Benzodiazepines are widely prescribed drugs. According to IMS Health™, there were 45.0 million alprazolam, 26.4 million lorazepam, 24.4 million clonazepam, 14.2 million diazepam, and 8.4 million temazepam prescriptions dispensed in the U.S. in 2009. In the U.S., benzodiazepines are prescribed for their sedative-hypnotic (e.g., temazepam, triazolam, flurazepam, and estazolam), anti-anxiety (e.g., alprazolam, chlordiazepoxide, clorazepate, diazepam, lorazepam, and oxazepam), muscle relaxant (e.g., diazepam), and anti-convulsant (e.g., diazepam and clonazepam) effects. They are also used as an adjunct to anesthesia (e.g., midazolam) and for treatment of alcohol withdrawal (e.g., chlordiazepoxide) and panic disorders (e.g., alprazolam and clonazepam). Most benzodiazepines are available as tablet and capsule preparations; several are also available as injectable preparations and as syrup.
Abstract
Benzodiazepines are a type of medication known as tranquilizers or minor tranquilizers, as opposed to the major tranquilizers used to treat psychosis. Familiar names of these drugs include diazepam (Valium), lorazepam (Ativan), clonazepam (Klonopin), and alprazolam (Xanax). They are some of the most commonly prescribed medications in the United States. When people without prescriptions take these drugs for their sedating or intoxicating effects, then use turns into abuse.
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Street Names
Benzos
Downers
Nerve Pills
Tranks
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Brand Names
Niravam
Xanax
Alzam
Anxirid
Azor
Xanor
Zopax
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History
The first benzodiazepine, chlordiazepoxide (Librium), was synthesized in 1955 by Leo Sternbach while working at Hoffmann–La Roche on the development of tranquilizers. The pharmacological properties of the compounds prepared initially were disappointing, and Sternbach abandoned the project. Two years later, in April 1957, co-worker Earl Reeder noticed a "nicely crystalline" compound left over from the discontinued project while spring-cleaning in the lab. This compound, later named chlordiazepoxide, had not been tested in 1955 because of Sternbach's focus on other issues. Expecting the pharmacology results to be negative and hoping to publish the chemistry-related findings, researchers submitted it for a standard battery of animal tests. However, the compound showed very strong sedative, anticonvulsant, and muscle relaxant effects. These impressive clinical findings led to its speedy introduction throughout the world in 1960 under the brand name Librium
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Pharmacology
All benzodiazepines are composed of a benzene ring fused to a seven-member diazepine ring. Most benzodiazepines also possess a phenyl ring attached at the 5-position of the diazepine ring. Small modifications of this basic structure account for the varied pharmacologic effects of these drugs.
Benzodiazepines produce CNS depression by enhancing the effects of the major inhibitory neurotransmitter, gamma-aminobutyric acid, thereby decreasing brain activity. Benzodiazepines are classified by their duration of action that ranges from less than 6 hours to more than 24 hours. Some benzodiazepines have active metabolites that prolong their effects.
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Uses
Benzodiazepines are widely prescribed drugs. According to IMS Health™, there were 45.0 million alprazolam, 26.4 million lorazepam, 24.4 million clonazepam, 14.2 million diazepam, and 8.4 million temazepam prescriptions dispensed in the U.S. in 2009. In the U.S., benzodiazepines are prescribed for their sedative-hypnotic (e.g., temazepam, triazolam, flurazepam, and estazolam), anti-anxiety (e.g., alprazolam, chlordiazepoxide, clorazepate, diazepam, lorazepam, and oxazepam), muscle relaxant (e.g., diazepam), and anti-convulsant (e.g., diazepam and clonazepam) effects. They are also used as an adjunct to anesthesia (e.g., midazolam) and for treatment of alcohol withdrawal (e.g., chlordiazepoxide) and panic disorders (e.g., alprazolam and clonazepam). Most benzodiazepines are available as tablet and capsule preparations; several are also available as injectable preparations and as syrup.
Benzodiazepines, particularly those having a rapid onset, are abused to produce a euphoric effect. Abuse of benzodiazepines is often associated with multiple-substance abuse. Diazepam and alprazolam are used in combination with methadone to potentiate methadone’s euphoric effect. Cocaine addicted patients use benzodiazepines to relieve the side effects (e.g., irritability and agitation) associated with cocaine binges. Benzodiazepines are also used to augment alcohol’s effects and modulate withdrawal states. The doses of benzodiazepines taken by abusers are usually in excess of the recommended therapeutic dose. Benzodiazepines have been used to facilitate sexual assault.
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Scheduling
Benzodiazepines are classified as schedule IV depressants under the Controlled Substances Act. Flunitrazepam is unique among the benzodiazepines in being placed in schedule IV but having schedule I penalties.
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Psychological and physical addiction liability
Psychological symptoms may include anxiety, panic attacks, odd sensations, feeling as if you are outside your body, feelings of unreality, or just feeling awful. Rarely, a serious mental breakdown can occur.
Physical symptoms may include sweating, being unable to sleep, headache, tremor, feeling sick, palpitations, muscle spasms and being oversensitive to light, sound and touch. Rarely, convulsions occur.
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Withdrawal Effects
Abdominal pains, cramps, diarrhea, bloated, diarhea, constipation, cramping, Dry throat, Dyspepsia;
Aching or painful jaw, dental/tooth pain, band around head, Bruxism (teeth grinding), Dysphagia (difficulty eating or swallowing), Increased or decreased saliva, Painful or tingling scalp, pains in temple, migraine, severe headaches, twitching of the head;
Aggressive behaviour, Agitation, Hyperactivity, hysterical or inappropiate laughter, Irrational rage, Irritability, obsessive behaviour;
Anxiety, Dyspnea (breathing difficulty), Fear, feelings of impending doom, Nervousness, Panic attacks, thoughts and feeling that you are dying;
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Long term effects
The long-term effects of benzodiazepines include drug dependence as well as the possibility of adverse effects on cognitive function, physical health, and mental health. There are significant risks associated with the long-term use of benzodiazepines.
Common effects include: nausea, headaches, dizziness, irritability, lethargy, sleep problems, memory impairment, personality changes, aggression, depression, agoraphobia, anxiety, and panic attacks, social deterioration as well as employment difficulties.
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Physical effects
Although most benzodiazepines trigger the same physical effects, their dosage and absorption time into the bloodstream can vary widely. Following are the physical effects:
Impaired motor coordination
Altered vision
Slurred speech, stuttering
Vertigo
Tremors
Respiratory depression
Dry mouth, abdominal discomfort, vomiting, diarrhea
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Psychological treatment options
Psychological treatments for benzodiazepine addiction comprises of two types of treatments. Firstly, they aim to assist individuals in making changes in their substance using behaviour, and secondly to assist individuals in addressing co-existing mental health disorders.
A second type of psychological therapy aims to address the underlying or additional mental health problems, such as anxiety or depression, post traumatic stress disorder.
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Medical Treatment
It is generally agreed that dosage should be tapered gradually in long-term benzodiazepine users.
Several drugs have been tested for their ability to alleviate benzodiazepine withdrawal symptoms; none have been shown to be generally effective. Clinical experience suggests that antidepressants are the most important since depressive symptoms, sometimes amounting to major depression, are common after withdrawal. Beta-blockers such as propranolol attenuate palpitations, tremor and muscle twitches but have little effect on subjective states and do not reduce the overall incidence of withdrawal symptoms or dropout rate in controlled trials of withdrawal
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Pychological Treament
The commonly recommended treatments for addicted patients should undergo medically supervised detoxification because the treatment dose must be gradually tapered. Inpatient or outpatient counseling can help the individual during this process.
Cognitive behavioral therapy, which focuses on modifying the patient's thinking, expectations, and behaviors, while at the same time increasing skills for coping with various life stressors, also has been used successfully to help individuals adapt to the discontinuation of benzodiazepines.
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Related drugs
Flunitrazepam
Gamma Hydroxybutyric Acid, or GHB
Chloral hydrate
Paraldehyde
Barbiturates
Glutethimide
Methaqualone
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Related Synthetics
Brotizolam
Estazolam
Flunitrazepam
Flurazepam
Haloxazolam
Loprazolam
Lormetazepam
Midazolam
Nimetazepam
Nitrazepam
Temazepam
Triazolam
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References
[1] http://www.emedicinehealth.com/benzodiazepine_abuse/article_em.htm
[2] http://www.deadiversion.usdoj.gov/drugs_concern/benzo_1.htm
[3] http://pubs.acs.org/doi/abs/10.1021/jm00187a001
[4] http://www.patient.co.uk/health/Benzodiazepines-and-Z-Drugs.htm
[5] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1934057/
[6] http://www.bcnc.org.uk/symptoms.html
[7] http://www.ncbi.nlm.nih.gov/pubmed/18323325
[8] http://www.cesar.umd.edu/cesar/drugs/benzos.asp
[9] http://www.emcdda.europa.eu/publications/drug-profiles/benzodiazepine
[10] http://www.drugslibrary.stir.ac.uk/documents/rb11_final.pdf
[11] http://www.benzo.org.uk/ashtbd.htm
