NR 565 ADVANCED PHARMACOLOGY FINAL EXAM 2025 – VERSION A
DOMAIN 1: PHARMACOKINETICS & PHARMACODYNAMICS
A 75-year-old patient with severe chronic pain is prescribed morphine for analgesia.
The prescriber chooses hydromorphone instead due to the patient’s renal
impairment (CrCl 25 mL/min). What is the primary pharmacokinetic rationale for this
change?
A) Morphine undergoes extensive first-pass metabolism, reducing its bioavailability.
B) Morphine’s active metabolite, morphine-6-glucuronide (M6G), accumulates in
renal impairment, causing neurotoxicity.
C) Hydromorphone is a prodrug that requires renal activation to be effective.
D) Morphine is highly protein-bound, and renal impairment displaces it, increasing
free drug.
Answer: B
1. Rationale: Morphine is metabolized in the liver to M6G (potent analgesic) and
morphine-3-glucuronide (neuroexcitatory). Both are renally excreted and
accumulate in renal impairment, leading to respiratory depression and
myoclonus. Hydromorphone does not have these toxic renally-cleared
metabolites.
A patient taking phenobarbital (a CYP450 enzyme inducer) is started on a new oral
contraceptive. What is the expected pharmacokinetic outcome?
A) Increased bioavailability of the contraceptive.
B) Decreased clearance of the contraceptive.
C) Increased clearance of the contraceptive, reducing its efficacy.
D) Inhibition of hepatic metabolism of the contraceptive.
Answer: C
2. Rationale: Phenobarbital induces CYP3A4 and CYP2C9, increasing the
metabolism (clearance) of oral contraceptives, leading to decreased serum
levels and potential contraceptive failure.
A drug has a half-life of 12 hours. How long will it take to reach approximately 94% of
steady-state concentration with continuous dosing?
A) 24 hours
B) 36 hours
C) 48 hours
D) 60 hours
Answer: C
3. Rationale: It takes approximately 4 to 5 half-lives to reach steady state. 4
half-lives (48 hours) equals 93.75%, which rounds to approximately 94%.
,Which of the following scenarios best describes a pharmacodynamic drug
interaction?
A) Cholestyramine binds to warfarin in the GI tract, preventing its absorption.
B) Phenytoin induces hepatic enzymes, increasing the metabolism of theophylline.
C) A beta-blocker masks the tachycardia normally experienced with hypoglycemia.
D) Probenecid blocks the renal tubular secretion of penicillin.
Answer: C
4. Rationale: Pharmacodynamic interactions occur when drugs have additive,
synergistic, or antagonistic effects at the receptor site. Masking the warning
signs of hypoglycemia (tachycardia) is an antagonistic pharmacodynamic
effect. A and D are pharmacokinetic (absorption/elimination). B is
pharmacokinetic (metabolism).
A patient with a genetic polymorphism resulting in a deficiency of the CYP2D6
enzyme is prescribed codeine for a fracture. What is the anticipated clinical
outcome?
A) Enhanced analgesia due to increased codeine levels.
B) Lack of analgesia because codeine cannot be converted to morphine.
C) Increased risk of respiratory depression due to rapid morphine accumulation.
D) Rapid clearance of codeine leading to subtherapeutic effects.
Answer: B
5. Rationale: Codeine is a prodrug that relies on CYP2D6 to be converted to its
active analgesic metabolite, morphine. A CYP2D6 poor metabolizer will not
convert codeine effectively, resulting in no analgesia.
A patient is prescribed a highly lipophilic drug. Which pharmacokinetic property is
most closely associated with lipophilic drugs?
A) High volume of distribution.
B) Primarily confined to the vascular compartment.
C) Rapid renal excretion without metabolism.
D) Short half-life.
Answer: A
6. Rationale: Lipophilic drugs readily cross cell membranes and distribute into
adipose tissue and organs, resulting in a large volume of distribution (Vd).
DOMAIN 2: CARDIOVASCULAR DISORDERS
According to the 2022 AHA/ACC Heart Failure Guidelines, which of the following
medication classes is foundational therapy for patients with Heart Failure with
reduced Ejection Fraction (HFrEF) to reduce mortality, regardless of diabetes status?
A) Calcium channel blockers
B) SGLT2 inhibitors (e.g., dapagliflozin)
C) Alpha-1 blockers
,D) Loop diuretics
Answer: B
7. Rationale: SGLT2 inhibitors (along with ARNI, Beta-blockers, and MRAs) are
the four pillars of guideline-directed medical therapy (GDMT) for HFrEF,
proven to reduce CV death and HF hospitalizations. Loop diuretics are for
symptom relief (fluid removal) but do not reduce mortality.
A patient with HFrEF is initiated on Sacubitril/Valsartan (Entresto). What is the critical
prescribing instruction regarding the transition from an ACE inhibitor?
A) Switch immediately from ACEi to Entresto at the same dose.
B) Allow a 36-hour washout period after stopping the ACEi before starting Entresto.
C) Co-administer the ACEi and Entresto for 2 weeks to ensure tolerance.
D) Reduce the ACEi dose by 50% when adding Entresto.
Answer: B
8. Rationale: Sacubitril inhibits neprilysin, which degrades bradykinin. Combined
with ACEi inhibition of ACE (which also breaks down bradykinin), this causes
profound, life-threatening angioedema. A 36-hour washout of the ACEi is
mandatory.
A patient with atrial fibrillation and a CHA2DS2-VASc score of 3 is prescribed
apixaban. What condition in this patient mandates a dose reduction of apixaban from
5 mg twice daily to 2.5 mg twice daily?
A) Age > 65 years.
B) Concurrent use of amiodarone.
C) Presence of two of the following: Serum creatinine ≥1.5 mg/dL, body weight ≤60
kg, age ≥80 years.
D) History of peptic ulcer disease.
Answer: C
9. Rationale: The FDA-approved dose reduction criteria for apixaban in
non-valvular AFib require meeting at least two of three criteria: Cr ≥1.5, weight
≤60 kg, or age ≥80.
A patient on warfarin has an INR of 7.2 but is not actively bleeding. According to
current guidelines, what is the most appropriate management?
A) Administer fresh frozen plasma (FFP) immediately.
B) Administer Phytonadione (Vitamin K) 2.5 to 5 mg orally.
C) Hold the next dose of warfarin and recheck INR in 24 hours.
D) Administer Prothrombin Complex Concentrate (PCC).
Answer: B
10.Rationale: For asymptomatic INR elevation >10, guidelines recommend
holding warfarin and giving oral Vitamin K (2.5-5 mg). FFP and PCC are
, reserved for life-threatening bleeding. Simply holding the dose is insufficient
for an INR this high due to the high risk of spontaneous bleeding.
A patient with a history of hypertension and benign prostatic hyperplasia (BPH) is
started on doxazosin. What is the primary cardiovascular adverse effect the
prescriber should warn the patient about?
A) Reflex tachycardia.
B) First-dose hypotension (syncope).
C) Peripheral edema.
D) Bradycardia.
Answer: B
11.Rationale: Alpha-1 blockers cause venous and arterial dilation. The first dose
can cause profound orthostatic hypotension, so it should be given at bedtime.
Which of the following calcium channel blockers is a dihydropyridine (DHP) and acts
primarily on vascular smooth muscle, making it a preferred agent for angina and
hypertension but contraindicated in HFrEF due to reflex tachycardia?
A) Diltiazem
B) Verapamil
C) Amlodipine
D) Atenolol
Answer: C
12.Rationale: Amlodipine is a DHP CCB. Diltiazem and verapamil are
non-dihydropyridines (act on the heart, causing bradycardia and negative
inotropy). Atenolol is a beta-blocker.
A patient with acute coronary syndrome (ACS) is prescribed ticagrelor instead of
clopidogrel. What is a unique adverse effect of ticagrelor that the patient must be
monitored for?
A) Thrombotic thrombocytopenic purpura (TTP).
B) Dyspnea.
C) Severe neutropenia.
D) Ototoxicity.
Answer: B
13.Rationale: Ticagrelor inhibits cellular uptake of adenosine, leading to dyspnea
in up to 14% of patients. TTP and severe neutropenia are rare adverse effects
associated with clopidogrel/ticlopidine.
A patient with stage 2 hypertension and a history of gout is being selected for initial
monotherapy. Which of the following is contraindicated?
A) Lisinopril
B) Losartan
C) Hydrochlorothiazide
DOMAIN 1: PHARMACOKINETICS & PHARMACODYNAMICS
A 75-year-old patient with severe chronic pain is prescribed morphine for analgesia.
The prescriber chooses hydromorphone instead due to the patient’s renal
impairment (CrCl 25 mL/min). What is the primary pharmacokinetic rationale for this
change?
A) Morphine undergoes extensive first-pass metabolism, reducing its bioavailability.
B) Morphine’s active metabolite, morphine-6-glucuronide (M6G), accumulates in
renal impairment, causing neurotoxicity.
C) Hydromorphone is a prodrug that requires renal activation to be effective.
D) Morphine is highly protein-bound, and renal impairment displaces it, increasing
free drug.
Answer: B
1. Rationale: Morphine is metabolized in the liver to M6G (potent analgesic) and
morphine-3-glucuronide (neuroexcitatory). Both are renally excreted and
accumulate in renal impairment, leading to respiratory depression and
myoclonus. Hydromorphone does not have these toxic renally-cleared
metabolites.
A patient taking phenobarbital (a CYP450 enzyme inducer) is started on a new oral
contraceptive. What is the expected pharmacokinetic outcome?
A) Increased bioavailability of the contraceptive.
B) Decreased clearance of the contraceptive.
C) Increased clearance of the contraceptive, reducing its efficacy.
D) Inhibition of hepatic metabolism of the contraceptive.
Answer: C
2. Rationale: Phenobarbital induces CYP3A4 and CYP2C9, increasing the
metabolism (clearance) of oral contraceptives, leading to decreased serum
levels and potential contraceptive failure.
A drug has a half-life of 12 hours. How long will it take to reach approximately 94% of
steady-state concentration with continuous dosing?
A) 24 hours
B) 36 hours
C) 48 hours
D) 60 hours
Answer: C
3. Rationale: It takes approximately 4 to 5 half-lives to reach steady state. 4
half-lives (48 hours) equals 93.75%, which rounds to approximately 94%.
,Which of the following scenarios best describes a pharmacodynamic drug
interaction?
A) Cholestyramine binds to warfarin in the GI tract, preventing its absorption.
B) Phenytoin induces hepatic enzymes, increasing the metabolism of theophylline.
C) A beta-blocker masks the tachycardia normally experienced with hypoglycemia.
D) Probenecid blocks the renal tubular secretion of penicillin.
Answer: C
4. Rationale: Pharmacodynamic interactions occur when drugs have additive,
synergistic, or antagonistic effects at the receptor site. Masking the warning
signs of hypoglycemia (tachycardia) is an antagonistic pharmacodynamic
effect. A and D are pharmacokinetic (absorption/elimination). B is
pharmacokinetic (metabolism).
A patient with a genetic polymorphism resulting in a deficiency of the CYP2D6
enzyme is prescribed codeine for a fracture. What is the anticipated clinical
outcome?
A) Enhanced analgesia due to increased codeine levels.
B) Lack of analgesia because codeine cannot be converted to morphine.
C) Increased risk of respiratory depression due to rapid morphine accumulation.
D) Rapid clearance of codeine leading to subtherapeutic effects.
Answer: B
5. Rationale: Codeine is a prodrug that relies on CYP2D6 to be converted to its
active analgesic metabolite, morphine. A CYP2D6 poor metabolizer will not
convert codeine effectively, resulting in no analgesia.
A patient is prescribed a highly lipophilic drug. Which pharmacokinetic property is
most closely associated with lipophilic drugs?
A) High volume of distribution.
B) Primarily confined to the vascular compartment.
C) Rapid renal excretion without metabolism.
D) Short half-life.
Answer: A
6. Rationale: Lipophilic drugs readily cross cell membranes and distribute into
adipose tissue and organs, resulting in a large volume of distribution (Vd).
DOMAIN 2: CARDIOVASCULAR DISORDERS
According to the 2022 AHA/ACC Heart Failure Guidelines, which of the following
medication classes is foundational therapy for patients with Heart Failure with
reduced Ejection Fraction (HFrEF) to reduce mortality, regardless of diabetes status?
A) Calcium channel blockers
B) SGLT2 inhibitors (e.g., dapagliflozin)
C) Alpha-1 blockers
,D) Loop diuretics
Answer: B
7. Rationale: SGLT2 inhibitors (along with ARNI, Beta-blockers, and MRAs) are
the four pillars of guideline-directed medical therapy (GDMT) for HFrEF,
proven to reduce CV death and HF hospitalizations. Loop diuretics are for
symptom relief (fluid removal) but do not reduce mortality.
A patient with HFrEF is initiated on Sacubitril/Valsartan (Entresto). What is the critical
prescribing instruction regarding the transition from an ACE inhibitor?
A) Switch immediately from ACEi to Entresto at the same dose.
B) Allow a 36-hour washout period after stopping the ACEi before starting Entresto.
C) Co-administer the ACEi and Entresto for 2 weeks to ensure tolerance.
D) Reduce the ACEi dose by 50% when adding Entresto.
Answer: B
8. Rationale: Sacubitril inhibits neprilysin, which degrades bradykinin. Combined
with ACEi inhibition of ACE (which also breaks down bradykinin), this causes
profound, life-threatening angioedema. A 36-hour washout of the ACEi is
mandatory.
A patient with atrial fibrillation and a CHA2DS2-VASc score of 3 is prescribed
apixaban. What condition in this patient mandates a dose reduction of apixaban from
5 mg twice daily to 2.5 mg twice daily?
A) Age > 65 years.
B) Concurrent use of amiodarone.
C) Presence of two of the following: Serum creatinine ≥1.5 mg/dL, body weight ≤60
kg, age ≥80 years.
D) History of peptic ulcer disease.
Answer: C
9. Rationale: The FDA-approved dose reduction criteria for apixaban in
non-valvular AFib require meeting at least two of three criteria: Cr ≥1.5, weight
≤60 kg, or age ≥80.
A patient on warfarin has an INR of 7.2 but is not actively bleeding. According to
current guidelines, what is the most appropriate management?
A) Administer fresh frozen plasma (FFP) immediately.
B) Administer Phytonadione (Vitamin K) 2.5 to 5 mg orally.
C) Hold the next dose of warfarin and recheck INR in 24 hours.
D) Administer Prothrombin Complex Concentrate (PCC).
Answer: B
10.Rationale: For asymptomatic INR elevation >10, guidelines recommend
holding warfarin and giving oral Vitamin K (2.5-5 mg). FFP and PCC are
, reserved for life-threatening bleeding. Simply holding the dose is insufficient
for an INR this high due to the high risk of spontaneous bleeding.
A patient with a history of hypertension and benign prostatic hyperplasia (BPH) is
started on doxazosin. What is the primary cardiovascular adverse effect the
prescriber should warn the patient about?
A) Reflex tachycardia.
B) First-dose hypotension (syncope).
C) Peripheral edema.
D) Bradycardia.
Answer: B
11.Rationale: Alpha-1 blockers cause venous and arterial dilation. The first dose
can cause profound orthostatic hypotension, so it should be given at bedtime.
Which of the following calcium channel blockers is a dihydropyridine (DHP) and acts
primarily on vascular smooth muscle, making it a preferred agent for angina and
hypertension but contraindicated in HFrEF due to reflex tachycardia?
A) Diltiazem
B) Verapamil
C) Amlodipine
D) Atenolol
Answer: C
12.Rationale: Amlodipine is a DHP CCB. Diltiazem and verapamil are
non-dihydropyridines (act on the heart, causing bradycardia and negative
inotropy). Atenolol is a beta-blocker.
A patient with acute coronary syndrome (ACS) is prescribed ticagrelor instead of
clopidogrel. What is a unique adverse effect of ticagrelor that the patient must be
monitored for?
A) Thrombotic thrombocytopenic purpura (TTP).
B) Dyspnea.
C) Severe neutropenia.
D) Ototoxicity.
Answer: B
13.Rationale: Ticagrelor inhibits cellular uptake of adenosine, leading to dyspnea
in up to 14% of patients. TTP and severe neutropenia are rare adverse effects
associated with clopidogrel/ticlopidine.
A patient with stage 2 hypertension and a history of gout is being selected for initial
monotherapy. Which of the following is contraindicated?
A) Lisinopril
B) Losartan
C) Hydrochlorothiazide
