NR 508 Advanced Pharmacology Final
Exam | 2025/2026 Verified 100%
Correct Answers – Chamberlain
Drug Mechanisms (Questions 1-30)
1. Question: A patient with refractory hypertension is prescribed a novel
endothelin receptor antagonist. This class primarily exerts its
antihypertensive effect through inhibition of which signaling pathway?
Options:
o A. RhoA/ROCK-mediated vasoconstriction
o B. cGMP-dependent vasodilation
o C. PI3K/Akt endothelial nitric oxide synthase activation
o D. JAK-STAT inflammatory cytokine cascade Answer: A.
RhoA/ROCK-mediated vasoconstriction Rationale: Endothelin
receptor antagonists (e.g., bosentan) block ET-1-induced
RhoA/ROCK signaling, reducing vascular smooth muscle contraction
and sodium retention; per ACC/AHA 2025, this mechanism
complements RAAS inhibition in resistant hypertension, with liver
function monitoring due to hepatotoxicity.
2. Question: In the pharmacodynamics of SGLT2 inhibitors like
empagliflozin, the primary renal glucose reabsorption blockade occurs at
which tubular segment, and what secondary osmotic effect enhances
diuresis? Options:
o A. Proximal convoluted tubule; glucosuria-induced natriuresis
o B. Loop of Henle; calcium reabsorption inhibition
o C. Distal convoluted tubule; potassium sparing
o D. Collecting duct; ADH antagonism Answer: A. Proximal
convoluted tubule; glucosuria-induced natriuresis Rationale: SGLT2
inhibitors inhibit Na+-glucose cotransport in the S1/S2 proximal
segments, causing osmotic diuresis and natriuresis that lowers blood
pressure and preload; ADA 2025 guidelines highlight this for
cardiorenal protection in T2DM, with UTI risk mitigation.
3. Question: A graduate student investigates the molecular basis of clopidogrel
resistance. This P2Y12 inhibitor's antiplatelet effect is mediated by
irreversible inhibition of ADP-induced platelet activation, but resistance
often stems from polymorphisms in which enzyme? Options:
, o A. CYP2C19
o B. CYP3A4
o C. ABCB1
o D. UGT1A1 Answer: A. CYP2C19 Rationale: Clopidogrel requires
CYP2C19-dependent bioactivation to its active thiol metabolite; poor
metabolizer alleles (*2/*3) reduce efficacy by 30%, per ACC/AHA
2025 DAPT guidelines, warranting alternatives like ticagrelor in high-
risk PCI patients.
4. Question: In the context of monoclonal antibody therapies for rheumatoid
arthritis, rituximab's B-cell depletion mechanism targets CD20, leading to?
Options:
o A. Antibody-dependent cellular cytotoxicity and complement
activation
o B. Direct apoptosis via caspase-8
o C. Inhibition of JAK-STAT signaling
o D. Blockade of TNF-alpha receptors Answer: A. Antibody-dependent
cellular cytotoxicity and complement activation Rationale: Rituximab
induces ADCC and CDC via NK cells and C1q binding, reducing
autoantibody production; ACR 2025 guidelines reserve for TNF
failures, with infusion reactions mitigated by premedication.
5. Question: A pharmacologist examines the G-protein coupled receptor
signaling of beta-2 agonists in asthma. The bronchodilation is primarily due
to? Options:
o A. Gs-protein activation increasing cAMP and PKA-mediated smooth
muscle relaxation
o B. Gi-protein inhibition of adenylyl cyclase
o C. Gq-protein PLC-IP3 pathway
o D. Beta-arrestin recruitment Answer: A. Gs-protein activation
increasing cAMP and PKA-mediated smooth muscle relaxation
Rationale: Beta-2 agonism elevates cAMP, phosphorylating MLCK
for dephosphorylation and relaxation; GINA 2025 endorses
LABA/ICS combos, with tachyphylaxis from receptor internalization.
6. Question: For a patient with chronic kidney disease, the calcimimetic
cinacalcet lowers PTH by allosteric modulation of which receptor? Options:
o A. Calcium-sensing receptor (CaSR) on parathyroid chief cells
o B. Vitamin D receptor (VDR)
o C. FGF23 receptor
o D. Phosphate transporter NaPi-IIa Answer: A. Calcium-sensing
receptor (CaSR) on parathyroid chief cells Rationale: Cinacalcet
sensitizes CaSR, suppressing PTH secretion and proliferation;
, KDIGO 2025 recommends for secondary hyperparathyroidism (iPTH
>300 pg/mL), with hypocalcemia monitoring.
7. Question: The mechanism of action of glucagon-like peptide-1 receptor
agonists (GLP-1RAs) like semaglutide in type 2 diabetes involves?
Options:
o A. G-protein coupled receptor activation enhancing insulin secretion
and slowing gastric emptying
o B. AMPK activation in liver
o C. SGLT2 inhibition in kidney
o D. DPP-4 prolongation Answer: A. G-protein coupled receptor
activation enhancing insulin secretion and slowing gastric emptying
Rationale: GLP-1R agonism glucose-dependently boosts incretin
effect, reducing A1C 1-1.5%; ADA 2025 first-line for CVD benefit,
with GI tolerance improving over time.
8. Question: In oncology pharmacology, PARP inhibitors like olaparib exploit
synthetic lethality in BRCA-mutated cancers by preventing? Options:
o A. Base excision repair of single-strand breaks
o B. Double-strand break homologous recombination
o C. Mismatch repair
o D. Non-homologous end joining Answer: A. Base excision repair of
single-strand breaks Rationale: PARP trapping converts SSBs to
DSBs, lethal in HR-deficient cells; NCCN 2025 maintenance for
ovarian cancer, with MDS risk in germline carriers.
9. Question: A pharmacodynamic interaction between warfarin and
amiodarone occurs because amiodarone inhibits which cytochrome P450
isozyme responsible for warfarin metabolism? Options:
o A. CYP2C9
o B. CYP3A4
o C. CYP1A2
o D. CYP2D6 Answer: A. CYP2C9 Rationale: Amiodarone's CYP2C9
inhibition prolongs S-warfarin half-life, elevating INR; ACC 2025
recommends 30-50% warfarin dose reduction with weekly
monitoring.
10.Question: The selective estrogen receptor modulator (SERM) raloxifene
reduces breast cancer risk by acting as an antagonist in mammary tissue
while agonism in bone prevents osteoporosis through? Options:
o A. ERα modulation inhibiting ER-positive cell proliferation
o B. Aromatase inhibition
o C. Progesterone receptor co-activation
Exam | 2025/2026 Verified 100%
Correct Answers – Chamberlain
Drug Mechanisms (Questions 1-30)
1. Question: A patient with refractory hypertension is prescribed a novel
endothelin receptor antagonist. This class primarily exerts its
antihypertensive effect through inhibition of which signaling pathway?
Options:
o A. RhoA/ROCK-mediated vasoconstriction
o B. cGMP-dependent vasodilation
o C. PI3K/Akt endothelial nitric oxide synthase activation
o D. JAK-STAT inflammatory cytokine cascade Answer: A.
RhoA/ROCK-mediated vasoconstriction Rationale: Endothelin
receptor antagonists (e.g., bosentan) block ET-1-induced
RhoA/ROCK signaling, reducing vascular smooth muscle contraction
and sodium retention; per ACC/AHA 2025, this mechanism
complements RAAS inhibition in resistant hypertension, with liver
function monitoring due to hepatotoxicity.
2. Question: In the pharmacodynamics of SGLT2 inhibitors like
empagliflozin, the primary renal glucose reabsorption blockade occurs at
which tubular segment, and what secondary osmotic effect enhances
diuresis? Options:
o A. Proximal convoluted tubule; glucosuria-induced natriuresis
o B. Loop of Henle; calcium reabsorption inhibition
o C. Distal convoluted tubule; potassium sparing
o D. Collecting duct; ADH antagonism Answer: A. Proximal
convoluted tubule; glucosuria-induced natriuresis Rationale: SGLT2
inhibitors inhibit Na+-glucose cotransport in the S1/S2 proximal
segments, causing osmotic diuresis and natriuresis that lowers blood
pressure and preload; ADA 2025 guidelines highlight this for
cardiorenal protection in T2DM, with UTI risk mitigation.
3. Question: A graduate student investigates the molecular basis of clopidogrel
resistance. This P2Y12 inhibitor's antiplatelet effect is mediated by
irreversible inhibition of ADP-induced platelet activation, but resistance
often stems from polymorphisms in which enzyme? Options:
, o A. CYP2C19
o B. CYP3A4
o C. ABCB1
o D. UGT1A1 Answer: A. CYP2C19 Rationale: Clopidogrel requires
CYP2C19-dependent bioactivation to its active thiol metabolite; poor
metabolizer alleles (*2/*3) reduce efficacy by 30%, per ACC/AHA
2025 DAPT guidelines, warranting alternatives like ticagrelor in high-
risk PCI patients.
4. Question: In the context of monoclonal antibody therapies for rheumatoid
arthritis, rituximab's B-cell depletion mechanism targets CD20, leading to?
Options:
o A. Antibody-dependent cellular cytotoxicity and complement
activation
o B. Direct apoptosis via caspase-8
o C. Inhibition of JAK-STAT signaling
o D. Blockade of TNF-alpha receptors Answer: A. Antibody-dependent
cellular cytotoxicity and complement activation Rationale: Rituximab
induces ADCC and CDC via NK cells and C1q binding, reducing
autoantibody production; ACR 2025 guidelines reserve for TNF
failures, with infusion reactions mitigated by premedication.
5. Question: A pharmacologist examines the G-protein coupled receptor
signaling of beta-2 agonists in asthma. The bronchodilation is primarily due
to? Options:
o A. Gs-protein activation increasing cAMP and PKA-mediated smooth
muscle relaxation
o B. Gi-protein inhibition of adenylyl cyclase
o C. Gq-protein PLC-IP3 pathway
o D. Beta-arrestin recruitment Answer: A. Gs-protein activation
increasing cAMP and PKA-mediated smooth muscle relaxation
Rationale: Beta-2 agonism elevates cAMP, phosphorylating MLCK
for dephosphorylation and relaxation; GINA 2025 endorses
LABA/ICS combos, with tachyphylaxis from receptor internalization.
6. Question: For a patient with chronic kidney disease, the calcimimetic
cinacalcet lowers PTH by allosteric modulation of which receptor? Options:
o A. Calcium-sensing receptor (CaSR) on parathyroid chief cells
o B. Vitamin D receptor (VDR)
o C. FGF23 receptor
o D. Phosphate transporter NaPi-IIa Answer: A. Calcium-sensing
receptor (CaSR) on parathyroid chief cells Rationale: Cinacalcet
sensitizes CaSR, suppressing PTH secretion and proliferation;
, KDIGO 2025 recommends for secondary hyperparathyroidism (iPTH
>300 pg/mL), with hypocalcemia monitoring.
7. Question: The mechanism of action of glucagon-like peptide-1 receptor
agonists (GLP-1RAs) like semaglutide in type 2 diabetes involves?
Options:
o A. G-protein coupled receptor activation enhancing insulin secretion
and slowing gastric emptying
o B. AMPK activation in liver
o C. SGLT2 inhibition in kidney
o D. DPP-4 prolongation Answer: A. G-protein coupled receptor
activation enhancing insulin secretion and slowing gastric emptying
Rationale: GLP-1R agonism glucose-dependently boosts incretin
effect, reducing A1C 1-1.5%; ADA 2025 first-line for CVD benefit,
with GI tolerance improving over time.
8. Question: In oncology pharmacology, PARP inhibitors like olaparib exploit
synthetic lethality in BRCA-mutated cancers by preventing? Options:
o A. Base excision repair of single-strand breaks
o B. Double-strand break homologous recombination
o C. Mismatch repair
o D. Non-homologous end joining Answer: A. Base excision repair of
single-strand breaks Rationale: PARP trapping converts SSBs to
DSBs, lethal in HR-deficient cells; NCCN 2025 maintenance for
ovarian cancer, with MDS risk in germline carriers.
9. Question: A pharmacodynamic interaction between warfarin and
amiodarone occurs because amiodarone inhibits which cytochrome P450
isozyme responsible for warfarin metabolism? Options:
o A. CYP2C9
o B. CYP3A4
o C. CYP1A2
o D. CYP2D6 Answer: A. CYP2C9 Rationale: Amiodarone's CYP2C9
inhibition prolongs S-warfarin half-life, elevating INR; ACC 2025
recommends 30-50% warfarin dose reduction with weekly
monitoring.
10.Question: The selective estrogen receptor modulator (SERM) raloxifene
reduces breast cancer risk by acting as an antagonist in mammary tissue
while agonism in bone prevents osteoporosis through? Options:
o A. ERα modulation inhibiting ER-positive cell proliferation
o B. Aromatase inhibition
o C. Progesterone receptor co-activation
