Pharmacology insomnia

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. 

Walsh JK, Schweitzer PK. Ten-year trends in the pharmacological treatment of insomnia. Sleep 1999 22 371-375. 

BZD effects on human sleep are well characterized (Mendelson 2001) (a) decreased sleep latency (b) decreased awakenings (c) increased stage II sleep (d) suppressed stage III and IV sleep (e) increased REM sleep latency (f) initial reduction and fragmentation of REM sleep. Discontinuation of BZD treatment after three to four weeks produces a rebound of REM sleep as well as slow-wave sleep (SWS). BZD and non-BZD compounds are pharmacological agents indicated in the management of anxiety, insomnia, and other conditions in which anxiety is the main symptom, and should be considered as symptomatic medications (Nishino et al. 2004). 

Chronic insomnia calls for careful assessment for a medical cause, non-pharmacologic treatment, and careful use of sedative-hypnotics (intermittently to prevent tolerance and dependence). 

Systemic effects of methamphetamine are similar to those of cocaine. Inhalation or IV injection results in an intense rush that lasts a few minutes. Methamphetamine has a longer duration of effect than cocaine. Pharmacologic effects include increased wakefulness, increased physical activity, decreased appetite, increased respiration, hyperthermia, euphoria, irritability, insomnia, confusion, tremors, anxiety, paranoia, aggressiveness, convulsions, increased heart rate and blood pressure, stroke, and death. 

Indeed, a pharmacological approach is the first line treatment in transient insomnia. Meanwhile, a behavioral or non-pharmacological approach is the recommended therapy for chronic insomnia, together with intermittent aid of pharmacological treatment [3]. 

The use of benzodiazepines should be avoided. There are other safer pharmacological alternatives. Benzodiazepine withdrawal may play a role in the occurrence of delirium in the elderly. Other withdrawal symptoms include tremor, agitation, insomnia and seizures (Turnheim 2003). Thus, when there is long-term use of benzodiazepines abrupt discontinuation might be difficult. Discontinuation should however not be withheld but done slowly and step-wise. If benzodiazepines are used in the elderly, short-acting benzodiazepines such as oxazepam are preferred, because they do not accumulate in the elderly to the same extent (Kompoliti and Goetz 1998). If short-acting benzodiazepines are used they should be prescribed with caution, at low doses, and for short periods. As with all pharmacotherapy the effects should be evaluated. Benzodiazepines are sometimes used as a behavioural control. One should always ask if this use is for the benefit of staff or the benefit of the patient. The presence of staff may be sufficient for behavioural control. 

Walsh JK. Pharmacologic management of insomnia. J Clin Psychiatry 2004 65(Supplement 16) 41-45. 

Benzodiazepines have similar pharmacological properties and are used in anxiety and insomnia. The choice of which benzodiazepine to use usually lies with the pharmacodynamic and pharmacokinetic properties, which vary across the class. For example, diazepam, flurazepam and nitrazepam have a prolonged duration of action whereas lorazepam and temazepam have a shorter duration of action. 

GHB was hrst synthesized in the laboratory by the French biochemist Henri Lahorit (1914-1995) in 1961. In the succeeding four decades, extensive research has been conducted on the pharmacological uses and effects of GHB. In general, those studies appear to suggest that GHB has some valuable applications in the medical sciences. It functions well as an anesthetic with apparently few or no serious side effects. Based on this research, the drug has been adopted in many parts of the world for use as a general anesthetic, a treatment for narcolepsy and insomnia, a treatment for alcoholism, and an aid in childbirth. 

As with all of the examined drugs in this chapter, methyprylon is intended for treating insomnia. The pharmacological effects of methyprylon are similar to those of barbiturates. However, barbiturates are beginning to give way, thanks to the introduction of benzodiazepines into medical practice. Synonyms for this drug are noctar, noludar, and others. 

Zolpidem (1) is an effective hypnotic agent indicated for the short-term treatment of insomnia. Zolpidem interacts with the GABAa receptor, and its pharmacological effect is blocked by the benzodiazepine-receptor antagonist fiumazenil (Sanger and Depoortere, 1998). Zolpidem displaces benzodiazepines more selectively from the cerebellum than the hippocampus or spinal cord, consistent with preferential interaction with the ajGABAA receptor subtype (sometimes referred to as the benzodiazepine coi receptor). Studies... 

If the balance between excitatory and inhibitory activity is shifted pharmacologically in favour of GABAergic transmission, then anxiolysis, sedation, amnesia and ataxia arise. On the other hand, an attenuation of the GABAergic system results in arousal, anxiety, restlessness, insomnia, exaggerated reactivity and even seizures. These pharmacological manifestations point to the contribution of inhibitory neurotransmission to the pathophysiology of brain disorders. A GABAergic deficit is particularly apparent in anx-... 

Before the introduction of the benzodiazepines, a number of drugs from different chemical and pharmacological classes were used in the treatment of anxiety and insomnia. However, these drugs are more toxic and produce more serious side effects than do the benzodiazepines. Many also have signihcant abuse potential. Consequently, most of these compounds are no longer widely used. These drugs include the barbiturates (e.g., pentobarbital, amobarbital), carbamates (e.g., meprobamate), piperidinediones (e.g., glutethimide), and alcohols (e.g., ethchlorvynol). 

In the treatment of children and adolescents with anxiety disorders clinicians have a wide variety of pharmacologic options beyond the antidepressants (Shader and Greenblatt, 1995 Lydiard et ah, 1996 Riddle et ah, 1999). The benzodiazepines (BZs), with their favorable safety profile and quick onset of action, are attractive alternatives for the treatment of acute anxiety. While the clinical effectiveness of buspirone has not been proven in children, buspirone is used alone or in combination with other drugs in the treatment of anxiety disorders. The antihistamines are often used to treat insomnia and may reduce acute mild agitation. Zolpidem (Ambien) is occasionally used for its sedative properties. This chapter reviews the structure, proposed mechanisms of action, pharmacodynamic principles, and pharmacokinetic principles of these drugs. 

Pharmacodynamics, antipsychotics also differ in their pharmacodynamics, i.e. their pharmacological and clinical profiles of action. A rough distinction is made between highly sedative, hypnotic antipsychotics (e.g. clopenthixol, levomepromazine) and other products with weaker initial sedative action (e.g. fluphenazine and haloperidol). Sedative antipsychotics are prescribed for states of major unrest, often combined with insomnia, whereas the less sedative antipsychotics are preferred for patients suffering from delusions and hallucinations but in whom heavy sedation during daytime is undesirable. 

CNS The caffeine and theophylline are pharmacologically CNS stimulants and produce alertness and cortical arousal, but in higher doses causes restlessness, nervousness and insomnia. 

As with most data for reboxetine, this information primarily comes from summary papers rather than primary sources (473, 474). With this caveat, the adverse-effect profile of reboxetine is consistent with its pharmacology as an NSRI. Thus, it is similar to that of desipramine and maprotiline but without the risk of serious CNS (i.e., seizures, delirium) or cardiac (i.e., conduction disturbances) toxicity. The most common adverse effects of reboxetine are dry mouth, constipation, urinary hesitancy, increased sweating, insomnia, tachycardia, and vertigo. Whereas the first three adverse effects are commonly called anticholinergic, they are well known to occur with sympathomimetic drugs as well. In other words, these effects can be either the result of decreased cholinergic tone or increased sympathetic tone, although they tend to be more severe with the former than the latter. In contrast to TCAs, reboxetine does not directly interfere with intracardiac conduction. The tachycardia produced by reboxetine, however, can be associated with occasional atrial or ventricular ectopic beats in elderly patients. 

---