NURS 676: Advanced Pharmacology for Psychiatric
Mental Health Nurse Practitioners – Final Exam
with Rationales
Domain I: Foundations of Psychopharmacology (Q1–10)
1. The mechanism of action of selective serotonin reuptake inhibitors (SSRIs)
involves:
a) Antagonism of postsynaptic serotonin (5-HT2) receptors
b) Inhibition of the reuptake of serotonin into the presynaptic neuron
c) Reversible inhibition of monoamine oxidase A (MAO-A)
d) Downregulation of norepinephrine transporters
Answer: b
Rationale: SSRIs block the serotonin transporter (SERT), preventing reuptake of
serotonin from the synapse, thereby increasing extracellular serotonin. They do
not directly antagonize postsynaptic receptors nor inhibit MAO-A.
2. A patient has been taking paroxetine for 2 years and wishes to discontinue.
Which strategy is most appropriate to minimize discontinuation syndrome?
a) Abrupt discontinuation with symptom monitoring
b) Switch to fluoxetine 20 mg daily for 1 week, then stop
c) Cross-taper with buspirone over 2 weeks
d) Gradual dose reduction over 4-6 weeks
Answer: d
Rationale: Paroxetine has a short half-life and high anticholinergic burden, leading
to a high risk of discontinuation syndrome. A slow taper over weeks reduces
symptom severity. Fluoxetine may be used for cross-taper but is not simply given
for 1 week.
3. The time delay of 2-4 weeks for therapeutic effect of most antidepressants is
thought to be due to:
a) Time required for drug plasma levels to reach steady state
b) Delayed adaptive changes in postsynaptic receptor sensitivity and second
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,messenger systems
c) Slow absorption from the gastrointestinal tract
d) First-pass metabolism in the liver requiring enzyme induction
Answer: b
Rationale: Although reuptake inhibition occurs within hours, downstream
changes (e.g., downregulation of β-adrenergic and 5-HT2 receptors, neurotrophic
effects) require weeks and correlate with clinical response.
4. A patient with CYP2D6 poor metabolizer phenotype is started on fluoxetine.
This patient is at increased risk for:
a) Therapeutic failure due to rapid drug clearance
b) Increased drug concentrations and adverse effects
c) Drug-induced lupus erythematosus
d) Paradoxical agitation requiring dose increase
Answer: b
Rationale: Fluoxetine and its active metabolite norfluoxetine are potent CYP2D6
inhibitors. A poor metabolizer already has reduced CYP2D6 activity, leading to
higher drug levels and greater risk of side effects (e.g., serotonin toxicity, QT
prolongation).
5. The cytochrome P450 enzyme most responsible for the metabolism of many
antidepressants and antipsychotics is:
a) CYP1A2
b) CYP2C9
c) CYP3A4
d) CYP2D6
Answer: d
Rationale: CYP2D6, though a minor fraction of liver CYP content, metabolizes
>25% of all drugs, including many SSRIs (except fluvoxamine), TCAs, antipsychotics
(risperidone, haloperidol, aripiprazole), and beta-blockers.
6. Which statement best describes therapeutic drug monitoring for lithium?
a) Blood levels should be drawn 2-4 hours after the last dose
b) Trough levels drawn 12 hours after the last dose are standard
c) Levels are only needed if toxicity is suspected
d) Saliva levels are more accurate than serum levels
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,Answer: b
Rationale: Standard practice is to draw a trough serum lithium level 12 hours after
the last dose (just before the next dose) to ensure steady-state measurement and
avoid post-distribution peaks.
7. A patient on carbamazepine reports developing a rash, fever, and facial
swelling. The priority action is:
a) Administer diphenhydramine and continue carbamazepine
b) Obtain a stat complete blood count with differential
c) Discontinue carbamazepine immediately and evaluate for Stevens-Johnson
syndrome
d) Increase the carbamazepine dose to overcome tolerance
Answer: c
Rationale: Fever, rash, and facial swelling suggest a severe cutaneous adverse
reaction (SCAR) such as Stevens-Johnson syndrome or DRESS. Carbamazepine
must be stopped immediately; further evaluation (dermatology, HLA testing) is
needed.
8. The primary rationale for combining two antidepressants of different classes is:
a) To accelerate the onset of therapeutic effect
b) To eliminate the need for psychotherapy
c) To target multiple neurotransmitter systems or reduce side effects
d) To lower the cost of treatment
Answer: c
Rationale: Combination therapy (e.g., SSRI + bupropion, or SSRI + mirtazapine)
can provide synergistic effects on different pathways (serotonin, norepinephrine,
dopamine) and counter adverse effects (e.g., bupropion to reduce SSRI-induced
sexual dysfunction).
9. Pharmacogenomic testing for HLA-B1502 allele is strongly recommended before
starting which medication?
a) Lamotrigine
b) Carbamazepine
c) Valproate
d) Oxcarbazepine
Answer: b
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, Rationale: HLA-B1502 screening is recommended for carbamazepine in Asian
populations due to strong association with SJS/TEN. The same allele is also a risk
factor for oxcarbazepine and phenytoin, but the strongest recommendation is for
carbamazepine.
10. The term "kindling" in psychopharmacology refers to:
a) Progressive enhancement of seizure activity with repeated subthreshold stimuli
b) The process of tapering benzodiazepines to prevent withdrawal
c) Induction of liver enzymes by chronic medication use
d) Desensitization of dopamine D2 receptors by antipsychotics
Answer: a
Rationale: Kindling is a phenomenon where repeated subconvulsive stimuli
gradually lower seizure threshold, eventually producing full seizures. It is also
used to explain worsening of alcohol or benzodiazepine withdrawal with repeated
episodes.
Domain II: Antidepressants (Q11–30)
11. A 45-year-old with major depressive disorder and comorbid generalized
anxiety disorder has failed trials of sertraline and escitalopram. Which
antidepressant has FDA approval for both MDD and GAD?
a) Bupropion
b) Mirtazapine
c) Venlafaxine XR
d) Trazodone
Answer: c
Rationale: Venlafaxine XR is FDA-approved for MDD, GAD, panic disorder, and
social anxiety disorder. Bupropion is not approved for GAD (may worsen anxiety).
Mirtazapine and trazodone are not FDA-approved for GAD.
12. Which SSRI is associated with the highest risk of drug-drug interactions due to
potent CYP2D6 inhibition?
a) Citalopram
b) Sertraline
c) Escitalopram
d) Fluoxetine
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Mental Health Nurse Practitioners – Final Exam
with Rationales
Domain I: Foundations of Psychopharmacology (Q1–10)
1. The mechanism of action of selective serotonin reuptake inhibitors (SSRIs)
involves:
a) Antagonism of postsynaptic serotonin (5-HT2) receptors
b) Inhibition of the reuptake of serotonin into the presynaptic neuron
c) Reversible inhibition of monoamine oxidase A (MAO-A)
d) Downregulation of norepinephrine transporters
Answer: b
Rationale: SSRIs block the serotonin transporter (SERT), preventing reuptake of
serotonin from the synapse, thereby increasing extracellular serotonin. They do
not directly antagonize postsynaptic receptors nor inhibit MAO-A.
2. A patient has been taking paroxetine for 2 years and wishes to discontinue.
Which strategy is most appropriate to minimize discontinuation syndrome?
a) Abrupt discontinuation with symptom monitoring
b) Switch to fluoxetine 20 mg daily for 1 week, then stop
c) Cross-taper with buspirone over 2 weeks
d) Gradual dose reduction over 4-6 weeks
Answer: d
Rationale: Paroxetine has a short half-life and high anticholinergic burden, leading
to a high risk of discontinuation syndrome. A slow taper over weeks reduces
symptom severity. Fluoxetine may be used for cross-taper but is not simply given
for 1 week.
3. The time delay of 2-4 weeks for therapeutic effect of most antidepressants is
thought to be due to:
a) Time required for drug plasma levels to reach steady state
b) Delayed adaptive changes in postsynaptic receptor sensitivity and second
1|Page
,messenger systems
c) Slow absorption from the gastrointestinal tract
d) First-pass metabolism in the liver requiring enzyme induction
Answer: b
Rationale: Although reuptake inhibition occurs within hours, downstream
changes (e.g., downregulation of β-adrenergic and 5-HT2 receptors, neurotrophic
effects) require weeks and correlate with clinical response.
4. A patient with CYP2D6 poor metabolizer phenotype is started on fluoxetine.
This patient is at increased risk for:
a) Therapeutic failure due to rapid drug clearance
b) Increased drug concentrations and adverse effects
c) Drug-induced lupus erythematosus
d) Paradoxical agitation requiring dose increase
Answer: b
Rationale: Fluoxetine and its active metabolite norfluoxetine are potent CYP2D6
inhibitors. A poor metabolizer already has reduced CYP2D6 activity, leading to
higher drug levels and greater risk of side effects (e.g., serotonin toxicity, QT
prolongation).
5. The cytochrome P450 enzyme most responsible for the metabolism of many
antidepressants and antipsychotics is:
a) CYP1A2
b) CYP2C9
c) CYP3A4
d) CYP2D6
Answer: d
Rationale: CYP2D6, though a minor fraction of liver CYP content, metabolizes
>25% of all drugs, including many SSRIs (except fluvoxamine), TCAs, antipsychotics
(risperidone, haloperidol, aripiprazole), and beta-blockers.
6. Which statement best describes therapeutic drug monitoring for lithium?
a) Blood levels should be drawn 2-4 hours after the last dose
b) Trough levels drawn 12 hours after the last dose are standard
c) Levels are only needed if toxicity is suspected
d) Saliva levels are more accurate than serum levels
2|Page
,Answer: b
Rationale: Standard practice is to draw a trough serum lithium level 12 hours after
the last dose (just before the next dose) to ensure steady-state measurement and
avoid post-distribution peaks.
7. A patient on carbamazepine reports developing a rash, fever, and facial
swelling. The priority action is:
a) Administer diphenhydramine and continue carbamazepine
b) Obtain a stat complete blood count with differential
c) Discontinue carbamazepine immediately and evaluate for Stevens-Johnson
syndrome
d) Increase the carbamazepine dose to overcome tolerance
Answer: c
Rationale: Fever, rash, and facial swelling suggest a severe cutaneous adverse
reaction (SCAR) such as Stevens-Johnson syndrome or DRESS. Carbamazepine
must be stopped immediately; further evaluation (dermatology, HLA testing) is
needed.
8. The primary rationale for combining two antidepressants of different classes is:
a) To accelerate the onset of therapeutic effect
b) To eliminate the need for psychotherapy
c) To target multiple neurotransmitter systems or reduce side effects
d) To lower the cost of treatment
Answer: c
Rationale: Combination therapy (e.g., SSRI + bupropion, or SSRI + mirtazapine)
can provide synergistic effects on different pathways (serotonin, norepinephrine,
dopamine) and counter adverse effects (e.g., bupropion to reduce SSRI-induced
sexual dysfunction).
9. Pharmacogenomic testing for HLA-B1502 allele is strongly recommended before
starting which medication?
a) Lamotrigine
b) Carbamazepine
c) Valproate
d) Oxcarbazepine
Answer: b
3|Page
, Rationale: HLA-B1502 screening is recommended for carbamazepine in Asian
populations due to strong association with SJS/TEN. The same allele is also a risk
factor for oxcarbazepine and phenytoin, but the strongest recommendation is for
carbamazepine.
10. The term "kindling" in psychopharmacology refers to:
a) Progressive enhancement of seizure activity with repeated subthreshold stimuli
b) The process of tapering benzodiazepines to prevent withdrawal
c) Induction of liver enzymes by chronic medication use
d) Desensitization of dopamine D2 receptors by antipsychotics
Answer: a
Rationale: Kindling is a phenomenon where repeated subconvulsive stimuli
gradually lower seizure threshold, eventually producing full seizures. It is also
used to explain worsening of alcohol or benzodiazepine withdrawal with repeated
episodes.
Domain II: Antidepressants (Q11–30)
11. A 45-year-old with major depressive disorder and comorbid generalized
anxiety disorder has failed trials of sertraline and escitalopram. Which
antidepressant has FDA approval for both MDD and GAD?
a) Bupropion
b) Mirtazapine
c) Venlafaxine XR
d) Trazodone
Answer: c
Rationale: Venlafaxine XR is FDA-approved for MDD, GAD, panic disorder, and
social anxiety disorder. Bupropion is not approved for GAD (may worsen anxiety).
Mirtazapine and trazodone are not FDA-approved for GAD.
12. Which SSRI is associated with the highest risk of drug-drug interactions due to
potent CYP2D6 inhibition?
a) Citalopram
b) Sertraline
c) Escitalopram
d) Fluoxetine
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