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10,900 | A new adjustable rear sight was added, allowing the rear sight to be dialed in for specific range settings between 300 and 800 meters to take full advantage of the ballistic characteristics of the SS109/M855 rounds and to allow windage adjustments without the need of a tool or cartridge. The flash suppressor was again ... | https://en.wikipedia.org/wiki?curid=19901 |
10,901 | A spent case deflector was incorporated into the upper receiver immediately behind the ejection port to prevent (hot) cartridge cases from striking left-handed users. The action was also modified, replacing the fully automatic setting with a three-round burst setting. When using a fully automatic weapon, inexperienced ... | https://en.wikipedia.org/wiki?curid=19901 |
10,902 | The handguard was modified from the original triangular shape to a round one, which better fit smaller hands and could be fitted to older models of the M16. The new handguards were also symmetrical so armories need not separate left- and right-hand spares. The handguard retention ring was tapered to make it easier to i... | https://en.wikipedia.org/wiki?curid=19901 |
10,903 | The new buttstock became ten times stronger than the original due to advances in polymer technology since the early 1960s. Original M16 stocks were made from cellulose-impregnated phenolic resin; the newer M16A2 stocks were engineered from DuPont Zytel glass-filled thermoset polymers and became a replacement part for t... | https://en.wikipedia.org/wiki?curid=19901 |
10,904 | A notch for the middle finger was added to the pistol grip as well as more texture to enhance the grip. The new pistol grips were engineered from Zytel glass-filled thermoset polymers. The M16A2 pistol grip became a replacement part for the preceding M16A1. | https://en.wikipedia.org/wiki?curid=19901 |
10,905 | The standard Model 645 M16A2 has a safe/semi/three-round burst selective fire trigger group. It became standard issue for the U.S. Marine Corps and Army. | https://en.wikipedia.org/wiki?curid=19901 |
10,906 | There is also a safe/semi/three-round burst/automatic selective fire trigger group Model 708 version of M16A2 rifle named "M16A2 Enhanced", used by some militaries around the world. | https://en.wikipedia.org/wiki?curid=19901 |
10,907 | The M16A3 is a modified version of the M16A2 adopted in small numbers by the U.S. Navy SEAL, Seabee, and Security units. It features the M16A1 selective fire trigger group providing "safe", "semi-automatic" and "fully automatic" modes. Otherwise it is externally similar to the M16A2. | https://en.wikipedia.org/wiki?curid=19901 |
10,908 | The M16A4 is the fourth generation of the M16 series. The iron sight/carrying handle assembly on the M16A2/M16A3 upper receiver, was replaced by a MIL-STD-1913 "Picatinny railed" flat-top upper receiver for mounting aiming optics or a removable iron sight/carrying handle assembly. The M16A4 rear aperture sights integra... | https://en.wikipedia.org/wiki?curid=19901 |
10,909 | Military issue rifles were also equipped with a full length quad Knight's Armament Company M5 RAS Picatinny railed hand guard (that holds zero on the top rail), allowing vertical grips, lasers, tactical lights, and other accessories to be attached, coining the designation M16A4 MWS (or Modular Weapon System) in U.S. Ar... | https://en.wikipedia.org/wiki?curid=19901 |
10,910 | A study of significant changes to Marine M16A4 rifles released in February 2015 outlined several new features that could be added from inexpensive and available components. Those features included: a muzzle compensator in place of the flash suppressor to manage recoil and allow for faster follow-on shots, though at the... | https://en.wikipedia.org/wiki?curid=19901 |
10,911 | In 2014, Marine units were provided with a limited number of adjustable stocks in place of the traditional fixed stock for their M16A4s to issue to smaller Marines who would have trouble comfortably reaching the trigger when wearing body armor. The adjustable stocks were added as a standard authorized accessory, meanin... | https://en.wikipedia.org/wiki?curid=19901 |
10,912 | The Marine Corps had long maintained the full-length M16 as their standard infantry rifle, but in October 2015 the switch to the M4 carbine was approved as the standard-issue weapon, giving Marine infantry a smaller and more compact weapon. Enough M4s were already in the inventory to re-equip all necessary units by Sep... | https://en.wikipedia.org/wiki?curid=19901 |
10,913 | In Vietnam, some soldiers were issued a carbine version of the M16 named XM177. The XM177 had a shorter barrel and a telescoping stock, which made it substantially more compact. It also possessed a combination flash hider/sound moderator to reduce problems with muzzle flash and loud report. The Air Force's GAU-5/A (XM1... | https://en.wikipedia.org/wiki?curid=19901 |
10,914 | The M4 carbine was developed from various outgrowths of these designs, including a number of -barreled A1 style carbines. The XM4 (Colt Model 720) started its trials in 1984, with a barrel of . The weapon became the M4 in 1991. Officially adopted as a replacement for the M3 "Grease Gun" (and the Beretta M9 and M16A2 fo... | https://en.wikipedia.org/wiki?curid=19901 |
10,915 | Colt also returned to the original "Commando" idea, with its Model 733, essentially a modernized XM177E2 with many of the features introduced on the M16A2. | https://en.wikipedia.org/wiki?curid=19901 |
10,916 | The Diemaco C7 and C8 are updated variants of the M16 developed and used by the Canadian Forces and are now manufactured by Colt Canada. The C7 is a further development of the experimental M16A1E1. Like earlier M16s, it can be fired in either semi-automatic or automatic mode, instead of the burst function selected for ... | https://en.wikipedia.org/wiki?curid=19901 |
10,917 | The C7 has been developed to the C7A1, with a Weaver rail on the upper receiver for a C79 3.4×28 optical sight, and to the C7A2, with different furniture and internal improvements. The Diemaco produced Weaver rail on the original C7A1 variants does not meet the M1913 "Picatinny" standard, leading to some problems with ... | https://en.wikipedia.org/wiki?curid=19901 |
10,918 | The C8 is the carbine version of the C7. The C7 and C8 are also used by "Hærens Jegerkommando", "Marinejegerkommandoen" and FSK (Norway), Denmark's Armed Forces (all branches), and the Netherlands Armed Forces as its main infantry weapon. Following trials, variants became the weapon of choice of the British SAS. | https://en.wikipedia.org/wiki?curid=19901 |
10,919 | The Mk 4 Mod 0 was a variant of the M16A1 produced for the U.S. Navy SEALs during the Vietnam War and adopted in April 1970. It differed from the basic M16A1 primarily in being optimized for maritime operations and coming equipped with a sound suppressor. Most of the operating parts of the rifle were coated in Kal-Guar... | https://en.wikipedia.org/wiki?curid=19901 |
10,920 | Developed to increase the effective range of soldiers in the designated marksman role, the U.S. Navy developed the Mark 12 Special Purpose Rifle (SPR). Configurations in service vary, but the core of the Mark 12 SPR is an 18" heavy barrel with muzzle brake and free float tube. This tube relieves pressure on the barrel ... | https://en.wikipedia.org/wiki?curid=19901 |
10,921 | The M231 Firing Port Weapon (FPW) is an adapted version of the M16 assault rifle for firing from ports on the M2 Bradley. The infantry's normal M16s are too long for use in a "buttoned up" fighting vehicle, so the FPW was developed to provide a suitable weapon for this role. | https://en.wikipedia.org/wiki?curid=19901 |
10,922 | With the expanding Vietnam War, Colt developed two rifles of the M16 pattern for evaluation as possible light sniper or designated marksman rifles. The Colt Model 655 M16A1 Special High Profile was essentially a standard A1 rifle with a heavier barrel and a scope bracket that attached to the rifle's carry handle. The C... | https://en.wikipedia.org/wiki?curid=19901 |
10,923 | These weapons can be seen in many ways to be predecessors of the U.S. Army's SDM-R and the USMC's SAM-R weapons. | https://en.wikipedia.org/wiki?curid=19901 |
10,924 | The M16 is the most commonly manufactured 5.56×45 mm rifle in the world. Currently, the M16 is in use by 15 NATO countries and more than 80 countries worldwide. Together, numerous companies in the United States, Canada, and China have produced more than 8,000,000 rifles of all variants. Approximately 90% are still in o... | https://en.wikipedia.org/wiki?curid=19901 |
10,925 | Benzodiazepines (BZD, BDZ, BZs), sometimes called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, insomnia, and seizures. The first benzodiazepine, chlordiazepoxide (Librium),... | https://en.wikipedia.org/wiki?curid=4781 |
10,926 | Benzodiazepines are depressants that enhance the effect of the neurotransmitter gamma-aminobutyric acid (GABA) at the GABA receptor, resulting in sedative, hypnotic (sleep-inducing), anxiolytic (anti-anxiety), anticonvulsant, and muscle relaxant properties. High doses of many shorter-acting benzodiazepines may also cau... | https://en.wikipedia.org/wiki?curid=4781 |
10,927 | Benzodiazepines are generally viewed as safe and effective for short-term use—about two to four weeks—although cognitive impairment and paradoxical effects such as aggression or behavioral disinhibition can occur. A minority of people have reactions such as worsened agitation or panic when they stop taking benzodiazepi... | https://en.wikipedia.org/wiki?curid=4781 |
10,928 | Taken in overdose, benzodiazepines can cause dangerous deep unconsciousness, but they are less toxic than their predecessors, the barbiturates, and death rarely results when a benzodiazepine is the only drug taken. Combined with other central nervous system (CNS) depressants such as alcohol and opioids, the potential f... | https://en.wikipedia.org/wiki?curid=4781 |
10,929 | Benzodiazepines possess psycholeptic, sedative, hypnotic, anxiolytic, anticonvulsant, muscle relaxant, and amnesic actions, which are useful in a variety of indications such as alcohol dependence, seizures, anxiety disorders, panic, agitation, and insomnia. Most are administered orally; however, they can also be given ... | https://en.wikipedia.org/wiki?curid=4781 |
10,930 | Because of their effectiveness, tolerability, and rapid onset of anxiolytic action, benzodiazepines are frequently used for the treatment of anxiety associated with panic disorder. However, there is disagreement among expert bodies regarding the long-term use of benzodiazepines for panic disorder. The views range from ... | https://en.wikipedia.org/wiki?curid=4781 |
10,931 | The American Psychiatric Association (APA) guidelines note that, in general, benzodiazepines are well tolerated, and their use for the initial treatment for panic disorder is strongly supported by numerous controlled trials. APA states that there is insufficient evidence to recommend any of the established panic disord... | https://en.wikipedia.org/wiki?curid=4781 |
10,932 | Guidelines issued by the UK-based National Institute for Health and Clinical Excellence (NICE), carried out a systematic review using different methodology and came to a different conclusion. They questioned the accuracy of studies that were not placebo-controlled. And, based on the findings of placebo-controlled studi... | https://en.wikipedia.org/wiki?curid=4781 |
10,933 | Benzodiazepines are usually administered orally; however, very occasionally lorazepam or diazepam may be given intravenously for the treatment of panic attacks. | https://en.wikipedia.org/wiki?curid=4781 |
10,934 | Benzodiazepines have robust efficacy in the short-term management of generalized anxiety disorder (GAD), but were not shown effective in producing long-term improvement overall. According to National Institute for Health and Clinical Excellence (NICE), benzodiazepines can be used in the immediate management of GAD, if ... | https://en.wikipedia.org/wiki?curid=4781 |
10,935 | Likewise, Canadian Psychiatric Association (CPA) recommends benzodiazepines alprazolam, bromazepam, lorazepam, and diazepam only as a second-line choice, if the treatment with two different antidepressants was unsuccessful. Although they are second-line agents, benzodiazepines can be used for a limited time to relieve ... | https://en.wikipedia.org/wiki?curid=4781 |
10,936 | A 2015 review found a larger effect with medications than talk therapy. Medications with benefit include serotonin-noradrenaline reuptake inhibitors, benzodiazepines, and selective serotonin reuptake inhibitors. | https://en.wikipedia.org/wiki?curid=4781 |
10,937 | Benzodiazepines are sometimes used in the treatment of acute anxiety, as they bring about rapid and marked relief of symptoms in most individuals; however, they are not recommended beyond 2–4 weeks of use due to risks of tolerance and dependence and a lack of long-term effectiveness. As for insomnia, they may also be u... | https://en.wikipedia.org/wiki?curid=4781 |
10,938 | Benzodiazepines can be useful for short-term treatment of insomnia. Their use beyond 2 to 4 weeks is not recommended due to the risk of dependence. The Committee on Safety of Medicines report recommended that where long-term use of benzodiazepines for insomnia is indicated then treatment should be intermittent wherever... | https://en.wikipedia.org/wiki?curid=4781 |
10,939 | The list of benzodiazepines approved for the treatment of insomnia is fairly similar among most countries, but which benzodiazepines are officially designated as first-line hypnotics prescribed for the treatment of insomnia varies between countries. Longer-acting benzodiazepines such as nitrazepam and diazepam have res... | https://en.wikipedia.org/wiki?curid=4781 |
10,940 | Since the release of non benzodiazepines in 1992 in response to safety concerns, individuals with insomnia and other sleep disorders have increasingly been prescribed nonbenzodiazepines (2.3% in 1993 to 13.7% of Americans in 2010), less often prescribed benzodiazepines (23.5% in 1993 to 10.8% in 2010). It is not clear ... | https://en.wikipedia.org/wiki?curid=4781 |
10,941 | Older adults should not use benzodiazepines to treat insomnia unless other treatments have failed. When benzodiazepines are used, patients, their caretakers, and their physician should discuss the increased risk of harms, including evidence that shows twice the incidence of traffic collisions among driving patients, an... | https://en.wikipedia.org/wiki?curid=4781 |
10,942 | Prolonged convulsive epileptic seizures are a medical emergency that can usually be dealt with effectively by administering fast-acting benzodiazepines, which are potent anticonvulsants. In a hospital environment, intravenous clonazepam, lorazepam, and diazepam are first-line choices. In the community, intravenous admi... | https://en.wikipedia.org/wiki?curid=4781 |
10,943 | When benzodiazepines were first introduced, they were enthusiastically adopted for treating all forms of epilepsy. However, drowsiness and tolerance become problems with continued use and none are now considered first-line choices for long-term epilepsy therapy. Clobazam is widely used by specialist epilepsy clinics wo... | https://en.wikipedia.org/wiki?curid=4781 |
10,944 | Chlordiazepoxide is the most commonly used benzodiazepine for alcohol detoxification, but diazepam may be used as an alternative. Both are used in the detoxification of individuals who are motivated to stop drinking, and are prescribed for a short period of time to reduce the risks of developing tolerance and dependenc... | https://en.wikipedia.org/wiki?curid=4781 |
10,945 | Benzodiazepines are the preferred choice in the management of alcohol withdrawal syndrome, in particular, for the prevention and treatment of the dangerous complication of seizures and in subduing severe delirium. Lorazepam is the only benzodiazepine with predictable intramuscular absorption and it is the most effectiv... | https://en.wikipedia.org/wiki?curid=4781 |
10,946 | Because of their muscle relaxant action, benzodiazepines may cause respiratory depression in susceptible individuals. For that reason, they are contraindicated in people with myasthenia gravis, sleep apnea, bronchitis, and COPD. Caution is required when benzodiazepines are used in people with personality disorders or i... | https://en.wikipedia.org/wiki?curid=4781 |
10,947 | In the United States, the Food and Drug Administration has categorized benzodiazepines into either category D or X meaning potential for harm in the unborn has been demonstrated. | https://en.wikipedia.org/wiki?curid=4781 |
10,948 | Exposure to benzodiazepines during pregnancy has been associated with a slightly increased (from 0.06 to 0.07%) risk of cleft palate in newborns, a controversial conclusion as some studies find no association between benzodiazepines and cleft palate. Their use by expectant mothers shortly before the delivery may result... | https://en.wikipedia.org/wiki?curid=4781 |
10,949 | The benefits of benzodiazepines are least and the risks are greatest in the elderly. They are listed as a potentially inappropriate medication for older adults by the American Geriatrics Society. The elderly are at an increased risk of dependence and are more sensitive to the adverse effects such as memory problems, da... | https://en.wikipedia.org/wiki?curid=4781 |
10,950 | Long-term use of benzodiazepines is associated with increased risk of cognitive impairment and dementia, and reduction in prescribing levels is likely to reduce dementia risk. The association of a history of benzodiazepine use and cognitive decline is unclear, with some studies reporting a lower risk of cognitive decli... | https://en.wikipedia.org/wiki?curid=4781 |
10,951 | Benzodiazepines are sometimes prescribed to treat behavioral symptoms of dementia. However, like antidepressants, they have little evidence of effectiveness, although antipsychotics have shown some benefit. Cognitive impairing effects of benzodiazepines that occur frequently in the elderly can also worsen dementia. | https://en.wikipedia.org/wiki?curid=4781 |
10,952 | The most common side-effects of benzodiazepines are related to their sedating and muscle-relaxing action. They include drowsiness, dizziness, and decreased alertness and concentration. Lack of coordination may result in falls and injuries, in particular, in the elderly. Another result is impairment of driving skills an... | https://en.wikipedia.org/wiki?curid=4781 |
10,953 | The long-term effects of benzodiazepine use can include cognitive impairment as well as affective and behavioural problems. Feelings of turmoil, difficulty in thinking constructively, loss of sex-drive, agoraphobia and social phobia, increasing anxiety and depression, loss of interest in leisure pursuits and interests,... | https://en.wikipedia.org/wiki?curid=4781 |
10,954 | Compared to other sedative-hypnotics, visits to the hospital involving benzodiazepines had a 66% greater odds of a serious adverse health outcome. This included hospitalization, patient transfer, or death, and visits involving a combination of benzodiazepines and non-benzodiapine receptor agonists had almost four-times... | https://en.wikipedia.org/wiki?curid=4781 |
10,955 | In September 2020, the U.S. Food and Drug Administration (FDA) required the boxed warning be updated for all benzodiazepine medicines to describe the risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions consistently across all the medicines in the class. | https://en.wikipedia.org/wiki?curid=4781 |
10,956 | The short-term use of benzodiazepines adversely affects multiple areas of cognition, the most notable one being that it interferes with the formation and consolidation of memories of new material and may induce complete anterograde amnesia. However, researchers hold contrary opinions regarding the effects of long-term ... | https://en.wikipedia.org/wiki?curid=4781 |
10,957 | While the definitive studies are lacking, the former view received support from a 2004 meta-analysis of 13 small studies. This meta-analysis found that long-term use of benzodiazepines was associated with moderate to large adverse effects on all areas of cognition, with visuospatial memory being the most commonly detec... | https://en.wikipedia.org/wiki?curid=4781 |
10,958 | Paradoxical reactions, such as increased seizures in epileptics, aggression, violence, impulsivity, irritability and suicidal behavior sometimes occur. These reactions have been explained as consequences of disinhibition and the subsequent loss of control over socially unacceptable behavior. Paradoxical reactions are r... | https://en.wikipedia.org/wiki?curid=4781 |
10,959 | While benzodiazepines may have short-term benefits for anxiety, sleep and agitation in some patients, long-term (i.e., greater than 2–4 weeks) use can result in a worsening of the very symptoms the medications are meant to treat. Potential explanations include exacerbating cognitive problems that are already common in ... | https://en.wikipedia.org/wiki?curid=4781 |
10,960 | The main problem of the chronic use of benzodiazepines is the development of tolerance and dependence. Tolerance manifests itself as diminished pharmacological effect and develops relatively quickly to the sedative, hypnotic, anticonvulsant, and muscle relaxant actions of benzodiazepines. Tolerance to anti-anxiety effe... | https://en.wikipedia.org/wiki?curid=4781 |
10,961 | A major disadvantage of benzodiazepines is that tolerance to therapeutic effects develops relatively quickly while many adverse effects persist. Tolerance develops to hypnotic and myorelaxant effects within days to weeks, and to anticonvulsant and anxiolytic effects within weeks to months. Therefore, benzodiazepines ar... | https://en.wikipedia.org/wiki?curid=4781 |
10,962 | Discontinuation of benzodiazepines or abrupt reduction of the dose, even after a relatively short course of treatment (two to four weeks), may result in two groups of symptoms—rebound and withdrawal. Rebound symptoms are the return of the symptoms for which the patient was treated but worse than before. Withdrawal symp... | https://en.wikipedia.org/wiki?curid=4781 |
10,963 | The most frequent symptoms of withdrawal from benzodiazepines are insomnia, gastric problems, tremors, agitation, fearfulness, and muscle spasms. The less frequent effects are irritability, sweating, depersonalization, derealization, hypersensitivity to stimuli, depression, suicidal behavior, psychosis, seizures, and d... | https://en.wikipedia.org/wiki?curid=4781 |
10,964 | Symptoms may also occur during a gradual dosage reduction, but are typically less severe and may persist as part of a protracted withdrawal syndrome for months after cessation of benzodiazepines. Approximately 10% of patients experience a notable protracted withdrawal syndrome, which can persist for many months or in s... | https://en.wikipedia.org/wiki?curid=4781 |
10,965 | Benzodiazepines have a reputation with patients and doctors for causing a severe and traumatic withdrawal; however, this is in large part due to the withdrawal process being poorly managed. Over-rapid withdrawal from benzodiazepines increases the severity of the withdrawal syndrome and increases the failure rate. A slo... | https://en.wikipedia.org/wiki?curid=4781 |
10,966 | Withdrawal is best managed by transferring the physically dependent patient to an equivalent dose of diazepam because it has the longest half-life of all of the benzodiazepines, is metabolised into long-acting active metabolites and is available in low-potency tablets, which can be quartered for smaller doses. A furthe... | https://en.wikipedia.org/wiki?curid=4781 |
10,967 | Nonbenzodiazepines are contraindicated during benzodiazepine withdrawal as they are cross tolerant with benzodiazepines and can induce dependence. Alcohol is also cross tolerant with benzodiazepines and more toxic and thus caution is needed to avoid replacing one dependence with another. During withdrawal, fluoroquinol... | https://en.wikipedia.org/wiki?curid=4781 |
10,968 | Withdrawal from long term benzodiazepines is beneficial for most individuals. Withdrawal of benzodiazepines from long-term users, in general, leads to improved physical and mental health particularly in the elderly; although some long term users report continued benefit from taking benzodiazepines, this may be the resu... | https://en.wikipedia.org/wiki?curid=4781 |
10,969 | Beyond the well established link between benzodiazepines and psychomotor impairment resulting in motor vehicle accidents and falls leading to fracture; research in the 2000s and 2010s has raised the association between benzodiazepines (and Z-drugs) and other, as of yet unproven, adverse effects including dementia, canc... | https://en.wikipedia.org/wiki?curid=4781 |
10,970 | A number of studies have drawn an association between long-term benzodiazepine use and neuro-degenerative disease, particularly Alzheimer's disease. It has been determined that long-term use of benzodiazepines is associated with increased dementia risk, even after controlling for protopathic bias. | https://en.wikipedia.org/wiki?curid=4781 |
10,971 | Some observational studies have detected significant associations between benzodiazepines and respiratory infections such as pneumonia where others have not. A large meta-analysis of pre-marketing randomized controlled trials on the pharmacologically related Z-Drugs suggest a small increase in infection risk as well. A... | https://en.wikipedia.org/wiki?curid=4781 |
10,972 | A Meta-analysis of observational studies has determined an association between benzodiazepine use and cancer, though the risk across different agents and different cancers varied significantly. In terms of experimental basic science evidence, an analysis of carcinogenetic and genotoxicity data for various benzodiazepin... | https://en.wikipedia.org/wiki?curid=4781 |
10,973 | The evidence suggesting a link between benzodiazepines (and Z-Drugs) and pancreatic inflammation is very sparse and limited to a few observational studies from Taiwan. A criticism of confounding can be applied to these findings as with the other controversial associations above. Further well-designed research from othe... | https://en.wikipedia.org/wiki?curid=4781 |
10,974 | Although benzodiazepines are much safer in overdose than their predecessors, the barbiturates, they can still cause problems in overdose. Taken alone, they rarely cause severe complications in overdose; statistics in England showed that benzodiazepines were responsible for 3.8% of all deaths by poisoning from a single ... | https://en.wikipedia.org/wiki?curid=4781 |
10,975 | A reversal agent for benzodiazepines exists, flumazenil (Anexate). Its use as an antidote is not routinely recommended because of the high risk of resedation and seizures. In a double-blind, placebo-controlled trial of 326 people, 4 people had serious adverse events and 61% became resedated following the use of flumaze... | https://en.wikipedia.org/wiki?curid=4781 |
10,976 | Individual benzodiazepines may have different interactions with certain drugs. Depending on their metabolism pathway, benzodiazepines can be divided roughly into two groups. The largest group consists of those that are metabolized by cytochrome P450 (CYP450) enzymes and possess significant potential for interactions wi... | https://en.wikipedia.org/wiki?curid=4781 |
10,977 | Many drugs, including oral contraceptives, some antibiotics, antidepressants, and antifungal agents, inhibit cytochrome enzymes in the liver. They reduce the rate of elimination of the benzodiazepines that are metabolized by CYP450, leading to possibly excessive drug accumulation and increased side-effects. In contrast... | https://en.wikipedia.org/wiki?curid=4781 |
10,978 | Benzodiazepines work by increasing the effectiveness of the endogenous chemical, GABA, to decrease the excitability of neurons. This reduces the communication between neurons and, therefore, has a calming effect on many of the functions of the brain. | https://en.wikipedia.org/wiki?curid=4781 |
10,979 | GABA controls the excitability of neurons by binding to the GABA receptor. The GABA receptor is a protein complex located in the synapses between neurons. All GABA receptors contain an ion channel that conducts chloride ions across neuronal cell membranes and two binding sites for the neurotransmitter gamma-aminobutyri... | https://en.wikipedia.org/wiki?curid=4781 |
10,980 | Different GABA receptor subtypes have varying distributions within different regions of the brain and, therefore, control distinct neuronal circuits. Hence, activation of different GABA receptor subtypes by benzodiazepines may result in distinct pharmacological actions. In terms of the mechanism of action of benzodiaze... | https://en.wikipedia.org/wiki?curid=4781 |
10,981 | The subset of GABA receptors that also bind benzodiazepines are referred to as benzodiazepine receptors (BzR). The GABA receptor is a heteromer composed of five subunits, the most common ones being two "α"s, two "β"s, and one "γ" (αβγ1). For each subunit, many subtypes exist (α, β, and γ). GABA receptors that are made ... | https://en.wikipedia.org/wiki?curid=4781 |
10,982 | The benzodiazepine class of drugs also interact with peripheral benzodiazepine receptors. Peripheral benzodiazepine receptors are present in peripheral nervous system tissues, glial cells, and to a lesser extent the central nervous system. These peripheral receptors are not structurally related or coupled to GABA recep... | https://en.wikipedia.org/wiki?curid=4781 |
10,983 | A benzodiazepine can be placed into one of three groups by its elimination half-life, or time it takes for the body to eliminate half of the dose. Some benzodiazepines have long-acting active metabolites, such as diazepam and chlordiazepoxide, which are metabolised into desmethyldiazepam. Desmethyldiazepam has a half-l... | https://en.wikipedia.org/wiki?curid=4781 |
10,984 | Benzodiazepines share a similar chemical structure, and their effects in humans are mainly produced by the allosteric modification of a specific kind of neurotransmitter receptor, the GABA receptor, which increases the overall conductance of these inhibitory channels; this results in the various therapeutic effects as ... | https://en.wikipedia.org/wiki?curid=4781 |
10,985 | The term "benzodiazepine" is the chemical name for the heterocyclic ring system (see figure to the right), which is a fusion between the benzene and diazepine ring systems. Under Hantzsch–Widman nomenclature, a diazepine is a heterocycle with two nitrogen atoms, five carbon atom and the maximum possible number of cumul... | https://en.wikipedia.org/wiki?curid=4781 |
10,986 | Benzodiazepine drugs are substituted 1,4-benzodiazepines, although the chemical term can refer to many other compounds that do not have useful pharmacological properties. Different benzodiazepine drugs have different side groups attached to this central structure. The different side groups affect the binding of the mol... | https://en.wikipedia.org/wiki?curid=4781 |
10,987 | Nonbenzodiazepines also bind to the benzodiazepine binding site on the GABA receptor and possess similar pharmacological properties. While the nonbenzodiazepines are by definition structurally unrelated to the benzodiazepines, both classes of drugs possess a common pharmacophore (see figure to the lower-right), which e... | https://en.wikipedia.org/wiki?curid=4781 |
10,988 | 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 1... | https://en.wikipedia.org/wiki?curid=4781 |
10,989 | The new group of drugs was initially greeted with optimism by the medical profession, but gradually concerns arose; in particular, the risk of dependence became evident in the 1980s. Benzodiazepines have a unique history in that they were responsible for the largest-ever class-action lawsuit against drug manufacturers ... | https://en.wikipedia.org/wiki?curid=4781 |
10,990 | Although antidepressants with anxiolytic properties have been introduced, and there is increasing awareness of the adverse effects of benzodiazepines, prescriptions for short-term anxiety relief have not significantly dropped. For treatment of insomnia, benzodiazepines are now less popular than nonbenzodiazepines, whic... | https://en.wikipedia.org/wiki?curid=4781 |
10,991 | Benzodiazepines have been detected in plant specimens and brain samples of animals not exposed to synthetic sources, including a human brain from the 1940s. However, it is unclear whether these compounds are biosynthesized by microbes or by plants and animals themselves. A microbial biosynthetic pathway has been propos... | https://en.wikipedia.org/wiki?curid=4781 |
10,992 | In the United States, benzodiazepines are Schedule IV drugs under the Federal Controlled Substances Act, even when not on the market (for example, nitrazepam and bromazepam). Flunitrazepam is subject to more stringent regulations in certain states and temazepam prescriptions require specially coded pads in certain stat... | https://en.wikipedia.org/wiki?curid=4781 |
10,993 | In Canada, possession of benzodiazepines is legal for personal use. All benzodiazepines are categorized as Schedule IV substances under the Controlled Drugs and Substances Act. | https://en.wikipedia.org/wiki?curid=4781 |
10,994 | In the United Kingdom, the benzodiazepines are Class C controlled drugs, carrying the maximum penalty of 7 years imprisonment, an unlimited fine or both for possession and a maximum penalty of 14 years imprisonment an unlimited fine or both for supplying benzodiazepines to others. | https://en.wikipedia.org/wiki?curid=4781 |
10,995 | In the Netherlands, since October 1993, benzodiazepines, including formulations containing less than 20 mg of temazepam, are all placed on List 2 of the Opium Law. A prescription is needed for possession of all benzodiazepines. Temazepam formulations containing 20 mg or greater of the drug are placed on List 1, thus re... | https://en.wikipedia.org/wiki?curid=4781 |
10,996 | In East Asia and Southeast Asia, temazepam and nimetazepam are often heavily controlled and restricted. In certain countries, triazolam, flunitrazepam, flutoprazepam and midazolam are also restricted or controlled to certain degrees. In Hong Kong, all benzodiazepines are regulated under Schedule 1 of Hong Kong's Chapte... | https://en.wikipedia.org/wiki?curid=4781 |
10,997 | Internationally, benzodiazepines are categorized as Schedule IV controlled drugs, apart from flunitrazepam, which is a Schedule III drug under the Convention on Psychotropic Substances. | https://en.wikipedia.org/wiki?curid=4781 |
10,998 | Benzodiazepines are considered major addictive substances. Non-medical benzodiazepine use is mostly limited to individuals who use other substances, i.e., people who engage in polysubstance use. On the international scene, benzodiazepines are categorized as Schedule IV controlled drugs by the INCB, apart from flunitraz... | https://en.wikipedia.org/wiki?curid=4781 |
10,999 | British law requires that temazepam (but "not" midazolam) be stored in safe custody. Safe custody requirements ensures that pharmacists and doctors holding stock of temazepam must store it in securely fixed double-locked steel safety cabinets and maintain a written register, which must be bound and contain separate ent... | https://en.wikipedia.org/wiki?curid=4781 |
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