Questions and Revised Correct Answers &
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Question 1
Which mechanism most accurately describes the therapeutic action of selective
serotonin reuptake inhibitors (SSRIs) at steady
-state dosing?
A. Immediate blockade of postsynaptic
-HT2A
5 receptors
B. Selective inhibition of the serotonin transporter (SERT) with subsequent
desensitization of somatodendritic
-HT1A
5 autoreceptors
C. Rapid increase in synaptic dopamine via reuptake inhibition
D. Direct agonism at -HT1B/1D
5 receptors
Correct Answer: B
Rationale: SSRIs exert their primary effect by blocking SERT, which increases synaptic
serotonin. Over –4
2 weeks, this leads to downregulation and desensitization of
presynaptic -5HT1A autoreceptors, removing the inhibitory brake on serotonin neuron
firing and resulting in sustained elevation of serotonin release in key-regulating
mood
circuits (hippocampus, prefrontal cortex).
Question 2
A patient with treatment
-resistant depression has failed multiple SSRIs and SNRIs.
Which agent’s multimodal mechanism provides both SERT inhibition and direct
- 5
HT1A partial agonism + 5-HT1B partial agonism + 5-HT3 antagonism?
A. Vilazodone
,B. Vortioxetine
C. Levomilnacipran
D. Desvenlafaxine
Correct Answer: B
Rationale: Vortioxetine is unique among currently approved antidepressants in
combining SERT inhibition with multiple direct receptor effects
-HT1A
(5 partial
agonist, 5-HT1B partial agonist, -5HT3/7 antagonist), which contributes to its
procognitive and an
xiolytic advantages beyond pure reuptake inhibition.
Question 3
Which antidepressant class carries the highest risk of lethal overdose due to sodium
channel blockade and QTc prolongation in addition to serotonin and norepinephrine
reuptake inhibition?
A. SSRIs
B. SNRIs
C. Tricyclic antidepressants (TCAs)
D. Bupropion
Correct Answer: C
Rationale: TCAs block cardiac sodium channels (class I antiarrhythmic effect) and
hERG potassium channels, producing dose
-dependent QRS widening and QTc
prolongation; overdose mortality is significantly higher than with SSRIs or SNRIs.
Question 4
A 68-year-old patient on phenelzine develops severe hypertension after eating aged
gouda cheese. The most likely mechanism is:
A. Inhibition of CYP2D6 leading to elevated phenelzine levels
, B. Irreversible inhibition of MAO
-A preventing tyramine metabolism
C. Direct α1-adrenergic agonism by phenelzine
D. Serotonin reuptake inhibition causing serotonin syndrome
Correct Answer: B
Rationale: Phenelzine irreversibly inhibits both MAO
-A and MAO-B. Dietary tyramine
is normally metabolized by gut and liver MAO
-A; when inhibited, tyramine is absorbed
systemically, displaces vesicular norepinephrine, and precipitates a hypertensive
. crisis
Question 5
Which atypical antipsychotic has the highest affinity for the dopamine D2 receptor
among currently available agents and is FDA
-approved for acute mania, schizophrenia,
and adjunctive treatment of MDD?
A. Quetiapine
B. Risperidone
C. Aripiprazole
D. Lurasidone
Correct Answer: B
Rationale: Risperidone and its active metabolite paliperidone exhibit the highest D2
occupancy at therapeutic doses among atypical antipsychotics, accounting for its robust
efficacy across mood and psychotic disorders but also higher risk of hyperprolactin
emia
and extrapyramidal symptoms compared to lower
-affinity agents.
Question 6
The primary mechanism by which aripiprazole differs from all other antipsychotics is:
A. Full antagonism at D2 receptors