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A benzodiazepine /ˌbɛnzɵdaɪˈæzɨpiːn/ (sometimes colloquially "benzo"; often abbreviated "BZD") is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring. The first benzodiazepine, chlordiazepoxide (Librium), was discovered accidentally by Leo Sternbach in 1955, and made available in 1960 by Hoffmann–La Roche, which has also marketed diazepam (Valium) since 1963.[1] Benzodiazepines enhance the effect of the neurotransmitter gamma-aminobutyric acid (GABA-A), resulting in sedative, hypnotic (sleep-inducing), anxiolytic (anti-anxiety), anticonvulsant, and muscle relaxant properties; also seen in the applied pharmacology of high doses of many shorter-acting benzodiazepines are amnesic-dissociative actions.[2] These properties make benzodiazepines useful in treating anxiety, insomnia, agitation, seizures, muscle spasms, alcohol withdrawal and as a premedication for medical or dental procedures.[3] 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.[4] In general, benzodiazepines are safe and effective in the short term, although cognitive impairments and paradoxical effects such as aggression or behavioral disinhibition occasionally occur.[5] Long-term use is controversial due to concerns about adverse psychological and physical effects, increased questioning of effectiveness and because benzodiazepines are prone to cause tolerance, physical dependence, and, upon cessation of use after long term use, a withdrawal syndrome.[6][7] Due to adverse effects associated with the long-term use of benzodiazepines, withdrawal from benzodiazepines, in general, leads to improved physical and mental health.[8][9] The elderly are at an increased risk of suffering from both short- and long-term adverse effects.[8][10] Withdrawal from a long term benzodiazepine addiction may cause tinnitus as a side effect. 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;[11] 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 depressants such as alcohol and opiates, the potential for toxicity and fatal overdose increases.[12] Benzodiazepines are commonly misused and taken in combination with other drugs of abuse.[13][14][15] In addition, all benzodiazepines are listed in Beer's List, which is significant in clinical practice. Moreover, in geriatric medicine, if benzodiazepines are necessary, those with short half-lives (e.g. lorazepam & oxazepam) are preferred, as they do not require hepatic oxidation.[citation needed]