Insomnia

Sleep disturbances are common in the elderly. These disturbances are often secondary to medical illness and/or medication use (Martin et al. 2000). Illnesses could be anxiety disorders or any illness that may disturb sleep due to pain or nocturia. Medications that may cause sleep disturbances are e.g. beta-blockers, corticosteroids and SSRIs. If the sleep disturbance is secondary the treatment should be focused on the underlying cause. If there is no such cause the sleep disturbance is said to be primary. First-line treatment should then be improvement of sleep hygiene (Box 4.1). 

Avoid evening use of stimulating agents, e.g. alcohol or caffeine Avoid day-time naps 

Avoid medications that may cause sleep disturbance Optimise treatment of conditions that may contribute to insomnia 

Before initiating any pharmacotherapy the patient should be asked about sleep-wake patterns, napping etc. Disturbed sleep is common among elderly (Vitiello 1997). In a study on persons 81 years or older, more than one third had problems with their sleep (Giron et al. 2002). There are better tolerated pharmacological alternatives than benzodiazepines (Hemmeter et al. 2000) and many times identifying problems that cause the sleep disturbance may solve the problem. 

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Chronic absorption of iodine causes iodism characterized by insomnia, inflammation of the eyes and nose, bronchitis, tremor, diarrhea, and weight... 

Anxiety disorders and insomnia represent relatively common medical problems within the general population. These problems typically recur over a person s lifetime (3,4). Epidemiological studies in the United States indicate that the lifetime prevalence for significant anxiety disorders is about 15%. Anxiety disorders are serious medical problems affecting not only quaUty of life, but additionally may indirecdy result in considerable morbidity owing to association with depression, cardiovascular disease, suicidal behavior, and substance-related disorders. 

Insomnia is a related psychiatric illness having potentially serious consequences. In any given year up to one-third of the general population may experience insomnia and consequently considerable impact on quaUty of life. Potentially serious psychosocial, health, and socioeconomic consequences may foUow. Many sedative—hypnotics additionally have a firmly estabUshed position within the field of anesthesiology as premedication, inducing agents, and/or for maintenance in intensive care medicine. 

Insomnia complaints are common in the general population and can be dichotomized into problems of delayed sleep onset and those related to sleep maintenance. Increasing attention is being focused on the adverse daytime effects of insomnia. Sleep disturbances become more common with increased age and are more prevalent in women. Sleep complaints arise from very diverse etiologies which prominently include concomitant primary... 

Pharmacological Profiles of Anxiolytics and Sedative—Hypnotics. Historically, chemotherapy of anxiety and sleep disorders rehed on a wide variety of natural products such as opiates, alcohol, cannabis, and kawa pyrones. Use of various bromides and chloral derivatives ia these medical iadications enjoyed considerable popularity early ia the twentieth century. Upon the discovery of barbiturates, numerous synthetic compounds rapidly became available for the treatment of anxiety and insomnia. As of this writing barbiturates are ia use primarily as iajectable general anesthetics (qv) and as antiepileptics. These agents have been largely replaced as treatment for anxiety and sleep disorders. 

The short-acting clomethia2ole [533-45-9] (1), sometimes used as therapy for sleep disorders ia older patients, shares with barbiturates a risk of overdose and dependence. Antihistamines, such as hydroxy2iae [68-88-2] (2), are also sometimes used as mild sedatives (see HiSTAMlNES AND HISTAMINE antagonists). Antidepressants and antipsychotics which have sedative effects are used to treat insomnia when the sleep disorder is a symptom of some underlyiag psychiatric disorder. 

Benzodiazepines, ie, the hiU BZR agonists, are prescribed for anxiety, insomnia, sedation, myorelaxation, and as anticonvulsants (97). Those benzodiazepines most commonly prescribed for the treatment of anxiety disorders are lorazepam (19), alprazolam (20), diazepam (21), bromazepam (22), chlorazepate (23), and oxazepam (24). These dmgs together represent about 70% of total... 

SSRIs are well tolerated. Adverse effects for compounds in this class include nervousness, tremor, dizziness, headache, insomnia, sexual dysfunction, nausea, and diarrhea. In addition, the tricycHc antidepressant clomipramine (33), which is a potent nonselective serotonin reuptake inhibitor, is approved for treatment of obsessive—compulsive disorder. 

SSRIs are widely used for treatment of depression, as well as, for example, panic disorders and obsessive—compulsive disorder. These dmgs are well recognized as clinically effective antidepressants having an improved side-effect profile as compared to the TCAs and irreversible MAO inhibitors. Indeed, these dmgs lack the anticholinergic, cardiovascular, and sedative effects characteristic of TCAs. Their main adverse effects include nervousness /anxiety, nausea, diarrhea or constipation, insomnia, tremor, dizziness, headache, and sexual dysfunction. The most commonly prescribed SSRIs for depression are fluoxetine (31), fluvoxamine (32), sertraline (52), citalopram (53), and paroxetine (54). SSRIs together represent about one-fifth of total worldwide antidepressant unit sales. 

Acute benzene poisoning results in CNS depression and is characterized by an initial euphoria followed by staggered gait, stupor, coma, and convulsions. Exposure to approximately 4000 ppm benzene results in complete loss of consciousness. Insomnia, agitation, headache, nausea, and drowsiness may persist for weeks after exposure (126). Continued inhalation of benzene to the point of euphoria has caused irreversible encephalopathy with tremulousness, emotional lability, and diffuse cerebral atrophy (125). In deaths arising from acute exposure, respiratory tract infection, hypo- and hyperplasia of sternal bone marrow, congested kidneys, and cerebral edema have been found at autopsy. 

Toxic effects of propranolol are related to its blocking P-adrenoceptor blocking actions. They include cardiac failure, hypotension, hypoglycemia, and bronchospasm. Propranolol is lipophilic and crosses the blood—brain barrier. Complaints of fatigue, lethargy, mental depression, nightmares, hallucinations, and insomnia have been reported. GI side effects include nausea, vomiting, diarrhea, and constipation (1,2). 

Krogsgaard-Larsen and co-workers have protected the P-keto functionality as a ketal as a modification to the traditional conditions so attack of hydroxylamine is directed towards the ester. They prepared hydroxamic acid 10 from ester 9 then cyclized with sulfuric acid to isoxazole 11, in route to 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP), a selective GABAa receptor agonist studied clinically for insomnia. 

Pentobarbital, marketed under the name Nembutal, is a barbiturate used i treating insomnia. It is synthesized in three steps from diethyl maionatt Show how you would synthesize the dialkylated intermediate, and then pre pose a mechanism for the reaction of that intermediate with urea to giv pentobarbital. 

A class of sedative/hypnotic type drug that exert their effects through the benzodiazepine binding site on GABAa receptors. The class consists both of molecules that contain the benzodiazepine moiety, for example diazepam, lorazepam and flunitrazepam, and the newer, non-benzodiazepine compounds such as zolpidem, zopiclone, indiplon and zaleplon. BzRAs are primarily used for the treatment of anxiety, insomnia and to elicit varying levels of sedation. The wide selection of compounds currently available affords the prescribing clinician extensive options in terms of relative efficacies and durations of action. 

Benzodiazepines are amongst the most frequently prescribed drugs they have well-established uses in the treatment of anxiety disorders (anxiolytics) and insomnia, preanaesthetic sedation, suppression of seizures, and muscle relaxation. 

The definition of desired therapeutic and side effects in the case of the benzodiazepines very much depends on the clinical problem in question. The sedative and hypnotic actions are desired effects in the treatment of insomnia, but undesired effects in the treatment of anxiety disorders. Effects that are usually undesired include daytime drowsiness, potentiation of the sedative effects of ethanol, and anterograde amnesia. They are mediated via the benzodiazepine site of GABAa receptors, since they can be antagonized with flumazenil. 

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