QUESTIONS

1. A 43-year-old very overweight man complains of not sleeping

well and feeling tired during the day. He tells his physician
that his wife is the cause of the problem because she wakes
him up several times during the night because of his loud
snores. This appears to be a breathing-related sleep disorder,
so you should probably write a prescription for
(A) Buspirone
(B) Eszopiclone
(C) Flurazepam
(D) Secobarbital
(E) None of the above
2. Which statement concerning the barbiturates is accurate?
(A) Abstinence syndromes are more severe during withdrawal
from phenobarbital than from secobarbital
(B) Alkalinization of the urine accelerates the elimination of
phenobarbital
(C) Barbiturates may increase the half-lives of drugs metabolized
by the liver
(D) Compared with barbiturates, the benzodiazepines exhibit
a steeper dose-response relationship
(E) Respiratory depression caused by barbiturate overdosage
can be reversed by flumazenil
3. A 24-year-old stockbroker has developed a nervous disposition.
He is easily startled, worries about inconsequential
matters, and sometimes complains of stomach cramps. At
night he grinds his teeth in his sleep. There is no history of
drug abuse. Diagnosed as suffering from generalized anxiety
disorder, he is prescribed buspirone. His physician should
inform the patient to anticipate
(A) A need to continually increase drug dosage because of
tolerance
(B) A significant effect of the drug on memory
(C) Additive CNS depression with alcoholic beverages
(D) That the drug is likely to take a week or more to begin
working
(E) That if he stops taking the drug abruptly, he will experience
withdrawal signs
4. Which of the following best describes the mechanism of
action of benzodiazepines?
(A) Activate GABAB receptors in the spinal cord
(B) Block glutamate receptors in hierarchical neuronal pathways
in the brain
(C) Increase frequency of opening of chloride ion channels
coupled to GABAA receptors
(D) Inhibit GABA transaminase to increase brain levels of
GABA
(E) Stimulate release of GABA from nerve endings in the
brain
5. An 82-year-old woman, otherwise healthy for her age, has difficulty
sleeping. Triazolam is prescribed for her at one half of
the conventional adult dose. Which statement about the use
of triazolam in this elderly patient is accurate?
(A) Ambulatory dysfunction does not occur in elderly
patients taking one half of the conventional adult dose
(B) Hypertension is a common adverse effect of benzodiazepines
in elderly patients
(C) Over-the-counter cold medications may antagonize the
hypnotic effects of the drug

(D) The patient may experience amnesia, especially if she also

consumes alcoholic beverages
(E) Triazolam is distinctive in that it does not cause rebound
insomnia on abrupt discontinuance
6. The most likely explanation for the increased sensitivity of
elderly patients after administration of a single dose of a benzodiazepine
is
(A) Changes in brain function accompanying aging
(B) Changes in plasma protein binding
(C) Decreased hepatic metabolism of lipid-soluble drugs
(D) Decreases in renal function
(E) Increased cerebral blood flow
7. A 28-year-old woman has sporadic attacks of intense anxiety
with marked physical symptoms, including hyperventilation,
tachycardia, and sweating. If she is diagnosed as suffering
from a panic disorder, the most appropriate drug to use is
(A) Clonazepam
(B) Eszopiclone
(C) Flurazepam
(D) Propranolol
(E) Ramelteon
8. Which drug used in the maintenance treatment of patients
with tonic-clonic or partial seizure states increases the hepatic
metabolism of many drugs including both warfarin and phenytoin?
(A) Buspirone
(B) Chlordiazepoxide
(C) Eszopiclone
(D) Phenobarbital
(E) Triazolam
9. A patient with liver dysfunction is scheduled for a surgical
procedure. Lorazepam or oxazepam can be used for preanesthetic
sedation in this patient without special concern regarding
excessive CNS depression because these drugs are
(A) Actively secreted in the renal proximal tubule
(B) Eliminated via the lungs
(C) Metabolized via conjugation extrahepatically
(D) Reversible by administration of naloxone
(E) Selective anxiolytics like buspirone
10. This drug used in the management of insomnia facilitates
the inhibitory actions of GABA, but it lacks anticonvulsant
or muscle-relaxing properties and has minimal effect on sleep
architecture. Its actions are antagonized by flumazenil.
(A) Buspirone
(B) Chlordiazepoxide
(C) Eszopiclone
(D) Ramelteon
(E) Phenobarbital

ANSWERS
1. Benzodiazepines and barbiturates are contraindicated in
breathing-related sleep disorders because they further compromise
ventilation. In obstructive sleep apnea (pickwickian
syndrome), obesity is a major risk factor. Buspirone is a selective
anxiolytic not a hypnotic. The best prescription you can
give this patient is to lose weight. The answer is E.
2. Withdrawal symptoms from use of the shorter-acting barbiturate
secobarbital are more severe than with phenobarbital.
The dose-response curve for benzodiazepines is flatter than
that for barbiturates. Induction of liver drug-metabolizing

enzymes occurs with barbiturates and may lead to decreases

in half-life of other drugs. Flumazenil is an antagonist at BZ
receptors and is used to reverse CNS depressant effects of
benzodiazepines. As a weak acid (pKa, 7), phenobarbital will
be more ionized (nonprotonated) in the urine at alkaline pH
and less reabsorbed in the renal tubule. The answer is B.
3. Buspirone is a selective anxiolytic with pharmacologic characteristics
different from those of sedative-hypnotics. Buspirone
has minimal effects on cognition or memory; it is not an
additive with ethanol in terms of CNS depression; tolerance is
minimal; and it has no dependence liability. Buspirone is not
effective in acute anxiety because it has a slow onset of action.
The answer is D.
4. Benzodiazepines exert most of their CNS effects by increasing
the inhibitory effects of GABA, interacting with components
of the GABAA receptor-chloride ion channel macromolecular
complex to increase the frequency of chloride ion channel
opening. Benzodiazepines do not affect GABA metabolism or
release, and they are not GABA receptor agonists because they
do not interact directly with the binding site for GABA. The
answer is C.
5. In elderly patients taking benzodiazepines, hypotension is
far more likely than an increase in blood pressure. Elderly
patients are more prone to the CNS depressant effects of
hypnotics; a dose reduction of 50% may still cause excessive
sedation with possible ambulatory impairment. Additive
CNS depression occurs commonly with drugs used in overthecounter cold medications, and rebound insomnia can
occur with abrupt discontinuance of benzodiazepines used as
sleeping pills. Alcohol enhances psychomotor depression and
the amnestic effects of the benzodiazepines. The answer is D.
6. Decreased blood flow to vital organs, including the liver and
kidney, occurs during the aging process. These changes may
contribute to cumulative effects of sedative-hypnotic drugs.
However, this does not explain the enhanced sensitivity of
the elderly patient to a single dose of a central depressant,
which appears to be due to changes in brain function that
accompany aging. The answer is A.
7. Alprazolam (not listed) and clonazepam are the most effective
of the benzodiazepines for the treatment of panic disorders.
Eszopiclone and flumazenil are hypnotics. Propranolol is
commonly used to attenuate excessive sympathomimetic
activity in persons who suffer from performance anxiety
(stage fright). The answer is A.
8. Chronic administration of phenobarbital increases the activity
of hepatic drug-metabolizing enzymes, including several
cytochrome P450 isozymes. This can increase the rate of
metabolism of drugs administered concomitantly, resulting
in decreases in the intensity and duration of their effects. The
answer is D.
9. The elimination of most benzodiazepines involves their
metabolism by liver enzymes, including cytochrome P450
isozymes. In a patient with liver dysfunction, lorazepam and
oxazepam, which are metabolized extrahepatically, are less
likely to cause excessive CNS depression. Benzodiazepines are
not eliminated via the kidneys or lungs. Flumazenil is used to
reverse excessive CNS depression caused by benzodiazepines.
The answer is C.
10. Only two of the drugs listed are used for insomnia, eszopiclone
and ramelteon. Eszopiclone, zaleplon, and zolpidem are

related hypnotics that, though structurally different from benzodiazepines,

appear to have a similar mechanism of action.
However, these drugs are not effective in seizures or in muscle
spasticity states. Compared with benzodiazepines, the newer
hypnotics are less likely to alter sleep patterns. Ramelteon
activates melatonin receptors in the suprachiasmatic nuclei.
Buspirone is not a hypnotic! The answer is C.