What are barbiturates?

History of Use

In 1864, German scientist Adolf Von Baeyer synthesized barbituric acid by condensing urea and malonic acid. The name reportedly came from a friend of the discoverer, or from the day of Saint Barbara. The acid itself did not induce any effect on the central nervous system. Subsequently, more than twenty-five hundred barbiturate compounds with pharmacological properties have been obtained.

In 1903, Emil Fischer and Joseph von Mering discovered an effective sedative, diethylbarbituric acid or barbital, which entered medicine under the trade name Veronal. Another barbiturate, phenobarbital (Luminal), was introduced in 1912.

By the mid-twentieth century, barbiturates became the most widely used
sedative-hypnotic medication and the most popular substances of abuse. Their lipid solubility rendered them quick to act and increased their hypnotic properties, but it decreased the duration of action. Collectively referred to as downers, barbiturates were taken alone or with ethanol to produce a feeling of relaxation and euphoria. In the United States, barbiturate abuse and addiction markedly increased in the 1950s and 1960s. The drugs became especially popular with actors and entertainers, as a way to cope with stress and uncertainty. (Elvis Presley chronically overused barbiturates, and an empty bottle of pentobarbital [Nembutal] was found on Marilyn Monroe’s nightstand after her death.) As safer drugs for people with sleep disorders became available, the use of barbiturates for this purpose declined.

The beginning of the twenty-first century, however, saw a modest increase in the popularity of barbiturates as substances of abuse. According to a national survey on drug use and health by the US Substance Abuse and Mental Health Services Administration, in the first years of this century an estimated 3.1 million people age twelve years and older had misused barbiturates. Deaths caused by overdose and suicide attempts using barbiturates still occur.

Barbiturates today are used clinically for anesthesia, pediatric sedation, status epilepticus treatment, and seizure prevention, and, in certain instances, for cases of traumatic brain injury. Some barbiturates are used to treat insomnia. Lesser known uses for barbiturates include treatment of essential hand tremor, cyclic vomiting, and hyperbilirubinemia in neonates. Among advocates of euthanasia and among those who commit suicide, barbiturates remain one of the most commonly employed drugs. Pentobarbital is the drug of choice for veterinary anesthesia and euthanasia.

Effects and Potential Risks

Barbiturates are classified according to their duration of action. The effects of ultra-short-acting drugs, such as Pentothal (used in surgical settings), last less than one hour. Short-acting barbiturates (such as Nembutal and Seconal) act for three to four hours and are more likely to be abused. The effects of intermediate-acting barbiturates (such as Amytal) last for six to eight hours, and those of long-acting barbiturates (such as Veronal and Luminal) last approximately twelve hours.

Like other sedative-hypnotic drugs, barbiturates produce relaxation or sleep. The mechanism underlying their effect is thought to be an enhancement of the neural inhibition induced by the neurotransmitter gamma-aminobutyric acid.

At regular doses, the effects of barbiturates vary depending on the user’s previous experience with the drug, the setting of use, and the mode of administration. A particular dose taken in the evening, for example, may induce sleep, whereas it may produce relaxed contentment, euphoria, and diminished motor skills during the day. Some users report sedation, fatigue, unpleasant drowsiness, nausea, vomiting, and diarrhea. A paradoxical state of excitement or rage also can occur. Users may experience a “hangover” phenomenon the day after drug administration. Hypersensitivity reactions, sensitivity to sunlight (photosensitivity), decreased sexual function, and impaired memory also have been reported. Tolerance to sedative and hypnotic effects develops after regular use.

Above-regular dosage of barbiturates induces a state of intoxication similar to that caused by ethanol. This resemblance, and tolerance development, may prompt some users to increase their drug intake. Mild intoxication is characterized by drunk-like behavior with slurred speech, unsteady gait, lack of coordination, abnormal eye movements, and an absence of alcohol odor.

The therapeutic dosage of any barbiturate is close to the lethal dose. Because of this narrow therapeutic window, severe intoxication or drug-induced death can easily occur. Intentional or accidental overdose results in extreme drowsiness, respiratory depression (with slow breathing), hypotension, hypothermia, renal failure, decreased reflexes, and, ultimately, coma and death. A person with suspected barbiturate overdose should be seen by a physician without delay.

Barbiturate use can cause both psychological and physical dependency and severe, even life-threatening, withdrawal
symptoms (such as anxiety, insomnia, tremors, increased heart rate, delirium, and seizures). Persons who want to stop taking this medication should do so under medical supervision only. Concomitant use of other sedative hypnotics, such as alcohol and benzodiazepines, leads to potentially dangerous synergistic effects.

Bibliography

Howard, Sherrel. "Benzodiazepines and Barbiturates." Drugs of Abuse: Pharmacology and Molecular Mechanisms. Ames: Wiley, 2014. 77–92. Print.

Lynton, Richard. “Barbiturates.” Haddad and Winchester’s Clinical Management of Poisoning and Drug Overdose. Eds. Michael W. Shannon, Stephen W. Borron, and Michael Burns. 4th ed. New York: Saunders, 2007. Print.

Marion, Nancy E., and Willard M. Oliver. Drugs in American Society: An Encyclopedia of History, Politics, Culture, and the Law. Santa Barbara: ABC-CLIO, 2014. Print.

Shannon, Joyce Brennfleck, ed. Drug Abuse Sourcebook. 3rd ed. Detroit: Omnigraphics, 2010. Print.

Weaver, Michael F. "Prescription Sedative Misuse and Abuse." Yale Journal of Biology and Medicine 88.3 (2015): 247–56. Print.