NEUROPHARMACOLOGY EXAM

September 4, 2015,
Name_________________________________________I.D_____________________
I.

J.C., a 22-year-old single, unemployed man, was brought into the emergency department
(ED) of a mental health hospital by the police after he was found running barefooted
downtown dodging cars in subzero weather. In the ER, J.C. was extremely frightened, and
stated they wont let me go.
J.C. is agitated easily and threatens the interviewer when asked questions regarding his
illness. J.C. said he came to this city 5 years ago to be the king of jazz music. He has no
close friends, and does not trust most people. He hears voices of dead people who tell
him he is worthless and will be killed. He says the newscasters on the television are
reading my mind and telling everyone my personal secrets. These problems and insomnia
have been disturbing him for the past year.
J.C. has no history of a previous psychiatric illness and has never been hospitalized. The
administrator at the Salvation Army confirms that J.C. has been living at the facility for 3
years. His behavior has always been rather odd and unusual, and has recently become
more agitated.
J.C. was given a complete physical examination, which was noncontributory. All of his
laboratory tests were within normal limits. The urine drug screen was negative.
J.C. is a thin, disheveled-looking man with very poor hygiene who appears much older than
his stated age. He is extremely suspicious of the interview and his surroundings, and
continually asks, Where am I, who are you, and what do you want? He also is agitated
easily.

1.

What is the most likely diagnosis? On what symptoms do you base your diagnosis?

2.

What are the specific treatment goals in J.C.?

3.

What drugs would you use to accomplish the first goal?

4.

J.C. was given a single dose of lorazepam 2 mg IM. His agitation resolved after the first
injection. What is the next medication decision needed for J.C., and what factors should be
considered when selecting an antipsychotic for the acute and stabilization phases?

5.

When should J.C.s target symptoms start to respond to olanzapine?

6.

It is 6 months later. Most of J.C.s symptoms have improved, he is residing in assisted

living housing, and he is working part-time at Goodwill Industries. Although he is not
troubled by any side effects, he sees no point in continuing his medication. Should they be
discontinued? What are current practice guidelines regarding long-term treatment?

II.

A.R. is a 25-year-old woman who presents to the student health clinic for a routine physical
examination. During her visit, A.R. states, Ive been feeling depressed lately and feel like
giving up. Her physical examination is unremarkable, and all laboratory tests are within
normal limits. A -human chorionic gonadotropin test is negative. She takes no

medications other than an oral contraceptive and denies drinking alcohol or using other
recreational substances.
When asked, A.R. states that she has had increasing periods of depressed mood over the past
few months and often finds herself crying for no particular reason. She reports that she has
no interest in her old hobbies. Over the last 2 months, her appetite has decreased and she
has lost 15 pounds. She is engaged to be married in 3 months, but feels hopeless about all
of the plans that she needs to make for her wedding. She has difficulty sleeping, and has no
energy during the day. She finds it difficult to concentrate or make decisions. This is a
major concern because she is a graduate student at the local university.
The mental status examination reveals an appropriately dressed female who appears sad but
who is alert, coherent, and logical. Her affect is constricted, apprehensive, and sad. Mood
is depressed, and she admits having suicidal ideation but no specific plans. She is oriented
to person, place, and time but shows some recent memory deficits. Her intelligence is
estimated to be above average. She denies hearing voices or other hallucinations. She has
good insight and judgment into her illness.
1.

What is your diagnosis?

2.

What is the risk of A.R. hurting herself? How should suicidal ideation be assessed?

3.

What drug options are available for A.R.s depressive symptoms? What considerations
should be made when selecting antidepressant therapy?

4.

A.R. is given a prescription for sertraline 50 mg QD PO and is asked to return to the clinic
in 4 weeks for follow-up. How soon should A.R.s target symptoms begin to resolve?

5.

What are the most common side effects reported with SSRIs, and how should they be
managed?

III.

S.L., a young woman, is brought to the emergency department (ED) unresponsive, except to
noxious stimuli. Her friends report an evening of heavy drinking on the occasion of her
twenty-first birthday. Her respirations are 8 breaths/min and shallow. Blood pressure (BP)
is 100/60 mm Hg, pulse is 100 beats/min, and temperature is 36 C. A stat arterial blood
gas determination reveals a pH of 7.29 (normal, 7.36 to 7.44), Pco2 of 52 mm Hg (normal,
35 to 45), and HCO3- of 19 mEq/L (normal, 21 to 27).

1.

Why is S.L.s respiratory status of concern?

2.

What therapy should be initiated to manage S.L.s respiratory depression?

3.

Thirty minutes later, the following laboratory results are reported: glucose, 49 mg/dL
(normal, 70 to 110); sodium (Na), 142 mEq/L (normal, 135 to 147); potassium (K), 3.5
mEq/L (normal, 3.5 to 5.0); chloride (CI), 104 mEq/L (normal, 95 to 105); HCO3-, 20
mEq/L (normal, 21 to 27); blood urea nitrogen (BUN), 18 mg/dL (normal, 5 to 22);
creatinine, 0.9 mg/dL (normal, 0.6 to 1.1); and ethanol, 475 mg/dL. Based on the blood
ethanol level, how severe is S.L.s intoxication?

4.

After the respiratory support needs of S.L. are attended to, what other clinical conditions
warrant attention in S.L.?

5.

What medical interventions can facilitate removal of ethanol from S.L.?

IV.

P.B., a 42-year-old woman, has five previous hospitalizations for manic and/or depressive
episodes. She has experienced approximately six severe mood swings in the past year;
including episodes of depression and hypomania. Despite adequate plasma levels, she has
not responded to a regimen that includes desipramine and lithium. The addition of
thioridazine (Mellaril) 100 mg HS resulted in no further improvement. She now presents as
depressed, with expressions of suicidal hopelessness about her condition, sleep disturbances,
and poor appetite.

1.

Why is P.B. failing to respond to lithium?

2.

Are any other mood stabilizers effective for maintenance of bipolar disorder?

3.

What additional options are available for bipolar patients who fail to respond to lithium,
valproic acid, or carbamazepine?

V.

N.K., a 25-year-old woman, has been employed as a bank clerk for the past 5 years. She
had an excellent work record until 6 months ago, when excessive absences and a tendency
to become easily upset at customers and co-workers became noticeable. Upon clinical
assessment, N.K. complains of being tired, irritable, and tense, with frequent stomach upset
and diarrhea. She has no history of mental illness; however, she admits to being stressed
and worrying too much about just little things, which she cannot seem to control no matter
how hard she tries. N.K. denies experiencing episodic attacks of severe anxiety (which
might be indicative of panic disorder), or of having obsessive-compulsive thoughts or
behaviors.
N.K.s physical examination is unremarkable, and she has no history of mental illness in her
family, although her mother was a nervous person. N.K. denies any past or present use of
any illicit substances or alcohol.
N.K. states that at times she has difficulty speaking, is unable to relax, and startles easily.
She realizes that work has been difficult for her lately and she has been told by her
supervisor that her job is in immediate jeopardy unless she improves her performance. N.K.
states that she just wants to be able to perform her job well, relax, and enjoy life. Her
insight and judgment are good, and she is motivated to obtain treatment. N.K. denies any
suicidal ideation.

1.

What would your diagnosis be and why?

2.

Based on the information presented in N.K.s case, how can it be determined whether
treatment is indicated? What are the goals of treatment?

3.

What factors should be considered in the process of selection of the most appropriate
treatment option for N.K.?

4.

The physician decides that N.K. is a good candidate for benzodiazepine treatment.
What factors are important in the selection of a particular benzodiazepine agent for
N.K.?
The pharmacokinetics properties of the benzodiazepine agents such as the half-life of a
drug, its active metabolites, its protein binding capacity, pathway of metabolism and the rate
of onset after oral administration are the main factors that are important to consider in the
drug selection of a particular benzodiazepine agent for N.K. For instance, Diazepam and

Chlordiazepoxide have half-lives between 10-40 hours and are metabolized to an active
metabolite desmethyldiazepam through hepatic oxidative pathways. This active metabolite
has a half-life of approximately 100 hours and this can lead to the drug accumulation and
prolonged clinical effects. Such properties of diazepam and Cholrdiazepoxide should be
taken as pre-caution in the elderly, in individuals taking drugs that interfere with
bezodiazapine metabolism or individuals with hepatic disease as it can be quite harmful.
Small, divided daily doses are strictly recommended to reduce side effects. another property
of benzodiazepine agents that should be noted is the degree of lipid solubility. The highly
lipophilic benzodiazepines are quickly redistributed out of the brain and that causes their
action duration is reduced. Benzodiazapines are costly and affordable generic versions such
as clonazepam and alprazolam are available for individuals who are not able to purchase the
expensive ones. When selecting an agent the potential drug interactions should also be
evaluated as it can alter the pharmacokinetics and clinical effects of the drugs. N.K. is not
taking other medications so treating her with benzodiazepine should not result in any
pharmacokinectic alterations. Lorazepam or alprazolam are highly potent, shorter-acting
agents would be appropriate for N.K.

5.

Lorazepam 0.5 mg TID is prescribed for N.K. What side effects may occur with
benzodiazepine treatment and how should N.K. be counseled regarding
benzodiazepine therapy?

6.

One month later, N.K. returns to the clinic. She reports that the lorazepam has been
extremely effective in relieving her anxiety, and she is currently taking 1 mg TID as directed
by her physician. However, her mother has told her that she will become addicted to
lorazepam, and she expresses a desire to stop taking the drug because of this concern. What
potential for abuse and dependence is associated with benzodiazepines? How should N.K.
be counseled regarding becoming addicted to lorazepam?

VI.

A.R. is a 14-year-old, 40-kg, female high school student. A.R. had three febrile seizures
when she was 3 years old. She received phenobarbital prophylaxis for about 6 months
following her second febrile seizure. Since then, she had no reported seizures until she had
a convulsion at school shortly after arriving for her first class of the morning. A teacher
who witnessed the episode describes her as behaving oddly before the seizure. She
abruptly got up from her classroom desk and began to walk clumsily toward the door; she
bumped into several desks and did not respond to the teachers attempts to redirect her back
to her seat. After approximately 1 minute of this behavior, she fell to the floor and
experienced an apparent generalized tonic-clonic seizure that lasted for approximately 90
seconds. During the episode, she was incontinent of urine and was described as turning kid
of blue. Following this episode, A.R. was transported to the hospital.
On arrival at the hospital, A.R. appeared drowsy and confused. Laboratory studies
including complete blood count (CBC), serum glucose, electrolytes, drug/alcohol screen,
and a lumbar puncture were normal. Physical examination and complete neurologic
evaluation were normal. An EEG showed diffuse slowing with focal epileptiform
discharges in the left temporal area; it was interpreted as abnormal. There was no history of
recent illness or injury, although A.R. had stayed up late several nights recently studying for
an examination.
A second seizure occurs in the hospital. The nursing staffs description of the episode is
similar to that provided by the observers at school. After recovery from each episode, A.R.
has no memory of events during the seizures; she only remembers a funny feeling in her
stomach and a buzzing in her head before she lost consciousness. She describes having
these feelings a couple of times in the past; she attributed them to just getting dizzy and
had not reported them to her parents. After these previous episodes, A.R. described feeling
mixed up and groggy for a few minutes.

1.

Considering the subjective and objective features of A.R.s seizures, what is the likely
diagnosis?

2.

What factors should be considered in a decision to treat A.R.s seizures with antiepileptic
medication?

3.

Discuss the AEDs commonly used for A.R.s seizure type. Based on the subjective and
objective data available, recommend a first-choice antiepileptic medication for A.R..

4.

Carbamazepine has been associated with hematologic and hepatic toxicities. What is the
incidence and significance of these potential toxicities? How should A.R. be monitored for
their occurrence?

5.

Over the following 6 weeks, A.R.s carbamazepine dose was gradually increased to 400 mg
BID (20 mg/kg per day). Until the last dose increase, she had been experiencing 1 or 2
complex partial seizures weekly; she had had only 1 generalized tonic-clonic seizure since
her hospitalization. One week following the increase to 20 mg/kg per day, her serum
carbamazepine concentration was 9 g/mL just before her first dose of the day. No seizures
occurred for 4 weeks and she tolerated the medication well. Subsequently, she again began
experiencing one seizure weekly. A repeated measurement of her trough serum
carbamazepine concentration was 6 g/mL. How might this change in serum concentration
and recurrence of seizure activity be explained?

6.

A.R.s dosage was increased to 600 mg BID. Four weeks later, she was still experiencing
approximately one complex partial seizure weekly. A repeat trough serum carbamazepine
concentration was reported as 6.5 g/mL. Upon questioning, A.R. denied missing doses of
medication and a tablet count confirmed apparent accurate drug intake. A.R. relates that she
experiences some mild nausea following her doses, but she has not vomited. It is noted that
her pharmacist has begun substituting generic carbamazepine tablets for the Tegretol that
was previously dispensed. What role, if any, might this change in carbamazepine tablet
brand have played in the failure of A.R.s serum concentrations to increase as expected?
What other factors might be considered in explaining this situation?

VII.

J.Y., a 29-year-old woman, presents to the clinic with a 5-month history of left-sided
pulsatile head pain recurring on a weekly basis. Her headaches are usually preceded by
unformed flashes of light bilaterally and a sensation of light-headedness. The ensuing pain
is always unilateral and is commonly associated with nausea, vomiting, and photophobia.
The headache is not relieved by two tablets of either aspirin 325 mg or ibuprofen 200 mg
and will usually last all day unless she is able to lie in a dark room and sleep. The
headaches usually interfere with her ability to continue work. J.Y. is unable to identify any
external factors that precipitate a migraine attack. Both J.Y.s mother and grandmother also
were affected by migraine headaches. Past medical history is unremarkable, and J.Y. denies

any other medical problems. Current medications include only the OTC analgesics for
headache and the contraceptive, Ortho-Novum 1/35. General physical and neurologic
examinations are within normal limits.
1.

What subjective and objective data from the above description are consistent with a
diagnosis of migraine with aura?

2.

What should be the general approach to the treatment of J.Y.s headache attacks?

3.

J.Y. recalls being told be her gynecologist that headaches are a possible side effect of oral
contraceptive use. She initially started oral contraceptives 2 years ago and did not associate
the medication with the recent onset of migraine attacks. Why should the use of Ortho
Novum 1/35 be discontinued in J.Y.?

4.

Ortho-Novum 1/35 was discontinued and J.Y. was fitted for a diaphragm. A drug was
prescribed to abort her migraine headaches. What would your choice be and why?

5.

J.Y. used sumatriptan 25 mg PO for her next two migraine headache attacks; however, her
relief was incomplete. J.Y. experienced another headache with severe nausea. She took
sumatriptan 25 mg PO but vomited immediately thereafter and the headache continued to
worsen throughout the day until she could no longer work. J.Y. was taken to the ED by a
friend. The diagnosis of intractable migraine was made. How should J.Y. be treated?

6.

J.Y. returns to the clinic 6 weeks later for follow-up. Her current medications include
sumatriptan and acetaminophen with codeine. Acetaminophen with codeine 30 mg (#20)
was prescribed by the ED physician who treated her single episode of intractable migraine.
Since that episode, about 75% of her headaches have responded to sumatriptan 50 mg orally.
The remainder of her attacks have been aborted with two acetaminophen with codeine
tablets and rest. Her concern is that these resistant headaches occur as often as once or

twice monthly and necessitate her taking the rest of the day off from work. J.Y. reports no
adverse effects to sumatriptan.
What further treatment should be recommended to reduce the frequency and severity of
J.Y.s migraine attacks?

VIII. J.E., a 34-year-old woman, is scheduled to undergo a gynecologic laparoscopy under

general anesthesia, on an out-patient basis. She is taken to surgery; anesthesia is induced
with propofol and maintained with isoflurane. Fentanyl is administered intraoperatively for
analgesia. Neuromuscular blockade produced by vecuronium is reversed with neostigmine
and glycopyrrolate. In the recovery room, J.E. becomes nauseated and has several emetic
episodes.
1.

What do you recommend?

2.

How could J.E.s anesthetic regimen have been modified to reduce the likelihood of PONV?

IX.

E.T. is a 36-year-old woman recovering for the surgical repair of a left tibia fracture that
resulted from a motor vehicle accident. She is otherwise healthy, with no other medical
conditions. Her medication history reveals no drug allergies or history of recreational drug
use, and occasional use of ibuprofen 400 mg PO Q 6 hr PRN for menstrual cramps.
Postoperatively, E.T. received acetaminophen 325 mg with codeine 30 mg, two tablets PO Q
3 hr for pain; however, this analgesic regimen has not controlled her pain adequately. After
extensive complaints, E.T.s analgesic medication was replaced with two tablets of
hydrocodone 5 mg with acetaminophen 500 mg Q 4 hr. In spite of these changes, E.T.
continues to complain of pain. Vital signs indicate the following; respiratory rate, 24
breaths/min; heart rate, 110 beats/min; blood pressure (BP), 140/85 mm Hg. She rates the
intensity of her pain as 8 on a 10-point scale.

1.

What is your assessment of E.T.s pain and what are reasonable analgesia goals for E.T.?

2.

Is the choice of acetaminophen with hydrocodone appropriate for E.T.?

3.

How should E.T.s hydrocodone dose be converted to oral morphine?

4.

E.T. complains of itching from her morphine, but shows no sign of rash. Whats the likely
cause and what can be done to alleviate the problem?

5.

What other adverse effects from morphine should be monitored for in E.T.? What
preventive measures should be considered?

6.

On the third day of her morphine treatment, E.T. appears agitated. Could her agitation be
attributed to her morphine?

7.

Could parenteral ketorolac (Toradol) be given to E.T. instead of the morphine?