Patterns of Abuse - Disorders of Sedative–Hypnotics

Patterns of Abuse

Some sedative–hypnotics, such as the short-acting barbiturates, are primary drugs of abuse, that is, they are injected for the “rush” or are taken orally to produce a state of disinhibition similar to that achieved with alcohol. Sedative hypnotics may also be taken in combination with other primary intoxicants, such as alcohol or heroin, to intensify the desired subjective effects.

Drug addicts may also use sedative–hypnotics to self-medicate withdrawal of drugs such as heroin. When the avowed intent is to stop the use of drugs such as heroin, physicians may be lured into thinking that addicts’ self-administration of sedative– hypnotics is not “abuse” but rather a reasonable approximation of medical use. While on occasion this may be the case, often it is not. Addicts’ episodic attempts to stop using heroin by self-medicating opiate withdrawal symptoms with sedative–hypnotics without entering drug abuse treatment is rarely successful, and may result in the secondary development of sedative–hypnotic dependence.

Addicts may also use sedative–hypnotics to reduce un-pleasant side effects of stimulants, particularly cocaine or meth-amphetamine. Impairment of judgment and memory produced by the sedative–hypnotic in combination with wakefulness of a stimulant may result in unpredictable behavior.

Barbiturates

Injection of a barbiturate is associated with the usual infectious risk of injecting street drugs, but the barbiturates are particularly pernicious if inadvertently injected into an artery or if the solu-tion is injected or leaked from a vein or artery into tissue sur-rounding the vessel. Barbiturates are irritating to tissue, and the affected tissue becomes indurated and may abscess. In addition, barbiturate solution injected into an artery produces intense va-soconstriction and blockage of the arterioles, resulting in gan-grene of areas supplied by the artery.

Methaqualone

Methaqualone (Quaalude) was removed from the US market in 1984 because of its abuse. Subsequently, it has continued to be sold on the street-drug black market. Some tablets sold on the black market as Quaalude contain methaqualone, apparently diverted from countries where methaqualone is still available; others con-tain diazepam, phenobarbital, or another sedative–hypnotic.

Benzodiazepines

Benzodiazepines are often used or misused by addicts to self-medicate opiate withdrawal, to intensify the CNS effects of methadone, or to ameliorate the adverse effects of cocaine or methamphetamine.

The benzodiazepine, flunitrazepam (Rohypnol, Narcozep), is singled out for additional discussion on benzo-diazepine abuse because of the media and legislative attention it received during the 1990s, and because it is still widely abused in Europe and other areas of the world. Flunitrazepam, a potent benzodiazepine hypnotic, was never marketed in the USA but is widely available by prescription in many other countries in 1- or 2-mg oral dosage forms and for injection.

Flunitrazepam has many street names, including rophies, ropies, roopies, roofies, ruffes, rofinol, loops and wheels. Tablets of Rohypnol have the name of the manufacturer Roche engraved on them and a number indicating the milligram strength (either 1 or 2). Drug abusers usually prefer the 2-mg tablets, which are often called “Roche dos” or just “Roche” (usually pronounced “row-shay”). Although flunitrazepam is similar in many respects to other benzodiazepines in abuse potential flunitrazepam is among the benzodiazepines with highest abuse potential and has considerable appeal among heroin addicts.

In the mid-1990s Rohypnol achieved notoriety as the “date-rape drug”. Because of the media attention, considerable public debate ensued and the US Congress was prompted to pass legislation increasing penalties for rape when Rohypnol or other drugs were used to facilitate it. Subsequently, GHB (gamma-hydroxybutyric acid), which has some properties of a sedative– hypnotic, was also called a “date-rape drug.”

Flunitrazepam and other benzodiazepines have also been associated with deaths among opiate addicts taking buprenor-phine. Although buprenorphine alone or benzodiazepines alone are rarely fatal, the combination appears to increase the risk of overdose. Benzodiazepines and buprenorphine may have syner-gistic action in suppressing respiration.

Zolpidem

Zolpidem (Ambien) is an imidazopyridine hypnotic, chemically unrelated to the benzodiazepines. However, it binds to a subu-nit of the same GABA–benzodiazepine complex as the benzo-diazepines and its sedative effects are reversed by the benzodi-azepine antagonist flumazenil.

A few case reports of abuse suggest that some patients in-crease the dosage many times above what is prescribed and that zolpidem produces a withdrawal syndrome similar to that of other sedative–hypnotics (Aragona, 2000). The case histories also de-scribe significant tolerance to the sedative effects of zolpidem.

Zolpidem is rapidly absorbed and has a short half-life (2.2 hours). Its sedative effects are additive with alcohol. Like triazolam, zolpidem decreases brain metabolism of glucose. In addition to dependence, zolpidem has produced idiosyncratic psychotic reactions.

Zaleplon

Like zolpidem, this drug is chemically unrelated to the benzodi-azepines and binds to the omega-1 receptor, which is a subunit of the GABA-benzodiazepine receptor. Studies in volunteers with a history of drug abuse suggest abuse potential similar to tria-zolam. Peak plasma concentration occurs about 1 hour following oral ingestion. It is rapidly metabolized with a half-life of about 1 hour. Impairment of short-term memory may occur at dosages of 10 to 20 mg.