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Thursday, May 19, 2011

Drug Treatment of Insomnia

Drug Treatment of Insomnia
Apart from the benzodiazepines, the sedative hypnotics are a group of drugs that depress the brain in a relatively non-selective manner. This results in a progressive change from drowsiness (sedation), sleep (hypnosis) to loss of consciousness, surgical anaesthesia, coma and finally cardiovascular and respiratory collapse and death. The central nervous system (CNS)depressant drugs include general anaesthetics, barbiturates and alcohols, including ethanol. Before the advent of the benzodiazepines, barbiturates in low doses were widely used as anxiolytics. A sedative drug is one that decreases CNS activity, moderates excitement and generally calms then individual, whereas a hypnotic produces drowsiness and facilitates the onset and maintenance of sleep from which the individual may be easily aroused. Historically the first sedative hypnotics to be introduced were the bromides in the mid 19th century, shortly followed by chloral hydrate, araldehyde and urethane. It was not until the early years of this century
that the first barbiturate, sodium barbitone, was developed and this was shortly followed by over 50 analogues, all with essentially similar pharmacological properties. The major breakthrough in the development of selective, relatively non-toxic sedative hypnotics followed the introduction of chlordiazepoxide in 1961. Most of the benzodiazepines in current use have been selected for their high anxiolytic potency relative to their central depressant effects. Because of their considerable safety, the benzodiazepines have now largely replaced the barbiturates and the alcohols, such as chloral hydrate and trichloroethanol, as the drugs of choice in the treatment of insomnia. The hypnotics are some of the most widely used drugs, over 15 million prescriptions being given for this group of drugs in Britain in 1985; the number of prescriptions for hypnotics has remained fairly constant over the last decade despite the reduction in anxiolytic prescriptions by about 50% over this same period. This situation is hard to reconcile with the fact that all benzodiazepines in current use have hypnotic properties if given in slightly higher therapeutic doses. This implies that what determines their use as anxiolytics, for day-time administration, or hypnotics, for night-time use, is largely a question of dose and marketing. As discussed in considerable detail elsewhere (see p. 213), there is a metabolic interrelationship between the commonly used 1,4-benzodiazepines and their mode of action is similar. It is of interest that the hypnotic benzodiazepines have received little media attention, in contrast to the anxiolytics of the same class, regarding their possible dependence-forming effects.

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