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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. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 1 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. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 2 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. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 3 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 4 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 5 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 6 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 7 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 8 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 9 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 10 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 11 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 12 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 13 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 14 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 15 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 16 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 17 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. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 18 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, nursece4less.com nursece4less.com nursece4less.com nursece4less.com 19 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 20 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 21 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 22 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 23 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 24 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. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 25 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 26 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 27 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. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 28 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 29 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. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 30 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. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 31 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 32 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 33 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 34 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 35 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 36 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 37 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. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 38 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. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 39 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. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 40 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 41 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 42 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 43 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 44 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, nursece4less.com nursece4less.com nursece4less.com nursece4less.com 45 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. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 46 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. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 47 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 48 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 49 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 50 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 51 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 52 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. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 53 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. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 54 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 55 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 56 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 57 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 58 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 59 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 60 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 61 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. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 62 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 63 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 64 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 the nursing knowledge needs met by completing the self-assessment of Knowledge Questions after reading the article, and providing feedback in the online course evaluation. Completing the study questions is optional and is NOT a course requirement. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 65 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. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 66 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 67 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 68 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 69 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 70 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. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 71 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 72 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 73 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. nursece4less.com nursece4less.com nursece4less.com nursece4less.com 74 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 75 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 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 76 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/ nursece4less.com nursece4less.com nursece4less.com nursece4less.com 77 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 risk: A therapeutic dilemma. Paediatrics and Child Health 14(3): 193195. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2690554/ 24. Bucher, J. T., Vu, D. M., Hojat, M. (2013). Psychostimulant drug abuse and personality factors in medical students. Medical Teacher 35(1): 5357. 25. Videbeck, S. L. (2011). Psychiatric-mental health nursing. Philadelphia, PA: Lippincott Williams & Wilkins 26. Peck, P. (2008, Apr.). AHA recommends ECG before starting stimulant therapy for ADHD. Retrieved from http://www.medpagetoday.com/Psychiatry/ADHD-ADD/9174 27. Westover, A. N., Halm, E. A. (2012). Do prescription stimulants increase the risk of adverse cardiovascular events?: A systematic review. BMC Cardiovascular Disorders 12(41). Retrieved from http://www.biomedcentral.com/1471-2261/12/41 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 78 28. Miranda, D. G., McMain, C. L., Smith, A. J. (2011). Medication-induced Q-T interval prolongation and torsades de pointes. US Pharmacist 36(2): HS2-HS8. Retrieved from http://www.uspharmacist.com/content/d/health%20systems/c/26648/ 29. Levi, M. S., et al. (2012). A comparison of methylphenidate-, amphetamine-, and methamphetamine-induced hyperthermia and neurotoxicity in male Sprague–Dawley rats during the waking (lights off) cycle. Neurotoxicology and Teratology 34(2012): 253-262. 30. NIDA for Teens. (2014, Aug.). Drug facts: Prescription stimulants. Retrieved from http://teens.drugabuse.gov/drug-facts/prescriptionstimulants 31. Huizinga, M. M. (2007, Oct.). Weight loss pharmacotherapy: A brief review. Clinical Diabetes 25(4): 135-140. Retrieved from http://clinical.diabetesjournals.org/content/25/4/135.long 32. American College of Physicians. (n.d.). Mood disorders. Retrieved from https://store.acponline.org/ebizatpro/images/ProductImages/books/sa mple%20chapters/PsychCh05.pdf 33. University of Maryland Medical Center. (2013, Jun.). Chronic fatigue syndrome. Retrieved from http://umm.edu/health/medical/reports/articles/chronic-fatiguesyndrome 34. Psych Central Professional. (2004). Provigil: Does it have the Midas touch? Retrieved from http://pro.psychcentral.com/provigil-does-ithave-the-midas-touch/002085.html 35. Therapeutic Guidelines. (2012, Oct.). Procedure-related pain in adults: Procedures with sedation. Retrieved from https://www.tg.org.au/etg_demo/desktop/tgc/agg/7313.htm 36. Bryant, B., Knights, K. (2011). Pharmacology for health professionals (4th ed.). Chatswood, NSW: Elsevier nursece4less.com nursece4less.com nursece4less.com nursece4less.com 79 37. See, S., Ginzburg, R. (2008). Choosing a skeletal muscle relaxant. American Family Physician 78(3): 365-370. Retrieved from http://www.aafp.org/afp/2008/0801/p365.html 38. Perkinson, R. R. (2012). Chemical dependency counseling: A practical guide (4th ed.). Thousand Oaks, CA: Sage Publishing 39. Chih-Yuan, H., et al. (2014, Mar.). The association between zolpidem and infection in patients with sleep disturbance. Journal of Psychiatric Research 54: 116-120. doi: http://dx.doi.org/10.1016/j.jpsychires.2014.03.017 40. Bertisch, S. M., Herzig, S. J., Winkelman, J. W., Buettner, C. (2014, Feb.). National use of prescription medications for insomnia: NHANES 1999-2010. Sleep 37(2): 343-349. doi: 10.5665/sleep.3410 The information presented in this course is intended solely for the use of healthcare professionals taking this course, for credit, from NurseCe4Less.com. The information is designed to assist healthcare professionals, including nurses, in addressing issues associated with healthcare. The information provided in this course is general in nature, and is not designed to address any specific situation. This publication in no way absolves facilities of their responsibility for the appropriate orientation of healthcare professionals. 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