NR 546 ADVANCED PHARMACOLOGY MIDTERM EXAM
2026/2027 | Tested Questions with Revised Answers | Across
the Lifespan | Pass Guaranteed - A+ Graded
Q1: Which neurotransmitter system is primarily responsible for the therapeutic effects
of selective serotonin reuptake inhibitors (SSRIs) in major depressive disorder?
A. Dopaminergic pathways in the mesolimbic system
B. Noradrenergic projections from the locus coeruleus
C. Serotonergic neurotransmission via 5-HT1A receptor downregulation and enhanced
synaptic serotonin. [CORRECT]
D. GABAergic interneurons in the hippocampus
Correct Answer: C
Rationale: SSRIs exert therapeutic effects through blockade of the serotonin transporter
(SERT), increasing synaptic serotonin availability. Chronic administration leads to
downregulation of 5-HT1A autoreceptors, enhancing neurotransmission. While
dopamine (A) and norepinephrine (B) systems are involved in depression, SSRIs
primarily target serotonin. GABA (D) is the target of benzodiazepines and some
anticonvulsants. The delayed clinical effect (2-4 weeks) correlates with 5-HT1A receptor
adaptation, not immediate serotonin increase.
Q2: A 28-year-old patient with major depressive disorder is prescribed fluoxetine 20mg
daily. Two weeks later, she reports increased anxiety, restlessness, and insomnia. What
is the most appropriate clinical response?
A. Discontinue fluoxetine immediately due to treatment failure
B. Add lorazepam 1mg TID for anxiety and continue fluoxetine
,C. Reassure the patient that these are common transient activation symptoms; consider
temporary dose reduction or slower titration. [CORRECT]
D. Switch to a tricyclic antidepressant
Correct Answer: C
Rationale: SSRIs frequently cause activation syndrome (anxiety, akathisia, insomnia) in
the first 2-4 weeks due to initial serotonin increase before receptor adaptation. This is
transient and not treatment failure. Discontinuation (A) is premature. Benzodiazepines
(B) may be used briefly but are not first-line. TCAs (D) have worse side effect profiles.
Evidence supports reassurance, slower titration, or temporary dose reduction. Activation
symptoms predict better eventual response in some studies.
Q3: Which cytochrome P450 enzyme is primarily responsible for the metabolism of
sertraline, and what is the clinical significance?
A. CYP1A2; significant interaction with smoking
B. CYP2D6; potential for drug interactions with tamoxifen and codeine. [CORRECT]
C. CYP3A4; major interaction with grapefruit juice
D. CYP2C19; significant genetic polymorphism affecting Asian populations
Correct Answer: B
Rationale: Sertraline is metabolized primarily by CYP2D6 and CYP3A4, with CYP2D6
being clinically significant. CYP2D6 poor metabolizers have 2-3x higher sertraline levels.
Importantly, sertraline is a moderate CYP2D6 inhibitor, reducing conversion of
tamoxifen to active endoxifen (decreasing efficacy) and codeine to morphine (reducing
analgesia). CYP1A2 (A) metabolizes fluvoxamine. CYP2C19 (D) primarily metabolizes
citalopram, escitalopram, and sertraline to a lesser extent.
,Q4: A patient on phenelzine (MAOI) presents to the emergency department with severe
headache, hypertension (210/120), diaphoresis, and hyperthermia after eating at a
restaurant. What is the priority intervention?
A. Administer sumatriptan for headache
B. Start nifedipine for hypertension
C. Discontinue phenelzine and administer phentolamine or nitroprusside for
hypertensive crisis; this is tyramine-induced hypertensive emergency. [CORRECT]
D. Administer cyproheptadine
Correct Answer: C
Rationale: This is tyramine-induced hypertensive crisis from dietary amines in aged
foods (cheese, wine, cured meats). MAOIs block tyramine metabolism, causing
norepinephrine release. Priority is stopping the offending agent and controlling blood
pressure with direct vasodilators (phentolamine, nitroprusside, or labetalol).
Beta-blockers alone are contraindicated (unopposed alpha stimulation worsens
hypertension). Sumatriptan (A) is contraindicated with MAOIs. Cyproheptadine (D) is for
serotonin syndrome. This is a medical emergency requiring ICU monitoring.
Q5: Which antidepressant carries the strongest FDA black box warning for QTc
prolongation and requires baseline and follow-up ECG monitoring?
A. Sertraline
B. Citalopram. [CORRECT]
C. Bupropion
D. Mirtazapine
Correct Answer: B
Rationale: Citalopram has a dose-dependent QTc prolongation risk, leading to FDA
maximum dose reduction to 40mg (20mg in patients >60 years or hepatic impairment).
, ECG monitoring is recommended at baseline and with dose increases. Risk increases
with CYP2C19 inhibitors. Escitalopram has less QTc effect. Sertraline (A) has minimal
QTc effect. Bupropion (C) and mirtazapine (D) do not significantly prolong QTc. Avoid
citalopram in congenital long QT syndrome, uncompensated heart failure, or
bradyarrhythmias.
Q6: A 67-year-old patient with depression, Parkinson's disease, and cognitive
impairment requires antidepressant therapy. Which agent is CONTRAINDICATED?
A. Escitalopram 10mg daily
B. Mirtazapine 15mg at bedtime
C. Paroxetine. [CORRECT]
D. Venlafaxine XR 37.5mg daily
Correct Answer: C
Rationale: Paroxetine is a potent anticholinergic SSRI with significant antimuscarinic
effects, worsening cognition and potentially exacerbating parkinsonism through
muscarinic receptor blockade. It also has the highest risk of discontinuation syndrome
due to short half-life and lack of active metabolites. In elderly patients with cognitive
concerns, avoid anticholinergic medications per Beers Criteria. Escitalopram (A) and
venlafaxine (D) are reasonable choices. Mirtazapine (B) may help with insomnia and
appetite but can worsen cognition at higher doses.
Q7: Which mechanism explains the rapid antidepressant effect of ketamine?
A. Monoamine oxidase inhibition
B. Blockade of NMDA glutamate receptors leading to increased BDNF and
synaptogenesis. [CORRECT]
C. Selective serotonin reuptake inhibition
D. Dopamine D2 receptor antagonism
2026/2027 | Tested Questions with Revised Answers | Across
the Lifespan | Pass Guaranteed - A+ Graded
Q1: Which neurotransmitter system is primarily responsible for the therapeutic effects
of selective serotonin reuptake inhibitors (SSRIs) in major depressive disorder?
A. Dopaminergic pathways in the mesolimbic system
B. Noradrenergic projections from the locus coeruleus
C. Serotonergic neurotransmission via 5-HT1A receptor downregulation and enhanced
synaptic serotonin. [CORRECT]
D. GABAergic interneurons in the hippocampus
Correct Answer: C
Rationale: SSRIs exert therapeutic effects through blockade of the serotonin transporter
(SERT), increasing synaptic serotonin availability. Chronic administration leads to
downregulation of 5-HT1A autoreceptors, enhancing neurotransmission. While
dopamine (A) and norepinephrine (B) systems are involved in depression, SSRIs
primarily target serotonin. GABA (D) is the target of benzodiazepines and some
anticonvulsants. The delayed clinical effect (2-4 weeks) correlates with 5-HT1A receptor
adaptation, not immediate serotonin increase.
Q2: A 28-year-old patient with major depressive disorder is prescribed fluoxetine 20mg
daily. Two weeks later, she reports increased anxiety, restlessness, and insomnia. What
is the most appropriate clinical response?
A. Discontinue fluoxetine immediately due to treatment failure
B. Add lorazepam 1mg TID for anxiety and continue fluoxetine
,C. Reassure the patient that these are common transient activation symptoms; consider
temporary dose reduction or slower titration. [CORRECT]
D. Switch to a tricyclic antidepressant
Correct Answer: C
Rationale: SSRIs frequently cause activation syndrome (anxiety, akathisia, insomnia) in
the first 2-4 weeks due to initial serotonin increase before receptor adaptation. This is
transient and not treatment failure. Discontinuation (A) is premature. Benzodiazepines
(B) may be used briefly but are not first-line. TCAs (D) have worse side effect profiles.
Evidence supports reassurance, slower titration, or temporary dose reduction. Activation
symptoms predict better eventual response in some studies.
Q3: Which cytochrome P450 enzyme is primarily responsible for the metabolism of
sertraline, and what is the clinical significance?
A. CYP1A2; significant interaction with smoking
B. CYP2D6; potential for drug interactions with tamoxifen and codeine. [CORRECT]
C. CYP3A4; major interaction with grapefruit juice
D. CYP2C19; significant genetic polymorphism affecting Asian populations
Correct Answer: B
Rationale: Sertraline is metabolized primarily by CYP2D6 and CYP3A4, with CYP2D6
being clinically significant. CYP2D6 poor metabolizers have 2-3x higher sertraline levels.
Importantly, sertraline is a moderate CYP2D6 inhibitor, reducing conversion of
tamoxifen to active endoxifen (decreasing efficacy) and codeine to morphine (reducing
analgesia). CYP1A2 (A) metabolizes fluvoxamine. CYP2C19 (D) primarily metabolizes
citalopram, escitalopram, and sertraline to a lesser extent.
,Q4: A patient on phenelzine (MAOI) presents to the emergency department with severe
headache, hypertension (210/120), diaphoresis, and hyperthermia after eating at a
restaurant. What is the priority intervention?
A. Administer sumatriptan for headache
B. Start nifedipine for hypertension
C. Discontinue phenelzine and administer phentolamine or nitroprusside for
hypertensive crisis; this is tyramine-induced hypertensive emergency. [CORRECT]
D. Administer cyproheptadine
Correct Answer: C
Rationale: This is tyramine-induced hypertensive crisis from dietary amines in aged
foods (cheese, wine, cured meats). MAOIs block tyramine metabolism, causing
norepinephrine release. Priority is stopping the offending agent and controlling blood
pressure with direct vasodilators (phentolamine, nitroprusside, or labetalol).
Beta-blockers alone are contraindicated (unopposed alpha stimulation worsens
hypertension). Sumatriptan (A) is contraindicated with MAOIs. Cyproheptadine (D) is for
serotonin syndrome. This is a medical emergency requiring ICU monitoring.
Q5: Which antidepressant carries the strongest FDA black box warning for QTc
prolongation and requires baseline and follow-up ECG monitoring?
A. Sertraline
B. Citalopram. [CORRECT]
C. Bupropion
D. Mirtazapine
Correct Answer: B
Rationale: Citalopram has a dose-dependent QTc prolongation risk, leading to FDA
maximum dose reduction to 40mg (20mg in patients >60 years or hepatic impairment).
, ECG monitoring is recommended at baseline and with dose increases. Risk increases
with CYP2C19 inhibitors. Escitalopram has less QTc effect. Sertraline (A) has minimal
QTc effect. Bupropion (C) and mirtazapine (D) do not significantly prolong QTc. Avoid
citalopram in congenital long QT syndrome, uncompensated heart failure, or
bradyarrhythmias.
Q6: A 67-year-old patient with depression, Parkinson's disease, and cognitive
impairment requires antidepressant therapy. Which agent is CONTRAINDICATED?
A. Escitalopram 10mg daily
B. Mirtazapine 15mg at bedtime
C. Paroxetine. [CORRECT]
D. Venlafaxine XR 37.5mg daily
Correct Answer: C
Rationale: Paroxetine is a potent anticholinergic SSRI with significant antimuscarinic
effects, worsening cognition and potentially exacerbating parkinsonism through
muscarinic receptor blockade. It also has the highest risk of discontinuation syndrome
due to short half-life and lack of active metabolites. In elderly patients with cognitive
concerns, avoid anticholinergic medications per Beers Criteria. Escitalopram (A) and
venlafaxine (D) are reasonable choices. Mirtazapine (B) may help with insomnia and
appetite but can worsen cognition at higher doses.
Q7: Which mechanism explains the rapid antidepressant effect of ketamine?
A. Monoamine oxidase inhibition
B. Blockade of NMDA glutamate receptors leading to increased BDNF and
synaptogenesis. [CORRECT]
C. Selective serotonin reuptake inhibition
D. Dopamine D2 receptor antagonism
