NURS 6521N Advanced
Pharmacology Midterm Exam
SECTION A: PHARMACOLOGICAL PRINCIPLES (Q1-10)
Question 1
A novel antihypertensive agent is discovered to increase intracellular cyclic GMP (cGMP)
concentrations in vascular smooth muscle, resulting in net vasodilation and decreased
systemic vascular resistance. The pharmacologic mechanism of this agent is MOST similar
to which prototype drug?
A. Lisinopril (ACE inhibitor)
B. Losartan (angiotensin II receptor blocker)
C. Nitroprusside (direct NO donor) [CORRECT]
D. Metoprolol (beta-1 selective blocker)
Correct Answer: C
Rationale: Nitroprusside spontaneously releases nitric oxide (NO), which diffuses into
vascular smooth muscle and activates soluble guanylyl cyclase (sGC), catalyzing the
conversion of GTP to cGMP. Elevated cGMP activates protein kinase G (PKG), leading to
sequestration of cytosolic calcium, myosin light chain dephosphorylation, and vasodilation.
The described novel drug shares this NO-cGMP-PKG signaling cascade. ACE inhibitors (A)
block angiotensin-converting enzyme, reducing angiotensin II and increasing bradykinin
(which indirectly increases NO but is not the primary mechanism). ARBs (B) antagonize AT1
receptors. Beta-blockers (D) competitively inhibit catecholamine binding to beta-adrenergic
receptors, reducing cAMP production.
Question 2
A 68-year-old male with atrial fibrillation on warfarin requires initiation of phenytoin for
seizure prophylaxis following neurosurgery. The prescriber anticipates a need to adjust
warfarin dosing. This interaction occurs primarily through which pharmacokinetic
mechanism?
,A. Phenytoin inhibits CYP2C9, reducing warfarin metabolism
B. Phenytoin induces CYP1A2, increasing R-warfarin clearance
C. Phenytoin induces CYP2C9 and CYP3A4, increasing S-warfarin metabolism [CORRECT]
D. Phenytoin displaces warfarin from albumin binding sites
Correct Answer: C
Rationale: Phenytoin is a potent hepatic enzyme inducer, specifically upregulating CYP2C9
and CYP3A4 isoforms. S-warfarin (the more potent enantiomer metabolized by CYP2C9)
clearance increases, potentially decreasing INR. However, phenytoin also has
enzyme-inhibiting properties acutely and displaces warfarin from albumin transiently, creating
a complex interaction where INR may initially rise then fall. The chronic effect is increased
warfarin metabolism requiring dose adjustment. Option A reverses the mechanism
(phenytoin induces, not inhibits). Option B incorrectly identifies CYP1A2 as the primary
pathway for R-warfarin. Option D describes a transient pharmacokinetic effect but not the
primary mechanism requiring chronic dose adjustment.
Question 3 (Calculation)
A 75-year-old female (weight 58 kg, SCr 1.4 mg/dL) requires gentamicin for a complicated
urinary tract infection. Using the Cockcroft-Gault equation, what is her estimated creatinine
clearance?
A. 32 mL/min [CORRECT]
B. 45 mL/min
C. 58 mL/min
D. 71 mL/min
Correct Answer: A
Rationale: The Cockcroft-Gault equation for females is: CrCl = [(140 - age) × weight (kg) ×
0.85] ÷ [72 × SCr (mg/dL)]. Calculation: [(140 - 75) × 58 × 0.85] ÷ [72 × 1.4] = (65 × 58 × 0.85) ÷
100.8 = 3204.5 ÷ 100.8 = 31.8 mL/min, rounded to 32 mL/min. This reduced renal function
necessitates extended dosing intervals (e.g., 24-48 hours) or therapeutic drug monitoring for
aminoglycosides to prevent nephrotoxicity and ototoxicity. The 0.85 factor accounts for
reduced muscle mass in females. Options B, C, and D represent calculation errors omitting
the female correction factor or using incorrect age/weight adjustments.
, Question 4 (Pharmacogenomics)
A 34-year-old female with Crohn's disease is scheduled to begin azathioprine therapy. Prior to
initiation, pharmacogenomic testing reveals she is homozygous for a non-functional allele of
the gene encoding thiopurine methyltransferase (TPMT). Based on this result, which clinical
action is MOST appropriate?
A. Proceed with standard dosing; genotype does not affect dosing
B. Reduce dose by 30-50% and monitor CBC closely
C. Reduce dose by 90% or consider alternative immunosuppressant [CORRECT]
D. Increase dose to overcome genetic deficiency
Correct Answer: C
Rationale: TPMT is the primary enzyme metabolizing thiopurines (azathioprine,
6-mercaptopurine) to inactive methylated products. Homozygous deficiency (TPMT*2/*3,
~0.3% population) results in shunting of drug toward toxic 6-thioguanine nucleotides, causing
profound myelosuppression. CPIC (Clinical Pharmacogenetics Implementation Consortium)
2025 guidelines recommend either drastically reduced dosing (6-10% standard dose) with
intensive monitoring or alternative agents (anti-TNF biologics, methotrexate). Heterozygotes
(intermediate metabolizers) require 30-50% dose reduction (B). Standard dosing (A) risks
fatal pancytopenia. Increasing dose (D) would exacerbate toxicity.
Question 5
A drug with a therapeutic index of 2.0 is characterized by which property?
A. High margin of safety; wide therapeutic window
B. Low margin of safety; narrow therapeutic window [CORRECT]
C. No difference between effective and toxic doses
D. Requires therapeutic drug monitoring only in renal failure
Correct Answer: B
Rationale: The therapeutic index (TI) is calculated as TD50/ED50 (median toxic dose divided
by median effective dose) or LD50/ED50 for lethal effects. A TI of 2.0 indicates the toxic
dose is only twice the effective dose, representing a narrow therapeutic window requiring
Pharmacology Midterm Exam
SECTION A: PHARMACOLOGICAL PRINCIPLES (Q1-10)
Question 1
A novel antihypertensive agent is discovered to increase intracellular cyclic GMP (cGMP)
concentrations in vascular smooth muscle, resulting in net vasodilation and decreased
systemic vascular resistance. The pharmacologic mechanism of this agent is MOST similar
to which prototype drug?
A. Lisinopril (ACE inhibitor)
B. Losartan (angiotensin II receptor blocker)
C. Nitroprusside (direct NO donor) [CORRECT]
D. Metoprolol (beta-1 selective blocker)
Correct Answer: C
Rationale: Nitroprusside spontaneously releases nitric oxide (NO), which diffuses into
vascular smooth muscle and activates soluble guanylyl cyclase (sGC), catalyzing the
conversion of GTP to cGMP. Elevated cGMP activates protein kinase G (PKG), leading to
sequestration of cytosolic calcium, myosin light chain dephosphorylation, and vasodilation.
The described novel drug shares this NO-cGMP-PKG signaling cascade. ACE inhibitors (A)
block angiotensin-converting enzyme, reducing angiotensin II and increasing bradykinin
(which indirectly increases NO but is not the primary mechanism). ARBs (B) antagonize AT1
receptors. Beta-blockers (D) competitively inhibit catecholamine binding to beta-adrenergic
receptors, reducing cAMP production.
Question 2
A 68-year-old male with atrial fibrillation on warfarin requires initiation of phenytoin for
seizure prophylaxis following neurosurgery. The prescriber anticipates a need to adjust
warfarin dosing. This interaction occurs primarily through which pharmacokinetic
mechanism?
,A. Phenytoin inhibits CYP2C9, reducing warfarin metabolism
B. Phenytoin induces CYP1A2, increasing R-warfarin clearance
C. Phenytoin induces CYP2C9 and CYP3A4, increasing S-warfarin metabolism [CORRECT]
D. Phenytoin displaces warfarin from albumin binding sites
Correct Answer: C
Rationale: Phenytoin is a potent hepatic enzyme inducer, specifically upregulating CYP2C9
and CYP3A4 isoforms. S-warfarin (the more potent enantiomer metabolized by CYP2C9)
clearance increases, potentially decreasing INR. However, phenytoin also has
enzyme-inhibiting properties acutely and displaces warfarin from albumin transiently, creating
a complex interaction where INR may initially rise then fall. The chronic effect is increased
warfarin metabolism requiring dose adjustment. Option A reverses the mechanism
(phenytoin induces, not inhibits). Option B incorrectly identifies CYP1A2 as the primary
pathway for R-warfarin. Option D describes a transient pharmacokinetic effect but not the
primary mechanism requiring chronic dose adjustment.
Question 3 (Calculation)
A 75-year-old female (weight 58 kg, SCr 1.4 mg/dL) requires gentamicin for a complicated
urinary tract infection. Using the Cockcroft-Gault equation, what is her estimated creatinine
clearance?
A. 32 mL/min [CORRECT]
B. 45 mL/min
C. 58 mL/min
D. 71 mL/min
Correct Answer: A
Rationale: The Cockcroft-Gault equation for females is: CrCl = [(140 - age) × weight (kg) ×
0.85] ÷ [72 × SCr (mg/dL)]. Calculation: [(140 - 75) × 58 × 0.85] ÷ [72 × 1.4] = (65 × 58 × 0.85) ÷
100.8 = 3204.5 ÷ 100.8 = 31.8 mL/min, rounded to 32 mL/min. This reduced renal function
necessitates extended dosing intervals (e.g., 24-48 hours) or therapeutic drug monitoring for
aminoglycosides to prevent nephrotoxicity and ototoxicity. The 0.85 factor accounts for
reduced muscle mass in females. Options B, C, and D represent calculation errors omitting
the female correction factor or using incorrect age/weight adjustments.
, Question 4 (Pharmacogenomics)
A 34-year-old female with Crohn's disease is scheduled to begin azathioprine therapy. Prior to
initiation, pharmacogenomic testing reveals she is homozygous for a non-functional allele of
the gene encoding thiopurine methyltransferase (TPMT). Based on this result, which clinical
action is MOST appropriate?
A. Proceed with standard dosing; genotype does not affect dosing
B. Reduce dose by 30-50% and monitor CBC closely
C. Reduce dose by 90% or consider alternative immunosuppressant [CORRECT]
D. Increase dose to overcome genetic deficiency
Correct Answer: C
Rationale: TPMT is the primary enzyme metabolizing thiopurines (azathioprine,
6-mercaptopurine) to inactive methylated products. Homozygous deficiency (TPMT*2/*3,
~0.3% population) results in shunting of drug toward toxic 6-thioguanine nucleotides, causing
profound myelosuppression. CPIC (Clinical Pharmacogenetics Implementation Consortium)
2025 guidelines recommend either drastically reduced dosing (6-10% standard dose) with
intensive monitoring or alternative agents (anti-TNF biologics, methotrexate). Heterozygotes
(intermediate metabolizers) require 30-50% dose reduction (B). Standard dosing (A) risks
fatal pancytopenia. Increasing dose (D) would exacerbate toxicity.
Question 5
A drug with a therapeutic index of 2.0 is characterized by which property?
A. High margin of safety; wide therapeutic window
B. Low margin of safety; narrow therapeutic window [CORRECT]
C. No difference between effective and toxic doses
D. Requires therapeutic drug monitoring only in renal failure
Correct Answer: B
Rationale: The therapeutic index (TI) is calculated as TD50/ED50 (median toxic dose divided
by median effective dose) or LD50/ED50 for lethal effects. A TI of 2.0 indicates the toxic
dose is only twice the effective dose, representing a narrow therapeutic window requiring
