WGU D345 Psychopharmacology for Advanced
Psychiatric Mental Health Practice – Post-Master’s
Certificate Nursing PMHNP Study Guide, Original
Practice Questions & Answers, D345 Assessment
Preparation, Comprehensive Psychopharmacology
Review, Psychiatric Medications, Pharmacokinetics
& Pharmacodynamics, Substance Use Disorders,
Medication Management, Patient Education, Drug
Therapy & Advanced PMHNP Practice
Question 1: A 34-year-old patient with treatment-resistant major depressive
disorder is started on esketamine nasal spray. Understanding its unique
mechanism, the PMHNP correctly explains that this medication's rapid
antidepressant effect is primarily attributed to what action?
A. Selective serotonin reuptake inhibition and increased 5-HT levels in the synaptic cleft.
B. Dopamine and norepinephrine reuptake blockade in the prefrontal cortex.
C. Non-competitive N-methyl-D-aspartate (NMDA) receptor antagonism leading to
increased glutamate release and synaptogenesis.
D. Monoamine oxidase inhibition resulting in decreased breakdown of
neurotransmitters.
CORRECT ANSWER: C. Non-competitive N-methyl-D-aspartate (NMDA)
receptor antagonism leading to increased glutamate release and
synaptogenesis.
Rationale: Esketamine, an enantiomer of ketamine, acts as a non-competitive NMDA
receptor antagonist. By blocking NMDA receptors on GABAergic interneurons, it
disinhibits glutamate release. This surge in glutamate triggers a cascade of events that
leads to synaptogenesis and increased neuroplasticity, producing rapid antidepressant
effects, often within hours. This is distinct from the slower mechanisms of traditional
antidepressants that target monoamine systems .
Question 2: A PMHNP is reviewing a patient's medication list and notes they
are a known CYP2D6 poor metabolizer. Which of the following antipsychotics,
if prescribed, would present the highest risk of adverse effects due to this
genetic variation?
A. Quetiapine (Seroquel)
B. Risperidone (Risperdal)
C. Aripiprazole (Abilify)
D. Olanzapine (Zyprexa)
CORRECT ANSWER: B. Risperidone (Risperdal)
Rationale: Risperidone is primarily metabolized by the CYP2D6 enzyme. In a poor
metabolizer, the drug's clearance is significantly reduced, leading to higher-than-
,expected plasma concentrations. This increases the risk of dose-dependent side effects,
most notably extrapyramidal symptoms (EPS) and hyperprolactinemia .
Question 3: A 17-year-old patient presents with persistent sleep-onset
insomnia after a transatlantic flight and is struggling to adjust to the new time
zone. Which of the following medications is FDA-approved for this specific
indication?
A. Zolpidem (Ambien) 5 mg
B. Ramelteon (Rozerem) 8 mg
C. Diphenhydramine (Benadryl) 25 mg
D. Trazodone 50 mg
CORRECT ANSWER: B. Ramelteon (Rozerem) 8 mg
Rationale: Ramelteon is a melatonin receptor agonist (MT1 and MT2) that is FDA-
approved for the treatment of sleep-onset insomnia. Its mechanism targets the
suprachiasmatic nucleus to help reset the circadian rhythm, making it a suitable choice
for jet lag. It is not a controlled substance and has no abuse potential .
Question 4: The PMHNP is providing education to a patient with Alzheimer's
disease who recently started donepezil (Aricept). The patient reports
experiencing nausea and vivid nightmares. The NP explains these side effects
are a direct result of:
A. Histamine receptor antagonism in the central nervous system.
B. Increased cholinergic activity in the brain and peripheral nervous system.
C. Dopamine D2 receptor blockade in the mesolimbic pathway.
D. Norepinephrine reuptake inhibition leading to central nervous system stimulation.
CORRECT ANSWER: B. Increased cholinergic activity in the brain and
peripheral nervous system.
Rationale: Donepezil is a cholinesterase inhibitor that works by preventing the
breakdown of acetylcholine. The resulting increase in central cholinergic activity is
responsible for its therapeutic effect but also commonly causes side effects such as
gastrointestinal distress (nausea, diarrhea) and sleep disturbances (insomnia, vivid
dreams) .
Question 5: A patient with bipolar I disorder is maintained on lithium
carbonate. Which of the following concurrent medications would pose the
greatest risk of increasing lithium levels and potentially causing toxicity?
A. Acetaminophen (Tylenol)
B. Hydrochlorothiazide (a thiazide diuretic)
C. Omeprazole (Prilosec)
D. Levothyroxine (Synthroid)
CORRECT ANSWER: B. Hydrochlorothiazide (a thiazide diuretic)
,Rationale: Thiazide diuretics decrease the renal clearance of lithium by increasing
sodium reabsorption in the proximal tubule, leading to a compensatory increase in
lithium reabsorption. This can cause lithium levels to rise into a toxic range. NSAIDs also
carry a similar risk. Monitoring lithium levels closely is crucial when a patient is started
on a thiazide diuretic.
Question 6: A 28-year-old patient with a history of opioid use disorder is being
treated with buprenorphine/naloxone (Suboxone). The PMHNP understands
that the pharmacological action of buprenorphine is best described as:
A. A full mu-opioid receptor antagonist.
B. A full mu-opioid receptor agonist.
C. A partial mu-opioid receptor agonist and a kappa-opioid receptor antagonist.
D. A partial mu-opioid receptor agonist with a "ceiling effect" for respiratory depression.
CORRECT ANSWER: D. A partial mu-opioid receptor agonist with a "ceiling
effect" for respiratory depression.
Rationale: Buprenorphine is a partial agonist at the mu-opioid receptor. This means it
produces a sub-maximal effect. A key clinical advantage is its "ceiling effect" for
respiratory depression, making it safer than full agonists like methadone. It also has a
high affinity for the receptor, which can displace other opioids.
Question 7: A patient on clozapine (Clozapine) for treatment-resistant
schizophrenia is found to have an absolute neutrophil count (ANC) of
800/mm³. According to the REMS (Risk Evaluation and Mitigation Strategy)
program, what is the most appropriate action for the PMHNP?
A. Continue the current dose and re-check the ANC in one week.
B. Immediately discontinue clozapine and initiate a workup for infection.
C. Reduce the dose by 50% and monitor for signs of infection.
D. Administer granulocyte colony-stimulating factor (G-CSF) and continue clozapine.
CORRECT ANSWER: B. Immediately discontinue clozapine and initiate a
workup for infection.
Rationale: Clozapine carries a black-box warning for severe neutropenia. The REMS
program mandates that clozapine be interrupted if the ANC falls below 1000/mm³. An
ANC of 800/mm³ is a critical value; the medication must be stopped immediately to
reduce the risk of life-threatening agranulocytosis and sepsis, and a thorough medical
workup is required.
Question 8: A 45-year-old patient with major depressive disorder is started on
an SSRI. At a 4-week follow-up, they report a significant improvement in mood
but are distressed by persistent sexual dysfunction. Which of the following is
the most evidence-based augmentation or switching strategy for managing this
side effect?
, A. Add low-dose aripiprazole (Abilify).
B. Add bupropion (Wellbutrin) to the regimen.
C. Switch to fluoxetine (Prozac).
D. Add a benzodiazepine to alleviate anxiety.
CORRECT ANSWER: B. Add bupropion (Wellbutrin) to the regimen.
Rationale: SSRI-induced sexual dysfunction is a common and distressing side effect.
Adding bupropion, which has a dopaminergic and noradrenergic mechanism, has been
shown in clinical trials to be an effective strategy to counteract this side effect. Switching
to bupropion monotherapy is also an option, but augmentation with bupropion is a
standard and effective approach.
Question 9: A PMHNP is assessing a patient who presents with symptoms of
depression, anhedonia, and significant psychomotor retardation. The patient
also reports hypersomnia and increased appetite. Which of the following is a
key consideration for differential diagnosis?
A. The patient has a "typical" presentation of Major Depressive Disorder (MDD).
B. These symptoms are more consistent with a diagnosis of Bipolar II Disorder, current
episode depressed.
C. The patient likely has a co-occurring substance use disorder.
D. These symptoms suggest a diagnosis of Persistent Depressive Disorder (Dysthymia).
CORRECT ANSWER: B. These symptoms are more consistent with a diagnosis
of Bipolar II Disorder, current episode depressed.
Rationale: A major depressive episode with "atypical" features (hypersomnia, increased
appetite, leaden paralysis, and rejection sensitivity) is more common in bipolar
depression than in unipolar depression. Screening for a history of hypomanic episodes is
essential to differentiate Bipolar II Disorder from MDD, as the treatment approach is
markedly different.
Question 10: A 72-year-old patient with Parkinson's disease is experiencing
visual hallucinations and paranoid delusions. The PMHNP is considering
pharmacologic management. Which of the following antipsychotics is the
preferred first-line choice due to its reduced risk of motor side effects?
A. Haloperidol (Haldol)
B. Quetiapine (Seroquel)
C. Pimavanserin (Nuplazid)
D. Risperidone (Risperdal)
CORRECT ANSWER: C. Pimavanserin (Nuplazid)
Rationale: Pimavanserin is a selective serotonin 5-HT2A inverse agonist approved
specifically for the treatment of psychosis associated with Parkinson's disease. Its
mechanism avoids dopamine D2 receptor blockade, making it the only antipsychotic
Psychiatric Mental Health Practice – Post-Master’s
Certificate Nursing PMHNP Study Guide, Original
Practice Questions & Answers, D345 Assessment
Preparation, Comprehensive Psychopharmacology
Review, Psychiatric Medications, Pharmacokinetics
& Pharmacodynamics, Substance Use Disorders,
Medication Management, Patient Education, Drug
Therapy & Advanced PMHNP Practice
Question 1: A 34-year-old patient with treatment-resistant major depressive
disorder is started on esketamine nasal spray. Understanding its unique
mechanism, the PMHNP correctly explains that this medication's rapid
antidepressant effect is primarily attributed to what action?
A. Selective serotonin reuptake inhibition and increased 5-HT levels in the synaptic cleft.
B. Dopamine and norepinephrine reuptake blockade in the prefrontal cortex.
C. Non-competitive N-methyl-D-aspartate (NMDA) receptor antagonism leading to
increased glutamate release and synaptogenesis.
D. Monoamine oxidase inhibition resulting in decreased breakdown of
neurotransmitters.
CORRECT ANSWER: C. Non-competitive N-methyl-D-aspartate (NMDA)
receptor antagonism leading to increased glutamate release and
synaptogenesis.
Rationale: Esketamine, an enantiomer of ketamine, acts as a non-competitive NMDA
receptor antagonist. By blocking NMDA receptors on GABAergic interneurons, it
disinhibits glutamate release. This surge in glutamate triggers a cascade of events that
leads to synaptogenesis and increased neuroplasticity, producing rapid antidepressant
effects, often within hours. This is distinct from the slower mechanisms of traditional
antidepressants that target monoamine systems .
Question 2: A PMHNP is reviewing a patient's medication list and notes they
are a known CYP2D6 poor metabolizer. Which of the following antipsychotics,
if prescribed, would present the highest risk of adverse effects due to this
genetic variation?
A. Quetiapine (Seroquel)
B. Risperidone (Risperdal)
C. Aripiprazole (Abilify)
D. Olanzapine (Zyprexa)
CORRECT ANSWER: B. Risperidone (Risperdal)
Rationale: Risperidone is primarily metabolized by the CYP2D6 enzyme. In a poor
metabolizer, the drug's clearance is significantly reduced, leading to higher-than-
,expected plasma concentrations. This increases the risk of dose-dependent side effects,
most notably extrapyramidal symptoms (EPS) and hyperprolactinemia .
Question 3: A 17-year-old patient presents with persistent sleep-onset
insomnia after a transatlantic flight and is struggling to adjust to the new time
zone. Which of the following medications is FDA-approved for this specific
indication?
A. Zolpidem (Ambien) 5 mg
B. Ramelteon (Rozerem) 8 mg
C. Diphenhydramine (Benadryl) 25 mg
D. Trazodone 50 mg
CORRECT ANSWER: B. Ramelteon (Rozerem) 8 mg
Rationale: Ramelteon is a melatonin receptor agonist (MT1 and MT2) that is FDA-
approved for the treatment of sleep-onset insomnia. Its mechanism targets the
suprachiasmatic nucleus to help reset the circadian rhythm, making it a suitable choice
for jet lag. It is not a controlled substance and has no abuse potential .
Question 4: The PMHNP is providing education to a patient with Alzheimer's
disease who recently started donepezil (Aricept). The patient reports
experiencing nausea and vivid nightmares. The NP explains these side effects
are a direct result of:
A. Histamine receptor antagonism in the central nervous system.
B. Increased cholinergic activity in the brain and peripheral nervous system.
C. Dopamine D2 receptor blockade in the mesolimbic pathway.
D. Norepinephrine reuptake inhibition leading to central nervous system stimulation.
CORRECT ANSWER: B. Increased cholinergic activity in the brain and
peripheral nervous system.
Rationale: Donepezil is a cholinesterase inhibitor that works by preventing the
breakdown of acetylcholine. The resulting increase in central cholinergic activity is
responsible for its therapeutic effect but also commonly causes side effects such as
gastrointestinal distress (nausea, diarrhea) and sleep disturbances (insomnia, vivid
dreams) .
Question 5: A patient with bipolar I disorder is maintained on lithium
carbonate. Which of the following concurrent medications would pose the
greatest risk of increasing lithium levels and potentially causing toxicity?
A. Acetaminophen (Tylenol)
B. Hydrochlorothiazide (a thiazide diuretic)
C. Omeprazole (Prilosec)
D. Levothyroxine (Synthroid)
CORRECT ANSWER: B. Hydrochlorothiazide (a thiazide diuretic)
,Rationale: Thiazide diuretics decrease the renal clearance of lithium by increasing
sodium reabsorption in the proximal tubule, leading to a compensatory increase in
lithium reabsorption. This can cause lithium levels to rise into a toxic range. NSAIDs also
carry a similar risk. Monitoring lithium levels closely is crucial when a patient is started
on a thiazide diuretic.
Question 6: A 28-year-old patient with a history of opioid use disorder is being
treated with buprenorphine/naloxone (Suboxone). The PMHNP understands
that the pharmacological action of buprenorphine is best described as:
A. A full mu-opioid receptor antagonist.
B. A full mu-opioid receptor agonist.
C. A partial mu-opioid receptor agonist and a kappa-opioid receptor antagonist.
D. A partial mu-opioid receptor agonist with a "ceiling effect" for respiratory depression.
CORRECT ANSWER: D. A partial mu-opioid receptor agonist with a "ceiling
effect" for respiratory depression.
Rationale: Buprenorphine is a partial agonist at the mu-opioid receptor. This means it
produces a sub-maximal effect. A key clinical advantage is its "ceiling effect" for
respiratory depression, making it safer than full agonists like methadone. It also has a
high affinity for the receptor, which can displace other opioids.
Question 7: A patient on clozapine (Clozapine) for treatment-resistant
schizophrenia is found to have an absolute neutrophil count (ANC) of
800/mm³. According to the REMS (Risk Evaluation and Mitigation Strategy)
program, what is the most appropriate action for the PMHNP?
A. Continue the current dose and re-check the ANC in one week.
B. Immediately discontinue clozapine and initiate a workup for infection.
C. Reduce the dose by 50% and monitor for signs of infection.
D. Administer granulocyte colony-stimulating factor (G-CSF) and continue clozapine.
CORRECT ANSWER: B. Immediately discontinue clozapine and initiate a
workup for infection.
Rationale: Clozapine carries a black-box warning for severe neutropenia. The REMS
program mandates that clozapine be interrupted if the ANC falls below 1000/mm³. An
ANC of 800/mm³ is a critical value; the medication must be stopped immediately to
reduce the risk of life-threatening agranulocytosis and sepsis, and a thorough medical
workup is required.
Question 8: A 45-year-old patient with major depressive disorder is started on
an SSRI. At a 4-week follow-up, they report a significant improvement in mood
but are distressed by persistent sexual dysfunction. Which of the following is
the most evidence-based augmentation or switching strategy for managing this
side effect?
, A. Add low-dose aripiprazole (Abilify).
B. Add bupropion (Wellbutrin) to the regimen.
C. Switch to fluoxetine (Prozac).
D. Add a benzodiazepine to alleviate anxiety.
CORRECT ANSWER: B. Add bupropion (Wellbutrin) to the regimen.
Rationale: SSRI-induced sexual dysfunction is a common and distressing side effect.
Adding bupropion, which has a dopaminergic and noradrenergic mechanism, has been
shown in clinical trials to be an effective strategy to counteract this side effect. Switching
to bupropion monotherapy is also an option, but augmentation with bupropion is a
standard and effective approach.
Question 9: A PMHNP is assessing a patient who presents with symptoms of
depression, anhedonia, and significant psychomotor retardation. The patient
also reports hypersomnia and increased appetite. Which of the following is a
key consideration for differential diagnosis?
A. The patient has a "typical" presentation of Major Depressive Disorder (MDD).
B. These symptoms are more consistent with a diagnosis of Bipolar II Disorder, current
episode depressed.
C. The patient likely has a co-occurring substance use disorder.
D. These symptoms suggest a diagnosis of Persistent Depressive Disorder (Dysthymia).
CORRECT ANSWER: B. These symptoms are more consistent with a diagnosis
of Bipolar II Disorder, current episode depressed.
Rationale: A major depressive episode with "atypical" features (hypersomnia, increased
appetite, leaden paralysis, and rejection sensitivity) is more common in bipolar
depression than in unipolar depression. Screening for a history of hypomanic episodes is
essential to differentiate Bipolar II Disorder from MDD, as the treatment approach is
markedly different.
Question 10: A 72-year-old patient with Parkinson's disease is experiencing
visual hallucinations and paranoid delusions. The PMHNP is considering
pharmacologic management. Which of the following antipsychotics is the
preferred first-line choice due to its reduced risk of motor side effects?
A. Haloperidol (Haldol)
B. Quetiapine (Seroquel)
C. Pimavanserin (Nuplazid)
D. Risperidone (Risperdal)
CORRECT ANSWER: C. Pimavanserin (Nuplazid)
Rationale: Pimavanserin is a selective serotonin 5-HT2A inverse agonist approved
specifically for the treatment of psychosis associated with Parkinson's disease. Its
mechanism avoids dopamine D2 receptor blockade, making it the only antipsychotic
