Sedative-hypnotics are drugs that have either a mild calming (sedative) or a sleep-producing (hypnotic) effect upon the central
nervous system (CNS), depending on the size of the dose administered. Agents in this category include the
barbiturates, chloral hydrate, paraldehyde, ethyl alcohol, bromides, antihistamines, glutethimide (Doriden), methyprylon (Noludar), and methaqualone (Quaalude). Methaqualone, however, is no longer manufactured in the United States because of the problems of abuse to which it gave rise. Other sedatives include such antianxiety drugs and muscle relaxants as chlordiazepoxide hydrochloride (Librium) and diazepam (Valium) and the benzodiazepine-derived hypnotics flurazepam (Dalmane), temazepam (Restoril), and triazolam (Halcion).
HISTORICAL DEVELOPMENT
Ethyl alcohol has been in use since the dawn of history as a nonmedicinal sedative; the bromides, on the other hand, were introduced into medicine in 1837 and appear to be the earliest prescribed sedatives. Now essentially obsolete, the bromides were popular for many years as anticonvulsants, that is, drugs used to treat epileptic convulsions. Barbituric acid was synthesized in 1864, and chloral hydrate, still widely used as a sedative-hypnotic, was introduced in 1869. Paraldehyde, introduced in 1882, has long been used to treat acute alcoholism, but the more recent drugs Librium and Valium are more effective and less toxic.
Phenobarbital, introduced in 1912 under the trade name Luminal, is still in use as a sedative-hypnotic and is a drug of choice for the management of epilepsy. The antihistamines and meprobamate are now considered sedative-hypnotic drugs.
Anxiety
The unpleasant emotional state of anxiety usually may be controlled by phenobarbital or by such currently popular antianxiety drugs as Librium or Valium and others, at doses that produce no outward signs or symptoms of sedation. If properly prescribed, such as for certain psychiatric conditions that have anxiety as a symptom, the antianxiety drugs have a rational place in therapy. Such drugs, however, are frequently overused and may be counterproductive or even hazardous in simple anxiety states, in which a little anxiety may actually be useful. Students studying for an examination or drivers who need to be alert to potential traffic accidents, for example, must be careful not to overuse the drugs.
Sleep
The barbiturates appear to induce sleep through a selective depressant action upon that portion of the CNS that is associated with wakefulness: the Reticular Activating System (RAS) (see sleep). Although sleep induced by barbiturates closely resembles normal sleep, proportionately less time is spent in the dreaming, rapid-eye movement (REM) phase during barbiturate sleep, which some authorities consider undesirable. Following withdrawal of the drug, REM phases increase, as do irregularities in sleep patterns associated with nightmares. Librium and Valium alter REM sleep to a lesser extent.
Barbiturates and hypnotics such as triazolam are effective against simple insomnia, although triazolam has been banned in Great Britain because of the severe side effects reported by some users. The kind of insomnia that accompanies deep depression, however, is a symptom of a severe psychiatric disturbance and is relieved only by controlling the depression. For this reason one of the tricyclic antidepressants, amitriptyline (Elavil), may be required instead of any hypnotic.
Anticonvulsant Activity
A drug of choice for petit mal epilepsy, phenobarbital has highly selective activity on the CNS that is not shared by other barbiturates. This activity is not related to sedation, because nonsedative doses are anticonvulsant; CNS stimulants, such as amphetamine, may counteract the sedative effects of phenobarbital without abolishing its anticonvulsant capability.
Narcoanalysis
Several barbituratesÑnotably amobarbital, phenobarbital, and thiopentalÑhave been used as aids in psychiatric diagnosis. In proper dosage, inhibitions are removed and communication of repressed thoughts is facilitated. Such drugs are often used as "truth serum."
CAUTIONS
Automatism
Automatism is a state of drug-induced confusion and often is a cause of accidental poisoning by barbiturates and other sedative-hypnotics, particularly in the elderly. In this state the patient forgets that the medication has been taken and therefore ingests more; the process is repeated until toxic quantities of drug have been ingested.
Tolerance and Addiction
Tolerance to the barbiturates appears to involve one of two mechanisms: enzyme induction and adaptation. The drug may stimulate the production or activity of liver enzymes that are normally responsible for the drug's metabolic breakdown or can allow the tissues to adapt to the drug in some unexplained manner. In either case the body requires greater amounts of the drug in order to produce the desired effect.
In addiction, withdrawal of the drug following repeated use may result in a syndrome often characterized by delirium and convulsions, compulsion to take the drug, and mental deterioration. Addiction to the barbiturates renders the addict incapable of functioning in society and may be a more serious addiction than that produced by narcotics. Tragically, physicians have overprescribed barbiturates, which has resulted in an alarming increase in the number of barbiturate addicts.