PART IV

Alcohol, the Barbiturates, the Tranquilizers, and Other Sedatives and Hypnotics

Though traditionally classified as a depressant, alcohol actually has a wide spectrum of apparently contradictory effects. At various dose levels and phases of the drinking cycle it may depress or stimulate, tranquilize or agitate. It may release inhibitions or put the drinker to sleep. Medically, alcohol was long prescribed as a tonic, a sedative, and a soporific, but its traditional role in medicine has now been taken over largely by the barbiturates, minor tranquilizers, and other sedatives and hypnotics.

Among the barbiturates are the "long-acting," such as phenobarbital, and the "short-acting," such as pentobarbital (Nembutal) and secobarbital (Seconal). As shown in Chapter 29, alcohol is very similar in effect to a short-acting barbiturate. ("Short-acting" means both that the drug's effects set in sooner and more abruptly and that they wear off sooner.)

The minor tranquilizers resemble the barbiturates in some respects and differ in others (see below); included among them are meprobamate (Miltown, Equanil), chlordiazepoxide (Librium), and diazepam (Valium). Also classified as sedatives and hypnotics are glutethimide (Doriden), ethchlorvynol (Placidyl), chloral hydrate, and others.

As used nonmedically in our society, alcohol is taken occasionally and in moderation with few undesirable side effects by the great majority of users. Its potential for harm, however–– mental and physical–– makes alcohol one of the most dangerous of all drugs to those who get drunk, to those who become addicted, and to those about them. An estimated 10 to 12 percent of all drinkers are alcoholics or "problem drinkers"; the number of alcoholics–– that is, alcohol addicts–– is estimated to total five million people. As with other addicting drugs, no user can foresee whether or when he will become addicted to alcohol.

Moderate use of long-acting barbiturates appears to carry less risk of addiction than the use of short-acting barbiturates or alcohol. The minor tranquilizers and some of the other sedatives and hypnotics also carry the hazard of addiction to lesser degrees. The use of virtually all of these drugs can produce symptoms like those of alcohol drunkenness–– nausea, incoordination, loss of inhibitions, violence, etc. The best-known withdrawal symptom is the "hangover," experienced at times by even moderate users of these drugs; convulsions, delirium tremens, and even death are among the risks shared by addicts following abrupt withdrawal.

Chapter 28.

The barbiturates for sleep and for sedation

Two of the most common afflictions for which human beings through the centuries have sought relief in drugs are anxiety and insomnia. During much of the nineteenth century, the opiates were prescribed to relieve those symptoms; but they were addicting. The bromide salts were also often used to induce sleep or "calm the nerves"; but they gradually lost popularity because of the risk of chronic bromide poisoning. Chloral hydrate and paraldehyde, both quite effective as sedatives and hypnotics (sleeping potions), have an objectionable taste and smell. Thus many conservative physicians, even after the turn of the century, continued to prescribe alcohol as the sedative and hypnotic of choice-a glass of wine in midmorning and midafternoon, perhaps, plus the traditional nightcap to induce sleep.

But a growing number of patients in need of sedatives and hypnotics were also ardent "teetotalers," who had "taken the pledge" of total abstinence from intoxicating beverages. Other patients didn't like the taste or smell of alcohol. Still others tended to take more alcohol than prescribed. Hence, despite the wide range of sedatives and hypnotics available at the end of the nineteenth century, the search for a better drug continued. It was in the course of this search that two German scientists, von Mering and Fischer, synthesized a new chemical called barbital, a derivative of barbituric acid.

Tested on both animals and humans, barbital seemed to have precisely the desired qualities. When a patient complaining of insomnia, for example, was given a capsule containing a moderate dose of barbital and told that it would facilitate sleep, the patient promptly fell asleep. Nervous, anxious patients given much smaller doses for daytime use and told the drug would "calm their nerves" found that it did. In 1903 barbital was introduced into general medical practice under the trade name Veronaland soon became very popular.

A second barbituric acid derivative, phenobarbital, was introduced under the trade name Luminal in 1912. More than 2,500 other barbiturates were subsequently synthesized, and some fifty of them were accepted for medical use–– as sedatives, as sleeping pills, and for other purposes. Long-acting barbiturates were developed for daytime sedation; short-acting barbiturates followed for prompt sedation and for inducing sleep without delay. Combinations were also introduced–– a short-acting barbiturate to put you to sleep combined with a long-acting one to keep you asleep.

These new drugs seemed to have notable advantages over their predecessors, including alcohol. They were odorless and tasteless. Precise quantities could be dispensed in capsule or tablet form. When barbiturates were taken as directed, in small doses for sedation and moderate doses for sleep, few side effects were noted. True, the short-acting barbiturates carried some risk of addiction, but there was no evidence that the long-acting barbiturates were addicting. After taking small daily doses for weeks or even months, a patient could discontinue without discomfort-much as most people can take a daily alcohol cocktail or nightcap without becoming addicted. It was hardly surprising, therefore, that the barbiturates became so popular among physicians and patients alike. By the end of the 1930s an estimated  billion grains were being taken each year in the United States alone.

The barbiturates remain exceedingly useful today. "Phenobarbital is one of our mainstays in the treatment of epilepsy and is almost irreplaceable for this purpose," a professor of internal medicine wrote in 1971. "Phenobarbital and . . . Librium [chlordiazepoxide, a tranquilizer] in small doses are extremely valuable in the management of high blood pressure, peptic ulcer, and anxiety. The majority of people who are given these drugs (it must be nearly 99.9 percent) never develop any dependence on them, so that in a relative sense they are quite safe." * Short-acting barbiturates, such as secobarbital and pentobarbital, he added, are another matter.

* Dr. Jerome H. Jaffe wrote (1970): "It has been found that 0.2 grams of pentobarbital [a short-acting barbiturates] per day can be ingested over many months without the development of any tolerance or physical dependence."

Footnotes
Chapter 28

1. Seth K. Sharpless, in  Goodman and Gilman, 4th ed. (1970), p. 98.

2. W. E. Hambourger, "A Study of the Promiscuous Use of the Barbiturates,"  JAMA, 108 (April 8, 1937): 1343.

3. Jerome H. Jaffe, in  Goodman and Gilman, 4th ed. (1970), p. 290.

4. Harris Isbell, personal communication, February 26, 1971.