|
|
Chapter 6 Depressants
Historically, people of almost every culture have used chemical agents to induce sleep, relieve stress, and allay anxiety. While alcohol is one of the oldest and most universal agents used for these purposes, hundreds of substances have been developed that produce central nervous system depression. These drugs have been referred to as downers, sedatives, hypnotics, minor tranquilizers, anxiolytics, and anti-anxiety medications. Unlike most other classes of drugs of abuse, depressants are rarely produced in clandestine laboratories. Generally, legitimate pharmaceutical products are diverted to the illicit market. A notable exception to this is a relatively recent drug of abuse, gamma hydroxybutyric acid (GHB). Choral hydrate and paraldehyde are two of the oldest pharmaceutical depressants still in use today. Other depressants, including gluthethimide, methaqualone, and meprobamate have been important players in the milieu of depressant use and abuse. However, two major groups of depressants have dominated the licit and illicit market for nearly a century, first barbiturates and now benzodiazepines. Barbiturates were very popular in the first half of the 20th century. In moderate amounts, these drugs produce a state of intoxication that is remarkably similar to alcohol intoxication. Symptoms include slurred speech, loss of motor coordination, and impaired judgment. Depending on the dose, frequency, and duration of use, one can rapidly develop tolerance, and physical and psychological dependence on barbiturates. With the development of tolerance, the margin of safety between the effective dose and the lethal dose becomes very narrow. That is, in order to obtain the same level of intoxication, the tolerant abuser may raise his or her dose to a level that may result in coma or death. Although many individuals have taken barbiturates therapeutically without harm, concern about the addiction potential of barbiturates and the ever-increasing number of fatalities associated with them led to the development of alternative medications. Today, less than 10 percent of all depressant prescriptions in the United States are for barbiturates. Benzodiazepines were first marketed in the 1960s. Touted as much safer depressants with far less addiction potential than barbiturates, today these drugs account for about one out of every five prescriptions for controlled substances. Although benzodiazepines produce significantly less respiratory depression than barbiturates, it is now recognized that benzodiazepines share many of the undesirable side effects of the barbiturates. A number of toxic central nervous system effects are seen with chronic high-dose benzodiazepine therapy, including headaches, irritability, confusion, memory impairment, and depression. The risk of developing over-sedation, dizziness, and confusion increases substantially with higher doses of benzodiazepines. Prolonged use can lead to physical dependence even at doses recommended for medical treatment. Unlike barbiturates, large doses of benzodiazepines are rarely fatal unless combined with other drugs or alcohol. Although primary abuse of benzodiazepines is well documented, abuse of these drugs usually occurs as part of a pattern of multiple drug abuse. For example, heroin or cocaine abusers will use benzodiazepines and other depressants to augment their "high" or alter the side effects associated with over-stimulation or narcotic withdrawal. There are marked similarities among the withdrawal symptoms seen with most drugs classified as depressants. In the mildest form, the withdrawal syndrome may produce insomnia and anxiety, usually the same symptoms that initiated the drug use. With a greater level of dependence, tremors and weakness are also present, and in its most severe form, the withdrawal syndrome can cause seizures and delirium. Unlike the withdrawal syndrome seen with most other drugs of abuse, withdrawal from depressants can be life threatening. BarbituratesBarbiturates 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 (Amytal®), 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. BenzodiazepinesThe 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, or treating 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, 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. FlunitrazepamFlunitrazepam (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. Gamma Hydroxybutyric Acid (GHB)In recent years, gamma hydroxybutyric acid (GHB) has emerged as a significant drug of abuse throughout the United States. Abusers of this drug fall into three major groups: (1) users take GHB for its intoxicant or euphoriant effects; (2) bodybuilders who abuse GHB for its alleged utility as an anabolic agent or as a sleep aid; and (3) individuals who use GHB as a weapon for sexual assault. These categories are not mutually exclusive and an abuser may use the drug illicitly to produce several effects. GHB is frequently taken with alcohol or other drugs that heighten its effects and is often found at bars, nightclubs, rave parties, and gyms. Teenagers and young adults who frequent these establishments are the primary users. Like flunitrazepam, GHB is often referred to as a "date-rape" drug. GHB involvement in rape cases is likely to be unreported or unsubstantiated because GHB is quickly eliminated from the body making detection in body fluids unlikely. Its fast onset of depressant effects may render the victim with little memory of the details of the attack. GHB produces a wide range of central nervous system effects, including dose-dependent drowsiness, dizziness, nausea, amnesia, visual hallucinations, hypotension, bradycardia, severe respiratory depression, and coma. The use of alcohol in combination with GHB greatly enhances its depressant effects. Overdose frequently requires emergency room care, and many GHB-related fatalities have been reported. Gamma butyrolactone (GBL) and 1,4-butanediol are GHB analogues that can be used as substitutes for GHB. When ingested, these analogues are converted to GHB and produce identical effects. GBL is also used in the clandestine production of GHB as an immediate precursor. Both GBL and 1,4-butanediol have been sold at health food stores and on various internet sites. The abuse of GHB began to seriously escalate in the mid-1990s. For example, in 1994, there were 55 emergency department episodes involving GHB reported in the Drug Abuse Warning Network (DAWN) system. By 2002, there were 3,330 emergency room episodes. DAWN data also indicated that most users were male, less than 25 years of age, and taking the drug orally for recreational use. GHB was placed in Schedule I of the CSA in March 2000. Gamma butyrolactone (GBL) was made a List I Chemical in February 2000. GHB has recently been approved as a medication (Xyrem®) for the treatment of cataplexy associated with some types of narcolepsy. This approved medication is in Schedule III of the CSA. ParaldehydeParaldehyde (Paral®) is a Schedule IV depressant used most frequently in hospital settings to treat delirium tremens associated with alcohol withdrawal. Many individuals who become addicted to paraldehyde have been initially exposed during treatment for alcoholism and, despite the disagreeable odor and taste, come to prefer it to alcohol. This drug is not used by injection because of tissue damage, and taken orally, it can be irritating to the throat and stomach. One of the signs of paraldehyde use is a strong, characteristic smell to the breath. Chloral HydrateThe oldest of the hypnotic (sleep inducing, depressants, chloral hydrate was first synthesized in 1832. Marketed as syrups or soft gelatin capsules, chloral hydrate takes effect in a relatively short time (30 minutes) and will induce sleep in about an hour. A solution of chloral hydrate and alcohol constituted the infamous "knockout drops" or "Mickey Finn." At therapeutic doses, chloral hydrate has little effect on respiration and blood pressure; however, a toxic dose produces severe respiratory depression and very low blood pressure. Chronic use is associated with liver damage and a severe withdrawal syndrome. Although some physicians consider chloral hydrate to be the drug of choice for sedation of children before diagnostic, dental, or medical procedures, its general use as a hypnotic has declined. Chloral hydrate, Noctec®, and other compounds, preparations, or mixtures containing choral hydrate are in Schedule IV of the CSA. Glutethimide and MethaqualoneGlutethimide (Doriden®) was introduced in 1954 and methaqualone (Quaalude®, Sopor®) in 1965 as safe barbiturate substitutes. Experience demonstrated, however, that their addiction liability and the severity of withdrawal symptoms were similar to those of barbiturates. By 1972, "luding out," taking methaqualone with wine, was a popular college pastime. Excessive use leads to tolerance, dependence, and withdrawal symptoms similar to those of barbiturates. In the United States, the marketing of methaqualone pharmaceutical products stopped in 1984, and methaqualone was transferred to Schedule I of the CSA. In 1991, glutethimide was transferred into Schedule II in response to an upsurge in the prevalence of diversion, abuse, and overdose deaths. Today, there is little medical use of glutethimide in the United States. MeprobamateMeprobamate was introduced as an anti-anxiety agent in 1955 and is prescribed primarily to treat anxiety, tension, and associated muscle spasms. More than 50 tons are distributed annually in the United States under its generic name and brand names such as Miltown® and Equanil®. Its onset and duration of action are similar to the intermediate-acting barbiturates; however, therapeutic doses of meprobamate produce less sedation and toxicity than barbiturates. Excessive use can result in psychological and physical dependence. Carisoprodol (Soma®), a skeletal muscle relaxant, is metabolized to meprobamate. This conversion may account for some of the properties associated with carisoprodol and likely contributes to its abuse. Newly Marketed DrugsZolpidem (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.
Depressants Identification To Top | Contents | Controlled
Substances Act | U.S. Chemical
Control
|
