DEA, Drug Information, Other Drugs: B

Barbiturates
Barbiturates were first introduced for medical use in the early 1900s. More than 2,500 barbiturates have been synthesized, and at the height of their popularity, about 50 were marketed for human use. Today, about a dozen are in medical use. Barbiturates produce a wide spectrum of central nervous system depression, from mild sedation to coma, and have been used as sedatives, hypnotics, anesthetics, and anticonvulsants. The primary differences among many of these products are how fast they produce an effect and how long those effects last. Barbiturates are classified as ultrashort, short, intermediate, and long-acting.

The ultrashort-acting barbiturates produce anesthesia within about one minute after intravenous administration. Those in current medical use are the Schedule IV drug methohexital (Brevital®), and the Schedule III drugs thiamyl (Surital®) and thiopental (Pentothal®). Barbiturate abusers prefer the Schedule II short-acting and intermediate-acting barbiturates that include amobarbital (Amyta®), pentobarbital (Nembutal®), secobarbital (Seconal®), and Tuinal (an amobarbital/secobarbital combination product). Other short and intermediate-acting barbiturates are in Schedule III and include butalbital (Fiorina®), butabarbital (Butisol®), talbutal (Lotusate®), and aprobarbital (Alurate®). After oral administration, the onset of action is from 15 to 40 minutes, and the effects last up to six hours. These drugs are primarily used for insomnia and preoperative sedation. Veterinarians use pentobarbital for anesthesia and euthanasia.

Long-acting barbiturates include phenobarbital (Luminal®) and mephobarbital (Mebaral®), both of which are in Schedule IV. Effects of these drugs are realized in about one hour and last for about 12 hours, and are used primarily for daytime sedation and the treatment of seizure disorders.

Benzodiazepines
The benzodiazepine family of depressants is used therapeutically to produce sedation, induce sleep, relieve anxiety and muscle spasms, and to prevent seizures. In general, benzodiazepines act as hypnotics in high doses, anxiolytics in moderate doses, and sedatives in low doses. Of the drugs marketed in the United States that affect central nervous system function, benzodiazepines are among the most widely prescribed medications. Fifteen members of this group are presently marketed in the United States, and about 20 additional benzodiazepines are marketed in other countries. Benzodiazepines are controlled in Schedule IV of the CSA.

Short-acting benzodiazepines are generally used for patients with sleep-onset insomnia (difficulty falling asleep) without daytime anxiety. Shorter-acting benzodiazepines used to manage insomnia include estazolam (ProSom®), flurazepam (Dalmane®), temazepam (Restoril®), and triazolam (Halcion®). Midazolam (Versed®), a short-acting benzodiazepine, is utilized for sedation, anxiety, and amnesia in critical care settings and prior to anesthesia. It is available in the United States as an injectable preparation and as a syrup (primarily for pediatric patients).

Benzodiazepines with a longer duration of action are utilized to treat insomnia in patients with daytime anxiety. These benzodiazepines include alprazolam (Xanax®), chlordiazepoxide (librium®), clorazepate (Tranxene®), diazepam (Valium®), halazepam (Paxipam®), lorzepam (Ativan®), oxazepam (Serax®), prazepam (Centrax®), and quazepam (Doral®). Clonazepam (Klonopin®), diazepam, and clorazepate are also used as anticonvulsants.

Benzodiazepines are classified in the CSA as depressants. Repeated use of large doses or; in some cases, daily use of therapeutic doses of benzodiazepines is associated with amnesia, hostility, irritability, and vivid or disturbing dreams, as well as tolerance and physical dependence. The withdrawal syndrome is similar to that of alcohol and may require hospitalization. Abrupt cessation of benzodiazepines is not recommended and tapering-down the dose eliminates many of the unpleasant symptoms.

Given the millions of prescriptions written for benzodiazepines (about 100 million in 1999), relatively few individuals increase their dose on their own initiative or engage in drug-seeking behavior. Those individuals who do abuse benzodiazepines often maintain their drug supply by getting prescriptions from several doctors, forging prescriptions, or buying diverted pharmaceutical products on the illicit market. Abuse is frequently associated with adolescents and young adults who take benzodiazepines to obtain a "high." This intoxicated state results in reduced inhibition and impaired judgment. Concurrent use of alcohol or other depressant; with benzodiazepines can be life threatening. Abuse of benzodiazepines is particularly high among heroin and cocaine abusers. A large percentage of people entering treatment for narcotic or cocaine addiction also report abusing benzodiazepines. Alprazolam and diazepam are the two most frequently encountered benzodiazepines on the illicit market.

Flunitrazepam (Rohypnol®) is a benzodiazepine that is not manufactured or legally marketed in the United States, but is smuggled in by traffickers. In the mid-1990s, flunitrazepam was extensively trafficked in Florida and Texas. Known as "rophies," "roofies," and "roach," flunitrazepam gained popularity among younger individuals as a "party" drug. It has also been utilized as a "date rape" drug. In this context, flunitrazepam is placed in the alcoholic drink of an unsuspecting victim to incapacitate them and prevent resistance from sexual assault. The victim is frequently unaware of what has happened to them and often does not report the incident to authorities. A number of actions by the manufacturer of this drug and by government agencies have resulted in reducing the availability and abuse of flunitrazepam in the United States.

Newly Marked Drugs

Zolpidem (Ambien®) and zaleplon (Sonata®) are two relatively new, benzodiazepine-like CNS depressants that have been approved for the short-term treatment of insomnia. Both of these drugs share many of the same properties as the benzodiazepines and are in Schedule IV of the CSA.

Buprenorphine
This drug is a semi-synthetic narcotic derived from thebaine and is currently being investigated for the treatment of narcotic addiction. Like methadone and LAAM, buprenorphine is potent (30 to 50 times the analgesic potency of morphine), has a long duration of action, and does not need to be injected. The buprenorphine products under development are sublingual tablets. Unlike the other treatment drugs, buprenorphine produces far less respiratory depression and is thought to be safer in overdose. Buprenorphine is currently available in the United States as an injectable Schedule III narcotic analgesic (Buprenex®) for human and veterinary use.

Butorphanol
While butorphanol can be made from thebaine, it is usually manufactured synthetically. It was initially available in injectable formulations for human (Stadol®) and veterinary (Torbugesic® and Torbutrol®) use. More recently, a nasal spray (Stadol NS®) became available, and significant diversion and abuse of this product led to the 1997 control of butorphanol in Schedule IV of the CSA. Butorphanol is a clear example of a drug gaining favor as a drug of abuse only after it became available in a form that facilitated its mode of administration (nasal spray v. injection).