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Benzodiazepine

The benzodiazepines are a class of drugs with hypnotic, anxiolytic, anticonvulsant, amnestic and muscle relaxant properties. Benzodiazepines are often used for short-term relief of severe, disabling anxiety or insomnia. Long-term use can be problematic due to the development of tolerance and dependency. They are believed to act on the GABA receptor GABAA, the activation of which dampens higher neuronal activity. They began to be widely prescribed for stress-related ailments in the 1960s and 1970s.

Members

Benzodiazepines are commonly divided into three groups. Short-acting compounds act for less than six hours and have few residual effects if taken before bedtime, but rebound insomnia may occur and they might cause wake-time anxiety. Intermediate-acting compounds have an effect for 6-10 hours, may have mild residual effects but rebound insomnia is not common. Long-acting compounds have strong sedative effects that persist. Accumulation may occur.

The various benzodiazepines are listed in order of the shortest acting to the longest acting (by the approximate elimination half-life of the drug), however this time may greatly vary between persons.

* triazolam (Halcion®) - 2 hours

* midazolam (Versed®, Hypnovel®) - 3 hours (1.8-6 hours)

* oxazepam (Serax®) - 4-15 hours

* chlordiazepoxide (Librium®) - 5-25 hours

* alprazolam (Xanax®) - 6-12 hours

* temazepam (Restoril®) 8-20 hours

* lorazepam (Ativan®) 10-20 hours

* bromazepam (Lexotan®) 10-20 hours

* estazolam (ProSom®) 10-24 hours

* flunitrazepam (Rohypnol®) 18-26 hours. Withdrawn from the market; considered a "date-rape drug"

* clonazepam (Klonopin®, Rivotril®) 18-50 hours

* quazepam (Doral®) 25-100 hours

* clorazepate (Tranxene®) 36-100 hours

* medazepam (Nobrium®) 36-150 hours

* prazepam (Centrax®) 36-200 hours

* diazepam (Valium®) 36-200 hours

* flurazepam (Dalmane®) 40-250 hours

The following are not benzodiazepines, but have similar effects:

* zolpidem (Ambien®)

* zaleplon (Sonata®)

* meprobamate (Miltown®)

Uses

Benzodiazepines are used in many situations, depending on their pharmacokinetics. The main use of the short-acting benzodiazepines is in insomnia, while anxiety responds better to medium- to long-acting substances that will be required all day. Midazolam is mostly used as an injection for sedation before surgical procedures.

Side-effects

Benzodiazepines have replaced the barbiturates because they have a lower abuse potential and relatively lower adverse reactions and interactions. Still, drowsiness, ataxia, confusion, vertigo, impaired judgement, and a number of other effects are common. Benzodiazepines may impair the ability to drive vehicles and to operate machinery. The impairment is worsened by consumption of alcohol, because both act as narcotics on the central nervous system. The effects of long-acting benzodiazepines can also linger over to the following day.

Abuse and dependence

Benzodiazepines induce physical dependence and are potentially addictive. An abrupt discontinuation of benzodiazepine input may result in convulsions, confusion, psychosis, or effects similar to delirium tremens.

Hence, every person on long-term or high dosage of any benzodiazepine should be carefully weaned off the drug.

Onset of the withdrawal syndrome might be delayed, and it might be delayed longer than the barbiturate withdrawal syndrome. Even when withdrawal from short-acting benzodiazepines often presents early.

The benzodiazepine withdrawal syndrome is characterized by:

* insomnia

* anxiety

* tremor

* perspiration

* loss of appetite

* delusions

Some of the withdrawal symptoms are identical to the symptoms for which the medication was originally prescribed. Benzodiazepines are valued by many patients for their ability to ameliorate existing conditions, whlie benzodiazepine dependency can cause them.

As it happens, benzodiazepines are the largest group of recreationally used drugs as well (Gerada & Ashforth 1997).

Intoxication

Benzodiazepine intoxication may lead to coma, but does not cause severe biochemical disturbances and therefore carries a relatively good prognosis. The antidote for all benzodiazepines is flumazenil (Annexate®), which is occasionally used empirically in patients presenting with unexplained loss of conciousness in emergency room setting.

Legal status

Flunitrazepam (Rohypnol®) and bromazepam (Lexotan®) are Schedule I narcotic agents, and not commercially available in the United States.

History

The first benzodiazepine, chlordiazepoxide (Librium®) was discovered serendipitously in 1954 by the Austrian scientist Dr Leo Sternbach (1908-), working for the pharmaceutical company Hoffmann-La Roche. Initially, he discontinued his work on the compound Ro-5-0690, but he "rediscovered" it in 1957 when an assistant was cleaning up the laboratory. Although initially discouraged by his employer, Sternbach conducted further research that revealed the compound was a very effective tranquillizer.


The information above is not intended for and should not be used as a substitute for the diagnosis and/or treatment by a licensed, qualified, health-care professional. This article is licensed under the GNU Free Documentation License. It incorporates material originating from the Wikipedia article "Benzodiazepine".

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