Sedative-hypnotic drugs

Drugs that reduce tension and calm anxiety at low doses and that produce drowsiness and facilitate the onset of sleep at higher doses are called sedative-hypnotics. Because this state of sleep is one from which a patient can normally be aroused, its production was once attributed to " hypnotic" actions, but the sleep that is induced is actually quite natural. Still higher doses of some sedative-hypnotics can produce deep unconsciousness sufficient to make them useful as general anesthetics.

The dose levels at which calm, sleep, or anesthesia are induced depend on the drug classes and their mechanisms of action. Since similar effects can be obtained with other drugs, such as analgesic opiates or antianxiety beazodiazepines, the principal characteristic of primary sedative-hypnotics is their selective ability to induce these actions without affecting mood or sensitivity to pain.

Alcoholic beverages and alcoholic extracts of opium were traditionally used as sedative-hypnotics, but the first substance introduced specifically as a sedative and as a hypnotic was a liquid solution of bromide salts. In 1869 chloral hydrate became the first synthetic organic molecule to be employed specifically for its sedative-hypnotic effect, and it was followed by several others, notably paraldehyde. (Chloral hydrate was used notoriously as " knock-out" drops.) Barbiturates, with their more complex organic ring structure, were introduced in the early 1900s, and hundreds of barbiturate analogues were then synthesized with varying potencies and durations of action. Potent analogues of barbiturates have been used to induce surgical anesthesia and to reduce voluntary inhibition during psychiatric interviews (for which they have sometimes been dubbed " truth serums"). Most of the barbiturates were discontinued after the development in the 1950s of the benzodiazepines, many of which exhibit the ideal properties of a short-acting, intense facilitator of natural sleep, with a reduced risk of adverse effects.

The means by which alcohol depresses brain function and produces sleep is not clear, however, it is certain that intoxicating doses of alcohol greatly incapacitate the processing of information, reduce reaction times, and depress skilled locomotor behaviours. No single neurotransmitter system has been definitively shown to be the locus of these behavioral effects, and multiple mechanisms may be involved. Barbiturates and benzodiazepines have similar but not identical actions at the behavioral and cellular level to those of alcohol. The benzodiazepines act on the inhibitory sites at which gamma-aminobutyric acid (GABA) is the neurotransmitter.

In certain persons low doses of alcohol, barbiturates, and some benzodiazepines produce transiently enhanced mood or euphoria, along with antianxiety effects. These behavioral effects can lead to abuse of these substances and to dependence upon them with prolonged use. High doses can depress critical centres in me brain stem for the regulation of cardiovascular and respiratory function.

When sedatives are taken frequently as sleeping tablets, tolerance and a reduction in effectiveness occurs. Despite popular beliefs to the contrary, alcoholic beverages in particular are only of modest benefit to induce sleep. On frequent exposure to alcohol the nervous system adapts to the drug, and this results in early morning awakening. Barbiturates can be selected to provide both early onset of sleep and a prolongation of sleep. Analysis of electroencephalographic patterns during barbiturate-induced sleep, however, shows that there is more disruption of sleep. There have been reports that some benzodiazepines used as sleep inducers produce less disruption of the sleep phases, a property that makes them especially useful for persons with sleep disturbances.