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Pharmacology of Sleep Disorders
in Children, Adults, and the Elderly
Jassin M. Jouria, MD
Dr. Jassin M. Jouria is a medical doctor, professor of academic
medicine, and medical author. He graduated from Ross
University School of Medicine and has completed his clinical
clerkship training in various teaching hospitals throughout
New York, including King’s County Hospital Center and Brookdale Medical Center, among
others. Dr. Jouria has passed all USMLE medical board exams, and has served as a test
prep tutor and instructor for Kaplan. He has developed several medical courses and
curricula for a variety of educational institutions. Dr. Jouria has also served on multiple
levels in the academic field including faculty member and Department Chair. Dr. Jouria
continues to serves as a Subject Matter Expert for several continuing education
organizations covering multiple basic medical sciences. He has also developed several
continuing medical education courses covering various topics in clinical medicine. Recently,
Dr. Jouria has been contracted by the University of Miami/Jackson Memorial Hospital’s
Department of Surgery to develop an e-module training series for trauma patient
management. Dr. Jouria is currently authoring an academic textbook on Human Anatomy &
Physiology.
ABSTRACT
In today’s world, sleep disruptions and disorders are growing more prevalent,
and it is not uncommon to utilize pharmacology to treat these issues. As our
understanding of sleep disorders grows, pharmacological solutions can be
tailored to each individual’s needs, regardless of age or other factors.
Medical professionals should understand the role that sedatives and
stimulants can play in treating sleep disorders, as well as the potential
adverse effects of these treatments, and the specific interactions that may
arise in each age group.
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Continuing Nursing Education Course Planners
William A. Cook, PhD, Director, Douglas Lawrence, MA, Webmaster,
Susan DePasquale, MSN, FPMHNP-BC, Lead Nurse Planner
Policy Statement
This activity has been planned and implemented in accordance with the
policies of NurseCe4Less.com and the continuing nursing education
requirements of the American Nurses Credentialing Center's Commission on
Accreditation for registered nurses. It is the policy of NurseCe4Less.com to
ensure objectivity, transparency, and best practice in clinical education for
all continuing nursing education (CNE) activities.
Continuing Education Credit Designation
This educational activity is credited for 4 hours. Nurses may only claim credit
commensurate with the credit awarded for completion of this course activity.
Pharmacology content is 4 hours.
Statement of Learning Need
The current research and developments in sleep medicine highlight a need
for nurses to be educated and updated on the importance of screening for
sleep disorders in children, adults and the elderly – to support early
intervention and to avoid poor health outcomes.
Course Purpose
To provide nurses and health team associates knowledge about sleep
disorders, health outcomes and treatments in all age groups.
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Target Audience
Advanced Practice Registered Nurses and Registered Nurses
(Interdisciplinary Health Team Members, including Vocational Nurses and
Medical Assistants may obtain a Certificate of Completion)
Course Author & Planning Team Conflict of Interest Disclosures
Jassin M. Jouria, MD, William S. Cook, PhD, Douglas Lawrence, MA,
Susan DePasquale, MSN, FPMHNP-BC – all have no disclosures
Acknowledgement of Commercial Support
There is no commercial support for this course.
Activity Review Information
Reviewed by Susan DePasquale, MSN, FPMHNP-BC.
Release Date: 2/15/2016
Termination Date: 8/30/2017
Please take time to complete a self-assessment of knowledge, on
page 4, sample questions before reading the article.
Opportunity to complete a self-assessment of knowledge learned
will be provided at the end of the course.
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1.
The oldest form of medications used as sedatives are:
a. non-benzodiazepines
b. barbiturates
c. benzodiazepines
d. antidepressants
2.
Which drug is classified as a short-acting benzodiazepine used
in the treatment of insomnia?
a. triazolam (Halcion)
b. temazepam (Restoril)
c. flurazepam (Dalmane)
d. clonazepam (Klonopin)
3.
Which type of barbiturate is typically used in the treatment of
seizures associated with epilepsy?
a. pentobarbital
b. secobarbital
c. phenobarbital
d. amobarbital
4.
Desipramine (Norpramin) is considered which type of
antidepressant?
a. monoamine oxidase inhibitor
b. selective serotonin reuptake inhibitor
c. atypical antidepressant
d. tricyclic antidepressant
5.
Which sleep disorder is most commonly seen as a side effect of
sedative use?
a. nocturnal enuresis
b. sleepwalking
c. REM behavior disorder
d. confusional arousals
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Introduction
Sleep disorders can be frustrating situations for those experiencing the
variety of symptoms and difficulties involved. Because sleep disorders often
cause different sleep problems, it may be difficult to pinpoint an exact
treatment. Some sleep disorders cause a lack of sleep or chronically
interrupted sleep cycles, while other conditions lead to chronic sleepiness
that interrupts daytime activities. Fortunately, many medications have been
developed that are recommended for treatment of specific sleep disorders,
whether patients experience too little or too much sleep.
Sedatives
Sedative medications are often prescribed or used among patients who have
difficulty falling asleep or staying asleep. Sedatives enable a person to feel
sleepy, which may more likely induce sleep when it is otherwise difficult to
come by. While sedatives may be effective at times, they are not necessarily
recommended for long-term use or as a nightly regimen to resolve such
sleep problems as insomnia or circadian rhythm disorders. If sedatives are
used, such as through prescription medications or purchased over the
counter, they are recommended for use on an “as needed” basis, rather than
taken consistently over a long period of time.6
It should also be noted that although sedatives can successfully treat such
conditions as insomnia or other conditions that cause difficulties with falling
asleep or staying asleep, they are a temporary measure. Once the patient
stops taking the medication, the original sleep issue often returns,
particularly if the underlying issue causing the sleep problem has not been
addressed. Sedatives should be considered as part of a broader therapy plan
or investigation for the true cause of the sleep disorder; then, sedatives may
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be used in conjunction with other forms of treatment so that the sleep
problem can ultimately be resolved, rather than the patient relying on a
medication to get to sleep every night.
Sedative Categories
Sedatives are useful as calming agents: they decrease excitement in the
brain from external stimuli and produce drowsiness. They decrease motor
activity, which then can help a person to fall asleep more easily. Many drugs
used for sleep are classified as sedative-hypnotics. They are a combination
of sedatives, just described, and hypnotic medications, which induce sleep.
Hypnotics may help a person to fall asleep and may also serve to prevent
frequent arousals, but the person should be able to awaken relatively easily.
Sedatives and hypnotics produce varying degrees of sleepiness and
depression in the central nervous system, ranging from mild sleepiness to
complete loss of consciousness and anesthesia, to coma, depending on the
dose and type of drug used.
Benzodiazepines
Benzodiazepines are one of the oldest forms of medications used as
sedative-hypnotics. They were originally developed and continue to be used
to treat mild anxiety; however, benzodiazepines have been found to improve
sleep among some people with insomnia. There have been several
benzodiazepines approved by the U.S. Food and Drug Administration (FDA)
specifically for the management of insomnia, which include estazolam
(ProSom®), flurazepam (Dalmane®), and triazolam (Halcion®).6
Benzodiazepines produce a feeling of calmness with their sedative activity.
They reduce aggression and anxiety. When used for sleep, benzodiazepines
reduce sleep latency, so the person who takes them falls asleep faster. The
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length of time spent in sleep and the reduction in arousals varies, depending
on the type of drug prescribed.15 The physician may take a patient history to
determine the extent of sleep difficulties occurring and then prescribe a
benzodiazepine medication based on the duration of action to promote sleep.
Benzodiazepines have varying degrees of length and duration of action.
While some are classified as long acting and others are classified as short
acting, the duration of action is also dependent on the dose prescribed.
Flurazepam is an example of a long-acting benzodiazepine that has been
approved for the management of insomnia. Its main metabolite has a very
long half-life, which is between 40 and 100 hours. Because of this, a person
who takes flurazepam for sleep is more likely to suffer from residual effects
of excessive daytime drowsiness. Elderly patients are at higher risk of drug
accumulation and toxicity if they take flurazepam on a regular basis for sleep
because of slowed excretion times. Alternatively, flurazepam may be more
useful as an anti-anxiety medication because of its long-term calming
effects.16
Temazepam (Restoril) is an example of an intermediate-acting
benzodiazepine that is also approved for treatment of insomnia.15
Temazepam has a shorter half-life compared to long-acting agents but in
some cases, residual effects of excessive daytime sleepiness may occur.
Temazepam works by shortening sleep latency and helping people to fall
asleep faster. It often produces very positive results when a person first
starts taking it; however, over time, tolerance may develop and the drug
may not achieve the initial effects it once did. Over time, its hypnotic effects
diminish, but it can be used successfully for several weeks without much of a
noticeable change in effects.16
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Triazolam (Halcion®) is classified as a short-acting benzodiazepine that is
helpful for people who are struggling to achieve sleep due to insomnia.
Triazolam, because of its short half-life of approximately 2½ hours, is most
beneficial for people who have difficulties with sleep onset, rather than with
maintaining lasting sleep. Additionally, its short half-life reduces the
incidences of residual effects and most people do not develop daytime
somnolence after taking it. In fact, it is more likely to cause periods of
wakefulness and alertness the following day after administration.16
Triazolam has been approved for use for the treatment of insomnia, but it
has also been shown to effectively manage other types of sleep disorders.
Triazolam has been successful in managing parasomnias, or unusual
activities that a person may perform while asleep. For example, triazolam
may reduce instances of sleepwalking, in which a person gets up out of bed
and may walk around the room, or may talk to others, all while still asleep.
Sleep terrors, which often occur during the transition between slow-wave
sleep and REM (rapid eye movement) sleep stages, develop as frightening
events in which a person may scream, shout, or otherwise act out in terror,
all while asleep. The person is difficult to calm or to awaken from sleep, even
though he or she appears to be awake. Following the event, the affected
person typically has no memory of what happened and goes back to sleep
quickly.
Sleep terrors often affect children, but they may occur in adults and in the
elderly, particularly when there is another underlying disorder or medical
condition involved, such as sleep apnea. Studies have shown that triazolam
may reduce the incidence of sleepwalking and sleep terrors among people
who suffer from these frightening and bizarre reactions; thereby improving
sleep habits and overall sleep efficiency.16
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Periodic limb movement disorder (PLMD), characterized by repeated
movements of the extremities, occurs while a person is asleep. The
movements most commonly occur in the lower extremities, but they may
affect the upper extremities as well. The affected person may flex the foot,
ankle, or hip, or may repeatedly extend the big toe. The movements occur
outside of the affected person’s control and result in fragmented sleep when
they repeatedly cause the person to awaken slightly every few minutes. The
movements associated with PLMD may occur several times per night or in
clusters.
The disorder more commonly occurs among people who are excessively tired
and who do not normally get enough quality sleep. In fact, it is worsened by
lack of sleep, even though the condition often further produces ineffective
sleep, creating an exhausting cycle. People who take triazolam have seen
some benefits in the reduction of episodes of PLMD. The medication may
help them to sleep better, thereby reducing limb movements during sleep,
or it may directly affect the body’s activity that causes the limb movements
in the first place.
Clonazepam, while not necessarily approved for the treatment of insomnia,
is a type of benzodiazepine that does help some people who have other
types of sleep difficulties. Clonazepam (Klonopin®) is a long-acting
benzodiazepine that is typically prescribed for the treatment of seizures
associated with epilepsy. However, it may also be beneficial for some people
who suffer from REM behavior disorder, which is a condition that occurs
when a person acts out in his or her sleep, most often during the REM stage
of sleep when dreaming.16
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The incidence of REM behavior disorder increases with age and it is most
common among older adults. The person may fall asleep and after
approximately 90 minutes, or the time at which the person is entering the
REM stage of sleep, he or she may get up out of bed, talk, yell, or move
about the room. In most cases of REM behavior disorder, the affected person
does not experience muscle atonia that normally occurs during the REM
stage of sleep and prevents a person from moving and acting out what they
are dreaming. When REM behavior disorder develops, the person typically
has less muscle paralysis during REM sleep and is able to get up and act out.
At times, the behavior can be aggressive; at the very least, it is disruptive to
not only the sleeping person, but to the person’s bed partner as well.
Unfortunately, a correlation has been found between REM behavior disorder
and the development of Parkinson’s disease, in which a person who
experiences regular episodes of REM behavior may be more likely to develop
Parkinson’s in the future. Because REM behavior disorder is also more
common among older adults, medication for this condition can help by
providing a calming affect and reducing these bizarre and sometimes
dangerous activities. An older adult with REM behavior disorder is at higher
risk of becoming injured while asleep if he or she is acting out; use of
clonazepam may provide enough of an effect to reduce episodes of REM
behavior, which can also decrease the risk of injury during these activities
while asleep.
Barbiturates
At one time, barbiturates were commonly used for their depressant effects
to induce sleep and to relieve anxiety and feelings of stress. Bayer
Laboratories in Munich, Germany originally introduced barbiturates in 1862.
By 1903, barbiturates were available for use by general practitioners and
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were mostly used in the treatment of anxiety or as sleeping pills. Up until
the 1960s, barbiturates were commonly prescribed and were one of the first
choices of pills available to provide a calming effect among anxious or sleepdeprived patients. Since that time, though, their use has declined, mostly
because of safety issues and the developments of new drugs that have taken
their place. Barbiturates are still used in some settings, though, and may be
part of some anesthesia regimens prior to surgical procedures. The
barbiturate known as phenobarbital is also still prescribed for the treatment
of seizures associated with epilepsy.11
Barbiturates act as central nervous system depressants, in a manner similar
to alcohol. They may make a person feel tired after taking them, which could
be useful for someone suffering from sleep difficulties or insomnia. However,
barbiturates also have many side effects and a high probability of abuse and
inappropriate use, which makes them less popular as sleep aids. Most
barbiturates have been replaced by benzodiazepines for use as medications
to manage sleeping problems, as benzodiazepines have been found to be
safer.10
There are several different types of barbiturates available, and they vary in
their length of action and onset. Shorter acting drugs may be used to quickly
induce sleep, while longer acting drugs are those more commonly used to
control anxiety or seizure activity. Short-acting barbiturates are those that
have duration of action of 2 to 4 hours. These drugs include pentobarbital
and secobarbital. Intermediate-acting drugs are those with duration of action
of 6 to 8 hours. An example of this type of barbiturate is amobarbital. Finally,
long-acting barbiturates are those with an action duration of 8 to 10 hours;
an example of this type of phenobarbital.11
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The impact that barbiturates have on sleep was a big reason for their
popularity after they were first introduced and in the years following their
initial marketing. People who had difficulties with falling asleep used
barbiturates successfully, but they also experienced feelings of euphoria,
which is the main effect associated with these drugs. Hence, the reason
these drugs became quite popular for sleep improvement and reduction in
anxiety was not only that they worked well for sleep problems, but also that
people felt great while taking them.
Over time, professionals realized some of the many negative effects
associated with barbiturate use, including increased tolerance and their
potential for dependence and addiction. Because of adverse effects,
addiction, and even deaths associated with barbiturates, they are less likely
to be prescribed as sleep aids. They are still used in some medical settings,
as mentioned, and they are found as street drugs as well.11
Hypnotics
As previously stated, hypnotics are medications that can induce sleep and
reduce the frequency of arousals after a person has gone to sleep. Many
sedative medications are actually classified as sedative-hypnotics in that
they not only induce sleep but they provide a relaxing or calming effect.
In addition to benzodiazepines as sedative-hypnotics, there is another class
of medications that are similar but are referred to as non-benzodiazepines.
These drugs work in the same part of the brain as benzodiazepines and
often have the same effects, but they are less likely to cause dependency
and have been shown to have fewer side effects. Some examples of nonbenzodiazepines that may be used for management of sleep problems
include zalepon (Sonata®), zolpidem (Ambien®), and eszopiclone
(Lunesta®).6
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Zaleplon is a short-acting hypnotic that works quickly to induce sleep among
people who struggle with insomnia. Because it works quickly, it is often more
effective for people who have difficulties with falling asleep, rather than
among those who have difficulty staying asleep. It typically starts to work
within 30 minutes of taking the drug.1 Patients who are prescribed this
medication should be advised not to perform other activities before trying to
go to sleep, as they could become too tired to complete activities or they
may be in danger if harmful outcomes occur. Additionally, the patient who
takes this drug should be sure to have at least 4 hours to sleep, otherwise,
negative side effects of excessive drowsiness or grogginess could occur.1
One of the most commonly prescribed sleep medications, zolpidem is
indicated for insomnia treatment. It lasts longer than zaleplon and when a
person takes it, he or she should be advised to get at least 7 hours of sleep.1
It may be more likely to produce dependence when compared to some other
non-benzodiazepines, particularly when it is taken on a long-term basis.19
In 2011, a new form of zolpidem was released under the name Intermezzo®.
It is a low-dose form of zolpidem that can be used among people who have
difficulty falling asleep or staying asleep but do not have 7 to 8 hours at
night to devote to sleep after taking standard zolpidem.1 For example, if a
person with insomnia falls asleep but awakes 2 hours later, he could take
Intermezzo to help themselves fall asleep, even though they may only have
6 hours left to sleep before getting up for the day.
Intermezzo should not be taken unless a person has at least 4 hours to
devote to sleep, and the person who takes it should not drive for at least
one hour after waking up. The drug has been shown to impair driving
considerably among people who take it, so caution must be used when
considering the time to drive after taking it. Also, it has been found that
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Intermezzo is excreted from the body at a different rate in men than among
women, so two doses are available; one that is more geared toward men
and one for women. The lower dose may be used among women who have
at least 4 hours to devote to sleep but it should still be taken only once per
night.20
Insomnia and sleep difficulties may be caused by other sleep disorders that
could also be helped with some non-benzodiazepine drugs. Restless legs
syndrome (RLS) is a disorder that is characterized by a feeling of itching,
crawling, or tingling under the skin in the lower extremities. The feeling may
come about suddenly and more commonly occurs in the evening and at
night. The person who experiences these feelings also has a strong urge to
move the legs or get up and walk, which typically relieves the sensations. As
a result, the frequent movements required to keep the uncomfortable
feelings in the legs at bay cause disrupted sleep or, at times, a lack of sleep
entirely.
Zolpidem may be used in the treatment of restless legs syndrome, although
it is not always a first line of defense against the condition. Use of zolpidem
is often reserved for those with severe symptoms of restless legs syndrome
and who suffer from significant insomnia. Although restless legs syndrome
may appear similar to periodic limb movement disorder, the two conditions
are separate. However, one aspect that they have in common is that they
have a cyclical effect associated with lack of sleep; insomnia and sleep
disruption often lead to an exacerbation of symptoms of restless legs
syndrome, which is similar to the effect of exhaustion on periodic limb
movement disorder. Then, when a person with restless legs syndrome has
even worse symptoms of the condition, his or her sleep is further disrupted.
Zolpidem may help with improving sleep associated with insomnia, which
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can prevent the exhaustion that is more likely to lead to symptoms of
restless legs syndrome.
Eszopiclone was the first drug approved for the treatment of insomnia that
could be taken on a long-term basis.1 Eszopiclone may help to reduce sleep
latency and may improve sleep overall so that the person who takes it may
have fewer arousals during the night and may wake up feeling more
refreshed. When compared to some other types of sleep medications,
eszopiclone may be considered less effective; however, it is less likely to be
abused as a recreational drug and may be less likely to cause dependence
among users.19
Despite their reputation as being safer to use than other types of sedative
medications, in some cases, these medications may continue to produce
residual effects that could potentially be harmful. In the spring of 2014,
officials at the U.S. Food and Drug Administration released a
recommendation that prescribers of eszopiclone (Lunesta) cut the standard
dose in half. Initial prescriptions for eszopiclone were typically 2 mg doses
but the FDA changed its recommendation for prescriptions to start at 1 mg.
The recommendation came after a study showed that people who took
eszopiclone had greater levels of psychomotor and memory impairment the
following day after taking the medication when compared with those who
took a placebo dose. In fact, some participants even showed coordination
problems up to 11 hours after taking the medicine.18
The change in prescription for eszopiclone is just one component of
continued vigilance when prescribing and recommending use of any
medication to promote sleep, whether it is benzodiazepines, nonbenzodiazepines, barbiturates, or other medications. Careful study of the
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effects of sedative-hypnotics is essential as ongoing maintenance for helping
people with sleep difficulties to find solutions and achieve better sleep.
Antihistamines
Antihistamines, while approved and marketed for use in the treatment of
allergic responses, actually have a side effect that causes drowsiness and
may be used to induce sleep in some situations. The most common
antihistamine used for this purpose is diphenhydramine (Benadryl®), which
may be used alone or in combination with other drugs to promote sleep.1
Diphenhydramine has been combined with some analgesics in over-thecounter preparations to promote sleep while controlling pain for some people.
Examples of these combinations include diphenhydramine with
acetaminophen (Tylenol PM®) or diphenhydramine with ibuprofen (Advil
PM®). The idea behind those using these drugs is to promote comfort
among people who may have difficulty falling asleep or staying asleep
because of pain. However, others who do not have pain but instead have
sleep difficulties and want an over-the-counter product that will work to
induce sleep often use them.
Antihistamines are also packaged without the addition of other medications
and marketed simply as sleep aids. In fact, most over-the-counter sleep aids
are simply antihistamines that are packaged for their off-label effects of
increased drowsiness. Some examples of over-the-counter products
marketed as sleep aids and that are antihistamines that contain
diphenhydramine include Nytol™ and Sominex®. Another type of
antihistamine, called doxylamine, may also be found in some nonprescription preparations that are used as sleep aids. Unisom® is an
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example of a medication marketed as a sleep aid and that can be purchased
over the counter, which contains doxylamine.6
While many people who take antihistamines for their allergies have noted
side effects of drowsiness and may be able to sleep better if they are
suffering from allergy symptoms that disrupt sleep, taking antihistamines
solely as a sleep aid is not always the best idea. Experts at Baylor College of
Medicine recommend avoiding antihistamines for regular use as a sleep aid,
despite the fact that they cause drowsiness, because of their side effects and
the potential for increased tolerance.5 Side effects of antihistamines are
usually mild and include altered mental status, urinary retention, and dry
mouth. While these might not be considered life-threatening events, they
can pose a danger in some patients, particularly the very young or the
elderly.
Some parents give their children antihistamines such as Benadryl to help
them sleep, particularly when sleep difficulties develop that affect
schoolwork or family life. However, this practice is not advisable because the
side effects could worsen behavior in children. Additionally, some elderly
patients may not tolerate the side effects of antihistamines, particularly
when they already have health issues associated with sleep disorders or
underlying medical problems that would be exacerbated by side effects of
these sleep aids.
Antihistamines are also not effective when considered for long-term use.
Most people develop a tolerance to the medication very quickly and must
use more with each dose to achieve the desired effect.5 Over time, this limits
how much a person is able to take to achieve sleep and can result in a costly
choice that is detrimental to health. In most cases, antihistamines may be
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used short term or on occasion, but they are not recommended as a first
choice of sleep aid.
People who are having difficulties sleeping, particularly those with insomnia
or circadian rhythm disorders, should be encouraged not to rely on over-thecounter sleep aids such as antihistamines. Instead, they should seek
professional help from a health care provider to get to the root of the
problem and find treatment methods that will resolve the condition instead
of bandaging it through these types of medication.
Antidepressants
Antidepressants may be prescribed if a person’s sleep problems are a
symptom of depression. Because depression and insomnia are closely tied
and often coincide with each other, insomnia may be well managed by
treating underlying depression. It may be difficult to determine the exact
cause of which disorder. A person with insomnia may develop depression
because of ongoing sleep difficulties, excessive daytime sleepiness, and
feelings of isolation; alternatively, insomnia and sleep difficulties are classic
symptoms associated with major depressive disorder. In some cases,
prescription antidepressants are useful in treating insomnia.
These drugs can be particularly helpful because they are not habit forming
and the risk of addiction with use is very low. They also have a low incidence
of side effects when compared with other medications used for sleep, such
as sedative-hypnotics or antihistamines. And, if a patient has other
symptoms of depression that impact sleep, such as mild pain,
antidepressants may also work to help offset a small amount of pain to
further promote sleep.
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Tricyclic antidepressants are a category of drugs used for the treatment of
insomnia in some cases. They promote sleep by blocking some
neurotransmitter transporters. Some patients are also prescribed tricyclic
antidepressants when they have daytime lethargy and somnolence, which
could be caused from a lack of sleep or as symptoms of depression. These
drugs are effective in reducing these symptoms as well. Some examples of
tricyclic antidepressants used for these purposes include desipramine
(Norpramin®) and protriptyline (Vivactil®).9
Monoamine oxidase inhibitors (MAOIs) are another form of antidepressant
that may occasionally be used in the treatment of sleep disorders. The type
of MAOI prescribed may depend on the related sleep problem.
Tranylcypromine (Parnate®) is a type of MAOI that may be used among
people who have hypersomnolence associated with depression and/or sleep
difficulties. Tranylcypromine is structurally similar to amphetamines and may
act as a stimulant for those who have difficulties staying awake.
Alternatively, phenelzine is another type of MAOI used for the treatment of
depression but that may help people suffering from insomnia. Phenelzine
(Nardil®) has a sedating effect and tends to suppress periods of REM sleep.9
Like some other antidepressants, though, this drug should be used carefully
in certain populations, particularly the very young and the elderly. It has
been shown to increase the risk of suicidal thoughts and may worsen
symptoms of depression. Because it is an MAOI, people who take phenelzine,
as well as tranylcypromine for the treatment of depression or sleep disorders,
must avoid foods and beverages that contain tyramine.
Tyramine is an amino acid found in some foods that works to regulate blood
pressure. When a person who uses MAOIs eats foods that contain tyramine,
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it causes a reaction in the body that can result in hypertensive crisis. Foods
that most commonly contain tyramine and that should be avoided include
aged cheeses, cured meats, and pickled or fermented vegetables.
Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are
commonly prescribed in the treatment of depression, but they may have
varied effects on sleep. Research studies have shown that some people who
take SSRI medications have had decreased levels of REM sleep, but have
also experienced increased periods of sleep latency and more frequent
arousals at night. Alternatively, some other patients who have taken SSRI
medications for depression have experienced excessive daytime drowsiness.9
Because of the varied responses in sleep outcomes associated with
depression and SSRI use as treatment, these drugs are often not considered
a first choice for treatment of sleep problems that may develop with
depression. Instead, it is recommended that people who use SSRI
medications for depression and who suffer from sleep problems should take
another form of medication to address the sleep issue directly, rather than
relying on the SSRI to remedy the situation.9
Trazodone (Oleptro®) is an atypical antidepressant that has been shown to
improve sleep among patients suffering from insomnia. At one time,
trazodone was prescribed for depression and patients who used it found the
benefit of also having fewer episodes of insomnia. However, the medication
almost worked too well at its prescribed dose and instead of insomnia,
people taking trazodone started suffering more from excessive daytime
drowsiness and somnolence. Clinicians eventually started cutting back the
standard dose of trazodone and found that at a smaller dose, it managed
insomnia quite well without the drawback of sleepiness. It is now often
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prescribed in conjunction with other types of antidepressants to manage
both depression and insomnia in affected patients.9
Antidepressants may be useful for some individuals but are not ideal for
everyone who has sleep difficulties. They should be used with caution among
children and adolescents who experience insomnia. Although children and
teens can have insomnia and depression, prescription antidepressants
should be carefully managed through a provider familiar with use of these
drugs within this specific population. One side effect of some antidepressants
is worsening symptoms of depression or even suicidal ideation, which can be
particularly harmful in children and teens.6
Effects on the Central Nervous System
Benzodiazepines work by acting on receptors of the neurotransmitter gabaaminobutyric acid (GABA) to increase its efficiency. When benzodiazepines
bind to GABA receptors, they stimulate them to take up GABA more
efficiently, thus potentiating its effects. By improving the effects of GABA,
the person feels calmer and has less feelings of nervousness or anxiety.17
Both benzodiazepines and barbiturates affect GABA receptors, but they bind
to different sites. Because benzodiazepines potentiate the work of GABA,
which is a subtler activity, they are considered safer to use than barbiturates,
which act directly on the GABA receptor.15
They are thought to affect sleep patterns by lengthening the amount of time
a person spends in stage 2 of sleep and decreasing time spent in stages 3
and 4, or slow-wave sleep. Benzodiazepines may also more likely reduce
time spent in REM sleep. The recommended use of these types of drugs is
for short-term sleep management only, as negative side effects can occur
when they are discontinued. For instance, benzodiazepines may decrease
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the amount of time a person spends in REM sleep, but when the drugs are
discontinued a rebound effect can occur. This causes the affected person to
spend much more time in REM sleep when they do sleep, thereby decreasing
the amounts of restorative sleep that would otherwise be gained from stages
3 and 4 of NREM (non-rapid eye movement) sleep.8
Barbiturates affect the central nervous system in a manner similar to alcohol.
They have a depressant effect, which initially makes a person feel tired after
use and which can induce sleep. Because of their depressant effects,
barbiturates slow nerve activity, which depresses muscle function, and slows
the heart rate and blood pressure. Barbiturates also affect brain activity and
can cause weakness, balance problems, slurred speech, and confusion.10
Barbiturates can accumulate in fat tissue in the body, so they may be stored
but then enter the bloodstream long after they have been taken. These
drugs have been known to cause impaired judgment among those who take
them, even if they are used for sleep. Lack of rational thinking that may
develop with barbiturate use could cause harm or could be dangerous for
those who take the drugs. If an adult takes a barbiturate as a sleeping pill,
he or she may be able to go to sleep, but during a time in which the person
is awake they could also make poor decisions or perform activities that are
dangerous and harmful.10 Often, the risks of side effects with barbiturates do
not outweigh the benefits of controlling sleep problems, particularly when
there are other safer drugs that may be prescribed as alternatives. Too high
of a dose can lead to coma or even death when the drug causes excess
sedation and anesthesia.
Non-benzodiazepines work in a manner similar to benzodiazepines in that
they impact the receptors for the neurotransmitter GABA in the body. They
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act in a manner similar to GABA to produce a calming effect and reduce
anxiety, but they are more specific in the subunits of the receptors that they
target when compared to benzodiazepines.1
Antidepressants are useful in regulating sleep habits associated with
insomnia by impacting the sleep-wakefulness cycle and altering the amount
of time a person spends in REM sleep. One benefit of reducing REM sleep is
that it may reduce the incidence of disturbing dreams that could be
associated with depression. Additionally, antidepressants have the added
benefit of altering levels of neurotransmitters such as dopamine, serotonin,
and norepinephrine, which all may affect sleep architecture.9
Tranylcypromine, which is a MAOI used in the treatment of depression, may
act as a stimulant because it is structurally similar to amphetamine drugs.
Tranylcypromine has been shown to lengthen the onset of sleep during sleep
latency testing, as well as increase the number of arousals a person has
after going to sleep.9 Because this drug causes an increase in wakefulness, it
may be prescribed for some patients who suffer from depression and who
have excessive daytime drowsiness.
Antihistamines work by blocking receptor sites in cells so that histamines in
the body cannot affect them. Histamines are released as part of the immune
system, typically in response to a foreign object, such as a substance that
could cause an infection. Inflammation results when histamine is released in
response to an allergen in the environment. When antihistamines block
receptor sites for histamines, they reduce inflammation and prevent the
allergic response that would normally occur in response to an allergen. When
the antihistamine medication works against the histamines in the body, it
also produces drowsiness. Drowsiness is typically considered a side effect of
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the medication since, when it is used as an allergy treatment, drowsiness is
not always a desired result.
Side Effects
Side effects of sedatives can vary but there are some side effects that are
common to many different brands and types of these drugs. The most
common side effects of sedative medications are daytime drowsiness,
headaches, dry mouth, constipation, difficulties with concentration, and
dizziness. Other more serious side effects that have also occurred with
sedatives and sleep aids include hallucinations, facial swelling, suicidal
thoughts and ideation, and significant lapses in memory.6
One of the most common side effects associated with sedative use is the
feeling of drowsiness or grogginess after taking the medication, which may
last well after the medication was taken. People who have taken sedative
medications at bedtime have complained of feeling groggy after waking up
the next morning, although the feeling slowly dissipates. For this reason, it is
important that those who take medications to induce sleep should ensure
that they take the drugs at an early enough time to get a full night’s rest.
For example, a patient should only take a sedative for sleep at a normal
bedtime when they know that sleep is attainable for at least the next 7
hours. The patient should avoid taking these types of medications in the
middle of the night or after several hours of trying to fall asleep, as he or
she may be extremely drowsy the next day, which could last for several
hours.6
Additionally, the grogginess associated with sedative use can cause
difficulties with performing certain activities and in some situations, could
put a patient in danger. Children who are given sedatives for sleep may have
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more difficulties in school and concentrating while in the classroom if they
continue to feel groggy after waking up. Older adults may also suffer from
significant feelings of grogginess after using sedative medications, placing
them at greater risk of injuries such as falls in the home. Anyone who is
feeling drowsy after taking sedative medications should avoid driving or
performing other activities that could increase the risk of injury.
Some sedative medications may actually worsen symptoms of sleep
disorders or may cause parasomnias, in which a person exhibits certain
behaviors while asleep. Sedative medications may be associated with
increased incidences of sleepwalking, in which a person gets up out of bed
while still asleep and moves around the room.6 He or she may talk or
mumble when encountered by others and may also try to leave the room or
the house. In some cases, sleepwalking can be harmful if there are objects
that could hurt the sleepwalking person or if he or she tries to leave the
house and becomes injured while outside.
Use of sedatives has also been associated with other types of parasomnias
as well, and the development of these behaviors may occur even if the
person has no prior history of the behaviors. Other parasomnias associated
with sedative use include sleep eating, in which a person consumes large
amounts of food while asleep, or sleep driving, which happens when a
person gets into a car or even drives while asleep and has no memory of the
event.6 Clearly, these can be dangerous or harmful behaviors, whether due
to weight gain associated with sleep eating or accidents or injuries from
driving while asleep. The risk of parasomnia development with sedative use
must be considered when these medications are prescribed.
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Pain Reduction
Benzodiazepines may be included as part of drug therapy for pain
management, particularly during healthcare procedures that would likely
cause pain. Sedation with benzodiazepines is often used during clinical
procedures to provide a calming effect and as part of a regimen to control
pain and anxiety in the patient undergoing a procedure. The amount of
sedation varies, depending on the amount and type of drugs administered.
Sedation may be classified as minimal conscious sedation to moderate and
then deep sedation, followed by anesthesia, which is typically used during
complete surgical procedures.38 The type and amount of sedation must be
modified to fit the procedure taking place.
While sedatives are often used during procedures, they must be combined
with some form of analgesic for pain control. Used alone, sedatives may
provide a relaxing effect and if too large of a dose is given, can lead to
unconsciousness, in which a patient would experience less pain. However,
when procedural sedation is used, its goal is to provide a calming effect that
minimizes fear and anxiety for the patient, which can make pain worse. It is
not appropriate to use extra sedation to compensate for inadequate
analgesia. This practice does not assist with the patient’s pain and could be
potentially harmful.38
Sedation is also used during procedures to provide amnesia for certain
events that are unpleasant. While the patient may be partially awake during
a procedure, use of a sedative may make the process more tolerable and the
patient may not remember the difficulties that occurred. The patient who
receives sedatives as part of a procedure should be carefully monitored
because of the interactions between the sedatives and the analgesics. Use of
the two types of drugs together can cause a synergistic effect that could lead
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to respiratory compromise. Because people react differently to various types
of drugs and an individual’s health tends to dictate his or her ability to
absorb and distribute the drug, the result of using sedatives with analgesics
can be unpredictable. They should be used with caution in any patient but
particularly among older adults and very young children.
Reduced Anxiety
Anxiety is a disordered state in which a person experiences feelings of
agitation, hypervigilance, uncertainty, and fear as a response to
circumstances or in anticipation of an upcoming situation. Anxiety may be
accompanied by physical symptoms that include sweating, shaking, rapid
heart rate, dry mouth, loss of appetite, diarrhea, and difficulties with
breathing.39 Sedative-hypnotic drugs may be prescribed for both feelings of
anxiety as well as the physical symptoms that accompany the situation.
Sedative-hypnotic drugs are often used in the treatment and management of
anxiety; in fact, many of the earliest sedatives were designed for anxiety
treatment but their effects on sleep were also recognized and they were
added to the regimen of drugs used for treatment of sleep disorders.
Sedatives work to reduce anxiety through different effects.
Benzodiazepines and non-benzodiazepines act on GABA receptors in the
body to potentiate the effects of GABA and cause a calming effect on the
body, thereby reducing anxiety. Barbiturates work as central nervous system
depressants to slow body processes, including the heart rate and respiratory
rate, which can slow a person down and reduce feelings of anxiety.
Sedatives are often used as short-term management of anxiety but many
patients have conditions that cause long-term psychological distress related
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to anxiety that is not necessarily managed in the short term with drugs.
Other conditions, such as obsessive-compulsive disorder (OCD), panic
disorder, post-traumatic stress disorder (PTSD), and phobias can all cause
feelings of anxiety that can be long term. Use of sedative-hypnotic drugs
may be warranted in some situations to provide a calming effect, particularly
during times of crises; however, if the goal is to manage the situation for
long-term care, other forms of therapy, such as cognitive-behavioral therapy
or counseling, should be instituted alongside the drug treatment.39
Children who suffer from anxiety typically use sedatives for anxiety on a
very short-term basis, if at all. In some children, opposite effects can
develop and instead of a reduction in anxiety, some children have reactions
of hostility, confusion, and increased excitability. Mild sedation with drugs
such as antihistamines may be more appropriate for use in children, rather
than some stronger drugs, such as benzodiazepines. In these cases,
sedative use for anxiety may be more likely in cases such as administration
of a sedative to control anxiety prior to a procedure, rather than continual
use for generalized anxiety in a child.39
Use of medications to treat anxiety in the elderly may also cause detrimental
effects. Because of the changes that occur with aging, some older adults
may be unable to effectively absorb or excrete sedative-hypnotic
medications, leading to potential toxicity. Some elderly patients, when
taking medications for anxiety, have paradoxical effects that result in the
opposite of the intended effect, including confusion, rage, and excitability.39
When anxiety leads to sleep difficulties such as insomnia, many older adults
benefit from prescription sedative-hypnotics to take on an as-needed basis
to promote sleep and to reduce restlessness and agitation.
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Long-acting medications are the treatment of choice for adults with anxiety
issues. These are more likely to provide a prolonged calming effect, rather
than to induce sleep or act in the short term. Examples of some sedativehypnotics used in the management of anxiety include clonazepam,
lorazepam, and flunitrazepam. Antidepressants may also be useful for
anxiety management, and although they may not provide a distinct sedative
effect, they can be calming and can help to manage symptoms of depression
if they are concurrent with anxiety.
Muscle Relaxation
Patients who develop musculoskeletal disorders or injuries that result in
muscle spasm and pain may need medications that provide muscle
relaxation effects. Sedative medications can be prescribed in some situations
to promote comfort and to provide a calming effect when muscle pain
persists. Muscle relaxants are used in situations such as low back pain,
fibromyalgia, neck or extremity pain, and tension headaches. Muscle pain
and spasms can be debilitating, affecting a patient’s abilities to perform at
work or at home.
Some examples of drugs that may be used as muscle relaxants include
cyclobenzaprine (Flexiril®) and carisoprodol (Soma). These drugs have been
shown to effectively manage muscle pain and spasm more than analgesics
alone. Muscle relaxants are often used as short-term therapy (less than 2
weeks) in situations that allow healing of the muscle tissues to take place
while the medication controls negative symptoms.
Although the name implies that the drugs directly impact the muscles, they
do not. Instead, they work in the brain to inhibit the motor neurons that
cause muscle contractions that lead to muscle spasms. Most muscle
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relaxants work by either inhibiting these neurons or reducing their
excitability, so that while the muscle may still receive messages that would
cause a spasm, the effect is minimized.
Medications used as muscle relaxants do have sedating effects and may
make patients who take them feel more calm and relaxed overall. They may
also make a person feel sleepy and so should not be taken when the affected
person needs to perform activities that require concentration, such as
driving. They may have a synergistic effect when used with other drugs,
particularly analgesics or sedatives, and so should be used with caution.
As with other sedative drugs, muscle relaxants can be useful in controlling
symptoms of pain and anxiety that occur with muscle spasm; however, they
should be carefully controlled to avoid abuse and dependence.
Medication Adverse Effects
Unfortunately, sedatives can have significant adverse effects that can impact
quality of life of those who take these drugs on a regular basis. An adverse
effect is any effect that is undesirable and that occurs with use of a
particular medication. Adverse effects of sedative use may cause physical
symptoms associated with the response of the drug in the body or they
could lead to other situations that can be extremely harmful to the affected
patient, such as addiction, symptoms of withdrawal, changes in behavior, or
reduced overall functioning.
Addiction and Withdrawal
Addiction and withdrawal are two adverse events that can occur with regular
sedative use. Because of the potential for tolerance and dependence on
these drugs, many people who use them find it difficult to stop using them.
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They may also need to increase their use to achieve similar effects, and
when they stop using the sedatives, they suffer from negative side effects
and complications.
Addiction is defined by Psychology Today as “a condition that results when a
person ingests a substance or engages in an activity that can be pleasurable,
but the continued use/act of which becomes compulsive and interferes with
ordinary life responsibilities, such as work, behaviors, or health.”13 People
who develop an addiction to a substance, such as a sedative medication,
may not be aware of the effects of their use of the substance, or how much
it is hurting themselves or others.
Symptoms of withdrawal may occur when a person abruptly stops taking the
medication. This may be more likely to occur when sedative medications are
used on a regular basis and then discontinued. Withdrawal symptoms may
include sweating, shakiness, or nausea. In some cases, if a person takes
sedatives as sleep aids for conditions such as insomnia, he or she may
experience a rebound effect. In other words, while the medication may have
worked to manage insomnia when taken regularly, once the medication is
stopped, the person may experience insomnia right away, and at times it
may be worse than before.6
Benzodiazepines may cause some adverse effects such as photosensitivity,
gastrointestinal symptoms, worsening depression or anxiety, and suicidal
ideation. Despite their therapeutic regulation through prescription from
health care providers, benzodiazepines may still cause drug dependency,
even when used in smaller doses;17 however, they are still considered safer
to use than some other types of sedatives, such as barbiturates.
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Medications such as barbiturates may have deleterious effects when they are
abruptly stopped. Barbiturates have a higher likelihood of causing
dependence and addiction; however, when a person tries to abruptly stop
taking the drugs, symptoms can be extremely uncomfortable, which can
make stopping the use of the drug very difficult in the long term. Symptoms
of barbiturate withdrawal include anxiety, rebound insomnia, seizures,
nausea, gastrointestinal distress, and hallucinations.10
Barbiturates are also highly likely to cause tolerance and addiction when
used consistently. Tolerance can develop rapidly, and when a person uses a
barbiturate medication as a sleep aid, tolerance for the medication may
develop after only a few nights of use. This occurs when the person requires
higher doses of the drug to achieve the same effect. In other words, when
first using the drug, the person was able to achieve sleep relatively easily,
but after using it for a while, he or she needs more of it to be able to fall
asleep.
Dependence and addiction to barbiturates is also likely, as people who use
these medications not only enjoy the feelings they provide but they also feel
that they need them for their purposes of prescription, such as improving
sleep or reducing anxiety. Dependence on barbiturates can and does develop
even when the drugs are medically supervised and prescribed by a health
care provider.11
Barbiturates may initially work to induce sleep, but they impact the amount
of REM sleep that a person gets, which actually works in the opposite
manner. The person who takes barbiturates to get to sleep may still have
disrupted sleep patterns and may not have refreshing sleep, leading to
daytime grogginess or excessive somnolence. Furthermore, once the person
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stops taking the barbiturates, he or she may take longer to return to normal
sleep patterns after using the drugs. The potential for REM rebound may also
occur when REM sleep that had been minimized with regular use of
barbiturates returns and there are excessive amounts of REM sleep each
night. Additionally, dreams that occur during REM sleep may be disturbing or
frightening.11 All of these factors may increase the risk of tolerance and
dependence on barbiturates when stopping the drugs is very uncomfortable
or harmful.
Some people become psychologically dependent on sedative medications, in
that once they take them for a period of time, they feel that they need the
medicine to sleep. In their minds, they depend on the medication and fear
trying to sleep without it. Some types of addictive behaviors occur not as a
result of physical dependence or tolerance, but because of psychological
stress and the drive for a feeling of comfort or relief. For example, a person
may have a psychological dependence on medications that stems from a
need to sleep and to find resolution from anxiety and insomnia. They may
seek out medications, such as sedatives, to help them with finding sleep or
to regulate their sleep patterns, but if the medication does not necessarily
work every time, they may seek out another substance or activity to meet
their needs instead.
Increased Tolerance of Other Drugs
As a person uses sedative drugs to achieve their desired effect — whether it
is to sleep, to control anxiety, or to reduce the pain from muscle spasms —
over time, tolerance can develop to the drug in that it takes more of the
drug to achieve the same effect. When a person initially takes a dose of a
drug, he or she may experience the effect quickly and feel that it is
successful; however, over time, the person may need to take more of the
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drug to achieve the same effect that they initially had because the body has
become tolerant of the drug. This tolerance occurs due to changes that
happen at the cellular level.
It is important to note that the cells always remember the substances to
which they become tolerant. For instance, if a person develops an increased
tolerance for flurazepam and must take more and more of it to achieve the
same effect, he or she has developed a tolerance for the drug. If the person
recognizes this as a problem and stops taking the drug but then takes it
again five years later, he or she will still have the same tolerance for the
drug. The body does not start over in this manner. This is also why addiction
recovery requires abstinence from the substance; the body remembers its
response to the substance and will return to the previous state of tolerance
where it last left off.41
It is the same with other drugs as well. If a person becomes tolerant of
using sedatives after a period of time, then he or she will also be more
tolerant of other drugs that also work in the same manner. This is referred
to as cross-tolerance and develops when a person becomes resistant to the
effects of some drugs because they are similar to other drugs to which he or
she has become tolerant.41 This may occur among drugs that have not been
used before if they have a similar action. The tolerance that develops seems
to impact all drugs of the same category.
This is an important concept to remember when working with patients who
routinely use sedative-hypnotic drugs for sleep or for other long-term effects.
Tolerance can build and can then affect the results of other medications. It
will not make a difference to prescribe a similar medication of a different
brand if the patient is complaining of high tolerance to the initial drug. The
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patient will respond to the second in the same way as the first. More
importantly, any patient who has developed tolerance for a sedativehypnotic drug should be further evaluated for underlying causes of the
situation that could be treated to prevent the need for using such drugs in
the first place. If long-term use results in tolerance, there may be other
factors that need to be addressed and treated to avoid the need for
continued pharmacological use of sedatives.
Sedative Intoxication
Sedative intoxication occurs from the excessive effects of sedatives in the
body. It may develop when a person is unaccustomed to using sedative
medications and has an exaggerated response, or it may also develop when
sedatives are combined with other medications or alcohol, which ultimately
produces extreme effects of the drug as well as negative side effects or
adverse outcomes.
Some sedatives, when combined with similar drugs or with alcohol, cause an
exaggerated effect and the person may feel euphoric or high. At times, this
intoxication can be unintentional, such as in the case of a person who takes
small doses of sedative medications for sleep but ends up having a couple of
glasses of wine at dinner. Without meaning to, the person may contribute to
excessive intoxication from the effects of the sedative combined with alcohol.
Sedative intoxication can occur with barbiturate use if the drugs are
combined with other substances, such as alcohol or other depressants.
Because barbiturates are depressants, when combined with other drugs of
the same type, they potentiate each other, causing even more extreme
effects.11 Combinations of barbiturates with other drugs have led to harmful
effects, including sedative intoxication and fatal overdose. For example, the
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death of Jimi Hendrix in 1970 was purportedly a result of an overdose of
barbiturates.9 The effects of barbiturates are similar to those of alcohol
intoxication, but they have the potential to be even more sedating than
alcohol and therefore more likely to be abused.11
The amount of intoxication and the outcome of the condition depend on
several factors, including the types of sedatives used, the times they were
ingested, and whether the sedatives have been used on a long- or shortterm basis. If caring for someone with sedative intoxication, it may also be
important to know the circumstances surrounding the ingestion of several
substances, the reasons for the ingestion, and whether the person has a
past history of drug or alcohol abuse.
Signs of intoxication are often similar to alcohol intoxication; the person may
have slurred speech, an unsteady gait, and may have an altered sense of
judgment. Greater levels of ingestion of sedatives or combinations of
sedatives with other medications or alcohol may induce altered levels of
consciousness, low blood pressure, hyporeflexia, and respiratory depression.
Other complications that have also been noted include hypothermia,
pulmonary edema, delayed gastric emptying, and skin lesions.12
Sedative intoxication can lead to dangerous complications because of the
exaggerated depressant effects. The patient with sedative intoxication is at
risk of apnea and hypoxia, respiratory arrest, and cardiac arrhythmias. If the
patient vomits while having a depressed respiratory drive, he or she is at
high risk of aspiration. The initial concerns when caring for a patient with
sedative intoxication are to protect and maintain the airway and maintain
circulatory status.12
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In some cases of sedative intoxication associated with benzodiazepines,
treatment with flumazenil (Romazicon®) may be effective to reverse
sedation and respiratory depression. Flumazenil binds to benzodiazepine
receptors and works as an antagonist; however, it can also cause symptoms
of withdrawal in some people.15 Flumazenil should only be used in cases
where the intoxication is known to be from benzodiazepines and not from
other medications or in situations where the intoxicating substances are
unknown.12
People who receive care and treatment for sedative intoxication should be
treated for the condition and then monitored to ensure that no further
adverse effects develop. Ultimately, it is also important to consider the
underlying causes of the intoxication in the first place. For instance, a person
who has a prescription for sedative medications may not be aware of the ill
effects caused by combining the medicine with alcohol, therefore, a
knowledge deficit is in place and more teaching is required. Alternatively, if
the patient was aware of the effects of the sedatives but developed
intoxication anyway, there may be another problem that requires treatment
or management, such as suicidal ideation or other intent for self harm.
Psychosocial Behaviors
People with underlying psychological disorders, such as depression or
anxiety, may develop a worsening of symptoms when they take certain
sedative medications, including benzodiazepines. According to
Aschenbrenner and Venable, people with depression and insomnia who take
benzodiazepine medications to induce sleep may have worse symptoms of
depression than if they had not taken the medication. Additionally, certain
benzodiazepines can cause other behavior problems, including an increase in
aggressive behavior, agitation, and hallucinations.8
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Some sedative-hypnotic medications have been shown to cause erratic or
bizarre behaviors while a person is asleep. Studies have shown that people
who take sedatives are at increased risk of nighttime behaviors, including
sleepwalking, sleep eating, and sleep driving. Behaviors such as sleep eating
and sleep driving are classified as complex sleep-related behaviors, which
are not only considered bizarre and erratic, but may also be dangerous.
Complex sleep-related behaviors are more commonly associated with
prescription sedatives than with over-the-counter preparations.14
When a patient receives a prescription for sleeping medications or begins to
take over-the-counter preparations or supplements, it is important to
provide education regarding the potential for a change in psychosocial
behaviors, particularly if there is another underlying mental illness present.
Although the U.S. FDA has required a change in labeling to notify consumers
of the risk of complications associated with certain sedatives, the nurse’s
role is also to educate clients taking these types of medications, in order that
they will be fully aware of the potential for complex behaviors as a result of
taking the medications.14
Information is available to consumers through the medication guides that
come as part of packaging but should also be reviewed by the nurse.
Additionally, the nurse should advise the patient to take the dose exactly as
it is prescribed and not attempt to take larger doses to change the effects of
the sedatives. Furthermore, patients should be advised not to mix the
sedatives with other types of medications or herbal preparations, particularly
those with depressant effects. If the patient notes that the sedatives are
causing psychosocial behaviors or that they are not effective in managing
sleep problems, it should be addressed with the health care provider instead
of attempting to tackle the problem without help.
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Stimulant Medications
Stimulant medications are used in numerous ways and are available in the
treatment of some sleep disorders, particularly those that result in excessive
daytime drowsiness. Even while used as prescription medications and
through the care of a healthcare provider, these drugs are likely to be
abused and to cause negative side effects that can lead to behavior
problems as well as dangerous physical complications. Despite many
stimulants being listed as controlled substances, there is also availability of
these medications for illicit use because of their effects.
Effects on the Central Nervous System
Stimulants work in the central nervous system by altering levels of
neurotransmitters, including dopamine and norepinephrine to improve mood,
reduce sleepiness, and generate positive feelings. Prescribed stimulant
medications work to improve wakefulness and reducing excessive daytime
sleepiness. The increase in dopamine caused by these drugs has an affect on
the circadian rhythm in the body, which ultimately improves alertness and
reduces feelings of sleepiness. Some amphetamines also affect other
neurotransmitters in the brain that may also improve alertness and affect
the sleep-wake cycle, including serotonin.2
Neurotransmitter regulation from stimulants also impacts the vascular
system, resulting in an increase in blood pressure and heart rate. The
increased heart rate pumps more blood throughout the body and the person
has to breathe faster to keep up. Because of these effects, some stimulant
drugs have been used for weight loss because their effects may be
somewhat similar to exercise on the cardiovascular system.
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Indications
Stimulants are indicated in conditions in which the person taking them needs
some form of stimulation. This may be such factors as help with staying
awake in some sleep disorders, or increasing attention span and the ability
to concentrate. Stimulants can be very useful in helping some people to
focus on their tasks and to stay awake when necessary, and they are
prescribed for various uses.
Narcolepsy
Narcolepsy is a disorder of excessive sleepiness, in which a person
experiences excessive daytime drowsiness and falls asleep quickly,
sometimes at inopportune times. The condition often calls for frequent
daytime naps to ward off drowsiness, sometimes every 3 to 4 hours.
Additionally, the patient with narcolepsy may have periods of microsleep, in
which he or she falls asleep during routine activities for very brief periods of
time but continues to perform the activities. After awakening from the
microsleep, that patient with narcolepsy typically has no memory of the
event or is not even aware that they slept at all.
People with narcolepsy often have to be careful with their activities to avoid
falling asleep when it could be dangerous. They may need to plan their time
so that they are not caught in positions where they become overly tired but
cannot sleep because of where they are or what they are doing. In addition
to excessive daytime sleepiness, narcolepsy also causes periods of cataplexy,
in which the affected person involuntarily loses muscle control. The loss of
control often occurs as a result of strong emotion, such as when laughing or
crying. The person may have a range in muscle loss, which could be as small
as facial drooping or as significant as loss of function and the ability to stand
or walk.
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Narcolepsy is most commonly treated with stimulant medications to help a
person to feel more alert and stay awake. The most common medication
used in the treatment of excessive sleepiness associated with narcolepsy is
modafinil (Provigil®). This drug helps a person with narcolepsy or idiopathic
hypersomnia to stay awake during the day and has been shown to improve
feelings of wakefulness and reduce involuntary sleep episodes.21
Modafinil is less likely to be habit forming or abused when compared with
some other forms of stimulant medications. It does not affect hormones that
are released during sleep, such as cortisol or growth hormone and it does
not interfere with voluntary sleep times, such as at night when a person
wants to go to sleep or when he or she chooses to take a nap during the day.
Some stimulants may be more likely to cause anxiety among patients who
use them but modafinil has not been shown to increase feelings of anxiety.
However, it does require a tapering-off period when discontinuing the
medication, or side effects could be severe. Some side effects of modafinil
include headache, nausea, and dizziness; additionally, some people develop
difficulties with falling asleep or staying asleep when taking modafinil, as its
stimulant effects may produce the opposite of the intended results.21
Another medication that is similar to modafinil and that is also used in the
treatment of excessive sleepiness associated with narcolepsy is armodafinil
(Nuvigil®). This drug is newer than modafinil and typically requires a
smaller dose to achieve the same effects. Because of this, it may be more
potent than modafinil but it works in a manner that is similar.21
Stimulants are the most common medications used in the treatment of
narcolepsy because they help a person to feel more awake and less sleepy.
Before the developments of modafinil and armodafinil, other types of
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stimulants were commonly prescribed to help with symptoms of narcolepsy,
including methylphenidate (Ritalin®), dextroamphetamine (Dexedrine®),
and methamphetamine (Desoxyn®). They have been shown to be effective
for several hours at a time and may also help to improve mood and feelings
of wellbeing. However, they have not been shown to be as effective in
helping people with narcolepsy as modafinil and may be thought of as a
second choice of treatment or for people who do not otherwise tolerate
modafinil or armodafinil.21
Weight Loss
Stimulant drugs have long been used to promote weight loss because they
are recognized for their effects on appetite and the central nervous system.
There have been numerous drugs developed that have been used for weight
loss but that have also later been removed from the market because of
negative side effects or adverse health effects. There are still some
medications currently approved for use in increasing weight loss. Most are
available only by prescription.
Stimulant drugs that promote weight loss are considered anorectics, since
they decrease appetite, which causes a person to feel less hungry and not
take in as many calories. The suppression of appetite occurs from the drug’s
effects on neurotransmitters and it can be successful, but people who take
stimulants for weight loss may also need to manage other side effects that
go along with taking these drugs.
Currently, stimulant medications that are approved for weight loss include
lorcaserin (Belviq®), phentermine (Adipex®), and Qsymia®, which is a
combination of phentermine and the drug topiramate, which is used to
control seizures.33 Another drug, sibutramine (Meridia), was used to promote
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weight loss but was withdrawn from the market in 2010 because research
showed an increased risk in adverse cardiovascular events associated with
its use.
Among the drugs approved for weight loss, phentermine may only be used
for short-term use, but lorcaserin and Qsymia are approved for long-term
use. Side effects of these drugs include headache, dizziness, nausea, dry
mouth, and constipation; these side effects are often related to the effects of
stimulant activity on the central nervous system and the cardiovascular
system.33
Another drawback of using stimulant medications for weight loss is that their
effects are often only temporary. They are designed for short-term use and
may produce modest weight loss, but without other lifestyle changes the
weight is often gained back after the drug is stopped.32 However, studies
have shown that many people prescribed weight loss medications and who
are obese have benefitted by losing excess weight while taking the drugs. A
modest weight loss of even 5 to 10 percent has been shown to improve
some health conditions and should be promoted among people who are
overweight and obese and who are at risk of health problems associated
with weight.
Although stimulants are effective at promoting weight loss and have helped
many people, they should be combined with education and ongoing
supportive care in techniques that help a patient to not only lose weight, but
also maintain it, particularly after use of the drug has ceased. The patient
must be educated about the importance of lifestyle factors, as well as caloric
intake and its effects on weight gain, and then encouraged to practice new
strategies that will promote weight loss to avoid gaining weight back after
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the drug is discontinued. While it may be helpful to use some stimulant
drugs for weight loss, ultimately, it is important to learn long-term solutions
to controlling weight and health, rather than relying on stimulant
medications.
Depression
Some stimulant drugs have been beneficial in the treatment and
management of depression. In most cases, stimulants are used in situations
where a patient’s depression has not responded to standard forms of
treatment and therapy. Stimulants are often combined with antidepressants
and used as adjuvant therapy. The most common types of stimulants used
in this manner are modafinil, D-amphetamine, and methylphenidate.34
Stimulants may be beneficial as adjunctive therapies partnered with
antidepressants because of their rapid response. In many cases, if a patient
is depressed and receives a prescription for antidepressants, it may take
several weeks for the drugs to reach therapeutic levels and for the patient to
start feeling better. When a stimulant is prescribed alongside the
antidepressant, the patient starts to feel some relief sooner because of the
stimulant effects, which can be helpful while waiting for the antidepressants
to fully take effect. For some people, stimulants help them to continue with
normal activities of daily living and to complete necessary tasks that might
have been difficult because of depression. Most patients who take stimulants
as part of treatment for depression start to feel more positive effects within
days of starting therapy.34
After short-term therapy with both stimulants and antidepressants, the
patient may be able to taper off the use of stimulants and may continue to
use antidepressants as single therapy. This combination of therapy has been
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shown to benefit patients who suffer from symptoms of depression that
impede the ability to function through activities of daily living, who have
difficulties with fatigue and lethargy, and who have difficulties with
concentration. The effects of the stimulant medications improve these
symptoms in time for the antidepressants to take effect. As with
prescriptions for any medication for depression, stimulants are used with
caution and regular follow-up is necessary to determine their outcomes and
effects on symptoms for patients who do not otherwise respond to standard
or conventional treatment.
Fatigue
Fatigue is the feeling of being tired or exhausted but rest or sleep does
typically not relieve that. It may be part of an underlying disorder, such as
chronic fatigue syndrome (CFS) or could be associated with any number of
medical conditions. Chronic fatigue syndrome, a condition characterized by
unremitting fatigue that significantly impacts the ability to perform regular
activities of daily living, also involves other symptoms that are often paired
with feelings of fatigue when it is related to other events. The patient with
fatigue may also experience muscle or joint pain, memory impairment,
difficulty with concentration, headaches, unrefreshing sleep, and general
malaise.35
Chronic fatigue can be associated with underlying conditions such as some
sleep disorders that result in impaired sleep cycles and therefore
unrefreshing sleep; depression and anxiety, uncontrolled stress, fibromyalgia,
and multiple chemical sensitivity.35 It has the potential to lead to multiple
complications, beyond an inability to function in a normal capacity. People
with chronic fatigue may have difficulties maintaining jobs and relationships,
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as they may be unable to perform tasks that others would otherwise
consider routine.
It may be difficult to come up with a treatment plan for a patient who suffers
from fatigue that is unrelieved by rest and sleep. Some stimulant drugs have
been used to help patients who suffer from chronic fatigue, particularly when
fatigue causes difficulties with concentration and memory. Stimulant
medications may provide enough stimulation that they can be used to help a
person achieve routine tasks that would otherwise be difficult to complete
because of chronic exhaustion. Stimulant drugs that are sometimes used for
the management of fatigue include methylphenidate, dexamphetamine, and
Adderall.35
Psych Central Professional states that modafinil, approved as a stimulant in
the treatment of narcolepsy, is often used in off-label methods for the
treatment of other disorders, including fatigue associated with depression. In
one study, patients who took modafinil as an adjunct therapy along with
their prescribed antidepressants were more likely to see a resolution in
feelings of fatigue when compared with those who took placebo. However,
the combination of modafinil and antidepressants helped with symptoms of
fatigue but not necessarily any other depressive symptoms, such as feelings
of sadness or hopelessness.36
Because fatigue can be debilitating, it makes sense that prescribing a
stimulant can help an affected patient to complete needed tasks that would
otherwise be overwhelming. However, just as with any other medical
condition that requires the use of stimulants for management, these drugs
must be carefully monitored and are not necessarily a first choice of therapy.
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Attentional Disruptions
Stimulant drugs, in addition to being prescribed to help people stay awake
when they have sleep disorders that cause persistent sleepiness, are also
typically prescribed for attention deficit hyperactivity disorder (ADHD). The
most common stimulants used in these situations include Adderall®,
Ritalin®, and Concerta®. They may be prescribed for the treatment of
ADHD among children and teens, but they are also used among adults.
ADHD causes difficulties with paying attention and focusing on tasks. Some
people with ADHD also have problems with behavior and activity, often
becoming hyperactive and impulsive, which can lead to difficulties with
completing schoolwork or performing well at a job. Although it should seem
that a stimulant medication would only worsen symptoms of hyperactivity
among people with attentional disruptions, stimulants often provide a sense
of calm and may help people to focus. They have also been shown to
improve feelings of wellbeing, self-esteem, and interactions with others,
which can improve relationships with family and friends.22
Stimulants modify the availability of neurotransmitters to improve focus and
concentration, as well as reduce impulsivity, leading to greater impulse
control. Methylphenidate is usually the first choice of medication for
increasing attention in ADHD, but it must be prescribed for children over age
6. Children as young as 3 years may be prescribed Adderall, a combination
amphetamine drug. This drug has an option of a long-acting dose, which can
help to control behavior and other symptoms throughout the day, so fewer
doses are necessary.37
Because ADHD may be associated with depression, stimulants can be
successful in helping to treat depressive symptoms that develop as well.
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They may be more effective when combined with an antidepressant if a child
or adult is having difficulties with symptoms of both conditions. Stimulants
have been shown to improve behavior, impulsivity, and hyperactivity among
children and adults with attentional disruptions, leading to calmer behavior
and a greater ability to complete tasks. This leads to more success in school,
at work, and in relationships for affected patients.
Adverse Effects
Stimulants have the potential to cause a number of adverse effects with
regular use for the management of sleep disorders. Because of the number
of side effects involved with these drugs, it is important that the prescribing
clinician first assess the presence of co-morbid conditions and disorders that
are already present in the patient at the beginning of treatment.
It is especially important to assess for the presence of conditions that mimic
or are otherwise similar to potential side effects that can occur. For example,
a patient with a history of mental illness may suffer from some paranoia that
could ultimately be exacerbated with stimulant use. In this case, the
paranoia is not necessarily an adverse effect of the medication, but instead,
the medication precipitated a worsening of symptoms that were already
present. There are a number of adverse effects that can develop with
stimulant use that providers must be aware of when prescribing these drugs
for treatment.
As mentioned earlier, stimulant medications can impact weight gain. In
children the effect of stimulants need to be monitored by a trained health
professional, and parents need to be educated on ways to trend and to
report delayed weight gain and growth in their children. A helpful online
resource by the Centers of Disease Control and Prevention (CDC) is available
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at http://www.cdc.gov/growthcharts/cdc_charts.htm. It provides guidance
and tools to health professionals and parents, such as growth charts, that
may be used to determine the consequences of stimulant medications on a
child’s normal growth.
Addiction/Withdrawal
Addiction to stimulant medications may be common in some populations, in
part because they can be obtained through prescription or through streetlevel activity. They not only produce positive feelings and euphoria, but
many people find that by taking them, they are able to be more productive
in their tasks. This further increases the risk of dependence on the drugs
when the affected individual feels that he or she is unable to complete
normal activities without the help of medication. While stimulant drugs may
initially be prescribed for treatment of sleep disturbances, the extra benefits
associated with the use lead some people to use them inappropriately, and
addiction can result.
Stimulants are normally taken in oral form and prescribers often start with a
low dose and increase as needed for therapeutic effect. However, the drugs
can be misused when they are taken in other ways, which produce different
effects. For example, some people may have learned that crushing the pills
and either injecting or snorting them increases their effects more rapidly,
resulting in faster results. Even when a person takes the medication orally as
it was intended, he or she may become dependent on using the drug to
continue to achieve pleasant feelings and to accomplish certain activities. If
a person continues to take stimulant medications inappropriately and it
causes difficulties with normal activities, is harmful to the person, or
significantly impacts relationships because of use, the person can be said to
have an addiction. In some cases, the affected individual may not want to
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stop taking the drug because of need and dependence. Many times, stopping
the drug after addiction develops becomes physically difficult and the person
may suffer symptoms of withdrawal.
Withdrawal symptoms from stimulant use can be unpleasant and are
sometimes prominent enough that an addicted person has more difficulty
letting go of the drug use because of the symptoms of withdrawal. Stimulant
withdrawal produces anxiety and irritability, fatigue, lethargy, and lack of
motivation. The person may have a physical craving for the drug, which can
be intense. In some cases, withdrawal increases feelings of suicidal ideation
and feelings of self-harm. Finally, some people who withdraw from over-use
of stimulants may experience anhedonia, in which the affected person is
unable to experience any pleasure in activities that would normally produce
positive or happy feelings.31
Hostility
Hostility can develop for a number of reasons among people; however,
increased hostility is associated with stimulant use. Hostility is a form of
verbal anger, in which a person expresses anger through abusive words, he
or she acts aggressively or threatening toward others, refuses to cooperate
when warranted, and violates rules or expected norms.26 Hostility may be
more likely to develop when a person feels threatened or has deep-seated
anger over an event or through circumstances. Hostility itself is harmful
through words, such as shouting, name-calling and threats. If uncontrolled,
hostility can then lead to aggression, which involves the physical action of
hurting someone or acting out against something.
Stimulant use is associated with an increase in negative behaviors
associated with aggression and hostility. Bucher, Vu, and Hojat
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demonstrated that hostility and aggression, as manifested by an increase in
verbal aggression, anger, rudeness, impatience, and quick temper, were
increased among students who used stimulant medications to help them
with studying and performance at school. The results were gathered through
the use of sample questionnaires, which showed not only an association
between aggressive and hostile behaviors with stimulant medication use, but
also a marginally significant association between impulse control problems
and stimulant medication use.25
Increased hostility and anger associated with stimulant use can further
perpetuate physical symptoms, some of which could also be side effects of
using these medications. For example, an increase in anger and hostility
leads to increased heart rate and blood pressure, which could negatively
impact a client who already has hypertension.26 Stimulant use is also
associated with cardiovascular events, and high blood pressure and coronary
artery disease that could develop with long-term hostility and anger can
further propagate both conditions to multiply risk factors.
The side effects of increased anger and hostility with stimulants may be the
result of the medication’s effects on brain neurotransmitters, such as
dopamine and norepinephrine. When these neurotransmitter levels are
altered, a person may be more likely to act impulsively. Hostility and anger
is also more commonly seen among some people with depression, which is
also related to altered neurotransmitter levels.26 Because sleep disorders are
commonly associated with depression, it can be difficult to determine the
appropriate type and amount of stimulant medication to use because of
untoward effects. Practitioners must carefully consider the mental health of
any patient who seeks help for sleep disorders that would involve prescribing
stimulant medications. For patients with depression, whether or not it is
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caused by the sleep disorder, prescription stimulants need to be monitored
carefully to determine if side effects such as hostility and aggression are
developing.
Paranoia
In 2007, the U.S. Food and Drug Administration released a warning about
the use of some stimulant medications and their effects on cognition and
behavior. The warning stated that prescribers of modafinil and armodafinil,
stimulants used in the treatment of narcolepsy, may be more likely to cause
side effects of anxiety, mania, hallucinations, and suicidal thinking. These
side effects are especially dangerous among patients with previous mental
health histories and providers should use caution when prescribing these two
stimulants for patients with histories of depression, bipolar disorder, or
psychosis.21
Paranoia may be more likely to develop among people who use stimulant
medications inappropriately. According to the National Institute on Drug
Abuse, increased abuse of stimulants, such as amphetamines used in the
treatment of ADHD, may lead to increased hostility and feelings of
paranoia.22 Paranoia, as described by Mental Health America, involves
feelings of being persecuted, and intense and/or irrational feelings of
suspicion toward others. The person with paranoia may have an exaggerated
sense of self-importance and feel as if everyone is thinking about him or her.
Additionally, paranoia may involve feelings of intense hatred toward others
when it is combined with suspicion, the person may feel severely angry
about one or more situations, and he or she may have a strong sense of
feeling betrayed in some manner.23
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A person who suffers from paranoia may demonstrate rigid and imposed
behaviors that can be irritating and annoying to others. The person is often
distrusting of other people and has a fixed set of beliefs about a situation,
which may or may not be true. Additionally, the paranoid person often has
difficulties with relating to others because of suspicion, he may feel hurt by
the actions of others; have difficulties forgiving others for offenses, even
when they are unintentional, and often feels that he or she is the target of
insults or attacks. Other symptoms associated with paranoia include
stubbornness, a self-righteous attitude toward others, self-involvement or
preoccupation with the self, demonstrating fear of hidden motives in others,
and a personality that is uptight with an inability to relax.23
Paranoia may be caused by a number of conditions and it is also classified as
part of some disorders such as paranoid personality disorder or paranoid
schizophrenia.23 When paranoia develops as a result of taking stimulant
medications, it may be necessary to change the medication regimen to
determine if symptoms of paranoia abate. Providers who prescribe
stimulants for the treatment of sleep disorders must carefully weigh the risks
of development of paranoia against the benefits of treatment, particularly
among patients with histories of mental illness.
Irregular Heartbeat
Use of stimulant medications has been associated with cardiac arrhythmias
and changes seen on ECG. In some situations, the result can be extremely
harmful or even deadly. The most common arrhythmias associated with
stimulant medication are prolonged Q-T intervals and Torsades de
pointes.[28] Prolonged Q-T intervals involve changes seen on the ECG of the
affected patient. The Q-T interval represents the time during the cardiac
electrical cycle when the ventricles are repolarized after initial depolarization.
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Medication use that prolongs the Q-T interval thereby prolongs the time it
takes for the ventricles to be repolarized. This typically develops because
stimulant medications cause changes in cardiac cell structure that impacts
sodium and potassium channels. Prolonged Q-T intervals may cause some
symptoms such as fainting and dizziness in affected patients; however,
among many in the population, the Q-T changes do not demonstrate any
symptoms at all. Instead, the ECG changes may lead to more serious
arrhythmias that eventually do produce symptoms. Stimulant use that
causes prolonged Q-T intervals may be more likely to lead to torsades de
pointes (represented in the EKG report below).29
Torsades de pointes is a type of ventricular tachycardia in which the ECG
shows QRS complexes that twist in an abnormal method around the baseline
of where they should be. Torsades de pointes actually means “twisting of
points,” which seems to describe the phenomenon well. It is associated with
a prolonged Q-T interval and occurs as a sudden burst of several beats in
which the heart rate escalates to over 200 bpm. On ECG interpretation, the
QRS complexes first appear positive, and then they flip and appear
negative.29
Torsades de pointes may occur after prolonged Q-T intervals, but this is not
always the case. When it does develop, it is usually not sustained and it
often dissipates spontaneously. However, with continued use of stimulant
medication, it has the potential to return repeatedly, meaning the affected
patient is at higher risk of developing life-threatening arrhythmias that can
lead to sustained ventricular tachycardia or even ventricular fibrillation.
Among people not previously diagnosed with heart disease, Torsades de
pointes may present as sudden cardiac death.
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Older adults may be at higher risk of developing cardiac arrhythmias if they
use stimulant medications for sleep disorders. Ages above 65 is a risk factor
for developing Torsades de pointes29 but older adults may also be at risk
because of the higher prevalence of cardiac disease associated with this
population when compared to middle-aged adults or children. Because
Torsades de pointes can be highly dangerous for affected patients, it is
important to perform a thorough cardiac assessment prior to prescribing
stimulant medications, which may involve a baseline ECG. Further, patients
who use stimulant medications and who develop any cardiac symptoms
should be thoroughly assessed with follow-up measures to best avoid cardiac
arrhythmias, which can be life threatening or even fatal.
High Body Temperature
Stimulant medications impact the circulatory system to cause
vasoconstriction, which increases blood pressure, but can also lead to
increased body temperature. High body temperature, or hyperthermia, is a
state in which a person’s body temperature is elevated to the point that it is
outside the normal range. Other defining characteristics associated with
hyperthermia include flushed skin, tachycardia, increased respiratory rate,
and skin that is warm to the touch. Hyperthermia that develops as a result
of stimulant use is typically related to increased amounts of stimulants to
the point of inappropriately excessive use or overdose. Levi, et al., reported
that at higher doses or when stimulant medications have been administered
intravenously, the medication has been shown to take on similar effects as
cocaine.30
Administration of stimulants has been shown to cause life-threatening,
malignant hyperthermia30 in which the affected person is also at risk of
neurological complications, including confusion and seizures as well as
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dehydration. For patients at risk of other health complications, including the
elderly and the very young, elevated body temperature as a result of
stimulant use can be significant and harmful. Stimulant prescribers must
routinely monitor the health of their patients and provide education on the
effects of use, including signs and symptoms of hyperthermia as well as
when to contact the healthcare provider for treatment.
Cardiovascular Failure
In addition to cardiac arrhythmias that may develop as part of stimulant use,
some people who are prescribed these medications are at higher risk of total
cardiovascular failure, which has been shown to lead to severe complications,
including shock and death. Older adults, in particular, are at higher risk of
developing cardiac complications with stimulant use because of their higher
rates of cardiovascular disease to begin with as well as alterations in drug
absorption, distribution, and excretion that may be more likely to occur in
this population.
Cardiovascular failure can develop with stimulant use in several ways.
Stimulants work by increasing heart rate and blood pressure, which places
extra stress on the cardiovascular system. When used among patients with a
previous cardiac history, the added stress on the heart not only worsens
cardiac symptoms but also could lead to cardiovascular collapse. Stimulants
also increase the body’s release of catecholamines, which are typically
increased during times of stress. The increase in these substances may be
more likely to induce vasospasm of major blood vessels of the circulatory
system, which impacts blood flow and tissue oxygenation.
Finally, stimulants are associated with an increase in vessel inflammation by
stimulating the creation of advanced glycation end-products (AGEs), which
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are typically pro-inflammatory.28 This increase in inflammation increases the
potential for atherosclerosis and decreased vessel size. Because of the
cardiovascular changes understood to occur with stimulants, the U.S. Food
and Drug Administration issued a warning in 2006 regarding the increased
risk of adverse cardiovascular events associated with prescription stimulant
medications.28
Because cardiovascular failure is a risk with use of stimulant medications, it
is essential that the provider check a thorough patient history and physical
prior to prescribing stimulant medications for the management of sleep
disorders. Important information to consider as part of the patient history
includes: history of hypertension, chest pain, heart palpitations, or dizziness
or fainting associated with exercise, a list of all medications and supplements
and their uses, and a history of rheumatic fever. For a child’s medical history,
the provider should assess for history of seizures, irregular heartbeat,
shortness of breath with exercise, history of viral illness, particularly if it
caused heart palpitations; and, a history of heart murmur or any other
cardiac abnormalities since birth.24
The family history should also be assessed for potentially inherited links to
cardiac anomalies that could possibly be related to cardiovascular
compromise with stimulant use. The provider should check for a family
history of relatives who died of sudden cardiac failure, particularly at an age
younger than 35 years, history of Marfan syndrome, cardiac anomalies,
genetic cardiac defects; and, any other deaths in the family history of young
family members whose deaths were unexplained.24 In addition to the family
history, the physical exam of the patient must include a cardiac assessment
of auscultation of heart rate, measurement of blood pressure, assessment
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for cardiac murmur or arrhythmias, and any physical suggestions of Marfan
syndrome, which is associated with sudden cardiac complications and death.
Patients who are starting stimulant medications for use with sleep disorders
may need an ECG prior to beginning therapy. Because of the risk of
cardiovascular collapse with stimulant use, the American Heart Association
(AHA) has stated that it is reasonable to consider an ECG on a patient
starting stimulant therapy, in order to establish a baseline of cardiac
rhythms. This is particularly true for children who are started on stimulants
used in the treatment of ADHD.27 Ultimately, while stimulants may cause an
increase in cardiac events, they affect people differently. Outcomes may
vary among users but it is important to determine background information
to use as a baseline when a prescription for stimulant medications is made.
Although there may be much discussion about increased cardiovascular
events among children who take stimulants for the treatment of ADHD, a
literature review by BMC Cardiovascular Disorders showed that, in most
studies, the risk of cardiovascular events among children who used
stimulants was low.28
Alternatively, increased incidence of cardiac events among adults was
demonstrated in several studies found in the same literature review.28 These
results may be attributable to a number of factors, including the increase in
heart disease and hypertension that already exists among adults when
compared to children, as well as the large amount of stimulant medications
prescribed for treatment of ADHD in children. It is therefore important to
conduct a thorough history and physical to assess for history of cardiac
disease and any heart anomalies present to assess the risk of cardiovascular
compromise with stimulant use. Further study about the risk of
cardiovascular failure among patients who need stimulants for sleep
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disorders, as well as the specific effects of these drugs in older adults, is still
warranted.
Herbal Medications And Vitamins
Many people have success with managing sleep difficulties by using herbal
preparations. These supplements, as well as extra vitamins, should be used
with caution, as they are not always well regulated. Additionally, anyone
using herbal preparations should notify their health care provider of what
and how much they are using, to ensure that it does not interfere with
prescribed medications. Some herbal preparations can negatively interact
with other medications, causing them to be less effective or resulting in
deleterious effects.
There are a number of supplements and herbal preparations that are
marketed as being sleep aids and are thought to help people who have sleep
disorders. Most supplements are used to induce sleep and are promoted
among people who have difficulties falling asleep or staying asleep, such as
those with insomnia. Examples of herbal preparations that may be
considered for inducing sleep include melatonin, valerian root, lavender,
balm leaf, chamomile, and passionflower.7 Alternatively, when a person
needs to stay awake, there may be options for herbal supplements that can
inhibit drowsiness and help a person to stay awake longer, such as in the
case of narcolepsy. Some types of herbal preparations that have been used
to manage symptoms of narcolepsy include gotu kola, St. John’s wort, and
gingko biloba.
Pros for Using Herbal Preparations
There are various benefits to using herbal preparations for the management
of sleep disorders. Many people find that purchasing herbs and supplements
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without a prescription is much easier than trying to obtain a prescription on
a regular basis. Over-the-counter preparations often allow consumers to pick
and choose what types of supplements they would like to try, based on what
they have read or heard. They may feel that using certain supplements
improves their health and if those they have tried do not, then they may
switch to something else.
There are supplements available in the form of oral tablets, teas, lozenges,
and other methods that can deliver nutrients to protect sleep habits. One
example of a commonly used supplement that may be taken to induce sleep
is melatonin. Melatonin supplements are synthetic forms of the hormone
that is naturally produced in the brain, which induces sleep. Some people
who have difficulties sleeping may not produce enough melatonin in their
bodies and they may have difficulties with falling asleep. The supplemental
melatonin that is available works by making the person feel sleepy, which is
what occurs when the body normally secretes the hormone in the evenings
when it is time to go to bed.
Melatonin can successfully help to induce sleep and may be useful among
people with sleep disorders such as: insomnia; circadian rhythm disorders,
such as advanced sleep phase disorder, which may develop in older adults;
or delayed sleep phase disorder, which is more common among adolescents.
Melatonin can also be useful for people who are suffering from jet lag after
traveling through different time zones, or for those who have difficulties
sleeping because they work various shifts that require them to stay awake
during the night.
Melatonin is available without a prescription and most people can buy it at
local pharmacies or shopping centers, where it is relatively inexpensive. It
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may be used in people of almost any age and has been given to children as
well as adults and the elderly with success. Another benefit of using
melatonin is that it does not cause many side effects or feelings of
grogginess the next day after it has been taken. For most people who take
melatonin, they are able to fall asleep rather quickly and do not develop
many negative side effects.
Valerian root is an herbal preparation that some people use to induce sleep.
It has been shown to be particularly effective among people who suffer from
insomnia and may be used in place of some types of sedatives or hypnotic
medications without adverse effects. Valerian root may work in a manner
similar to muscle relaxants, which results in increased drowsiness and
relaxation. Studies have shown that it can induce sleep and result in a
normal night’s sleep for people who normally have sleep difficulties;
additionally, it may also improve feelings of well being during the daytime
for those who take it.7
While there are numerous other therapies available that can be used for
different sleep disorder issues, each person who uses supplements or herbal
remedies must decide on his own what will work and be effective as well as
what to give up. Some people like the idea of using natural supplements and
look for medications and drugs that can be used without a prescription or
without adding more drugs to their regimen. This may be true for people
who take more than one drug already and do not wish to add more.
Furthermore, certain vitamins have been shown to have antioxidants and
other positive properties that can improve or maintain health. Many people
prefer to take vitamins and supplements because they feel as if they are
helping their bodies and taking care of their own health. By researching the
background of certain types of preparations and reading labels, consumers
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may successfully use some of these therapies for management of sleep
disorders and other issues.
Cons for Using Herbal Preparations
While the market for herbal supplements and vitamins is extensive, these
preparations are not necessarily all they claim to be. There may be some
preparations that effectively manage the symptoms or health issues they are
touted to claim; alternatively, there are many others that may contain fillers
in their packaging or that do nothing at all. Consumers must be very careful
when choosing complementary or alternative supplements because they can
not only end up losing money, but they could harm their health by taking
too many unnecessary products. It can be difficult to make choices about
what to use for help, particularly when a person is suffering from a sleep
disorder. A person with disrupted sleep may desperately want to find a
supplement or vitamin that can help establish normal sleep routines again.
Just like medications, though, herbal preparations and vitamins need to be
considered in entirety for their effects and availability.
For example, while melatonin has been widely used to induce sleep among
people who struggle with falling asleep, it does have some negative effects.
Like other supplements sold on the herbal market, melatonin is not
regulated by the U.S. FDA, so the actual amount of what is available in each
tablet may or may not be exactly as the bottle says. Additionally, because it
is not regulated, there is the potential for other substances to show up in the
bottle, some of which could be harmful, especially if a reputable company
does not manufacture the product.
There is no set dose recommended for melatonin, although some physicians
and health care providers may have standards or general guidelines to follow.
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However, many people who hear of melatonin and its positive effects may
decide to buy it and use it for sleep without knowing how much to take.
Without a recommended dose, a person could take too little or too much
melatonin at one time. Although toxicity is rare, without a set dosage of how
much to take, finding the right amount of what is needed to induce sleep
may occur over a period of trial and error.
Additionally, valerian root, while being shown in some studies to be
successful at helping people to fall asleep and improving overall quality of
life, may take longer to actually take effect. Research has shown that it can
take several days of use before the effects of the supplement are achieved,
during which time sleep problems may still persist. Additionally, the
absorption, distribution, and excretion of valerian root have not been
sufficiently studied in humans, as most research on this supplement has
been conducted in animals.7 The efficacy of this supplement as a sleep aid
then becomes somewhat anecdotal and people with sleep difficulties may try
it as another method of trying to fall asleep. The problem with this is that
since its absorption and excretion have not been extensively studied, it may
affect some people differently than others.
Valerian root should not be used among women who are pregnant because
of its unknown effects on the fetus. It is also not recommended for children
under the age of 12. Patients with certain other conditions, such as liver
disease or a history of seizures, should not use valerian root as well.7 It can
be difficult to look past marketing gimmicks and advertisements that claim
to fix sleep problems, particularly when the affected person wants to achieve
normal sleep habits. When it comes to using herbal remedies and vitamins in
the management of sleep disorders, it is best for the patient to talk to a
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professional and to gain appropriate advice about the best use of these
items.
Research
Sleep and sleep disorders are often considered mysteries not only to those
who suffer from them but also for those who must treat them. Research is
ongoing in many areas about the effects of different drugs on sleep
patterns; and professionals continue to find solutions to sleep problems that
keep people up at night or cause enough difficulties that adequate sleep is
difficult to maintain. Historically, drugs have been used in the management
of sleep disorders but may have later been taken off the market for use
when it was discovered that certain medications led to adverse outcomes.
Ongoing research is necessary to continually discover both positive and
negative effects of medications used for sleep among different populations to
better determine what is most effective as a form of treatment. For example,
the drug zolpidem, which is used for insomnia, has been implicated as
possibly causing an increased risk of infections in patients who take it to help
them sleep. Current research is underway to determine the effects of
zolpidem on study participants.42 With enough results pointing in one
direction or another, officials can then make decisions about the safety and
efficacy of these drugs.
In addition to continuing research about drug effectiveness, some groups
study populations and the groups of people who use sleep medications for
help with sleep disorders. For instance, the National Health and Nutrition
Examination Survey (NHANES) is a program that conducts numerous studies
on various health and nutrition topics. NHANES has also studied the affects
of medication use on certain populations. The group recently completed
another study that showed a continued rise in the amount of prescription
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medications used for insomnia among community-dwelling adults.[43] These
types of population studies help professionals to better understand trends in
the community and to stay informed about the processes of prescribing
medications, as well as the outcomes that medications have on the public
who uses them.
Summary
Sleep disorders can impact almost every area of life when they become
disruptive to the point that adequate and refreshing sleep is hard to achieve.
For many years, medications have been available to help people fall asleep
or stay awake. While some medications have been effective and used for
many years, others have come and gone when the results were not effective
or were even harmful.
Providers have a number of options available for prescribing or
recommending help to patients who suffer from sleep disorders, and many
of these drugs can be used for other conditions as well, such as depression
or weight loss. Continued research and study about medications and their
effects on sleep is essential to understand the effects of drugs and
prescriptions that are designed to help people with their sleep habits. By
continuing to study this area, clinicians can be better informed about the
best ways to help their patients achieve restful and refreshing sleep.
Please take time to help NurseCe4Less.com course planners evaluate
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1.
The oldest form of medications used as sedatives are:
a. non-benzodiazepines
b. barbiturates
c. benzodiazepines
d. antidepressants
2.
Which drug is classified as a short-acting benzodiazepine used
in the treatment of insomnia?
a. triazolam (Halcion)
b. temazepam (Restoril)
c. flurazepam (Dalmane)
d. clonazepam (Klonopin)
3.
Which type of barbiturate is typically used in the treatment of
seizures associated with epilepsy?
a. pentobarbital
b. secobarbital
c. phenobarbital
d. amobarbital
4.
Which best describes Intermezzo?
a. A CNS depressant that induces sleep in a manner similar to alcohol
b. A low-dose form of zolpidem that can be used among those who do
not have 8 hours to devote to sleep
c. A long-acting benzodiazepine typically used among people with REM
behavior disorder
d. The first drug approved for the treatment of insomnia that could be
taken on a long-term basis.
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5.
Desipramine (Norpramin) is considered which type of
antidepressant?
a. monoamine oxidase inhibitor
b. selective serotonin reuptake inhibitor
c. atypical antidepressant
d. tricyclic antidepressant
6.
A patient is given a prescription for phenelzine, a MAOI used
for the treatment of insomnia and depression. Which food
would the nurse counsel the client to avoid?
a. pickles
b. turkey
c. yogurt
d. green beans
7.
Which sleep disorder is most commonly seen as a side effect of
sedative use?
a. nocturnal enuresis
b. sleepwalking
c. REM behavior disorder
d. confusional arousals
8.
Which of the following is a symptom seen with barbiturate
withdrawal?
a. rash
b. incontinence
c. joint pain
d. hallucinations
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9.
An involuntary loss of muscle control associated with
narcolepsy is called:
a. cachexia
b. catharsis
c. cataplexy
d. chalazion
10.
Which is an example of a stimulant medication used for the
treatment of weight loss?
a. Adderall
b. Armodafinil
c. Phentermine
d. Eszopiclone
11.
Stimulant medications may be likely to cause dependence and
addiction because:
a. they are calming and they relieve anxiety
b. they control pain and provide analgesia
c. they are inexpensive and usually available without a prescription
d. they help people accomplish tasks and achieve their goals
12.
What best describes hostility?
a. A form of verbal anger, in which a person expresses anger through
abusive words
b. The physical action of hurting someone or acting out against
something
c. Feelings of being persecuted, and intense and/or irrational feelings
of suspicion toward others
d. A disordered state in which a person experiences feelings of
agitation, hypervigilance, uncertainty, and fear
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13.
Which medical history is most important to consider when
prescribing stimulant medications to manage sleep?
a. a diagnosis of leukemia
b. a history of lung disease
c. a diagnosis of gastrointestinal reflux
d. a history of schizophrenia
14.
Torsades de pointes can be dangerous because it can lead to:
a. severe bradycardia
b. ventricular fibrillation
c. flipped T waves
d. asystole
15.
A nurse is discussing a new prescription for methylphenidate
with a patient. Which information from the patient’s family
history would be most important to note?
a. A history of Marfan syndrome
b. A first-degree relative with diabetes mellitus
c. A father who died of lung cancer
d. A sister with Down syndrome
16.
Stimulants contribute to cardiovascular complications by:
a. decreasing the release of catecholamines, which are created during
times of stress
b. blocking pro-inflammatory substances, which would normally
protect the cardiac muscle
c. potentially placing more stress on the heart by increasing heart rate
and blood pressure
d. destroying macrophages, which are important for preventing
changes in myocardial cells
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17.
Which is an example of an herbal preparation that may be used
to induce sleep for those with insomnia?
a. gingko biloba
b. gotu kola
c. lavender
d. garlic
18.
Which describes a benefit of using melatonin?
a. It does not cause feelings of grogginess the next day after use
b. It induces sleep within 4 hours of administration
c. It decreases REM-stage sleep and dreams
d. It promotes wakefulness in the morning
19.
What has been shown to be a disadvantage of using valerian
root to fall asleep?
a. It does not last longer than 4 hours
b. It can take several days to take effect
c. It is expensive and only available by prescription
d. It must be crushed and dissolved before use
20.
Current research has studied which potential outcome from the
use of zolpidem?
a. interstitial lung disease
b. infection
c. urinary retention
d. nightmares
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21.
When taking flurazepam elderly patients are at higher risk
a. of drug accumulation and toxicity.
b. because of slowed excretion times.
c. *Both answers a and b above.
d. None of the above (flurazepam is safe for elderly patients).
22.
Lorcaserin and Qsymia are weight loss drugs approved for
a. short-term use.
b. *long-term use.
c. 30 days or less only.
d. Answers a and c above.
23.
Zolpidem, used for insomnia, has been implicated as possibly
causing
a. *increased risk of infections.
b. overeating.
c. weight gain.
d. Both b and c above.
24.
Zaleplon is a hypnotic that
a. *is a short-acting.
b. is a long-acting.
c. typically works within 1 hour.
d. causes daytime sedation if taken >8 hours prior to arising.
25.
Triazolam has been
a. approved for treatment of insomnia
b. shown to effectively manage other types of sleep disorders.
c. successful in managing parasomnias
d. *All of the above.
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26.
Temazepam (Restoril) is
a. a long-acting benzodiazepine.
b. approved for treatment of insomnia due to mania.
c. *a drug that helps people fall asleep faster.
d. Answers a and b above.
27.
Sedative intoxication can occur with barbiturate use if
a. combined with alcohol or other depressants.
b. combined with other potentiating drugs (of the same type).
c. taken with certain herbal preparations, i.e., Valerian.
d. *Both a and b above.
28.
Children with anxiety typically use sedatives
a. on a very short-term basis.
b. that are mild, such as antihistamines.
c. for symptom relief but may experience the opposite effect of
excitement.
d. *All of the above.
29.
True or False. Tyramine is an amino acid available in
supplement form that is recommended for people prescribed
MAOIs to help maintain normal blood pressure.
a. True
b. *False
30.
Flurazepam is a
a. *long-acting benzodiazepine
b. short-acting benzodiazepine
c. benzodiazepine with a half-life of 4-6 hours
d. Both answers b and c above
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31.
Intermezzo is a drug shown to impair driving and
a. is excreted from the body at different rates between men and
women.
b. has two available doses, one geared for men and the other for
women.
c. should should be taken only once per night by women.
d. *All of the above.
32.
Tricyclic antidepressants
a. promote sleep by blocking some neurotransmitter transporters.
b. are used to treat daytime lethargy and somnolence
c. are not used for sleep but for daytime lethargy and somnolence
d. *both a and b above.
33.
Tranylcypromine is a
a. *MAOI used in the treatment of depression
b. SSRI used in the treatment of depression
c. Tricyclic used in the treatment of depression and insomnia
d. None of the above.
34.
True or False. Tranylcypromine may act as a stimulant because
it is structurally similar to amphetamine drugs. It causes an
increase in wakefulness and may be prescribed for some
patients who suffer from depression and who have excessive
daytime drowsiness.
a. *True
b. False
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35.
Up until the 1960s, __________________ were commonly
prescribed and were one of the first choices of pills available to
provide a calming effect among anxious or sleep-deprived
patients.
a. *barbiturates
b. benzodiazepines
c. tricyclics
d. sedative-hypnotics
36.
Flumazenil (Romazicon®) may be effective to
a. promote sedation by augmenting a sedative drug.
b. *reverse sedation and respiratory depression.
c. prevent symptoms of withdrawal from a drug.
d. Both a and c above.
37.
Stimulants are often combined with antidepressants and used
as adjuvant therapy. The most common types of stimulants
used in this manner are:
a. Modafinil
b. D-amphetamine
c. Methylphenidate
d. *All of the above
38.
When REM behavior disorder develops, the person
a. *has less muscle paralysis during REM sleep and can act out
b. has more muscle paralysis during REM sleep and unable to act out.
c. is unable to behave aggressively.
d. is in a catatonic state.
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39.
Triazolam has been shown to not only reduce the incidence of
sleepwalking, but
a. pica
b. *sleep terrors
c. overeating while asleep
d. None of the above.
40.
When prescribing a stimulant medication, the clinician needs to
monitor the patient carefully for
a. *hostility and aggression
b. weight loss
c. tremors
d. insomnia
Correct Answers:
1.
C
11. D
21. C
31. D
2.
A
12. A
22. B
32. D
3.
C
13. D
23. A
33. A
4.
B
14. B
24. A
34. A
5.
D
15. A
25. D
35. A
6.
A
16. C
26. C
36. B
7.
B
17. C
27. D
37. D
8.
D
18. A
28. D
38. A
9.
C
19. B
29. B
39. B
10. C
20. B
30. A
40. A
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References Section
The reference section of in-text citations include published works intended as
helpful material for further reading. Unpublished works and personal
communications are not included in this section, although may appear within
the study text.
1.
University of Maryland Medical Center (2013, Sep.). Insomnia.
Retrieved from
http://umm.edu/health/medical/reports/articles/insomnia
2.
Harvard Medical School. (2013, Jul). Narcolepsy: Medications. Retrieved
from http://healthysleep.med.harvard.edu/narcolepsy/treatingnarcolepsy/medications
3.
Coggins, M. D. (2013). Unintentional weight loss and appetite
stimulants. Today’s Geriatric Medicine 6(3): 10. Retrieved from
http://www.todaysgeriatricmedicine.com/archive/050613p10.shtml
4.
Ng, B., O’Brien, A. (2009). Beyond ADHD and narcolepsy:
Psychostimulants in general psychiatry. Advances in Psychiatric
Treatment 15: 297-305. Retrieved from
http://apt.rcpsych.org/content/15/4/297.full
5.
Benson, D. (2013, Oct.). Trouble sleeping? Experts say skip
antihistamines. Baylor College of Medicine News. Retrieved from
https://www.bcm.edu/news/sleep-disorders/experts-warn-againstantihistmaines-sleep-aid
6.
Robinson, L., Kemp. G. (2013, May). Sleeping pills and natural sleep
aids. Retrieved from
http://www.helpguide.org/life/sleep_aids_medication_insomnia_treatm
ent.htm
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7.
Kraft, K., Hobbs, C. (2011). Pocket guide to herbal medicine. Stuttgart,
Germany: Thieme
8.
Aschenbrenner, D. S., Venable, S. J. (2009). Drug therapy in nursing
(3rd ed.). Philadelphia, PA: Lippincott Williams & Wilkins
9.
Winokur, A., Demartinis, N. (2012, Jun.). The effects of antidepressants
on sleep. Retrieved from http://www.psychiatrictimes.com/sleepdisorders/effects-antidepressants-sleep
10. Chudler, E. H. (n.d.). Barbiturates. Retrieved from
https://faculty.washington.edu/chudler/barb.html
11. Maisto, S., Galizio, M., Connors, G. (2011). Drug use and abuse (7th
ed.). Stamford, CT: Cengage Learning
12. Cooper, J. S., (2013, Apr.). Sedative-hypnotic toxicity. Retrieved from
http://emedicine.medscape.com/article/818430-overview
13. Psychology Today. (n.d.). What is addiction? Retrieved from
http://www.psychologytoday.com/basics/addiction
14. U. S. Food and Drug Administration. (2013, Dec.). Side effects of sleep
drugs. Retrieved from
http://www.fda.gov/forconsumers/consumerupdates/ucm107757.htm
15. Buch, J. G. (2010). Quick review of pharmacology. [ebook]. PDU
Medical College
16. Pollak, C., Thorpy, M. J., Yager, J. (2010). The encyclopedia of sleep
and sleep disorders. New York, NY: Facts on File
17. The Brain from Top to Bottom. (n.d.). How drugs affect
neurotransmitters. Retrieved from
http://thebrain.mcgill.ca/flash/i/i_03/i_03_m/i_03_m_par/i_03_m_par_
benzodiazepines.html
18. Botelho, G. (2014, May). FDA cuts recommended Lunesta dose in half.
Retrieved from http://www.cnn.com/2014/05/15/health/lunesta-fdadoses/
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19. Sleep Dex. (n.d.). The Z-drugs: Non-benzodiazepine hypnotics.
Retrieved from http://www.sleepdex.org/nonbenzo.htm
20. University of Maryland Medical Center. (2013, Sep.). Narcolepsy.
Retrieved from
http://umm.edu/health/medical/reports/articles/narcolepsy
21. National Institute on Drug Abuse. (2014, Jan.). Drug facts: Stimulant
ADHD medications - methylphenidate and amphetamines. Retrieved
from http://www.drugabuse.gov/publications/drugfacts/stimulant-adhdmedications-methylphenidate-amphetamines
22. Mental Health America. (n.d.). Paranoia and paranoid disorders.
Retrieved from
http://www.mentalhealthamerica.net/conditions/paranoia-andparanoid-disorders
23. Sichilima, T., Rieder, M. J. (2009, Mar.). Adderall and cardiovascular
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