Pass A Drug Test for Benzodiazepine Drugs

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

Benzodiazepines are generally classified as minor tranquilizers useful in the management of anxiety. Benzodiazepines include drugs such as diazepam (Valium®), chlordiazepoxide (Librium®), oxazepam (Serax®), lorazepam (Ativan®), alprazolam (Xanax®), clonazepam (Clonopin®), and others. Some, such as flurazepam (Dalmane®), alprazolam (Xanax®) and triazolam (Halcion®), are used as sleeping aids. They have generally replaced barbiturates in the induction of sleep and sedation. Clonazepam (Clonopin®) is useful in the treatment of epilepsy. Many common benzodiazepines are detected in urine by their metabolites oxazepam and nordiazepam. Benzodiazepines are prescription drugs and occasionally sold on the illicit market. They are widely prescribed and relatively free of dangerous acute toxic overdose effects. Some illicit fake methaqualone (Quaalude) from Mexico actually contains large doses of diazepam.

Pharmacological Effects

Benzodiazepines have varied effects and as many as 2,000 have been synthesized. They act selectively on the polysynaptic pathways throughout the central nervous system. Benzodiazepine receptor sites have been identified in the brain. The mechanism of action may be related to the metabolism of gamma aminobutyric acid (GABA). Benzodiazepines undergo extensive biotransformation (metabolism) and identification of the particular benzodiazepine is best performed on blood following a positive urine screening.

Laboratory Methods
The immunoassays (EIA) are utilized to detect benzodiazepines in urine. All positives are confirmed by GC/MS.

Cutoff and Detection Post Dose

Cutoff by immunoassay is 200 ng/ml for benzodiazepine metabolites. This level is sufficient to detect the most common benzodiazepines for 48-72 hours post single dose and as long as a week post dose under some circumstances. GC/MS cutoff levels for the various benzodiazepine metabolites is 100 ng/ml.

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