Psicofarmacologia Flashcards

1
Q

21.1.
An 80-year-old woman in an assisted care facility was started
2 weeks ago on nightly doses of quetiapine due to episodes of
drowsiness, confusion, and ataxia. The symptoms largely
resolved after two doses. However, she now has had muscle
stiffness and drooling for the last 3 days, and the ataxia has
been replaced by a shuffling gait. She is also on memantine
and hydrochlorothiazide. Vital signs on evening nursing
rounds are T 98.8 F, BP 130/85, pulse 80, and respirations 16.
Mental status examination reveals a well-nourished female in
no acute distress. She is pleasant and cooperative. Her mood is
“7 out of 10” with congruent affect. She denies suicidal
ideation or auditory or visual hallucinations. She is oriented to
person, place, time, and situation. What is the most
appropriate treatment to address this patient’s current
symptoms?

A. Begin propranolol

B. Begin bromocriptine

C. Discontinue quetiapine

D. Begin tetrabenazine

E. Begin benztropine

A

21.1. E. Begin benztropine
The patient is displaying symptoms of neuroleptic-induced
parkinsonism, for which the treatment of choice is an anticholinergic
agent such as benztropine, amantadine or diphenhydramine.
Neuroleptic malignant syndrome, for which dantrolene or
bromocriptine would be used, would present with autonomic
instability such as hyperthermia and increased pulse and blood
pressure. As she has shown marked improvement in the original
symptoms with the quetiapine, it would be best to try to treat the
side effect as opposed to starting a new medication which may or
may not be effective, and which can lead to the same side effect.
Propranolol would be used for akathisia, which would present with
hyperkinesis as opposed to bradykinesis, while tetrabenazine would
be used for tardive dyskinesia, which likely would not appear this
quickly, and would involve choreoathetoid movements.
Antihistamines such as diphenhydramine can also be used as an
alternative to anticholinergics.

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2
Q

21.2.
What neuroleptic-induced movement disorder is more likely
to occur in men than women?

A. Neuroleptic-induced parkinsonism

B. Neuroleptic malignant syndrome (NMS)

C. Acute dystonia

D. Acute akathisia

E. Tardive dyskinesia (TD)

A

21.2. C. Acute dystonia
Of all of the common neuroleptic-induced mood disorders,
medication-induced acute dystonia is more likely to occur in men,
particularly those under age 30 years. Neuroleptic-induced
parkinsonism is more likely to affect older women, NMS is more
likely to affect younger women, and acute akathisia and TD are most
likely to affect middle-aged women.

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3
Q

21.3.
A 27-year-old man presents to the outpatient clinic for
medication management of his 9-year diagnosis of
schizophrenia. He is currently on risperidone, which has kept
him stable and out of the hospital for the past year. He has
been on haloperidol, fluphenazine, quetiapine, and
ziprasidone. Though each was initially helpful, he was
eventually hospitalized because “they just stopped working.”
He remarks that this has been his longest period without
hospitalization since he was first diagnosed, and does not want
to make medication changes. However, he complains that he
“can’t keep my tongue in my mouth. It’s embarrassing.” He
notes that he also cannot stop clenching and unclenching his
fists. Abnormal involuntary movement scale (AIMS) test
reveals a severity rating of 3, incapacitation rating of 2, and
awareness rating of 3. What is the best step to relieve this
patient’s movement symptoms?

A. Decrease risperidone dose
B. Change risperidone to clozapine
C. Begin benztropine
D. Begin valbenazine
E. Change risperidone to aripiprazole

A

21.3. D. Begin valbenazine
The patient has a moderate level of tardive dyskinesia (TD) which is
causing him a moderate amount of distress. The first approach
considered should be to lower the dose of the offending agent.
However, given the patient’s history of hospitalizations and his
stated preference not to adjust his current regimen, neither a
decrease in dose nor a change to another agent would be the best
choice. If the risperidone becomes ineffective in the future, clozapine
would be a strong consideration, as it is unlikely to cause TD and can
even decrease it. Benztropine is not helpful for TD. A VMAT2
inhibitor such as valbenazine would be first-line treatment

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4
Q

21.4.
Which serotonin–dopamine antagonist is most likely to cause
akathisia?

A. Aripiprazole
B. Olanzapine
C. Clozapine
D. Quetiapine
E. Ziprasidone

A

21.4. A. Aripiprazole
Aripiprazole is the most likely of the serotonin–dopamine
antagonists to cause akathisia due to its high potency (high D2
blockade). Olanzapine and clozapine have low levels of D2 blockade,
while quetiapine and ziprasidone have low to medium levels of D2
blockade

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5
Q

21.5.
Which serotonin–dopamine antagonist is most likely to cause
extrapyramidal symptoms?

A. Aripiprazole
B. Risperidone
C. Olanzapine
D. Quetiapine
E. Ziprasidone

A

21.5. B. Risperidone
Risperidone is most likely of the serotonin–dopamine antagonists to
cause extrapyramidal symptoms, and resembles haloperidol, in
terms of side effects, at higher doses. Aripiprazole is most likely to
cause akathisia

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6
Q

21.6.
A 37-year-old man with bipolar disorder presents to the
urgent care clinic with complaints of painful sores on his chest
and in his mouth. He states that, 3 days ago, he developed a
cough, body aches, and felt “sick.” He believed he had the flu,
so he stayed home and hydrated. Yesterday, he noticed a
purplish rash on his chest. When he woke this morning, part of
the rash had blistered and peeled, and had become painful. He
also noticed an ulcer in his mouth. His medications are
valproic acid and lamotrigine. Vitals are temperature 99.8,
pulse 90, and respirations 20. BP taken on the lower left arm
is 160/90. Examination reveals a purplish rash on his chest
and upper part of his arms, with intermittent peeling and
blistering. Four blisters are present on the oral mucosa. What
is the next most appropriate step in treatment?

A. Give a dose of oral diphenhydramine and a prescription to
take twice a day until the rash resolves
B. Send him to the emergency department
C. Administer IV diphenhydramine in the office and observe
the rash
D. Prescribe bromocriptine and advise him to go to the
emergency department if symptoms do not resolve by the
next day
E. Advise he discontinue his medications and follow up the
next day with the prescribing physicians

A

21.6. B. Send him to the emergency department
The patient is showing classic signs and symptoms of Stevens–
Johnson syndrome. Though it can be caused by any medication, it is
linked to lamotrigine and can manifest at any time the medication is
used, not just during titration. The presence of valproic acid raises
the blood level of lamotrigine, so if the two are used simultaneously,
the lamotrigine either should be reduced, or titrated very slowly. As
Stevens–Johnson is a potentially life-threatening condition, those
who show symptoms should go to the emergency department
immediately. He will need to permanently stop the lamotrigine

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7
Q

21.7.
A 78-year-old man is brought to the emergency department
by nursing home staff following 2 weeks of increasing agitation
and confusion. He has diagnoses of hypertension, bipolar
disorder, and diabetes mellitus, for which he is on
hydrochlorothiazide (HCTZ), aripiprazole, metformin, and
oxcarbazepine. The nursing home staff reports that his vitals
have been normal over the past week, and he has had no
physical complaints except for being more tired than usual.
Symptoms do not correlate with a specific time of day. A
month ago, his speech started getting pressured and he had
difficulty getting to sleep, so oxcarbazepine was increased. At
that time, HgB A1c was 5.4, cholesterol was 180, and
triglycerides were 150. Currently, vital signs are within normal
limits. On examination, he is lethargic, and is alert and
oriented to person, but not place and time. What lab result is
most likely to be abnormal?

A. Glucose
B. Potassium
C. Sodium
D. Hemoglobin
E. White blood cell count

A

21.7. C. Sodium
Symptoms of confusion, agitation, and lethargy can be caused by
hyponatremia, which can occur in individuals taking oxcarbazepine,
especially the elderly. Acute hyperglycemia can cause confusion and
lethargy, but his A1c would be expected to have been higher a month
ago if he were having several repeated episodes of glucose spikes.
Infection could cause similar symptoms, but a fever would be
expected. Fatigue can be a symptom of both low hemoglobin and low
potassium (from HCTZ), but confusion and agitation are usually not.

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8
Q

21.8.
A 27-year-old woman is brought by emergency medical
services (EMS) on a hotter-than-usual summer day to the
emergency department due to an abrupt onset of difficulty
standing, hand tremors, and confusion. She had just
completed a citywide marathon 30 minutes ago when she was
noticed by other runners to stumble and fall to the ground.
She was not able to give her name, and said at the time that
she was in her house in a different city. She has a diagnosis of
bipolar disorder and has been stable on extended-release
lithium and lamotrigine for the last 10 years. The electronic
medical record shows that her lithium level was 1.0 at her last
outpatient psychiatry appointment a week ago. Current vitals
are T 99.7 F, BP 100/60, pulse 60, and respirations 14.
Lithium level is 2.0. Physical examination reveals coarse hand
tremors, ataxia, and horizontal nystagmus. What is the next
best step in treatment?

A. Intravenous saline
B. Gastric lavage
C. Administration of activated charcoal
D. Hemodialysis
E. Whole bowel irrigation

A

21.8. D. Hemodialysis
The patient is experiencing acute lithium toxicity caused by
increased blood levels secondary to dehydration. This can occur
when someone perspires more than usual and does not properly
rehydrate. The first-line treatment for acute lithium intoxication is
hemodialysis, though gastric lavage could be considered in the case
of regular-release preparations, and whole-bowel irrigation for
sustained-release preparations. Lithium does not adhere well to
activated charcoal. The lithium needs to be removed, not just diluted
by IV saline, as lithium toxicity can be fatal.

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9
Q

21.9.
A 36-year-old male is discovered by his mother on the floor of
his bathroom after she returned home from work. EMS is
called, and he is found to be dead at the scene. On the floor is
an empty bottle of her amitriptyline and an empty bottle of his
lamotrigine, both of which had been filled the day before. She
states that he had no medical illnesses besides bipolar disorder
and did not use drugs. A suicide note is found at the scene.
What is the most likely mechanism of his death?

A. Inhibition of sodium current into myocardial cells
B. Acute hypothalamic dopamine blockade
C. Stimulation of postsynaptic 5-HT1A and 5-HT2A receptors
D. Acute norepinephrine release secondary to tyramine
ingestion
E. Delayed type IV hypersensitivity reaction

A

21.9. A. Inhibition of sodium current into myocardial cells
Tricyclic antidepressants (TCAs) have largely been replaced by SSRIs
due to the safety profile of the latter. A concern with TCAs is suicide
by overdose, with death being caused by cardiac toxicity. The overall
mechanism of death is hypotension caused by a reduction in
peripheral resistance and QRS complex prolongation due to an
inhibition of sodium into myocardial cells. Acute hypothalamic
dopamine blockade is the mechanism behind neuroleptic malignant
syndrome. Stimulation of postsynaptic 5-HT1A and 5-HT2A
receptors is the mechanism behind serotonin syndrome. Acute
norepinephrine release following tyramine ingestion is the
mechanism of a hypertensive crisis caused by some monoamine
oxidase inhibitors (MAOIs). A delayed type IV hypersensitivity
reaction is a theoretical mechanism of Stevens–Johnson syndrome.
https://emj.bmj.com/content/18/4/236

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10
Q

21.10.
In addition to alcohol and benzodiazepines, withdrawal from
what class of psychoactive medications can be fatal?

A. Stimulants (cocaine, methamphetamine, etc.)
B. Monoamine oxidase inhibitors (MAOIs)
C. Barbiturates
D. Tricyclic antidepressants
E. Opioids

A

21.10. C. Barbiturates
Though the muscle aches, abdominal cramping, agitation, GI upset,
and other unpleasant symptoms of opioid withdrawal can make
people wish they were dead, the process is not life-threatening.
Stimulant withdrawal can lead to fatigue, vivid dreams, sleep
disturbances, hyperphagia, and psychomotor changes, but is not
deadly. Stopping tricyclics and MAOIs can lead to a nonfatal
discontinuation syndrome consisting of flu-like symptoms,
insomnia, nausea, imbalance, sensory disturbances, and
hyperarousal. Barbiturate withdrawal includes anxiety, restlessness,
tremor, dizziness, psychosis, and seizures. If left untreated,
withdrawal can lead to hyperthermia, circulatory failure, and death.

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11
Q

21.11.
In addition to lithium, what psychotropic medication carries
an U.S. Food and Drug Administration (FDA) warning for
pregnant women due to an increased risk of cardiac
malformation?

A. Carbamazepine
B. Valproic acid
C. Lamotrigine
D. Citalopram
E. Paroxetine

A

21.11. E. Paroxetine
Carbamazepine and valproic acid both can lead to neural tube
defects. Lamotrigine may cause oral clefts. Citalopram can cause QT
interval prolongation and ventral tachycardia at high doses in the
person taking the medication, but is not known to be associated with
birth defects. In 2005, the FDA issued an alert that paroxetine
increases the risk of heart defects when taken during the first
trimester.

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12
Q

21.12.
A 9-year-old boy diagnosed with autism spectrum disorder
at age 2 is brought to the outpatient clinic due to worsening
aggression and irritability over the last 2 months. He was
started on sertraline for depression 6 months ago. At that
time, in addition to irritability, he displayed decreased
appetite, loss of interest in playing video games, lethargy,
and poor concentration at school, resulting in his grades
dropping from Bs to Ds. Since treatment, only the irritability
has remained. He now occasionally bites himself and shows
aggression toward his parents, teachers, and behavioral
therapist. He has not physically attacked anyone, but his
parents are worried that may soon occur. New therapeutic
techniques have been marginally ineffective. The parents
note that he has always displayed these behaviors, but that
they have increased in frequency and intensity. He has no
chronic medical illnesses and is on no other medications.
Vital signs are within normal limits and physical
examination is noncontributory. He is begrudgingly
cooperative, but calm. What is the next best step in
treatment for this child?

A. Increase sertraline
B. Obtain a head CT
C. Begin aripiprazole
D. Admit the child to the hospital
E. Change therapists

A

21.12. C. Begin aripiprazole
Irritability can be a core symptom of depression in children.
However, given that he no longer displays any of the other symptoms
of depression, his current behaviors are likely not a relapse or
exacerbation, so increasing sertraline would be of little benefit. There
are currently no indications for a head CT. He is not at present a
danger to himself or others, so hospitalization is not indicated.
Aripiprazole, as is risperidone, is indicated for irritability in children
and adolescents with autism spectrum disorder. Given that they have
tried many other measures, and behaviors are intensifying, a
medication intervention is warranted. A decrease in irritability and
aggression may help him engage more in therapy. Given that his
current symptoms are not limited to just the therapist, and that his
therapist is trying new techniques, changing to a different therapist
would likely be of little benefit.

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13
Q

21.13.
What atypical antipsychotic is most likely to lead to weight
gain?

A. Risperidone
B. Quetiapine
C. Olanzapine
D. Paliperidone
E. Aripiprazole

A

21.13. C. Olanzapine
Though all atypicals can cause weight gain, olanzapine consistently
leads to more weight gain more frequently. The weight gain is not
dose related and continues over time. Clozapine is also consistent in
leading to weight gain

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14
Q

21.14.
An 18-year-old man is admitted to the hospital for firstbreak
psychosis after locking himself in his college dorm
room for 2 days because he felt that was the only way “to
keep the demons away from me.” Medical workup in the
emergency department found no etiology for the psychotic
symptoms. He was first started on haloperidol, which led to a
stiff neck, which was mostly relieved with benztropine. A
trial of fluphenazine caused his eyes to fix in an upward
deviation. Risperidone led to the same effects. He is on no
other medications and has no chronic medical illnesses.
Body mass index (BMI) is 17. What medication should be
tried next to manage his symptoms?

A. Aripiprazole
B. Quetiapine
C. Clozapine
D. Chlorpromazine
E. Asenapine

A

21.14. B. Quetiapine
The patient has had extrapyramidal side effects (EPS) with two firstgeneration
antipsychotics and a serotonin–dopamine antagonist
(albeit risperidone, which behaves most like a first-generation
medication in regards to EPS), which shows how sensitive he is to
this particular side effect. Quetiapine would be the next best option
given that it is the serotonin–dopamine antagonist least likely to lead
to EPS. Though chlorpromazine is a low potency, highly
anticholinergic medication, first-generation antipsychotics lead to
more EPS in general, so it should be avoided as well.

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15
Q

21.15.
In addition to lurasidone, what serotonin–dopamine
antagonist must be taken with food to achieve maximum
effect?

A. Aripiprazole
B. Iloperidone
C. Lurasidone
D. Quetiapine
E. Ziprasidone

A

21.15. E. Ziprasidone
Bioavailability of ziprasidone doubles when taken with food of at
least 500 calories. Though it was originally believed that the calories
had to be high in fat, that was not supported in studies.
https://pubmed.ncbi.nlm.nih.gov/18007569/

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16
Q

21.16.
A 24-year-old man presents to the outpatient clinic for
follow-up of schizophrenia. He was diagnosed 6 months ago,
and symptoms have been adequately controlled with
risperidone. He is greatly distressed by breast enlargement,
and states that he stopped taking the medication a week ago
after he noticed milk discharge from his chest. He is willing
to try another medication, but refuses to take anything that
can cause the same symptoms. He has a current BMI of 23.
BMI prior to starting medication was 21. He is also on
amiodarone for congenital heart disease. He has no known
drug allergies. Which of the following medications should be
considered for this patient?

A. Aripiprazole
B. Asenapine
C. Iloperidone
D. Quetiapine
E. Ziprasidone

A

21.16. A. Aripiprazole
Though any serotonin–dopamine antagonist antipsychotic can
elevate prolactin levels, asenapine, like risperidone, can cause
galactorrhea and gynecomastia. It also, like quetiapine, iloperidone,
and ziprasidone, can increase QTc interval and should be avoided in
patients on antiarrhythmics, such as amiodarone, that prolong QTc.
Even if he were not on an antiarrhythmic, a diagnosis of congenital
heart disease should give pause to the prescription of a medication
that is known to prolong QTc interval. Aripiprazole does not cause
significant QTc interval changes and does not usually cause
significant weight gain or prolactin elevation

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17
Q

21.17.
The parents of a 26-year-old man who is diagnosed with
schizophrenia called the office to say that they were not able
to get him to the lab yesterday for his weekly complete blood
count (CBC) for clozapine. When they went to the pharmacy,
they were denied the patient’s dose of medication. They note
that the patient has not missed a lab appointment in 4
months, and state that they can get his blood drawn the next
morning. They request assistance with getting him the
clozapine. How should the physician respond?

A. Send in a prescription for one dose of medication
B. Call the pharmacy to authorize an override
C. Send a prescription to a different pharmacy
D. Affirm that the medication cannot be dispensed
E. Call the lab and explain the situation

A

21.17. D. Affirm that the medication cannot be dispensed
Clozapine absolutely cannot be dispensed without current lab results
sent to the pharmacy, so sending a prescription to another
pharmacy, or writing a prescription for one dose, would be of no use.
As this rule in inviolable, explaining the situation to the pharmacy or
the lab will also prove fruitless. The parents will need to be told that
the medication cannot be dispensed. Missing a blood draw also
means that he has to restart the 6 months of weekly blood draws
before he can move to biweekly draws.

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18
Q

21.18.
Iloperidone must be titrated slowly to avoid what side effect?

A. Sedation
B. Tachycardia
C. Orthostatic hypotension
D. QTc prolongation
E. Akathisia

A

21.18. C. Orthostatic hypotension
While sedation and tachycardia are common side effects of
iloperidone, the medication must be titrated slowly in order to avoid
orthostatic hypotension. Titration speed does not affect the QTc
prolongation that may occur at doses of 12 mg bid. The rate of
akathisia is similar to that of placebo.

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19
Q

21.19.
A 19-year-old man presents to the outpatient psychiatry
clinic for follow-up management of his diagnosis of
schizophrenia 8 weeks ago. At the time of initial
presentation, he had had a 6-month history of auditory
hallucinations and paranoia, which were preceded by an 8-
month history of withdrawing from family and friends and
staying in his room so that he would not “be subject to the
influence of the emperor.” After an extensive workup, he was
started on aripiprazole, and he and the family were provided
with psychoeducation on the illness. He was on a low dose
for 2 weeks, then a medium dose for 2 weeks, then the
maximum recommended dose for 4 weeks. Today, his
parents report that his behavior is unchanged. They attest
that they watch him take and swallow his medication every
morning, which he does with no hesitation. What should be
the next step in treatment?

A. Augment with a first-generation antipsychotic
B. Continue aripiprazole for another 4 weeks
C. Change to clozapine
D. Change to a different, nonclozapine, serotonin–dopamine
antagonist
E. Change to the long-acting injectable form of aripiprazole

A

21.19. D. Change to a different, nonclozapine, serotonin–
dopamine antagonist
The patient appears to have gotten no therapeutic benefit from 8
weeks of aripiprazole, with 4 of them being at the maximum dosage.
At this point, aripiprazole can be considered a treatment failure, and
would likely be no more effective with additional time on the
medication. Had he shown any improvement, continuing the current
dose for another 4 weeks, or augmentation with a first-generation
antipsychotic would have been reasonable. Clozapine is used once a
person has been shown to be refractory to several antipsychotic
medications. The treatment of choice at this time would be to change
to a different serotonin–dopamine antagonist.

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20
Q

21.20.
A 30-year-old woman on a telepsych appointment with a
psychiatrist complains of “being so depressed for the last
month that I can’t get out of bed. That’s why I couldn’t come
in.” She states that she was diagnosed with major depressive
disorder (MDD) 10 years ago, and has had six such episodes
in that time, which also included increased appetite,
decreased concentration, withdrawal from friends and
family, and poor energy. She reports that the symptoms
usually resolve in about 2 months, and that she will “ride it
out” because she does not like to take medication. She notes
that her husband is very understanding during these periods
and does extra work around the house while she recovers.
She is concerned this time because she has started to hear
voices over the last 3 days telling her that she should kill
herself. “This is the most depressed I have ever been, and
these voices are scaring me. I don’t know what to do!” She is
diagnosed with hypothyroidism, which has been well
controlled with synthetic thyroid hormone. Thyroid function
tests done 3 months ago were in the normal range. She has
no other medical illnesses and is on no other medications.
Mental status examination reveals an anxious affect. She is
tearful at times. She states that she is willing to “do whatever
it takes” to get better. What should be the treatment for this
patient?

A. An antidepressant medication only
B. An antipsychotic medication only
C. An antidepressant and an antipsychotic medication
D. Electroconvulsive therapy (ECT) only
E. ECT and an antidepressant medication

A

21.20. C. An antidepressant and an antipsychotic
medication
The patient is experiencing MDD with psychotic features, as the
psychosis emerged during the most severe of her depressive
episodes. Had she had steady psychotic symptoms with intermittent
episodes of depression, the diagnosis would be schizoaffective
disorder, depressive type. First-line treatment for MDD with
psychotic features consists of treating both the depression with an
antidepressant and the psychosis with an antipsychotic. Though
treatment with only an antidepressant should eventually lead to
resolution of the psychosis once the depression remits, this would
likely take weeks, and she is having command hallucinations of
suicide, which warrants aggressive treatment. ECT is also effective
for this diagnosis, but given that she is medication naïve and not in
imminent danger of self-harm, medication should be tried first.

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21
Q

21.21.
What is the usual mechanism of orthostatic hypotension
from first-generation antipsychotics?

A. Beta-2 receptor agonism
B. D2 receptor antagonism
C. Alpha-1 receptor blockade
D. Acetylcholine receptor antagonism
E. H1 receptor blockade

A

21.21. C. Alpha-1 receptor blockade
Orthostatic hypotension is a result of alpha-1 receptor blockade. H1
receptor blockade leads to sedation. D2 receptor antagonism is the
mechanism that leads to symptom relief in psychotic disorders, as
well as Parkinsonian and prolactin side effects. Acetylcholine
antagonism, which is stronger in low-potency, first-generation
antipsychotics, includes side effects such as dry mouth, blurred
vision, constipation, and urinary retention. Beta-2 receptor agonism
can lead to trembling, increased heart rate, nervousness, and
headache.

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22
Q

21.22.
Increased secretion of prolactin caused by antipsychotic
medication dopamine receptor blockade occurs via what
neuroanatomical tract?

A. Mesocortical
B. Mesolimbic
C. Nigrostriatal
D. Tuberoinfundibular

A

21.22. D. Tuberoinfundibular
Prolactin secretion is usually kept in check via dopamine release.
Once that dopamine release is blocked by antipsychotics, prolactin
increases. Dopamine blockade in the mesocortical pathway leads to a
blockade of reward and pleasure, as well as an increase in negative
symptoms. Dopamine blockade in the nigrostriatal pathway can lead
to Parkinsonian symptoms. Blockade in the mesolimbic system leads
to the desired reduction in positive symptoms.

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23
Q

21.23.
A 25-year-old man is hospitalized for the third time in 6
years for acute psychosis after attacking his girlfriend “to
make her less attractive to the men on the TV.” During the
first hospitalization, he was diagnosed with schizophrenia
after an extensive medical workup and started on
ziprasidone. Per the electronic medical record, he stopped
going to the outpatient psychiatrist 6 months later and
received no more refills. He was prescribed risperidone
during his last hospitalization 3 years ago, which markedly
decreased auditory and visual hallucinations. He then
followed up monthly at the outpatient clinic and was
moderately compliant with his medications. Over the last
year, his visits became infrequent and he reported taking his
medication only one to two times a week at his last visit 3
months ago. Vital signs are within normal limits and urine
drug screen is negative. He is stabilized on paliperidone in
the hospital and discharged on paliperidone palmitate. After
discharge, he asks the outpatient psychiatrist how long he
needs to stay on the medication. What is the most
appropriate response?

A. 3 to 6 months
B. 1 year
C. 2 to 3 years
D. 4 to 5 years
E. Indefinitely

A

21.23. E. Indefinitely
After one psychotic episode, a patient should be maintained on an
antipsychotic for about 1 to 2 years, and after the second episode,
about 5 years. After the third episode, medication should be
maintained indefinitely, with possible attempts to decrease the
dosage every 6 to 12 months, depending on the patient’s history.

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24
Q

21.24.
A 55-year-old woman who was diagnosed with obsessivecompulsive
disorder (OCD) 2 months ago returns to the
outpatient clinic for a follow-up appointment. At the time of
diagnosis, she reported that she was greatly distressed by her
ritual of checking the house several times to make sure that
she left no electrical appliances on prior to leaving the house
and going to bed which has made her late for work and
shortened her sleep time. The Yale-Brown Obsessive-
Compulsive Scale (Y-BOCS) showed symptoms in the severe
range. She was started on sertraline at that time and quickly
titrated up to a medium dose. At her follow-up appointment
4 weeks later, she reported that she no longer is late for
work, but has been close to being so several times. Y-BOCS at
that time was in the high-moderate range, and sertraline was
titrated to the maximum dose. Today, she states that she has
had some more improvement, and is comfortably on time for
work due to checking a fewer number of times, but she still
checks. Y-BOCS is in the low-moderate range. She is also
diagnosed with diabetes, for which she is on metformin.
Vitals are within normal limits. Physical examination is
noncontributory. Mental status examination reveals a mood
of “better, but not great,” with congruent affect. Which is the
most appropriate next step in treatment?

A. Prescribe a supratherapeutic dose of sertraline
B. Augment with risperidone
C. Continue current dose
D. Change to a different selective serotonin reuptake inhibitor
(SSRI)
E. Change to serotonin norepinephrine reuptake inhibitor
(SNRI)

A

21.24. C. Continue current dose
OCD typically takes a higher dose of an SSRI for a longer amount of
time than when treating depression. Whereas maximum effect at a
certain dose for depression may be reached around 6 weeks,
maximum effect for OCD may not be achieved for several months.
The patient continues to improve at every 4-week visit, and the
medication is at the highest dose. Therefore, the medication should
be continued at the current dose. Though there is some evidence for
supratherapeutic dosing in some individuals, that is not considered
best practice. This also would speak against adding risperidone, as
would her current diagnosis of diabetes, and also speaks against
changing to a new medication when the one she is on is effective

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25
21.25. What is the most common long-term side effect of SSRIs? A. Nausea B. Headache C. Sedation D. Sexual dysfunction E. Anxiety
21.25. D. Sexual dysfunction Nausea is a common side effect of SSRIs due to activation of 5HT3 gut receptors. However, this usually resolves in a few weeks. SSRIs are often used for headache, especially migraine prophylaxis, and result in an incidence of headaches of about 20%, similar to that of placebo. Some SSRIs can lead to initial anxiety or worsening of anxiety, which can be often mitigated by starting at a lower dose and titrating slowly, and usually resolves in a few weeks. About 25% of people taking an SSRI report sleep difficulty such as insomnia or somnolence. Between 50% and 80% of people who take SSRIs report sexual side effects such as anorgasmia, delayed orgasm, and premature ejaculation. Sexual dysfunction tends not to remit with time, and may lead to changing to a non-SSRI such as bupropion or mirtazapine.
26
21.26. A 30-year-old woman presents to the outpatient clinic with complaints of anxiety “all the time over every little thing.” She states that she has always been “the family worrywart,” and that others tell her that she is making life more stressful than it has to be, “but I just can’t help it. I always think of the worst possible scenario for everything.” She endorses difficulty getting to sleep due to “thinking about all the things I have to get done the next day.” She also complains of headaches, poor concentration, and feeling “edgy.” Though this has been a lifelong problem, she came today because “I’m just tired of feeling this way.” She reports that she has had a “heart rhythm issue” since birth, but is on no medications. She reports a family history of anxiety and breast cancer. Vitals are within normal limits and physical examination is noncontributory. What SSRI is relatively contraindicated in this patient? A. Citalopram B. Escitalopram C. Fluoxetine D. Fluvoxamine E. Sertraline
21.26. A. Citalopram Citalopram has been shown to lengthen the QT interval, more so when taken with an antipsychotic. It is not recommended for anyone with congenital long QT syndrome. Thought this patient is not exactly sure what her heart rhythm issue is, given the chance that it could be long QT syndrome, and the multiple other SSRIs available, it would be prudent to avoid using citalopram.
27
21.27. A 40-year-old woman who has a 15-year history of bipolar disorder, which has been well controlled with lithium, calls the clinic to report symptoms of diarrhea, headache, and restlessness since taking her new dose of escitalopram 6 hours ago. Four weeks ago, she reported difficulty sleeping, poor concentration and appetite, lethargy, and anhedonia. She had not had a manic episode in 10 years, and agreed to begin escitalopram. At her clinic appointment yesterday, she reported that symptoms of depression had improved, but she still had some depressed mood and anhedonia, so the dose of escitalopram was increased. Lithium level was 0.9. What is the most likely cause of the patient’s current symptoms? A. Emergence of a co-occurring anxiety disorder B. The beginning of a manic episode C. A sharp increase in plasma serotonin D. An acute increase in plasma lithium concentration E. Atypical symptoms of depression
21.27. C. A sharp increase in plasma serotonin Addition of an SSRI to lithium can lead to serotonin syndrome, which can occur when the SSRI is first added or when the dose is increased. Symptoms usually begin hours after taking the medication and start with diarrhea, restlessness, and agitation, and can progress to symptoms including autonomic instability, hyperthermia, delirium, coma, and death if left untreated. The first order of treatment is to immediately stop taking the SSRI. If symptoms progress, she should go to the nearest emergency department. Diarrhea is not a symptom of anxiety disorders, atypical depression, or mania. Co-administration of SSRIs does not raise the lithium level, as lithium is not metabolized by the liver
28
21.28. The likelihood of SSRI discontinuation syndrome is most closely associated with what property of the medication? A. Half-life B. Protein binding C. CYP 450 metabolism D. Potency E. Bioavailability
21.28. A. Half-life The likelihood of developing SSRI discontinuation syndrome is based on the half-life of the medication. For this reason paroxetine, with a half-life of 21 hours, is most likely to lead to discontinuation syndrome, while fluoxetine, with a half-life of 4 to 6 days of the parent drug and 9.3 days of the active metabolite, is least likely. Therefore, one strategy to mitigate withdrawal effects caused by the termination of other SSRIs is to change the person’s medication to fluoxetine, then taper off of that
29
21.29. A 54-year-old man who has been on a moderate dose of venlafaxine for generalized anxiety disorder for 20 years tells his physician that he feels the medication is beginning to lose effectiveness. He is noticing that he is starting to worry about “anything and everything,” which is disrupting his sleep, and would “like to get a handle on this before it gets out of control.” He has been happy with his medication so far, and wants to increase it. He is also diagnosed with hypercholesterolemia, type I diabetes, and has smoked a pack a day for the last 35 years. He has an insulin pump and is on simvastatin. Vital signs are T 98.8 F, BP 130/85, pulse 90, and respirations 18. The venlafaxine is increased to the highest dose. Which of the following physiologic measurements should now be monitored more closely? A. Blood glucose B. BMI C. Blood pressure D. Serum lipids E. Oxygen level
21.29. C. Blood pressure Venlafaxine, most notably the instant release formulation, can lead to a dose-related sustained increase in blood pressure. Unlike serotonin–dopamine antagonists, venlafaxine is not known to lead to changes in weight, blood glucose, or serum lipids. Impaired oxygenation could result from the smoking history, not venlafaxine.
30
21.30. The low level of sexual dysfunction from bupropion is thought to be attributed to what pharmacologic property of the medication? A. Downstream stimulation of dopamine reward pathways B. Short half-life of 12 hours C. Decreased evening plasma levels D. Lack of serotonin reuptake inhibition E. Downstream stimulation of norepinephrine receptors
21.30. D. Lack of serotonin reuptake inhibition Sexual side effects of antidepressants are mostly mediated by serotonin, though the exact mechanism is still unknown. Bupropion does not act on serotonin, which is thought to be the reason that it leads to low sexual dysfunction. Bupropion both ultimately stimulates dopamine reward pathways and norepinephrine receptors, as the medication inhibits the reuptake of both neurotransmitters. Those actions do not correlate with sexual dysfunction, though increased reward pathway stimulation could lead to increased libido. Bupropion is usually administered in the morning, leading to decreased evening plasma levels, but this is unrelated to sexual dysfunction, as is the half-life of the medication.
31
21.31. Bupropion is contraindicated in individuals with what medical condition? A. Hepatitis B. Epilepsy C. Congenital QT prolongation D. Hypertension E. Renal disease.
21.31. B. Epilepsy Bupropion confers a dose-dependent risk of seizures of 0.05% at 300 mg/day and 0.1% at 400 mg/day, and is contraindicated for persons with epilepsy. Hypertension may occur in some patients, so it should be used with caution in those with that condition. Likewise, it should be used with caution in individuals with severe cirrhosis or hepatic impairment, or renal impairment, but is not contraindicated. Bupropion is not known to affect QTc interval.
32
21.32. In addition to blockade of postsynaptic serotonin 5HT2 and 5HT3 receptors, mirtazapine’s antidepressant effects are mediated through what pharmacologic mechanism? A. Inhibition of serotonin and norepinephrine reuptake B. Inhibition of norepinephrine and dopamine reuptake C. Antagonism of presynaptic alpha-2 receptors D. Activation of serotonin 5HT1A receptors E. Serotonin–dopamine antagonism
21.32. C. Antagonism of presynaptic alpha-2 receptors Mirtazapine is unique in that it increases the amount of serotonin and norepinephrine via antagonism of presynaptic alpha-2 adrenergic receptors, which inhibit release of those two neurotransmitters. Inhibition of serotonin and norepinephrine reuptake is the mechanism of action of SNRIs such as venlafaxine and duloxetine. Inhibition of serotonin and dopamine reuptake is the mechanism of action of bupropion. Stimulation of serotonin 5HT1A receptors is one of the mechanisms of vilazodone and buspirone. Serotonin–dopamine antagonism is the mechanism of action of “atypical” antipsychotics such as risperidone, ziprasidone, and olanzapine.
33
21.33. An 86-year-old female resident at a senior living facility complains of difficulty remembering the names of others in the facility over the last 3 weeks. Her adult children report that she has been calling them over the last 3 weeks and crying about how she was a horrible mother. They note no pattern in the time of day of her calls. She has been waking up in the morning 2 to 3 hours earlier than usual, with difficulty returning to sleep. Appetite has decreased to the point that she picks at her meals or skips them altogether. She has not gone to the community bingo games in the past week, and makes little effort to get out of the bed. On mental status examination, she is alert and oriented to person, but responds with “I don’t know” when asked about place and time, as well as on several measures of cognition, such as serial 7s. She gives minimal effort on the clock-drawing test. Her mood is, “I just don’t feel good,” with congruent, dysphoric affect. Vital signs are within normal limits. Which of the following medications should be used in the treatment of this patient? A. Mirtazapine B. Memantine C. Risperidone D. Trimethoprim-sulfamethoxazole E. Hydroxyzine
21.33. A. Mirtazapine The patient is showing symptoms of depression and depressionrelated cognitive dysfunction (also known as pseudodementia). As opposed to primary dementia, the progression of memory loss was rapid, she is distressed by the memory loss, and she does not try hard on the mental status examination, as opposed to trying and getting answers wrong. Also, her symptoms do not follow a pattern of worsening in the evening, which would be suggestive of sundowning, a delirium that is sometimes present in those with dementia. In this patient, the cognitive symptoms are in addition to the regular symptoms of major depressive disorder, so she should be treated with an antidepressant. Mirtazapine would be an especially good choice due to its side effects of appetite stimulation and somnolence. Memantine would be given for a true dementia. Risperidone could be given if she were sundowning. An antibiotic could be given if she were shown to have a UTI or other infection which could lead to delirium. Though hydroxyzine can be helpful for sleep, it would not help with the primary problem of depression, and should be used with caution, as should any anticholinergic medication in the elderly.
34
21.34. A 60-year-old man presents to an outpatient psychiatrist to establish care after moving to a new city. He states that he was diagnosed with major depressive disorder 35 years ago and has been on nefazodone since then and does not want to discontinue it. Prior to continuing the prescription, the psychiatrist should order what lab test? A. Liver function B. Serum glucose C. Thyroid stimulating hormone (TSH) D. Creatinine E. Complete blood count
21.34. A. Liver function Brand-name nefazodone (Serzone) has been discontinued in the United States since 2004. However, generic formulations are still available. The medication can cause severe elevation of hepatic enzymes, which in rare cases has led to death. Patients on the medication should have serial hepatic function tests
35
21.35. Trazodone can cause what physiologic medical emergency? A. Status epilepticus B. Priapism C. Ventricular fibrillation D. Acute renal failure E. Ketoacidosis
21.35. B. Priapism Though rare at a rate of about one in 10,000, trazodone can lead to priapism, usually within the first 4 weeks of treatment. This is a medical emergency that can require an injection of an alpha-1 agonist agent into the cavernosum of the penis. In some cases, surgery is required
36
21.36. Tricyclic antidepressants (TCAs) exert their therapeutic effect by what primary pharmacologic mechanism? A. Alpha-1 and alpha-2 receptor antagonism B. Serotonin and norepinephrine reuptake inhibition C. Cholinergic muscarinic receptor antagonism D. Norepinephrine and dopamine reuptake inhibition E. Serotonin, norepinephrine, and dopamine reuptake inhibition
21.36. B. Serotonin and norepinephrine reuptake inhibition TCAs work by blocking reuptake of serotonin and norepinephrine in a similar manner to medications such as venlafaxine and duloxetine. However, TCAs have greater anticholinergic and antihistaminergic side effects due to their antagonism of cholinergic muscarinic receptors. They also antagonize H1 receptors, which leads to sedation. In addition, they block alpha-1 receptors, which leads to orthostatic hypotension, the most common cardiovascular autonomic side effect. Serotonin, norepinephrine, and dopamine reuptake inhibition are part of the mechanism of monoamine oxidase inhibitors (MAOIs).
37
21.37. A 43-year-old female with a diagnosis of obsessivecompulsive disorder (OCD) returns to the outpatient clinic due to continued symptoms despite being on sertraline for the last 3 months. She states that the medication has been no more effective than the fluoxetine and paroxetine she has been on, each for 12 weeks at the highest dose. She has no other illnesses and is on no other medications. What medication should be tried next? A. Bupropion B. Fluvoxamine C. Clomipramine D. Amitriptyline E. Selegiline
21.37. C. Clomipramine Clomipramine is uniquely effective for the treatment of OCD, with some symptom relief observed in as little as 2 to 4 weeks, and improvement sometimes continuing for 4 to 5 months. Other tricyclic antidepressants (TCAs) do not show the same efficacy. Monoamine oxidase inhibitors (MAOIs) such as selegiline have not been shown to be especially helpful for OCD. Though SSRIs are first line for OCD, trying a fourth SSRI would likely not be of much benefit after failing three. Bupropion is not effective for OCD, as it has no action on serotonin. Though fluvoxamine is approved and known for treatment of OCD, it has not been shown to be any more or less effective than any other SSRI
38
21.38. A 76-year-old man presents to the outpatient clinic with a complaint of, “I’m depressed and I can’t go on.” He states that since his spouse died 4 weeks ago, “I can’t sleep, I can’t eat, and there is no reason to live. We were together for 50 years!” He has stopped socializing with friends and stays in his house, crying on and off throughout the day out of grief and because “I’m too exhausted to do anything else.” He has lost 10 pounds in the last month. He denies suicidal ideation, but states that “even though I would never kill myself, I want to die.” He is on metformin for diabetes and pilocarpine and acetazolamide for narrow-angle glaucoma. Which of the following medications for his symptoms is relatively contraindicated? A. Vortioxetine B. Paroxetine C. Venlafaxine D. Amitriptyline E. Selegiline
21.38. D. Amitriptyline Though all of the medications are possible treatments for depression, tricyclic antidepressants (TCAs) should be avoided in patients with narrow-angle glaucoma, as their anticholinergic effects can exacerbate the condition
39
21.39. A tricyclic should be used as the antidepressant of last resort in individuals with which health condition? A. Heart disease B. Pregnancy C. Liver disease D. Epilepsy E. Renal disease
21.39. A. Heart disease Tricyclic antidepressants (TCAs) can cause a myriad of side effects and can exacerbate problems from preexisting conditions. They can possibly induce seizures in patients with epilepsy, but such persons can still use TCAs with a “start low, go slow” initiation and titration. There is not a definitive link between TCAs and birth defects, though TCAs should be discontinued 1 week before delivery, if possible, as they cross the placenta and neonatal withdrawal can occur. TCAs can cause increases in serum transaminases, and in a small percentage, fulminant acute hepatitis. However, they can still be used in patients with liver disease. There is no contraindication in persons with renal disease, as it is metabolized in the liver with little to no excretion in the urine. TCAs, at usual therapeutic doses, can cause tachycardia, flattened T waves, prolonged QT intervals, and depressed ST segments, and should be used in persons with any heart disease only after SSRIs and other antidepressants have been deemed ineffective. They are contraindicated in persons with a QTc greater than 450 ms
40
21.40. The 2-week washout period needed before starting another antidepressant after the last dose of an irreversible monoamine oxidase inhibitor (MAOI) is to give time for what physiologic mechanism to occur? A. The drug to detach from monoamine presynaptic transporters B. The drug to detach from postsynaptic monoamine receptors C. The body to synthesize new monoamine oxidase D. Decrease in plasma concentration after five half-lives of time E. Hepatic metabolism and excretion of both the parent drug and active metabolite
21.40. C. The body to synthesize new monoamine oxidase Irreversible MAOIs work by permanently inhibiting monoamine oxidase. The body takes about 2 weeks to synthesize new, uninhibited enzyme.
41
21.41. A 55-year-old man presents to his primary care physician with feelings of “not having any get up and go” for the last month. He states that for nearly all of his life he has enjoyed fishing every weekend, but now “I just don’t feel like doing it.” He is surprised that he often feels run down, even though he is in the bed for 10 to 12 hours some weekends, which is an increase from his prior 7 to 8. He reports gaining 10 pounds in the last 6 months, even though his appetite has been decreased for the last month. He denies current or past suicidal ideation. He occasionally takes colchicine for flares of gout, but otherwise has no history of medical problems and is on no other medications. Vital signs are within normal limits and physical examination is noncontributory. Mental status examination reveals a “down” mood with congruent affect. There is no suicidal ideation. Cognition is intact. What lab tests should the physician order as part of the workup for the patient’s current symptoms? A. Uric acid B. Complete blood count (CBC) C. Urinalysis D. Thyroid function E. Plasma colchicine level
21.41. D. Thyroid function The patient is describing classic symptoms of depression, for which hypothyroidism can be a cause, and therefore should be a part of a standard depression workup. Colchicine is not known to cause depression either in standard doses or in overdose. Likewise, gout itself, which can lead to an increase in uric acid, is also not known to primarily cause depression, though in some studies people with recurrent attacks of gout were more likely to be depressed compared with the general population. There is no indication in the history for a urinalysis or CBC, which are not typical labs drawn during the workup for depression
42
21.42. Ketamine acts with what pharmacodynamic effect on Nmethyl- D-aspartate (NMDA) receptors? A. Allosteric modulator B. Antagonist C. Agonist D. Partial agonist E. Inverse agonist
21.42. B. Antagonist The putative antidepressant mechanism of ketamine and esketamine is the antagonism of NMDA receptors.
43
21.43. A 28-year-old man returns to the outpatient clinic after being diagnosed with bipolar I disorder, most recent episode manic, and starting on lithium 4 weeks ago. He states that he feels “stable, not so up and down,” and that he has been able to sleep for 7 hours a night again, which is a sharp increase from the previous 1 to 2 hours. He feels that the medication has been helpful, but he complains of his hands shaking, most notably when he writes with a pen or engages in some other fine-motor task. He is on no other medications and has no other illnesses. He last took the medication 8 hours ago. On examination, a fine tremor is present, most notably in his fingers when he holds his arms out. Neurologic examination reveals a normal gait and reflexes. Extraocular muscles are intact with no nystagmus. What is the most likely cause of the patient’s tremor? A. Gradual lithium toxicity B. Lithium-induced hyperthyroidism C. Normal lithium side effect D. Lithium withdrawal E. Acute lithium overdose
21.43. C. Normal lithium side effect A fine motor tremor is not uncommon at a therapeutic lithium dose. However, a course tremor could indicate lithium toxicity or overdose. Though lithium has been known to cause both hyper and hypothyroidism, the latter of which could cause a tremor, neither would likely develop within 4 weeks. Lithium withdrawal does not cause tremor, and with a half-life of 18 to 24 hours in young adults, he would not be withdrawing after only 7 hours.
44
21.44. Lithium use during the first trimester of pregnancy is associated with which congenital birth defect? A. Tetralogy of Fallot B. Spina bifida C. Neural tube defects D. Ebstein anomaly E. Anencephaly
21.44. D. Ebstein anomaly Neural tube defects and anencephaly are associated with valproate use during pregnancy. Spina bifida is associated with carbamazepine and valproate. Ebstein anomaly is associated with lithium.
45
21.45. In a person who takes immediate-release lithium twice a day, when should the lithium level be drawn? A. At any time B. As soon as possible after taking a dose C. Around 12 hours after taking a dose D. Around 6 hours after taking a dose E. Between 1 and 6 hours after taking a dose
21.45. C. About 12 hours after taking a dose Blood levels for lithium, like that for carbamazepine and valproic acid, should be drawn at the trough, right before the next dose. In twice-a-day dosing, that would usually be about 12 hours after a given dose.
46
21.46. A 27-year-old female, who was diagnosed with bipolar I disorder 7 years ago, comes to the outpatient clinic for a routine follow-up appointment. Her illness has been wellcontrolled with valproate for the past 5 years. During the 2 years since her diagnosis, she has been hospitalized six times due to acute manic episodes and suicidal ideation. She was initially prescribed lithium but stopped it because, “It took away my creativity and dulled me out.” She has also been on paliperidone, olanzapine, aripiprazole, risperidone, lamotrigine, and carbamazepine, all of which were discontinued either due to side effects or lack of efficacy. She does not want to take a long-acting injection. She reports that her current medication “keeps me stable. Without it, I would be back in the hospital.” She reports that she and her husband now want to have a child, and are concerned about the effects of valproate on the fetus, but states, “I can’t get sick and go back into the hospital. I finally have my life together.” What should the physician recommend regarding the patient’s concerns? A. Discontinuing valproate until after the first trimester B. Beginning folic acid supplementation C. Changing to a different antiepileptic medication D. Changing to a different antipsychotic medication E. Lowering the dose of valproate until it reaches below 50 μg/mL
21.46. B. Beginning folic acid supplementation As with any pregnancy and mental illness, the risk of an exacerbation or relapse must be weighed against the risk of harm to the fetus. In this case, given six hospitalizations for acute mania in 2 years despite trying several other medications, the risk of relapse, and possible fetal harm due to actions taken while manic, is high. The patient also states that she does not want to risk relapse. She has already been on numerous other antiepileptic and antipsychotic medications, so the likelihood of another proving to be as effective and without intolerable side effects within the next year is relatively low. Though one should “treat the patient and not the lab results,” a valproate level below 50 μg/mL is considered to be subtherapeutic, and would be risky for someone who easily becomes manic. Likewise, discontinuing the medication until she gets pregnant and gets through the first trimester is risky. Daily folic acid supplementation of 1 to 4 mg daily can decrease the risk of valproate-induced neural tube defects. If after preconceptual education about this option she wishes to continue with the plan for pregnancy, this would be the safest course for her.
47
21.47. In addition to a complete blood count (CBC), what laboratory test should be routinely ordered in patients taking valproate? A. Blood urea nitrogen (BUN)/creatinine B. Liver function C. Thyroid function D. Lipid panel E. Glucose
21.47. B. Liver function Valproate can lead to thrombocytopenia, so a CBC should be drawn at 1 month and every 6 to 24 months afterward. Valproate can also lead to hepatotoxicity, so liver function tests (LFTs) should be drawn on the same schedule. Thyroid and renal function tests should be drawn periodically for patients on lithium. Glucose and lipid panels should be drawn periodically for patients on atypical antipsychotics.
48
21.48. A 36-year-old man diagnosed with bipolar I disorder with rapid cycling was started on olanzapine 3 weeks ago when he was hospitalized during his first manic episode. One week after that, while still hospitalized, he was started on lamotrigine and discharged a week later. He has been titrating as directed, and would be on day 21 today. He calls the outpatient clinic this morning to report that he left the lamotrigine at home while the family was on a weeklong trip, and asks how he should proceed with taking it. He is on no other medications besides olanzapine. What should be recommended to the patient? A. Restart the titration from the beginning (day 1) B. Restart the titration time from the most recent increase (day 14) C. Resume the titration from where he left off (day 16) D. Continue with the scheduled titration (day 21)
21.48. A. Restart the titration from the beginning (day 1) Due to the possibility of Stevens–Johnson syndrome when lamotrigine is titrated too rapidly, if more than four consecutive doses are missed, titration should be restarted from the beginning
49
21.49. A 35-year-old woman was started on carbamazepine and diagnosed with bipolar I disorder while hospitalized due to acute mania 4 months ago. She has been on the same dose for the last 2 months. She presents to the outpatient clinic today for a routine follow-up. Though she complains of occasional nausea from the medication, she has found that it is tolerable if she takes it with food, “and a little nausea is much better than being in the hospital, so I still take it every day.” She notes that she started thyroid hormone replacement therapy a month ago due to hypothyroidism. She worries that she is becoming manic because she is only needing to sleep 6 hours instead of her usual 8, and because “I think my concentration isn’t as good.” She denies other symptoms of mania, suicidal ideation, or impairment at her job. What is the most likely cause of the patient’s current symptoms? A. Decreased efficacy over time (“poop out”) B. Noncompliance due to side effects C. Increase in carbamazepine metabolism D. Drug interaction with thyroid hormone E. Induction of mania from thyroid hormone
21.49. C. Increase in carbamazepine metabolism Carbamazepine induces its own metabolism over time by autoinducing the hepatic enzymes that metabolize it, leading to a decrease in half-life from an average of 26 hours to an average of 12 hours. The enzyme induction reaches its maximum level after 3 to 5 weeks. Four months of therapy is likely too early for “poop out,” especially since she has been on the current dose for only 2 months. The patient is not giving indications of noncompliance. Carbamazepine does not interact with thyroid hormone, and its antimanic effects are often augmented by thyroid hormone. Thyroid hormone is not known to induce mania.
50
21.50. A 24-year-old man with a diagnosis of bipolar disorder presents to the outpatient clinic for a routine follow-up. He has been on quetiapine for the past 4 months, resulting in a “stable” mood. He is pleased with the treatment except for an increase in weight of 10 pounds over the past 2 months, leading to an increase in BMI from 23 to 24.4, despite exercising four times a week and eating a 1,800 cal/day diet. He takes no other medications. Vital signs are normal, and physical examination is unremarkable. Glucose and lipid profile prior to the start of the treatment were within normal limits. Besides metformin, what medication could be most helpful in mitigating this patient’s weight gain? A. Aripiprazole B. Methylphenidate C. Topiramate D. Oxcarbazepine E. Mixed amphetamine salts
21.50. C. Topiramate Topiramate is sometimes used to mitigate the weight gain caused by some psychotropic medications and can even lead to weight loss. Metformin is used to mitigate changes in blood glucose caused by atypical antipsychotics and can also reduce body weight. While aripiprazole is less likely to lead to significant weight gain than many other atypicals, it is not associated with weight loss. Similarly, oxcarbazepine, while not usually leading to weight gain, does not usually lead to weight loss. While mixed amphetamine salts and methylphenidate could lead to weight loss, they are not used for that purpose, and would not be used in someone with a psychotic disorder, if possible
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21.51. What is the most common side effect of benzodiazepine use? A. Ataxia B. Dizziness C. Mild cognitive impairment D. Drowsiness E. Drug rash
21.51. D. Drowsiness Drowsiness is the most common adverse effect of benzodiazepines, which is sometimes exploited to treat insomnia. Ataxia occurs in fewer than 2%, and dizziness in fewer than 1%. Mild cognitive impairment is infrequent, and allergic reactions to benzodiazepines are rare.
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21.52. Flumazenil can reverse the adverse effects of what drug? A. Alcohol B. Barbiturates C. Opioids D. Benzodiazepines E. Tricyclics
21.52. D. Benzodiazepines Flumazenil can be used to reverse the adverse psychomotor, amnestic, and sedative effects of benzodiazepines. It does not reverse the effects of ethanol, barbiturates, or opioids, and in patients who have also overdosed on other drugs, such tricyclics, the reversal of benzodiazepine effects on those drugs can lead to their toxic effects, such as seizures and cardiac arrhythmias
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21.53. A 21-year-old man is brought to the emergency department after his friends called EMS due to him passing out and not being able to be aroused 2 hours later. His friends told the emergency medical technicians (EMTs) that they had all been drinking more heavily than usual, and that he had consumed seven drinks in 3 hours. In the emergency department, the EMR from the outpatient clinic reveals that he is diagnosed with type I diabetes mellitus (DM) and panic disorder, and that he has an insulin pump and was started on sertraline and clonazepam a week ago. What vital sign is most likely to be abnormal? A. Blood pressure B. Heart rate C. Respirations D. Temperature
21.53. C. Respirations The combination of a benzodiazepine and alcohol or other central nervous system (CNS) depressant can lead to severe and possibly fatal respiratory depression. Some stimulants such as cocaine can raise blood pressure and lead to tachycardia, while others such as MDMA can raise body temperature.
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21.54. Buspirone has been shown to be effective as a primary treatment of what disorder? A. Obsessive-compulsive disorder (OCD) B. Major depressive disorder C. Generalized anxiety disorder D. Panic disorder E. Social phobia
21.54. C. Generalized anxiety disorder Buspirone has only shown effectiveness as a primary agent in the treatment of generalized anxiety disorder. It has also shown some effectiveness in major depressive disorder, but only as an augmenting agent. It has not been shown to be effective in the treatment of panic disorder, OCD, or social phobia
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21.55. A 45-year-old woman presents to the outpatient clinic with a complaint of, “I have performance anxiety.” She states that she has been a concert pianist for the last 15 years, and that she started becoming anxious before she had to perform after she made a mistake 6 months ago during a concert, “and probably no one noticed, but I did. Since then, I’ve been terrified that I’ll mess up again.” She denies anxiety in other situations, and continues to perform, “but it’s getting harder every time. If this keeps up, I’m going to have to stop playing.” She is diagnosed with type II diabetes mellitus, for which she is on metformin. She also takes fish oil and vitamin C “to keep myself healthy.” Vital signs are within normal limits. Physical examination is unremarkable. Which of the following medications often used in the treatment of her symptoms is relatively contraindicated in this patient? A. Clonazepam B. Propranolol C. Sertraline D. Desvenlafaxine E. Hydroxyzine
21.55. B. Propranolol The patient is describing social anxiety, for which the treatment of choice is an SSRI, though an SNRI could also be used. For more immediate relief, a benzodiazepine or a beta blocker is often used. Hydroxyzine would be less useful for such a situation due to its sedative properties. A beta blocker is relatively contraindicated in someone with diabetes, as it can antagonize the normal physiologic response to hypoglycemia. However, there are times during which the benefit of treatment with a beta blocker can outweigh the risk.
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21.56. A 30-year-old woman is brought to the emergency department (ED) by EMS after her husband called due to her being confused, calling him by her father’s name and lapsing in out of consciousness. At the ED, he reports that she told him before bed she had mistakenly mixed up her thyroid medicine, of which she takes three pills a night, with her sleeping medicine, of which she only takes one a night. He adds that she told him she had acquired the sleeping medicine “from a friend.” He does not know the names of the medications. Temperature is 98.8 F, blood pressure is 140/95, pulse 90, and respirations 10. Neurologic examination reveals ataxia, hyporeflexia, and lateral nystagmus. On mental status examination, she is confused and oriented to person, but not place or time. What is the likely causal agent of her current symptoms? A. Temazepam B. Trazodone C. Amobarbital D. Hydroxyzine E. Doxepin
21.56. C. Amobarbital Signs and symptoms of overdose of barbiturates such as amobarbital include confusion, nystagmus, ataxia, areflexia or hyporeflexia, delirium, and respiratory depression. In decades past, they were commonly prescribed for sleep, but their use has fallen out of favor with the advent of much safer alternatives
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21.57. What medication used for sleep can cause amnesia and automatic behaviors, such as nighttime eating and driving as side effects? A. Melatonin B. Ramelteon C. Eszopiclone D. Zolpidem E. Prazosin
21.57. D. Zolpidem Zolpidem has been associated with amnesia and automatic behaviors, such as eating and driving, while not conscious. Though eszopiclone is in the same family of medications as zolpidem (nonbenzodiazepine GABA agonists), eszopiclone does not seem to have the same side effect. Melatonin and ramelteon (melatonin receptor agonists) do not have this side effect, nor does prazosin, often used for nightmares associated with posttraumatic stress disorder (PTSD).
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21.58. A 28-year-old man presents to the VA outpatient department 3 months after returning from overseas, where he served in the armed forces as a combat medic. He states that he has had problems sleeping for the last 10 weeks because “every time I close my eyes at night, I have vivid dreams of limbs blown off and dead soldiers littering the field.” He states that he saw a fellow soldier “die in my arms before we could get him to a medical field station.” He adds that he gets startled and is triggered by sudden loud noises, which “take me right back to the battlefield.” During a recent holiday in which neighbors shot off fireworks, he had to stay in a rural hotel “because the flashbacks were so bad.” He has never been on medication. He states that the lack of a full night’s sleep is what bothers him the most, and that “I can handle the other stuff by myself if it weren’t for these dreams every night.” Vitals are within normal limits. Physical examination is noncontributory. What is the most common side effect of the medication used to treat this patient’s chief complaint? A. Priapism B. Amnesia C. Weight gain D. Dizziness E. Automatic behaviors
21.58. D. Dizziness Though not FDA approved for treating nightmares, prazosin is often used for that purpose, especially in patients with PTSD. As it is an alpha-2 antagonist that lowers blood pressure in standing and supine positions, dizziness is the most common side effect. Priapism can be caused by trazodone, but that is relatively rare. Amnesia and automatic behaviors can be caused by zolpidem. Some use an atypical antipsychotic for insomnia, which should not routinely be done as the risk of weight gain and metabolic problems is not necessarily dose related
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21.59. A 9-year-old boy who was diagnosed 4 weeks ago with attention-deficit/hyperactivity disorder (ADHD), hyperactive-impulsive type, returns to the outpatient clinic for follow-up after starting methylphenidate. His mother reports that she started him on 5 mg twice a day, and increased the medication by 5 mg/week up to 20 mg twice a day with minimal effect except for a decrease in appetite. He is still getting notes from school about his unruly behavior. What is the next step in the medication management of this child? A. Increase the methylphenidate to a maximum of 30 mg twice a day B. Change the medication to atomoxetine C. Augment the medication with clonidine D. Change the medication to mixed amphetamine salts E. Augment the medication with bupropion
21.59. D. Change the medication to mixed amphetamine salts Both methylphenidate and amphetamine preparations of stimulants are effective about 75% of the time. In patients who do not respond to one of the medications, about 70% will respond to the other, which should be tried unless there is a contraindication. Atomoxetine is considered second-line therapy for ADHD, and alpha-2 agonists and bupropion are further down. If there has been a negligible therapeutic effect at 20 mg twice a day, yet the patient is experiencing side effects, increasing the dose further is unlikely to be of much benefit
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21.60. A 10-year-old girl is brought to the outpatient clinic by her parents after a referral from school due to the child “staring off into space” for the last 4 months. Her teacher reported that she has forgotten to turn in her homework several times and that her desk is disorganized. At home, she takes 30 minutes to do a 10-minute school assignment, which is then littered with careless mistakes. “She is making C’s when we know she has the ability to make A’s.” Her parents also report that she “sometimes doesn’t seem to be listening when we talk to her. She’s not ignoring us, her mind is just somewhere else.” She was diagnosed with persistent motor tic disorder 3 years ago, and though she displays symptoms, she says she is not bothered by them. She is on no medications. Vital signs are within normal limits. Physical examination is noncontributory. What is the first-line pharmacologic treatment for this child? A. Atomoxetine B. Methylphenidate C. Clonidine D. Bupropion E. Guanfacine
21.60. B. Methylphenidate The first-line pharmacologic treatment for ADHD, inattentive type is a stimulant. It had long been thought that stimulants can exacerbate tics, but current research has shown that this is not an absolute, with some research showing that tics may improve after stimulant treatment. However, some tics may worsen with methylphenidate, but this is not a contraindication to attempting a stimulant. The other treatments may be effective, but they are not first line
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21.61. A 7-year-old boy who has been on lisdexamfetamine for the last 6 months is brought by his parents to the outpatient clinic for a 2-month follow-up on his progress at school. He is seen by the nurse, who takes his height, weight, and vitals. What measurement is most likely to have decreased since he began the medication? A. Heart rate B. Respirations C. Weight D. Height E. Blood pressure
21.61. C. Weight Stimulant medications can cause the heart rate and blood pressure to increase, not decrease. Though growth suppression is often a concern, studies do not support long-term growth suppression as a side effect. Even if it were to occur, the child would not lose height, just not gain as much as projected. A notorious and common side effect of stimulants is anorexia, which can lead to a measurable weight loss. This can sometimes be mitigated by giving the medication after a meal or by adding caloric supplements during the day.
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21.62. What is atomoxetine’s mechanism of action? A. Alpha-2 agonism B. Dopamine reuptake inhibition C. Increased dopamine release D. Norepinephrine reuptake inhibition E. GABA inhibition
21.62. D. Norepinephrine reuptake inhibition Atomoxetine works by inhibiting the presynaptic norepinephrine transporter, thus decreasing norepinephrine reuptake. Clonidine and guanfacine are alpha-agonists used in the treatment of ADHD. Bupropion works by inhibiting norepinephrine and dopamine reuptake. Stimulants increase dopamine and norepinephrine release. Flumazenil is a GABA inhibitor used to reverse the effects of benzodiazepines
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21.63. Place buprenorphine, methadone, and naltrexone in order of effect on the μ-opioid receptor from agonist to antagonist. A. Methadone > naltrexone > buprenorphine B. Naltrexone > methadone > buprenorphine C. Buprenorphine > methadone > naltrexone D. Naltrexone > buprenorphine > methadone E. Methadone > buprenorphine > naltrexone F. Buprenorphine > naltrexone > methadone
21.63. E. Methadone > buprenorphine > naltrexone Methadone is a full μ-opioid receptor agonist which is used for shortand long-term opioid detoxification as well as maintenance. Buprenorphine is a partial μ-opioid receptor agonist, and therefore produces a milder withdrawal than a full agonist. Naltrexone is a μ- opioid antagonist that reverses the effects of opioid receptor agonists and precipitates a withdrawal reaction.
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21.64. A 45-year-old man on methadone maintenance therapy for the last 5 years presents to the emergency department with complaints of headache, anxiety, nausea, and jitteriness. He states that the symptoms began 4 days ago when he stopped going to the methadone clinic and have gotten progressively worse. He states that he wants to “be done with all this addiction stuff, so I figured I’d go cold turkey.” He now feels he underestimated the withdrawal symptoms, but still wants to “push through.” What medication would be most appropriate for the patient at this time? A. Methadone B. Buprenorphine C. Clonidine D. Naltrexone E. Tramadol
21.64. C. Clonidine The patient is experiencing classic withdrawal from a μ-opioid agonist. Given that he has expressed a desire to come off of such drugs/medications, restarting methadone, or starting buprenorphine or tramadol, would be counter to his wishes. Naloxone could make him feel worse, as it would displace any residual methadone. Clonidine is used to mitigate the adrenergic effects of withdrawal, such as jitteriness and anxiety. However, it will not help the gastrointestinal (GI) symptoms
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21.65. A 55-year-old woman is being discharged from the hospital after her sixth day of detoxification from alcohol. During the admission, she had been on a protocol to monitor for alcohol withdrawal and was given chlordiazepoxide on two occasions. Today, she states that she is ready to stop drinking, but the craving for alcohol is what perpetually leads to relapse. She is on sertraline for depression. Vital signs are within normal limits. What pharmacologic agent would be most helpful to decrease the chance of relapse? A. Diazepam B. Disulfiram C. Clonidine D. Acamprosate E. Naltrexone
21.65. E. Naltrexone The patient cites alcohol cravings as the main reason for relapse, which opioid receptor antagonists can reduce, especially when paired with an SSRI, according to some studies. Diazepam, like alprazolam and chlordiazepoxide, is often used in protocols such as the Clinical Institute Withdrawal Assessment Alcohol Scale Revised to treat agitation from withdrawal and prevent seizures. Clonidine is used in the treatment of some acute symptoms of opioid withdrawal. The COMBINE study did not show evidence for an increased benefit from acamprosate over naltrexone. Disulfiram does not help with cravings. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2945872/
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21.66. Disulfiram works by what mechanism? A. Glutamate transmission reduction B. Aldehyde dehydrogenase inhibition C. Opioid receptor antagonism D. GABA transmission enhancement E. Displacement of ethanol from GABA receptors
21.66. B. Aldehyde dehydrogenase inhibition Disulfiram exerts its therapeutic effect of causing adverse physiologic reactions after the consumption of alcohol by inhibiting aldehyde dehydrogenase, which therefore blocks alcohol metabolism. This subsequently causes an increase in blood acetaldehyde which leads to nausea, headache, vomiting, flushing, and many other unpleasant reactions. Acamprosate theoretically works by increasing GABA transmission and decreasing glutamate transmission. Though opioid receptor antagonists such as naloxone can be used in the treatment of alcohol use disorder, that mechanism is not present in disulfiram. Disulfiram does not compete with ethanol’s binding to GABA receptors (in the way that flumazenil works by blocking GABA benzodiazepine receptors).
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21.67. A 10-year-old boy is brought to the urgent care by his grandmother, who reports that the child became sweaty and shaky 2 hours ago. She states that he did not eat breakfast or lunch today “because he said his stomach hurt.” The child states that his head hurts and that he could not sleep well last night. His grandmother reports that she picked him up from his parents’ house after school 2 days ago to keep him over the weekend. She adds that he usually takes medication for ADHD every day, “but I don’t think he really needs it, so I didn’t give it to him. If they want to give it to him again tonight when I take him home, they can.” He is on no other medications and has no other illnesses. Vitals are T 98.8 F, BP 140/85, pulse 90, respirations 22. Physical examination is significant for bilateral hand tremors. What is the most likely medication the child is prescribed? A. Atomoxetine B. Amphetamine salts C. Methylphenidate D. Clonidine E. Lisdexamphetamine
21.67. D. Clonidine The child is exhibiting signs and symptoms of clonidine withdrawal, which can begin about 20 hours after the last dose, or if one to two doses have been missed. The child likely took the medication for ADHD at night, and therefore would have last taken it on Thursday night and missed it on Friday and Saturday nights. Discontinuation syndrome consists of anxiety, restlessness, agitation, tremor, abdominal pain, and increased heart rate, blood pressure, and respirations, all of which would be expected with rebound alpha-2 agonist disinhibition. Once he restarts the clonidine, his blood pressure should return to normal
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21.68. A 78-year-old woman is brought by her son to the outpatient clinic who states, “I’m ready for medicine for my mother now.” He recounts how his mother was diagnosed with Alzheimer dementia 5 years ago. At that time, the physician suggested that his mother starts on a cognitive enhancement medication, but he did not want her on another medication in addition to the atorvastatin, lisinopril, and metformin she was already taking for hypercholesterolemia, hypertension, and diabetes. He states that her dementia has progressed to the point that neither he nor his two siblings can safely care for her anymore at any of their homes. She has wandered out of the house during the night, frequently forgets who they are, and has left the stove and oven on, nearly burning down the house on more than one occasion. They are actively looking for a secure living facility. Vitals are normal, and physical examination reveals an agitated woman who looks older than her stated age, with no acute examination findings. Which of the following cognitive enhancement medications is most appropriate? A. Donepezil B. Tacrine C. Galantamine D. Rivastigmine E. Memantine
21.68. E. Memantine The patient’s disease has progressed in severity to the point that she needs constant, supervised care. She is also forgetting some of the most well-known people in her life. Donepezil, rivastigmine, galantamine, and tacrine are all cholinesterase inhibitors that are indicated for mild to moderate Alzheimer disease. Only memantine, an NMDA blocker, is indicated for moderate to severe disease.
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21.69. An 18-year-old man presents to the outpatient primary care clinic for a yearly physical examination. He has no chronic medical illnesses and is on no medications. During the sexual history, he states that he has never had sexual intercourse, “and the guys at school are giving me a hard time about being a virgin.” He has been dating the same girl for a month, and admits that he has no romantic feelings for her. He has tried to have vaginal sex with her “so that everyone will stop making fun of me,” but found that he could not maintain an erection. He admits to trying sildenafil, “but it didn’t work. I still couldn’t get hard.” He denies drug use, states that he gets morning erections, and has no difficulty with masturbation. What is the most likely cause of the lack of response to the medication? A. He has a fast nitric oxide metabolizer B. The dose he is taking is too low for his age C. He is not sexually attracted to his girlfriend D. He did not take the medication with a high-fat meal E. Nitric oxide depletion due to frequent masturbation
21.69. C. He is not sexually attracted to his girlfriend Sildenafil ultimately works by inhibiting phosphodiesterase (PDE)-5, which regulates the concentration of cyclic guanosine monophosphate (cGMP). cGMP causes smooth muscle relaxation in the corpus cavernosum of the penis, which allows for blood flow, leading to turgidity and tumescence. The whole cascade starts with nitric oxide (NO) increasing cGMP synthesis. NO is only released with sexual stimulation. Therefore, if someone is not sexually stimulated for whatever reason, NO will not be released, and the sildenafil will have no substance upon which it can act.
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21.70. A 22-year-old man with a diagnosis of schizoaffective disorder, who has been hospitalized for 2 days due to acute psychosis, was noted by staff yesterday to have been “quieter than usual.” He walked around the unit looking confused, though when questioned, was oriented to person, place, and situation. The next morning, he did not report to the day area for breakfast. The unit nurse found him in bed with his pillow soaked with sweat. He did not respond to questions. When the nurse attempted to take his blood pressure, she had difficulty bending his arm to get it out from under the sheet. Vitals are T 39 C (102.2 F), BP 150/95, pulse 110, and respirations 20. He was started on haloperidol 3 days ago upon admission. He is also on escitalopram. What is the most likely cause of this patient’s current condition? A. Serotonin syndrome B. Malignant hypothermia C. Neuroleptic malignant syndrome (NMS) D. Malignant catatonia E. Extrapyramidal side effects (EPS)
21.70. C. Neuroleptic malignant syndrome (NMS) The patient is showing classic signs and symptoms of NMS brought on by haloperidol. Malignant hyperthermia can have a similar presentation, but is precipitated by anesthetic agents and succinylcholine. Malignant catatonia can also present in a similar fashion, but is usually heralded by a prodrome of several weeks of psychosis, agitation, and catatonic excitement. Serotonin syndrome usually includes shivering, ataxia, nausea, and vomiting, which are not present in NMS. EPS does not include the autonomic instability of NMS. https://www.uptodate.com/contents/neurolepticmalignant- syndrome? search=neuroleptic%20malignant%20syndrome&source=search_res ult&selectedTitle=1∼150&usage_type=default&display_rank=1#H11