NSG552 Psychopharmacology Exam 1 - 2026/2027
| Grade A Questions & Verified Answers |
Psychiatric Medication Management
Section 1 – Neurobiology, PK/PD, Foundational Principles (≈ 12 questions)
Q1
A 67-year-old woman with major depressive disorder is started on paroxetine 20 mg hs.
She is otherwise on tamoxifen for ER+ breast cancer. Four weeks later she presents
with hot flashes, crying spells, and a 19-item HDRS score that doubled from baseline.
Which pharmacokinetic phenomenon best explains loss of antidepressant efficacy as
well as tumor-treatment failure?
A. UGT1A1 induction by tamoxifen
B. CYP2D6 inhibition by paroxetine
C. P-gp efflux saturation in the blood-brain barrier
D. Competitive albumin binding leading to higher free tamoxifen
Correct Answer: B
Rationale: Paroxetine is a potent CYP2D6 inhibitor → blocks conversion of tamoxifen to
its active metabolite endoxifen (sub-therapeutic levels) and may also raise paroxetine
levels via feed-back inhibition, but the clinical picture here is loss of both oncologic and
,antidepressant control due to 2D6 inhibition. A, C, and D do not explain the dual failure;
B is the only mechanism supported by FDA and ASCO warnings.
Q2
A 30-year-old male with treatment-resistant schizophrenia is on clozapine 350 mg bid.
His trough WBC is 3,200/mm³ (baseline 6,000). Plasma clozapine level is 1,900 ng/mL
(target 350–600). Genotype shows CYP1A2*1F/*1F (ultra-rapid) and he smokes 1 ppd.
Which kinetic change explains the 4-fold elevation?
A. Smoking induces CYP1A2 → lowers level (incorrect direction)
B. CYP1A2 ultra-rapid genotype → lowers level (incorrect direction)
C. Concomitant fluconazole recently started for thrush inhibited CYP3A4 & CYP2C19,
secondary pathways for clozapine
D. Patient doubled dose himself because of auditory hallucinations
Correct Answer: C
Rationale: Although smoking and *1F allele lower clozapine levels, the addition of a
moderate CYP2C19/CYP3A4 inhibitor (fluconazole) blocks alternative clearance routes,
shunting metabolism back to the now-saturated CYP1A2 → accumulation. A & B would
predict sub-therapeutic, not supra-therapeutic levels. D is possible but not supported by
the scenario; C is the best pharmacokinetic explanation.
Q3
A 24-year-old healthy volunteer receives a single 10 mg IV dose of morphine. A
simultaneous CSF sample shows an AUC only 8 % of plasma AUC. Which CNS barrier
mechanism best accounts for the low CSF penetration?
, A. High lipid solubility of morphine
B. Active uptake by P-glycoprotein at choroid plexus epithelium
C. High ionization at pH 7.4
D. Extensive first-pass hepatic metabolism
Correct Answer: B
Rationale: Morphine is a P-gp substrate; efflux transporters at the choroid plexus and
capillary endothelium limit CNS exposure. A is false (morphine is hydrophilic relative to
fentanyl). C is false (35 % non-ionized at pH 7.4). D irrelevant after IV dosing.
Q4
A 56-year-old with hepatic cirrhosis (Child-Pugh B) is prescribed duloxetine 60 mg daily
for neuropathic pain. After 5 days he develops myoclonus, diaphoresis, and tremor. His
duloxetine level is 5× the usual upper limit. Which enzyme/transporter failure is most
contributory?
A. CYP2D6 polymorphism
B. Reduced glucuronidation via UGT1A3
C. Portosystemic shunting → decreased first-pass hepatic extraction
D. Renal P-gp over-expression
Correct Answer: C
Rationale: Duloxetine undergoes high first-pass hepatic metabolism; cirrhosis allows
more drug into systemic circulation. CYP2D6 (A) is unchanged, glucuronidation (B) is
minor, and renal P-gp (D) irrelevant for a hepatically cleared drug.
| Grade A Questions & Verified Answers |
Psychiatric Medication Management
Section 1 – Neurobiology, PK/PD, Foundational Principles (≈ 12 questions)
Q1
A 67-year-old woman with major depressive disorder is started on paroxetine 20 mg hs.
She is otherwise on tamoxifen for ER+ breast cancer. Four weeks later she presents
with hot flashes, crying spells, and a 19-item HDRS score that doubled from baseline.
Which pharmacokinetic phenomenon best explains loss of antidepressant efficacy as
well as tumor-treatment failure?
A. UGT1A1 induction by tamoxifen
B. CYP2D6 inhibition by paroxetine
C. P-gp efflux saturation in the blood-brain barrier
D. Competitive albumin binding leading to higher free tamoxifen
Correct Answer: B
Rationale: Paroxetine is a potent CYP2D6 inhibitor → blocks conversion of tamoxifen to
its active metabolite endoxifen (sub-therapeutic levels) and may also raise paroxetine
levels via feed-back inhibition, but the clinical picture here is loss of both oncologic and
,antidepressant control due to 2D6 inhibition. A, C, and D do not explain the dual failure;
B is the only mechanism supported by FDA and ASCO warnings.
Q2
A 30-year-old male with treatment-resistant schizophrenia is on clozapine 350 mg bid.
His trough WBC is 3,200/mm³ (baseline 6,000). Plasma clozapine level is 1,900 ng/mL
(target 350–600). Genotype shows CYP1A2*1F/*1F (ultra-rapid) and he smokes 1 ppd.
Which kinetic change explains the 4-fold elevation?
A. Smoking induces CYP1A2 → lowers level (incorrect direction)
B. CYP1A2 ultra-rapid genotype → lowers level (incorrect direction)
C. Concomitant fluconazole recently started for thrush inhibited CYP3A4 & CYP2C19,
secondary pathways for clozapine
D. Patient doubled dose himself because of auditory hallucinations
Correct Answer: C
Rationale: Although smoking and *1F allele lower clozapine levels, the addition of a
moderate CYP2C19/CYP3A4 inhibitor (fluconazole) blocks alternative clearance routes,
shunting metabolism back to the now-saturated CYP1A2 → accumulation. A & B would
predict sub-therapeutic, not supra-therapeutic levels. D is possible but not supported by
the scenario; C is the best pharmacokinetic explanation.
Q3
A 24-year-old healthy volunteer receives a single 10 mg IV dose of morphine. A
simultaneous CSF sample shows an AUC only 8 % of plasma AUC. Which CNS barrier
mechanism best accounts for the low CSF penetration?
, A. High lipid solubility of morphine
B. Active uptake by P-glycoprotein at choroid plexus epithelium
C. High ionization at pH 7.4
D. Extensive first-pass hepatic metabolism
Correct Answer: B
Rationale: Morphine is a P-gp substrate; efflux transporters at the choroid plexus and
capillary endothelium limit CNS exposure. A is false (morphine is hydrophilic relative to
fentanyl). C is false (35 % non-ionized at pH 7.4). D irrelevant after IV dosing.
Q4
A 56-year-old with hepatic cirrhosis (Child-Pugh B) is prescribed duloxetine 60 mg daily
for neuropathic pain. After 5 days he develops myoclonus, diaphoresis, and tremor. His
duloxetine level is 5× the usual upper limit. Which enzyme/transporter failure is most
contributory?
A. CYP2D6 polymorphism
B. Reduced glucuronidation via UGT1A3
C. Portosystemic shunting → decreased first-pass hepatic extraction
D. Renal P-gp over-expression
Correct Answer: C
Rationale: Duloxetine undergoes high first-pass hepatic metabolism; cirrhosis allows
more drug into systemic circulation. CYP2D6 (A) is unchanged, glucuronidation (B) is
minor, and renal P-gp (D) irrelevant for a hepatically cleared drug.
