Barbiturates are a class of sedative-hypnotic drugs that reduce activity in the central nervous system. Derived from barbituric acid, they slow down brain activity, producing effects from mild sedation to general anesthesia. First synthesized in 1864, barbiturates gained widespread medical use in the early 20th century for their calming properties and effectiveness in managing sleep and neurological disorders. Despite their historical significance, their widespread use has declined due to concerns about dependence and overdose.
How Barbiturates Affect the Body
Barbiturates exert their effects by enhancing the activity of gamma-aminobutyric acid (GABA), the brain’s primary inhibitory neurotransmitter. They bind to specific sites on the GABA-A receptor, prolonging the opening of chloride ion channels within neurons. This allows more negatively charged chloride ions to enter the cell, making the neuron less excitable, a process known as hyperpolarization. This reduces overall brain activity, leading to central nervous system depression, which causes sedation, reduced anxiety, and muscle relaxation. At higher doses, barbiturates can also inhibit excitatory neurotransmitters like glutamate, contributing to their potent depressant actions.
Medical Applications
Historically, barbiturates were widely used for a range of medical conditions due to their central nervous system depressant properties. They served as sedatives to calm patients, hypnotics to induce sleep, and anticonvulsants to control seizures, such as with phenobarbital. These medications were also employed as anesthetics, with ultra-short-acting barbiturates like thiopental used to induce general anesthesia.
Even with their decline in general use, some barbiturates retain specific medical applications. Phenobarbital continues to be used as a treatment for certain types of epilepsy, particularly in low-resource countries where it is a cost-effective option. In emergency situations, intravenous barbiturates may be used to induce a coma to manage severe conditions like increased intracranial pressure or refractory status epilepticus. Butalbital, often combined with acetaminophen and caffeine, is also approved for relieving tension headaches.
Dangers and Overdose
Barbiturate use carries significant risks, including dependence and addiction. Tolerance can rapidly develop, meaning individuals require progressively higher doses to achieve the same effects, which increases the risk of dependence. Both physical and psychological dependence can occur with regular use, impacting a person’s ability to function without the drug.
Abruptly stopping barbiturate use can lead to severe and potentially life-threatening withdrawal symptoms. These symptoms can include anxiety, restlessness, nausea, vomiting, insomnia, and tremors, typically appearing within 6 to 36 hours after the last dose. In more severe cases, withdrawal can manifest as hallucinations, delirium, high fevers, and seizures, requiring immediate medical attention.
An overdose of barbiturates can be fatal, primarily due to severe respiratory depression where breathing becomes slow, shallow, or stops. Other signs of overdose include extreme drowsiness, confusion, slurred speech, impaired coordination, a slow heart rate, low blood pressure, and decreased body temperature. An overdose can progress to a deep coma and, without prompt intervention, lead to respiratory arrest and death.
Combining barbiturates with other central nervous system depressants, such as alcohol or opioids, greatly increases the danger. These combinations amplify the sedative effects, intensifying respiratory depression, and significantly increasing the risk of coma and fatal outcomes. Even at lower doses, mixing these substances can lead to severe complications.
Why Their Use Declined
The widespread prescribing of barbiturates significantly declined due to the introduction of safer alternatives. Benzodiazepines, such as Valium and Xanax, emerged as a preferred choice for treating anxiety and insomnia starting in the 1950s and 1960s. Benzodiazepines also enhance GABA activity but provide a wider therapeutic index, meaning a larger difference between an effective dose and a toxic dose. This makes accidental overdose much less likely compared to barbiturates.
While both drug classes have the potential for dependence, barbiturates are considered to have a higher potential for addiction and more severe withdrawal symptoms. The narrow therapeutic range of barbiturates, where small increases in dosage can lead to dangerous or fatal effects, contributed to their reduced use. This, coupled with their high potential for abuse and severe dependence, led to a significant shift in medical practice.