic bioavailability?
A) Oral
B) Sublingual
C) Intravenous
D) Intramuscular
Correct Answer: Sublingual
, Rationale: The sublingual route allows direct absorption into the systemic circulation via the rich venous
network under the tongue, bypassing the portal circulation and hepatic first-pass metabolism. Oral
administration undergoes extensive first-pass metabolism. Intravenous administration also bypasses
first-pass but is invasive; sublingual is the least invasive non-oral route that effectively bypasses first-
pass.
6. A drug has a volume of distribution (Vd) of 500 L. Which statement best describes the clinical
significance of this Vd?
A) The drug is primarily confined to the plasma compartment
B) The drug is highly protein-bound
C) The drug is extensively distributed into tissues
D) The drug has a short elimination half-life
Correct Answer: The drug is extensively distributed into tissues
Rationale: A Vd of 500 L far exceeds total body water (~42 L), indicating extensive tissue distribution.
Drugs with large Vd are sequestered in tissues, have long half-lives, and are not easily removed by
hemodialysis. Highly protein-bound drugs typically have small Vd, as they are largely confined to the
vascular compartment.
7. A patient with hypertension is started on a beta-blocker. Which receptor subtype is primarily
responsible for the drug's negative chronotropic effect on the heart?
A) Beta-1
B) Beta-2
C) Alpha-1
D) Alpha-2
Correct Answer: Beta-1
Rationale: Beta-1 receptors are predominant in the heart, where their stimulation increases heart rate
(chronotropy) and contractility. Beta-1 blockade produces negative chronotropic and inotropic effects.
Beta-2 receptors mediate bronchodilation and vasodilation. Alpha-1 and alpha-2 receptors are
adrenergic but are not primarily responsible for cardiac chronotropy.
8. A patient is prescribed a cholinergic agonist for postoperative ileus. Which receptor subtype mediates
the desired increase in gastrointestinal motility?
A) Nicotinic
