1.
Directions: questions 1-3
Match each neuroleptic drug with the appropriate description (each lettered option can be
selected once, more than once, or not at all):
This drug has a high affinity for D4 receptors
Correct Answer
C. Clozapine
Explanation
Clozapine has a high affinity for D4 receptors.
2.
Directions: questions 1-3
Match each neuroleptic drug with the appropriate description (each lettered option can be
selected once, more than once, or not at all):
This drug is a phenothiazine with high risk of extrapyramidal adverse effects
Correct Answer
D. FlupHenazine
Explanation
Fluphenazine is a phenothiazine drug that is known to have a high risk of extrapyramidal adverse effects.
3.
Directions: questions 1-3
Match each neuroleptic drug with the appropriate description (each lettered option can be
selected once, more than once, or not at all):
This drug can cause sialorrhea in up to 70% of patients
Correct Answer
C. Clozapine
Explanation
Clozapine can cause sialorrhea in up to 70% of patients.
4.
A 44-year-old woman was admitted to the psychiatric hospital for the sixth time since
the age of 32. She was confuse and threatening, saying “the voices are back”. The
woman had received an antipsychotic therapy for several years but she stopped her
medications one month prior to this admission. Physical examination showed
involuntary, abnormal movements manifested by tongue protrusion, frequent blinking
and continuous writhing of harms and legs. This syndrome was most likely due to a
drug-induced primary dysfunction in which of the following brain regions?
Correct Answer
D. Striatum
Explanation
Learning objective: describe the site of action of neuroleptics-induced tardive dyskinesia.
Answer: D
The many years of antipsychotic therapy and the signs and symptoms of the patient indicate
that she was most likely suffering from tardive dyskinesia, an extrapyramidal syndrome caused
by long-term neuroleptic treatment. The cause of the syndrome is unknown but one of the most
commonly accepted hypothesis relates the syndrome to an up-regulation of D2 receptors in
caudate-putamen.
A, B, C, E, F) All these structures can be involved in the actions of neuroleptics but the primary
dysfunction underlying tardive dyskinesia occurs in the striatum.
5.
A 28-year-old man recently diagnosed with paranoid schizophrenia, started a treatment
with aripiprazole, one tablet daily. The therapeutic effect of this drug was most likely
mediated by blockade of dopaminergic transmission in which of the following brain
structures?
Correct Answer
C. Mesolimbic mesocortical systems
Explanation
Learning objective: list the brain structure that most likely mediated the therapeutic effects
of neuroleptics.
Answer: C
The antipsychotic action of neuroleptics is now thought to be produced (at least in part) by they
ability to block dopaminergic transmission in the mesolimbic and mesocortical systems. Since
most of the atypical neuroleptics and some of typical ones can block 5-HT2A receptors, it is
thought that also this blockade can play a role in the therapeutic effect of these drugs.
Blockade of 5-HT2A receptors independent of D2 antagonism has not been demonstrated to
produce antipsychotic effect. However it is possible that the combined blocking action on both
dopamine and 5-HT2a receptors underlie the enhanced therapeutic efficacy of atypical
neuroleptics.
A) The blockade of dopaminergic transmission in the tuberoinfundibular system mediates the
drug -induced hyperprolactinemia, an adverse effect of typical neuroleptics.
B, D, E) Dopaminergic transmission in these system is negligible.
6.
A 65-year-old woman was admitted to the psychiatric hospital because of the
appearance of involuntary movements including tongue protrusion, frequent blinking,
facial grimacing and writhing movements of her legs. The woman was diagnosed with
chronic paranoid schizophrenia 10 years previously and had taken several antipsychotic
drugs since then. Present medication included fluphenazine, two tablet daily. Which of
the following molecular actions most likely mediated the adverse effect of the drug in the
patient’s disease?
Correct Answer
E. Up-regulation of D2 receptors in caudate-putamen
Explanation
Learning objective: describe the actions that likely mediate neuroleptic-induced tardive
dyskinesia.
Answer: E
The history and the signs of the patient indicate that she was most likely suffering from tardive
dyskinesia, a serious extrapyramidal adverse effect of neuroleptic drugs. The exact cause of
the syndrome is unknown but one of the most commonly accepted hypothesis relates the
syndrome to an up-regulation of D2 receptors in caudate-putamen.
A, B, C, D) (see explanation above)
7.
A 82-year-old man, resident in a nursing facility, presented with a complete urinary
retention. The man had a long history of hypertension and prostatic hyperplasia and was
presently treated with hydrochlorothiazide, captopril, and prazosin. Two days ago he
became agitated and hostile, refused to cooperate and tried to assault other residents.
He received 50 mg of chlorpromazine IM and a second injection eight hours later. Which
of the following would be the most likely explanation of his urinary retention?
Correct Answer
B. Chlorpromazine-induced relaxation of the detrusor muscle
Explanation
Learning objective: explain the mechanism of chlorpromazine-induced urinary retention.
Answer: B
Prostatic hyperplasia is the most common cause of difficulty in urination in aged men. If a drug
with antimuscarinic effects, like chlorpromazine, is given to a man with prostatic hyperplasia,
the medication can trigger a complete urinary retention due to relaxation of the detrusor muscle
of the bladder.
A) Chlorpromazine has no effect on the urine formation.
C) Actually captopril can increase diuresis by inhibiting aldosterone production.
D, E) These prazosin induced effects would have facilitated, not hindered, the voiding of the
bladder.
8.
A 37-year-old man complained of dry mouth, constipation and blurred vison while
reading the newspaper. The man, recently diagnosed with a schizoid disorder, started a
treatment with clozapine two weeks ago. The blockade of which of the following
receptors most likely mediated the adverse effects the patient was suffering from?
Correct Answer
E. M3
Explanation
Learning objective: explain the mechanism of the autonomic adverse effects of clozapine.
Answer: E
Some atypical neuroleptics like clozapine have significant blocking activity on muscarinic
receptors. The symptoms of the patient are classic antimuscarinic effects due to clozapine.
Blockade of M3 receptors in the intestinal system cause a decrease in peristalsis and blockade
of M3 receptors in the ciliary muscle cause a loss of accommodation for near vision.
A, B, C, D) (see explanation above)
9.
A 60-year-old man complained to his physician of obstinate constipation. The man
recently diagnosed with a schizoaffective disorder, started a treatment with olanzapine,
two tablet daily. The blockade of which of the following pairs of receptors most likely
mediated the adverse effect of the drug?
Correct Answer
E. Muscarinic and 5-HT2
Explanation
Learning objective: explain the mechanism of olanzapine induced constipation.
Answer: E
Neuroleptics can have significant antimuscarinic and antiserotonergic properties both in the
central and autonomic nervous system. Atypical neuroleptics like olanzapine can cause a
substantial blockade of muscarinic and serotonergic receptors in the gut which can explain the
constipation caused by this drug.
A, B, C, D, E) In all these items at least one of the mentioned receptors is minimally involved in
gastrointestinal motility.
10.
A 24-year-old woman complained to her physician of amenorrhea of two months
duration and of a white discharge from her breast during the past week. The woman had
been on haloperidol and paroxetine for three months to treat a schizoaffective disorder.
She was medication compliant and her illness was well controlled. Which of the following
mechanisms was most likely responsible for the patient’s symptoms?
Correct Answer
D. Blockade of dopamine receptors in the pituitary
Explanation
Learning objective: explain the mechanism of neuroleptic induced hyperprolactinemia.
Answer: D
The amenorrhea and galactorrhea are adverse effects of neuroleptics that are related to their
blockade of D2 receptors in the anterior pituitary gland. Dopamine acts as a prolactin inhibiting
factor by activating these receptors in the pituitary. When D2 receptors are blocked prolactin
secretion increases. High plasma levels of prolactin can result in amenorrhea, galactorrhea and
anovulation in women, while azoospermia, impotence and gynecomastia can develop in men.
All typical neuroleptics can cause the above mentioned symptoms, whereas atypical
neuroleptics are not associated with hyperprolactinemia.
11.
A new potential neuroleptic drug was given IV to a healthy volunteer during a phase I
clinical trial. It was known that the drug had significant blocking activity on D2, H1 And
5-HT2A receptors. The subject was asked about the subjective symptoms he felt during
the experiment. Which of the following pairs of mental effects were most likely reported
by the subject?
Correct Answer
C. DyspHoria, sleepiness
Explanation
Learning objective: describe the mental effects of neuroleptics in normal individuals.
Answer: C
In normal persons neuroleptics do not cause euphoria, but rather a feeling of unpleasantness
and discomfort, i.e. dysphoria. Neuroleptic induced dysphoria can explain, at least in part, why
these drugs have no abuse liability. In addition to their antipsychotic effects several
neuroleptics, have pronounced sedative properties (likely mediated by the blockade of H1 and
5-HT2A receptors which account for the sleepiness induced by these drugs.
A, B, D) These effects would be caused by psychostimulant drugs like amphetamines.
E) Actually neuroleptics decrease delusions and perseveration that are classic psychotic
symptoms.
12.
A 17-year-old boy complained of a stiff neck and a protruding tongue on day two of
the admission to the psychiatric emergency room. The patient was brought to the
emergency room because of assaultive behavior toward his mother. He struck her after
an heavy drinking because he saw that she was about to kill him with a knife. A drug
treatment was started to control his assaultive behavior and he received 3 IM injections
over 24 hours. Which of the following drugs most likely caused the patient’s symptoms?
Correct Answer
A. Haloperidol
Explanation
Learning objective: describe the neuroleptic-induced acute dystonia.
Answer: A
The signs of the patient and the disorder for which he was treated suggest that he suffered from
acute dystonia, an extrapyramidal symptom that usually occurs after few days of high dose
neuroleptic therapy. Acute dystonias present with a sudden onset of brief abnormal postures
like tongue protrusion, oculogyris crisis, torticollis and unusual position in the trunks and limbs.
All the extrapyramidal adverse effects of neuroleptics occur more often with high potency drugs
like haloperidol and fluphenazine.
C, E , F) These neuroleptics have a lower risk of extrapyramidal adverse effects compared to
haloperidol.
B, D) Sedative-hypnotic drugs like benzodiazepines and ethanol have a negligible risk of acute
dystonia.
13.
A 30-year-old man, recently diagnosed with paranoid schizophrenia, became
increasingly restless, was unable to sit or lie down for more than few minutes, and
referred that he wanted “to jump out of my skin”. Two week ago the patient had started a
therapy with fluphenazine, one tablet daily. Which of the following disorders was the
patient most likely suffering from?
Correct Answer
D. Akathisia
Explanation
Learning objective: describe the fluphenazine induced akathisia
Answer: D
Akathisia is one of the dose-dependent extrapyramidal disorders that can be caused by
neuroleptics. These disorders occur most frequently with butyrophenones and the piperazine
side-chain phenothiazines like fluphenazine. Akathisia is characterized by subjective feeling of
restlessness and objective signs of pacing, rocking and inability to sit or stand in one place for
extended period of time. The disorder develops within days to weeks after initiating a
neuroleptic therapy.
A, C, F) These are other extrapyramidal disorders that can be caused by neuroleptics, but the
symptoms are dissimilar so that the differential diagnosis is not difficult.
B) Neuroleptics can rarely cause tonic-clonic seizures, but not complex partial seizures
E) Actually neuroleptic can relieve catatonic signs of schizophrenic patients.
14.
A 27-year-old man complained of feeling “ real slow”and of a bilateral hand tremor
that improved when he picked up his coffee cup. The man suffering from paranoid
schizophrenia was currently treated in an outpatient program. Physical examination
showed cogwheel rigidity in both harms, a stooped posture and a shuffling gait. Which
of the following drugs most likely caused the adverse effects the patient was suffering
from?
Correct Answer
B. Haloperidol
Explanation
Learning objective: describe the haloperidol-induced pseudoparkinsonism.
Answer: B
The symptoms and signs of the patient indicate that he was most likely suffering from
neuroleptic-induced pseudoparkinsonism. The syndrome is caused by blockade of D2
receptors in caudate-putamen and is more likely with neuroleptics that have the highest affinity
for D2 receptors, like fluphenazine or haloperidol.
A, C, D, E) These neuroleptics have lower affinity for D2 receptors, so pseudoparkinsonism is
less likely.
15.
A 42-year-old woman was brought to the emergency room with increased agitation
and confusion. Physical examination revealed temperature of 104° F, pulse of 125 bpm,
labile blood pressure, profuse diaphoresis, sialorrhea and muscle rigidity. The woman,
recently diagnosed from a schizoaffective disorder, had started a therapy few days
previously. Which of the following drugs most likely caused the patient’s syndrome?
Correct Answer
C. Haloperidol
Explanation
Learning objective: describe the neuroleptic malignant syndrome.
Answer: C
The clinical picture is typical of neuroleptic malignant syndrome (NMS), a rare, yet potentially
lethal complication that may present in a sudden, unpredictable fashion. The etiology of NMS is
unknown but a proposed mechanism suggests that a neuroleptic-induced excessively rapid
blockade of dopaminergic receptors in the diencephalon may play a role. It is uncertain wether
NMS is a specific entity or a variant of malignant hyperthermia. This latter disorder is most
commonly associated with administration of halogenated inhalational anesthetics and
depolarizing muscle relaxants. It has a shorter duration (3-5 days) than NMS (5-30 days).
A, B, D, E) All these drugs are not neuroleptics.
16.
A-46-year-old woman complained to her physician that recently her arms began to
writhe continuously, her mouth to pucker involuntarily and her eyes to blink frequently.
The woman had been suffering from a psychiatric disorder for three years and had been
under high dose psychotropic treatment for two years. Which of the following drugs
most likely caused the patient’s symptoms?
Correct Answer
F. Haloperidol
Explanation
Learning objective: describe the neuroleptic -induced tardive dyskinesia.
Answer: F
The symptoms of the patient and the time of appearance of the disorder indicate that she is
most likely suffering from tardive dyskinesia due to neuroleptic medication. Tardive dyskinesia
is a syndrome of persistent and involuntary hyperkinetic movements that occur in persons
taking long term neuroleptics. The symptoms involve the face (tics, blinking, grimacing) tongue
(protrusion, tremor, writhing) lips (smacking, pursing, puckering) neck (torticollis) and limbs (toe
tapping, pill rolling). Tardive dyskinesia appears after long-term treatment (more than three
months, usually after one or two years), is twice as common in women than in men, and can
occur with all typical neuroleptics especially when high doses are given, like in the present
case.
A, C) Atypical neuroleptics have a lower risk of extrapyramidal adverse effects including tardive
dyskinesia.
B, C, E) These drug have negligible or no risk of tardive dyskinesia.
17.
A 35-year-old woman, found unconscious in a park in a hot summer, was brought to
the hospital. The woman, who had been a resident in a psychiatric unit for the past two
years due to a chronic mental disorder, had recently shown improvement in her target
symptoms and enjoyed outside privileges. She had left the ward for jogging two hour
before being found in the park. Her rectal temperature was 106 °F and a diagnosis of heat
stroke was made. Which of the following drugs most likely contributed to the appearance
of the patient’s stroke?
Correct Answer
B. Clozapine
Explanation
Learning objective: describe the neuroleptic-induced impairment of the thermoregulatory
function.
Answer: B
The body ability to thermoregulate is dependent upon an intact hypothalamic thermoregulatory
center. High doses of neuroleptics strongly diminish the thermoregulatory function of the
hypothalamus. Moreover clozapine can also interfere peripherally with the sweating
mechanisms because of its antimuscarinic properties. The result is poikilothermia, in which the
body cannot respond to heat or cold and patients become hypothermic or hyperthermic
depending on the surrounding temperature. Therefore in an environment of high temperature
neuroleptics can favor heat stroke, especially if the person is exercising, like in the present
case.
A, C, D, E, F) All the other listed drugs do not cause impairment of the hypothalamic
thermoregulatory center, at therapeutic doses.
18.
A 62-year-old schizophrenic woman was hospitalized because of palpitation and
light-headedness of 2 hours duration. Physical examination showed a patient in
moderate distress with the following vital signs: blood pressure 110/85 mm Hg, hear rate
158 bpm, respiration 20 breaths/min. An ECG disclosed polymorphic ventricular
tachycardia. Upon questioning the patient admitted she had recently increased the
dosage of her prescribed psychotropic drug because of her augmenting agitation. Which
of the following drugs most likely caused the patient’s symptoms and signs?
Correct Answer
B. Thioridazine
Explanation
Learning objective: describe the cardiac adverse effect of thioridazine.
Answer: B
Because of her disease the woman was most likely under neuroleptic therapy.
Neuroleptics (mainly thioridazine and clozapine) can cause ECG changes including
prolongation of QT interval which can lead to polymorphic ventricular tachycardia. Thioridazine
effect on QT interval is dose-related and has led to a black box warning in the FDA approved
product labeling.
A, C, D) These drug can increase the risk of polymorphic ventricular tachycardia under certain
conditions but they are not antipsychotic drugs and are not currently used in schizophrenia.
E, F) These drugs do not cause prolongation of QT interval.
19.
A 51-year-old woman, resident in a psychiatric unit, complained about feeling dizzy to
the point of fainting upon standing up rapidly. The patient was hospitalized because in
the last three months she became increasingly agitated and afraid. She was convinced
that people near her house were devils, plotting about stealing her money and cutting
her throat. The patient started a psychotropic medication two week previously. Which of
the following drugs most likely caused the patient’s symptoms?
Correct Answer
B. Risperidone
Explanation
Learning objective: describe the postural hypotension induced by atypical neuroleptics.
Answer: B
The symptoms of the patient indicate that she was most likely suffering from postural
hypotension. Atypical neuroleptic (with the exception of clozapine) have become first line
agents for the treatment of an acute psychotic episode, mainly because of few or no acutely
occurring extrapyramidal side effects. Most atypical neuroleptics have significant blocking
activity on alpha-1 receptors and so postural hypotension is a frequent adverse effect, like in
the present case.
A) Haloperidol is used to treat an acute psychotic episode but postural hypotension is a rare
adverse effect since it has minimal blocking activity on alpha-1 receptors.
C, D, E, F) These drug are devoid of antipsychotic properties.
20.
A 34-year-old woman complained to his physician that during intercourse erection
was difficult to achieve and ejaculation was delayed. The man, recently diagnosed with
paranoid schizophrenia, was treated initially with haloperidol but he was switched to
another drug because of the appearance of symptoms of pseudoparkinsonism. Which of
the following drugs most likely caused the patient’s symptoms?
Correct Answer
D. Thioridazine
Explanation
Thioridazine is the most likely drug to have caused the patient's symptoms. Thioridazine is a typical antipsychotic medication that can cause side effects such as pseudoparkinsonism, which includes symptoms like difficulty with movement, tremors, and muscle stiffness. The patient's switch from haloperidol to another drug suggests that the symptoms appeared after starting the new medication, and thioridazine is the most likely culprit among the given options.