Benzodiazepines /ˌbɛnzɵdaɪˈæzɨpiːn/ (sometimes colloquially "benzos"; often abbreviated "BZD") are a class of psychoactive drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. The first such drug, chlordiazepoxide (Librium), was discovered accidentally by Leo Sternbach in 1955, and made available in 1960 by Hoffmann–La Roche - which, since 1963, has also marketed the benzodiazepine diazepam (Valium). In 1977 benzodiazepines were globally the most prescibed medications.
Benzodiazepines enhance the effect of the neurotransmitter gamma-aminobutyric acid (GABA) at the GABAA receptor, resulting in sedative, hypnotic (sleep-inducing), anxiolytic (anti-anxiety), anticonvulsant, and muscle relaxant properties. High doses of many shorter-acting benzodiazepines may also cause anterograde amnesia and dissociation. These properties make benzodiazepines useful in treating anxiety, insomnia, agitation, seizures, muscle spasms, alcohol withdrawal and as a premedication for medical or dental procedures. Benzodiazepines are categorized as either short-, intermediate-, or long-acting. Short- and intermediate-acting benzodiazepines are preferred for the treatment of insomnia; longer-acting benzodiazepines are recommended for the treatment of anxiety.
Benzodiazepines are generally viewed as safe and effective for short-term use, although cognitive impairment and paradoxical effects such as aggression or behavioral disinhibition occasionally occur. A minority of people can have paradoxical reactions such as worsened agitation or panic. Long-term use is controversial due to concerns about adverse psychological and physical effects, decreasing effectiveness, and physical dependence and withdrawal. Due to adverse effects associated with the long-term use of benzodiazepines, withdrawal from benzodiazepines, in general, leads to improved physical and mental health. The elderly are at an increased risk of suffering from both short- and long-term adverse effects.
There is controversy concerning the safety of benzodiazepines in pregnancy. While they are not major teratogens, uncertainty remains as to whether they cause cleft palate in a small number of babies and whether neurobehavioural effects occur as a result of prenatal exposure; they are known to cause withdrawal symptoms in the newborn. Benzodiazepines can be taken in overdoses and can cause dangerous deep unconsciousness. However, they are much less toxic than their predecessors, the barbiturates, and death rarely results when a benzodiazepine is the only drug taken; however, when combined with other central nervous system (CNS) depressants such as ethanol and opioids, the potential for toxicity and fatal overdose increases. Benzodiazepines are commonly misused and taken in combination with other drugs of abuse. In addition, all benzodiazepines are listed in Beers List, which is significant in clinical practice.
Diazepam /daɪˈæzɨpæm/, first marketed as Valium /ˈvæliəm/, is a medication of the benzodiazepine type. It is commonly used to treat a range of conditions including anxiety, alcohol withdrawal syndrome, benzodiazepine withdrawal syndrome, muscle spasms, seizures, trouble sleeping, and restless legs syndrome. It may also be used to cause memory loss during certain medical procedures. It can be taken by mouth, inserted into the rectum, injected into muscle, or injected into a vein. When given into a vein effects begin in one to five minutes and last up to an hour. By mouth effects may take 40 minutes to begin.
Common side effects include sleepiness and trouble with coordination. Serious side effects are rare. They include suicide, decreased breathing, and an increased risk of seizures if used too frequently in those with epilepsy. Occasionally excitement or agitation may occur. Long term use can result in tolerance, dependence, and withdrawal upon dose reduction. Abrupt stopping after long term use can be potentially dangerous. After stopping cognitive problems may persist for six months or longer. They are not recommended during pregnancy or breastfeeding. Its mechanism of action is by increasing the effect of the neurotransmitter gamma-Aminobutyric acid (GABA).
Diazepam was first synthesized by Leo Sternbach, and was first manufactured by Hoffmann-La Roche. It has been one of the most frequently prescribed medications in the world since its launch in 1963. In the United States it was the highest selling medication between 1968 and 1982, selling more than two billion tablets in 1978 alone. In 1985 the patent ended, and there are now more than 500 brands available on the market. Diazepam is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.
Alprazolam /ælˈpræzəlæm/ or /ælˈpreɪzəlæm/ (trade name Xanax /ˈzænæks/), available under other generic names, is a short-acting anxiolytic of the benzodiazepine class of psychoactive drugs commonly used and FDA approved for the medical treatment of panic disorder, and anxiety disorders, such as generalized anxiety disorder (GAD) or social anxiety disorder (SAD). It was the 12th most prescribed medicine in 2010. Alprazolam, like other benzodiazepines, binds to specific sites on the GABAA receptor. It possesses anxiolytic, sedative, hypnotic, skeletal muscle relaxant, anticonvulsant, and amnestic properties. Alprazolam is available for oral administration in compressed tablet (CT) and extended-release capsule (XR) formulations.
Alprazolam has a fast onset of action and symptomatic relief. Ninety percent of peak effects are achieved within the first hour of using either the CT formulation or the XR formulation in preparation for panic disorder, and full peak effects are achieved in 1.5 and 1.6 hours respectively. Peak benefits achieved for generalized anxiety disorder (GAD) may take up to a week. Tolerance to the anxiolytic/antipanic effects is controversial with some authoritative sources reporting the development of tolerance, and others reporting no development of tolerance; tolerance will however, develop to the sedative-hypnotic effects within a couple of days. Withdrawal symptoms or rebound symptoms may occur after ceasing treatment abruptly following a few weeks or longer of steady dosing, and may necessitate a gradual dose reduction.
Alprazolam was first released by Upjohn (now a part of Pfizer). It is covered under U.S. Patent 3,987,052, which was filed on 29 October 1969, granted on 19 October 1976, and expired in September 1993. Alprazolam was released in 1981. The first approved indication was panic disorder and within two years of its original marketing Upjohn's Xanax became a blockbuster drug in the US. Presently, Alprazolam is the most prescribed and the most misused benzodiazepine on the U.S. retail market. The potential for misuse among those taking it for medical reasons is controversial with some expert reviews stating that the risk is low and similar to that of other benzodiazepine drugs and others stating that there is a substantial risk of misuse and dependence in both patients and non-medical users of alprazolam and that the pharmacological properties of alprazolam, high affinity binding, high potency, having a short elimination half-life as well as a rapid onset of action may increase the misuse potential of alprazolam. Compared to the large number of prescriptions, relatively few individuals increase their dose on their own initiative or engage in drug-seeking behavior. Alprazolam is classified as a schedule IV controlled substance by the U.S. Drug Enforcement Administration (DEA).