NR 546 MIDTERM EXAM 3-SET PACKAGE DEAL 2026/2027 |
Verified Q&A with Rationales
SET 1: QUESTIONS 1-63
1. A 45-year-old female with a history of major depressive disorder (MDD) and chronic
insomnia is started on trazodone 50 mg at bedtime. Which of the following best describes the
primary mechanism of action of trazodone at this dose?
A. Selective serotonin reuptake inhibition (SSRI)
B. Antagonism of 5-HT2A receptors and weak inhibition of serotonin reuptake
C. Strong antagonism of histamine H1 receptors
D. Agonism at melatonin MT1 and MT2 receptors
Answer: B. Trazodone is a serotonin antagonist and reuptake inhibitor (SARI). At low doses (e.g.,
50 mg), its primary effect is antagonism at the 5-HT2A receptor, which disinhibits downstream
serotonin release and promotes sleep, along with weak serotonin reuptake inhibition. Its
antihistamine properties are minimal compared to other sedating antidepressants.
2. A 32-year-old male with schizophrenia is experiencing significant negative symptoms such
as avolition and social withdrawal. He is currently on risperidone 4 mg daily. Which of the
following medication changes is most likely to target these negative symptoms effectively?
A. Increase risperidone to 6 mg daily.
B. Switch to aripiprazole.
C. Add lamotrigine 100 mg daily.
D. Switch to cariprazine.
Answer: D. Cariprazine is a partial agonist at D2 and D3 receptors with high affinity for D3
receptors, which are located in mesolimbic and mesocortical pathways. D3 receptor partial
agonism is associated with improvement in negative and cognitive symptoms. Aripiprazole also
has partial agonism but is less potent at D3.
3. A patient with bipolar I disorder is prescribed lithium. The provider orders a baseline serum
creatinine and BUN. Which of the following is the primary rationale for these baseline labs?
A. Lithium is extensively metabolized by the kidneys.
B. Lithium competes with sodium for reabsorption in the proximal tubule and can cause
nephrogenic diabetes insipidus.
C. Lithium has a narrow therapeutic index and renal impairment significantly increases the risk
of toxicity.
D. Hypothyroidism is a common side effect of lithium.
Answer: C. Lithium is excreted renally, and any impairment in renal function can lead to toxic
accumulation. The therapeutic index is narrow (0.6-1.2 mEq/L), and toxicity is life-threatening.
,Option B describes a mechanism of a side effect, but the rationale for baseline labs is to assess
renal clearance.
4. Which of the following pharmacodynamic properties is shared by both quetiapine and
olanzapine that contributes significantly to their metabolic side effect profiles?
A. High affinity for H1 receptors.
B. Strong antagonism at 5-HT2C and H1 receptors.
C. Antagonism at M1 receptors.
D. Partial agonism at D2 receptors.
Answer: B. Both quetiapine and olanzapine are potent antagonists at histamine H1 and
serotonin 5-HT2C receptors. Antagonism at H1 leads to sedation and weight gain. Antagonism at
5-HT2C leads to increased appetite and weight gain, which contributes to the high risk of
metabolic syndrome with these agents. M1 antagonism causes anticholinergic effects but is less
associated with weight gain.
5. A 28-year-old female with social anxiety disorder is started on paroxetine. She calls the
clinic after 3 days reporting nausea and "feeling wired." What is the most appropriate initial
response from the provider?
A. Discontinue the medication immediately due to an adverse reaction.
B. Reassure the patient that these symptoms are common early side effects and often subside
within 1-2 weeks, and discuss strategies like taking the medication with food.
C. Increase the dose to see if the symptoms resolve with a higher dose.
D. Add hydroxyzine to manage the anxiety and nausea.
Answer: B. SSRIs commonly cause initial gastrointestinal distress (nausea) and activation
(jitteriness) due to increased serotonin in the gut and brainstem. These are typically transient.
Reassurance and supportive management are the first-line approaches. Discontinuation is
premature, dose increase would worsen symptoms, and adding another agent is not the initial
step.
6. A 60-year-old male with Parkinson’s disease and comorbid major depressive disorder is
started on a medication that is a norepinephrine-dopamine reuptake inhibitor (NDRI). Which
medication is most likely being prescribed, and what is a key advantage in this patient
population?
A. Sertraline; it has no significant drug interactions.
B. Bupropion; it has a lower risk of sexual dysfunction and can improve psychomotor
retardation.
C. Duloxetine; it also treats neuropathic pain.
D. Bupropion; it can worsen motor symptoms but is effective for depression.
Answer: B. Bupropion is the primary NDRI. It is a great choice for depression in Parkinson's
because it does not antagonize dopamine (which would worsen motor symptoms), and it has a
,lower incidence of sexual side effects compared to SSRIs/SNRIs. It may also provide mild
improvement in energy.
7. A patient is switched from fluoxetine to phenelzine (an MAOI). The provider instructs the
patient to wait at least 5 weeks before starting phenelzine. What is the primary reason for
this extended washout period?
A. Fluoxetine has a long half-life due to its active metabolite, norfluoxetine, which can take
weeks to eliminate.
B. Fluoxetine is highly protein-bound, delaying its clearance.
C. MAO enzymes take 5 weeks to regenerate after fluoxetine discontinuation.
D. Phenelzine requires 5 weeks to reach steady-state therapeutic levels.
Answer: A. Fluoxetine has a half-life of 1-3 days, but its active metabolite, norfluoxetine, has a
half-life of 7-15 days. This can lead to a significant washout period. Concurrent use of an MAOI
with residual SSRI can cause serotonin syndrome. A 5-week washout is recommended to avoid
this.
8. A 25-year-old female with generalized anxiety disorder (GAD) and a history of alcohol use
disorder is being considered for pharmacotherapy. Which medication would be the most
appropriate and safe choice for this patient?
A. Alprazolam.
B. Buspirone.
C. Diazepam.
D. Zolpidem.
Answer: B. Buspirone is a non-benzodiazepine anxiolytic that is a 5-HT1A partial agonist. It has
no abuse potential, minimal sedation, and is safe in patients with a history of substance use
disorder. Benzodiazepines like alprazolam and diazepam are Schedule IV controlled substances
with high abuse potential. Zolpidem is a hypnotic for sleep, not GAD.
9. A 50-year-old male with schizophrenia is being treated with clozapine. His absolute
neutrophil count (ANC) drops to 1100/mm³. Which of the following is the most appropriate
action according to the REMS program?
A. Continue clozapine and recheck ANC in one week.
B. Reduce the dose of clozapine by half.
C. Immediately stop clozapine and initiate the REMS monitoring protocol for mild neutropenia.
D. Stop clozapine, and do not restart it under any circumstances.
Answer: C. According to the clozapine REMS program, an ANC between 1000 and 1500/mm³ is
considered mild neutropenia. Clozapine must be interrupted immediately, and daily ANC
monitoring is required until the ANC is >1500/mm³. Rechallenge may be considered if no other
causes are found and benefits outweigh risks.
, 10. Which of the following gene polymorphisms is most strongly associated with a higher risk
of developing neuroleptic malignant syndrome (NMS)?
A. CYP2D6 poor metabolizer status.
B. DRD2 TaqIA polymorphism.
C. ANKK1 polymorphism.
D. No specific gene polymorphism has been definitively established as a strong predictor of
NMS.
Answer: D. While genetic factors may play a role, no specific gene polymorphism (including
DRD2 variants) has been definitively validated as a clinically useful predictor of NMS. The
pathophysiology involves a complex interplay of dopamine receptor blockade, and risk is
sporadic.
11. A patient on valproic acid for bipolar disorder is prescribed lamotrigine. The provider must
be cautious because valproic acid:
A. Increases the clearance of lamotrigine, requiring higher doses.
B. Decreases the clearance of lamotrigine, increasing the risk of Stevens-Johnson syndrome.
C. Competes with lamotrigine for protein binding, reducing its efficacy.
D. Has a synergistic effect on weight gain.
Answer: B. Valproic acid inhibits the glucuronidation of lamotrigine, effectively doubling its
serum levels and increasing the risk of serious rash, including Stevens-Johnson syndrome (SJS).
Dosing of lamotrigine must be significantly reduced (e.g., 25 mg every other day) when used
with valproate.
12. A 70-year-old female is started on donepezil for Alzheimer's disease. A family member
reports the patient is experiencing vivid dreams and difficulty sleeping. What is the most
likely explanation?
A. Donepezil is a cholinesterase inhibitor that enhances REM sleep, leading to insomnia.
B. Donepezil causes an increase in central acetylcholine, which can lead to vivid dreams and
insomnia.
C. The patient is experiencing a paradoxical reaction to donepezil.
D. Donepezil is an NMDA receptor antagonist that can cause psychosis.
Answer: B. Donepezil is a cholinesterase inhibitor that increases acetylcholine throughout the
brain. Increased cholinergic transmission is associated with vivid dreams, insomnia, and other
sleep disturbances. This is a known side effect, not a paradoxical reaction.
13. A patient is prescribed methylphenidate for ADHD. Which of the following describes the
drug's primary mechanism for improving attention?
A. It is a selective norepinephrine reuptake inhibitor.
B. It blocks the dopamine transporter (DAT) and norepinephrine transporter (NET), increasing
synaptic dopamine and norepinephrine.
Verified Q&A with Rationales
SET 1: QUESTIONS 1-63
1. A 45-year-old female with a history of major depressive disorder (MDD) and chronic
insomnia is started on trazodone 50 mg at bedtime. Which of the following best describes the
primary mechanism of action of trazodone at this dose?
A. Selective serotonin reuptake inhibition (SSRI)
B. Antagonism of 5-HT2A receptors and weak inhibition of serotonin reuptake
C. Strong antagonism of histamine H1 receptors
D. Agonism at melatonin MT1 and MT2 receptors
Answer: B. Trazodone is a serotonin antagonist and reuptake inhibitor (SARI). At low doses (e.g.,
50 mg), its primary effect is antagonism at the 5-HT2A receptor, which disinhibits downstream
serotonin release and promotes sleep, along with weak serotonin reuptake inhibition. Its
antihistamine properties are minimal compared to other sedating antidepressants.
2. A 32-year-old male with schizophrenia is experiencing significant negative symptoms such
as avolition and social withdrawal. He is currently on risperidone 4 mg daily. Which of the
following medication changes is most likely to target these negative symptoms effectively?
A. Increase risperidone to 6 mg daily.
B. Switch to aripiprazole.
C. Add lamotrigine 100 mg daily.
D. Switch to cariprazine.
Answer: D. Cariprazine is a partial agonist at D2 and D3 receptors with high affinity for D3
receptors, which are located in mesolimbic and mesocortical pathways. D3 receptor partial
agonism is associated with improvement in negative and cognitive symptoms. Aripiprazole also
has partial agonism but is less potent at D3.
3. A patient with bipolar I disorder is prescribed lithium. The provider orders a baseline serum
creatinine and BUN. Which of the following is the primary rationale for these baseline labs?
A. Lithium is extensively metabolized by the kidneys.
B. Lithium competes with sodium for reabsorption in the proximal tubule and can cause
nephrogenic diabetes insipidus.
C. Lithium has a narrow therapeutic index and renal impairment significantly increases the risk
of toxicity.
D. Hypothyroidism is a common side effect of lithium.
Answer: C. Lithium is excreted renally, and any impairment in renal function can lead to toxic
accumulation. The therapeutic index is narrow (0.6-1.2 mEq/L), and toxicity is life-threatening.
,Option B describes a mechanism of a side effect, but the rationale for baseline labs is to assess
renal clearance.
4. Which of the following pharmacodynamic properties is shared by both quetiapine and
olanzapine that contributes significantly to their metabolic side effect profiles?
A. High affinity for H1 receptors.
B. Strong antagonism at 5-HT2C and H1 receptors.
C. Antagonism at M1 receptors.
D. Partial agonism at D2 receptors.
Answer: B. Both quetiapine and olanzapine are potent antagonists at histamine H1 and
serotonin 5-HT2C receptors. Antagonism at H1 leads to sedation and weight gain. Antagonism at
5-HT2C leads to increased appetite and weight gain, which contributes to the high risk of
metabolic syndrome with these agents. M1 antagonism causes anticholinergic effects but is less
associated with weight gain.
5. A 28-year-old female with social anxiety disorder is started on paroxetine. She calls the
clinic after 3 days reporting nausea and "feeling wired." What is the most appropriate initial
response from the provider?
A. Discontinue the medication immediately due to an adverse reaction.
B. Reassure the patient that these symptoms are common early side effects and often subside
within 1-2 weeks, and discuss strategies like taking the medication with food.
C. Increase the dose to see if the symptoms resolve with a higher dose.
D. Add hydroxyzine to manage the anxiety and nausea.
Answer: B. SSRIs commonly cause initial gastrointestinal distress (nausea) and activation
(jitteriness) due to increased serotonin in the gut and brainstem. These are typically transient.
Reassurance and supportive management are the first-line approaches. Discontinuation is
premature, dose increase would worsen symptoms, and adding another agent is not the initial
step.
6. A 60-year-old male with Parkinson’s disease and comorbid major depressive disorder is
started on a medication that is a norepinephrine-dopamine reuptake inhibitor (NDRI). Which
medication is most likely being prescribed, and what is a key advantage in this patient
population?
A. Sertraline; it has no significant drug interactions.
B. Bupropion; it has a lower risk of sexual dysfunction and can improve psychomotor
retardation.
C. Duloxetine; it also treats neuropathic pain.
D. Bupropion; it can worsen motor symptoms but is effective for depression.
Answer: B. Bupropion is the primary NDRI. It is a great choice for depression in Parkinson's
because it does not antagonize dopamine (which would worsen motor symptoms), and it has a
,lower incidence of sexual side effects compared to SSRIs/SNRIs. It may also provide mild
improvement in energy.
7. A patient is switched from fluoxetine to phenelzine (an MAOI). The provider instructs the
patient to wait at least 5 weeks before starting phenelzine. What is the primary reason for
this extended washout period?
A. Fluoxetine has a long half-life due to its active metabolite, norfluoxetine, which can take
weeks to eliminate.
B. Fluoxetine is highly protein-bound, delaying its clearance.
C. MAO enzymes take 5 weeks to regenerate after fluoxetine discontinuation.
D. Phenelzine requires 5 weeks to reach steady-state therapeutic levels.
Answer: A. Fluoxetine has a half-life of 1-3 days, but its active metabolite, norfluoxetine, has a
half-life of 7-15 days. This can lead to a significant washout period. Concurrent use of an MAOI
with residual SSRI can cause serotonin syndrome. A 5-week washout is recommended to avoid
this.
8. A 25-year-old female with generalized anxiety disorder (GAD) and a history of alcohol use
disorder is being considered for pharmacotherapy. Which medication would be the most
appropriate and safe choice for this patient?
A. Alprazolam.
B. Buspirone.
C. Diazepam.
D. Zolpidem.
Answer: B. Buspirone is a non-benzodiazepine anxiolytic that is a 5-HT1A partial agonist. It has
no abuse potential, minimal sedation, and is safe in patients with a history of substance use
disorder. Benzodiazepines like alprazolam and diazepam are Schedule IV controlled substances
with high abuse potential. Zolpidem is a hypnotic for sleep, not GAD.
9. A 50-year-old male with schizophrenia is being treated with clozapine. His absolute
neutrophil count (ANC) drops to 1100/mm³. Which of the following is the most appropriate
action according to the REMS program?
A. Continue clozapine and recheck ANC in one week.
B. Reduce the dose of clozapine by half.
C. Immediately stop clozapine and initiate the REMS monitoring protocol for mild neutropenia.
D. Stop clozapine, and do not restart it under any circumstances.
Answer: C. According to the clozapine REMS program, an ANC between 1000 and 1500/mm³ is
considered mild neutropenia. Clozapine must be interrupted immediately, and daily ANC
monitoring is required until the ANC is >1500/mm³. Rechallenge may be considered if no other
causes are found and benefits outweigh risks.
, 10. Which of the following gene polymorphisms is most strongly associated with a higher risk
of developing neuroleptic malignant syndrome (NMS)?
A. CYP2D6 poor metabolizer status.
B. DRD2 TaqIA polymorphism.
C. ANKK1 polymorphism.
D. No specific gene polymorphism has been definitively established as a strong predictor of
NMS.
Answer: D. While genetic factors may play a role, no specific gene polymorphism (including
DRD2 variants) has been definitively validated as a clinically useful predictor of NMS. The
pathophysiology involves a complex interplay of dopamine receptor blockade, and risk is
sporadic.
11. A patient on valproic acid for bipolar disorder is prescribed lamotrigine. The provider must
be cautious because valproic acid:
A. Increases the clearance of lamotrigine, requiring higher doses.
B. Decreases the clearance of lamotrigine, increasing the risk of Stevens-Johnson syndrome.
C. Competes with lamotrigine for protein binding, reducing its efficacy.
D. Has a synergistic effect on weight gain.
Answer: B. Valproic acid inhibits the glucuronidation of lamotrigine, effectively doubling its
serum levels and increasing the risk of serious rash, including Stevens-Johnson syndrome (SJS).
Dosing of lamotrigine must be significantly reduced (e.g., 25 mg every other day) when used
with valproate.
12. A 70-year-old female is started on donepezil for Alzheimer's disease. A family member
reports the patient is experiencing vivid dreams and difficulty sleeping. What is the most
likely explanation?
A. Donepezil is a cholinesterase inhibitor that enhances REM sleep, leading to insomnia.
B. Donepezil causes an increase in central acetylcholine, which can lead to vivid dreams and
insomnia.
C. The patient is experiencing a paradoxical reaction to donepezil.
D. Donepezil is an NMDA receptor antagonist that can cause psychosis.
Answer: B. Donepezil is a cholinesterase inhibitor that increases acetylcholine throughout the
brain. Increased cholinergic transmission is associated with vivid dreams, insomnia, and other
sleep disturbances. This is a known side effect, not a paradoxical reaction.
13. A patient is prescribed methylphenidate for ADHD. Which of the following describes the
drug's primary mechanism for improving attention?
A. It is a selective norepinephrine reuptake inhibitor.
B. It blocks the dopamine transporter (DAT) and norepinephrine transporter (NET), increasing
synaptic dopamine and norepinephrine.
