Diethyl ether , or simply ether , is an organic compound with the chemical formula (CH 3 CH 2 ) 2 O , sometimes abbreviated as Et 2 O . It is a colourless, highly volatile , sweet-smelling ("ethereal odour"), extremely flammable liquid . It belongs to the ether class of organic compounds. It is a common solvent . It was formerly used as a general anesthetic .
129-418: Diazepam , sold under the brand name Valium among others, is a medicine of the benzodiazepine family that acts as an anxiolytic . It is used to treat a range of conditions, including anxiety , seizures , alcohol withdrawal syndrome , muscle spasms , insomnia , and restless legs syndrome . It may also be used to cause memory loss during certain medical procedures. It can be taken orally (by mouth), as
258-428: 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 administration is not practical and so rectal diazepam or buccal midazolam are used, with a preference for midazolam as its administration
387-528: A premedication for medical or dental procedures. Benzodiazepines are categorized as 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 of two to four weeks, although cognitive impairment and paradoxical effects such as aggression or behavioral disinhibition can occur. According to
516-844: A suppository inserted into the rectum, intramuscularly (injected into muscle), intravenously (injection into a vein) or used as a nasal spray . When injected intravenously, effects begin in one to five minutes and last up to an hour. When taken by mouth, effects begin after 15 to 60 minutes. Common side effects include sleepiness and trouble with coordination. Serious side effects are rare. They include increased risk of 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 symptoms on dose reduction. Abrupt stopping after long-term use can be potentially dangerous. After stopping, cognitive problems may persist for six months or longer. It
645-630: A better ability to permeate cells. The balance between its lipophilic and hydrophilic characteristics can impact various aspects of the molecule’s behavior, including its solubility, absorption, distribution, metabolism, and potential interactions within the biological system. Diazepam is overall a stable molecule. The British Pharmacopoeia lists it as being very slightly soluble in water, soluble in alcohol, and freely soluble in chloroform. The United States Pharmacopoeia lists diazepam as soluble 1 in 16 ethyl alcohol, 1 in 2 of chloroform, 1 in 39 ether , and practically insoluble in water. The pH of diazepam
774-401: 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), was discovered accidentally by Leo Sternbach in 1955, and was made available in 1960 by Hoffmann–La Roche , which followed with
903-1006: A common side effect. Depression and disinhibition may emerge. Hypotension and suppressed breathing ( hypoventilation ) may be encountered with intravenous use. Less common side effects include nausea and changes in appetite, blurred vision, confusion, euphoria , depersonalization and nightmares. Cases of liver toxicity have been described but are very rare. 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, and an inability to experience or express feelings can also occur. Not everyone, however, experiences problems with long-term use. Additionally, an altered perception of self, environment and relationships may occur. A study published in 2020 found that long-term use of prescription benzodiazepines
1032-404: A degree of polarity or hydrophilicity and represents the collective surface area of polar atoms, like oxygen or nitrogen, along with their connected hydrogen atoms. A TPSA value of 32,7 Ų signifies a moderate level of polarity within the compound. TPSA is especially useful in medical chemistry as it shows the ability of a molecule to permeate cells. Molecules with PSA value smaller than 60-70 Ų has
1161-411: A distinct problem for them and necessitating the need for more effective long-term treatment (e.g., psychotherapy, serotonergic antidepressants). 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
1290-536: A first-line long-term treatment of insomnia. However, the UK National Institute for Health and Clinical Excellence did not find any convincing evidence in favor of Z-drugs. NICE review pointed out that short-acting Z-drugs were inappropriately compared in clinical trials with long-acting benzodiazepines. There have been no trials comparing short-acting Z-drugs with appropriate doses of short-acting benzodiazepines. Based on this, NICE recommended choosing
1419-590: A first-line therapy for panic disorder; benzodiazepine use has been found to interfere with therapeutic gains from these therapies. Benzodiazepines are usually administered orally; however, very occasionally lorazepam or diazepam may be given intravenously for the treatment of panic attacks . 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
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#17327721027091548-434: A higher rate of notable withdrawal symptoms, up to 100%. Rebound anxiety , more severe than baseline anxiety, is also a common withdrawal symptom when discontinuing diazepam or other benzodiazepines. Diazepam is therefore only recommended for short-term therapy at the lowest possible dose owing to risks of severe withdrawal problems from low doses even after gradual reduction. The risk of pharmacological dependence on diazepam
1677-450: A higher rate of terminating seizures and a more prolonged anticonvulsant effect. Diazepam gel was better than placebo gel in reducing the risk of non-cessation of seizures. Diazepam is rarely used for the long-term treatment of epilepsy because tolerance to its anticonvulsant effects usually develops within six to twelve months of treatment, effectively rendering it useless for that purpose. The anticonvulsant effects of diazepam can help in
1806-487: A history of a substance use disorder , such as an alcohol use disorder , or a history of aggressive behavior. In some people, diazepam may increase the propensity toward self-harming behavior and, in extreme cases, may provoke suicidal tendencies or acts. Very rarely dystonia can occur. Diazepam may impair the ability to drive vehicles or operate machinery. The impairment is worsened by consumption of alcohol, because both act as central nervous system depressants . During
1935-538: A lack of long-term effectiveness. As for insomnia, they may also be used on an irregular/"as-needed" basis, such as in cases where said anxiety is at its worst. Compared to other pharmacological treatments, benzodiazepines are twice as likely to lead to a relapse of the underlying condition upon discontinuation. Psychological therapies and other pharmacological therapies are recommended for the long-term treatment of generalized anxiety disorder. Antidepressants have higher remission rates and are, in general, safe and effective in
2064-811: A long half-life and long-acting active metabolites , can be used as an alternative. 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, fluoroquinolone -based antibiotics are best avoided if possible; they displace benzodiazepines from their binding site and reduce GABA function and, thus, may aggravate withdrawal symptoms. Antipsychotics are not recommended for benzodiazepine withdrawal (or other CNS depressant withdrawal states) especially clozapine , olanzapine or low potency phenothiazines , e.g., chlorpromazine as they lower
2193-410: A long half-life thus withdrawal symptoms are tolerable. The process is very slow (usually from 14 to 28 weeks) but is considered safe when done appropriately. An individual who has consumed too much diazepam typically displays one or more of these symptoms in a period of approximately four hours immediately following a suspected overdose: Although not usually fatal when taken alone, a diazepam overdose
2322-572: A prolonged treatment with benzodiazepines as the add-on to an antidepressant may be justified. 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 . Benzodiazepines are sometimes used in the treatment of acute anxiety , since they result in 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
2451-412: A result of abrupt or over-rapid withdrawal. Abrupt withdrawal can be dangerous and lead to excitotoxicity , causing damage and even death to nerve cells as a result of excessive levels of the excitatory neurotransmitter glutamate . Increased glutamatergic activity is thought to be part of a compensatory mechanism to chronic GABAergic inhibition from benzodiazepines. Therefore, a gradual reduction regimen
2580-608: A slow and gradual dose reduction regimen. Tolerance develops to the therapeutic effects of benzodiazepines; for example tolerance occurs to the anticonvulsant effects and as a result benzodiazepines are not generally recommended for the long-term management of epilepsy. Dose increases may overcome the effects of tolerance, but tolerance may then develop to the higher dose and adverse effects may increase. The mechanism of tolerance to benzodiazepines includes uncoupling of receptor sites , alterations in gene expression , down-regulation of receptor sites , and desensitisation of receptor sites to
2709-488: A study published by William Procter, Jr. in the American Journal of Pharmacy as early as 1852 showed that there were differences in formulation to be found between commercial manufacturers, between international pharmacopoeia , and from Hoffman's original recipe. It is also used to treat hiccups through instillation into the nasal cavity. The recreational use of ether also took place at organised parties in
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#17327721027092838-419: 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 intravenously , intramuscularly , or rectally . In general, benzodiazepines are well tolerated and are safe and effective drugs in the short term for a wide range of conditions. Tolerance can develop to their effects and there
2967-462: A withdrawal period typified by rebound insomnia and a prolonged period of anxiety and agitation. 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 residual effects that may persist into
3096-428: A worsening of the very symptoms the medications are meant to treat. Potential explanations include exacerbating cognitive problems that are already common in anxiety disorders, causing or worsening depression and suicidality, disrupting sleep architecture by inhibiting deep stage sleep, withdrawal symptoms or rebound symptoms in between doses mimicking or exacerbating underlying anxiety or sleep disorders, inhibiting
3225-495: A year or more may be needed to withdraw. 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 further benefit is that it is available in liquid form, which allows for even smaller reductions. Chlordiazepoxide , which also has
3354-661: Is a risk of life-threatening interactions with these drugs. 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. 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
3483-481: Is also a risk of dependence , and upon discontinuation a withdrawal syndrome may occur. These factors, combined with other possible secondary effects after prolonged use such as psychomotor, cognitive, or memory impairments, limit their long-term applicability. The effects of long-term use or misuse include the tendency to cause or worsen cognitive deficits , depression, and anxiety. The College of Physicians and Surgeons of British Columbia recommends discontinuing
3612-416: Is associated with an increase in all-cause mortality among those age 65 or younger, but not those older than 65. The study also found that all-cause mortality was increased further in cases in which benzodiazepines are co-prescribed with opioids, relative to cases in which benzodiazepines are prescribed without opioids, but again only in those age 65 or younger. Compared to other sedative-hypnotics, visits to
3741-545: Is associated with increased dementia risk, even after controlling for protopathic bias . Diethyl ether Most diethyl ether is produced as a byproduct of the vapor-phase hydration of ethylene to make ethanol . This process uses solid-supported phosphoric acid catalysts and can be adjusted to make more ether if the need arises: Vapor-phase dehydration of ethanol over some alumina catalysts can give diethyl ether yields of up to 95%. Diethyl ether can be prepared both in laboratories and on an industrial scale by
3870-683: 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 decline in former users, some finding no association and some indicating an increased risk of cognitive decline. 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
3999-620: Is considered a medical emergency and generally requires the immediate attention of medical personnel. The antidote for an overdose of diazepam (or any other benzodiazepine) is flumazenil (Anexate). This drug is only used in cases with severe respiratory depression or cardiovascular complications. Because flumazenil is a short-acting drug, and the effects of diazepam can last for days, several doses of flumazenil may be necessary. Artificial respiration and stabilization of cardiovascular functions may also be necessary. Though not routinely indicated, activated charcoal can be used for decontamination of
Diazepam - Misplaced Pages Continue
4128-478: Is controversial because of concerns about decreasing effectiveness , physical dependence , benzodiazepine withdrawal syndrome , and an increased risk of dementia and cancer . The elderly are at an increased risk of both short- and long-term adverse effects , and as a result, all benzodiazepines are listed in the Beers List of inappropriate medications for older adults. There is controversy concerning
4257-538: Is critical. However, this advantage is offset by the possibility of developing benzodiazepine dependence . APA does not recommend benzodiazepines for persons with depressive symptoms or a recent history of substance use disorder . APA guidelines state that, in general, pharmacotherapy of panic disorder should be continued for at least a year, and that clinical experience supports continuing benzodiazepine treatment to prevent recurrence. Although major concerns about benzodiazepine tolerance and withdrawal have been raised, there
4386-409: Is easier and more socially acceptable. 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 worldwide and clonazepam is popular in
4515-516: Is extremely flammable and may form explosive vapour/air mixtures. Since ether is heavier than air it can collect low to the ground and the vapour may travel considerable distances to ignition sources. Ether will ignite if exposed to an open flame, though due to its high flammability, an open flame is not required for ignition. Other possible ignition sources include – but are not limited to – hot plates, steam pipes, heaters, and electrical arcs created by switches or outlets. Vapour may also be ignited by
4644-399: Is given for longer than 24 hours. Sedatives and sleeping pills, including diazepam, have been associated with an increased risk of death. 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
4773-482: Is immiscible with and less dense than water. Although immiscible, it has significant solubility in water (6.05 g/(100 ml) at 25 °C ) and dissolves 1.5 g/(100 g) (1.0 g/(100 ml)) water at 25 °C. Diethyl ether has a high cetane number of 85–96 and, in combination with petroleum distillates for gasoline and diesel engines, is used as a starting fluid because of its high volatility and low flash point . Ether starting fluid
4902-854: Is limited to a narrow window within 90 minutes after each dose". 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 are unlikely to be effective long-term treatments for sleep and anxiety. While BZD therapeutic effects disappear with tolerance, depression and impulsivity with high suicidal risk commonly persist. Several studies have confirmed that long-term benzodiazepines are not significantly different from placebo for sleep or anxiety. This may explain why patients commonly increase doses over time and many eventually take more than one type of benzodiazepine after
5031-677: Is listed in the Table II precursor under the United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances as well as substances such as acetone , toluene and sulfuric acid . The compound may have been synthesised by either Jābir ibn Hayyān in the 8th century or Ramon Llull in 1275. It was synthesised in 1540 by Valerius Cordus , who called it "sweet oil of vitriol" ( oleum dulce vitrioli ) –
5160-460: Is moderately lipophilic with LogP (Octanol-Water Partition Coefficient) value of 2,82 and hydrophilic with a TPSA (Topological Polar Surface Area) value of 32.7 Ų. The LogP value indicates that diazepam has a tendency to dissolve more readily in lipid-based environments, such as chloroform, acetone, ethanol and ether, compared to water. While the TPSA value implies that a segment of the molecule exhibits
5289-572: Is neutral (i.e., pH = 7). Due to additives such as benzoic acid/benzoate in the injectable form. Diazepam has a shelf life of five years for oral tablets and three years for IV/IM solutions. Diazepam should be stored at room temperature (15–30 °C). The solution for parenteral injection should be protected from light and kept from freezing. The oral forms should be stored in air-tight containers and protected from light. Diazepam can absorb into plastics, so liquid preparations should not be kept in plastic bottles or syringes, etc. As such, it can leach into
Diazepam - Misplaced Pages Continue
5418-483: Is no evidence for significant dose escalation in patients using benzodiazepines long-term. For many such patients, stable doses of benzodiazepines retain their efficacy over several years. 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
5547-594: Is not impaired. Short-term benzodiazepine use does not lead to tolerance, and the elderly are more sensitive to them. Additionally, after stopping benzodiazepines, cognitive problems may last at least six months; it is unclear if these problems last for longer than six months or are permanent. Benzodiazepines may also cause or worsen depression. Infusions or repeated intravenous injections of diazepam when managing seizures, for example, may lead to drug toxicity, including respiratory depression, sedation and hypotension . Drug tolerance may also develop to infusions of diazepam if it
5676-474: Is not recommended during pregnancy or breastfeeding. Its mechanism of action works by increasing the effect of the neurotransmitter gamma -aminobutyric acid (GABA). Diazepam was patented in 1959 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 best-selling medication between 1968 and 1982, selling more than 2 billion tablets in 1978 alone. In 2022, it
5805-454: Is not recommended. People suspected of being dependent on benzodiazepine drugs should be very gradually tapered off the drug. Withdrawals can be life-threatening, particularly when excessive doses have been taken for extended periods of time. Equal prudence should be used whether dependence has occurred in therapeutic or recreational contexts. Diazepam is a good choice for tapering for those using high doses of other benzodiazepines since it has
5934-458: Is not the only drug to target these GABA A receptors. Drugs such as flumazenil also bind to GABA A to induce their effects. Diazepam appears to act on areas of the limbic system , thalamus , and hypothalamus , inducing anxiolytic effects. Benzodiazepine drugs including diazepam increase the inhibitory processes in the cerebral cortex . Benzodiazepine Benzodiazepines ( BZD , BDZ , BZs ), colloquially known as " benzos ", are
6063-424: Is recommended. 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 some cases a year or longer. Protracted symptoms tend to resemble those seen during
6192-412: Is required when benzodiazepines are used in people with personality disorders or intellectual disability because of frequent paradoxical reactions . In major depression , they may precipitate suicidal tendencies and are sometimes used for suicidal overdoses. Individuals with a history of excessive alcohol use or non-medical use of opioids or barbiturates should avoid benzodiazepines, as there
6321-421: Is safely used in patients with shock as it preserves the baroreceptor reflex . Its minimal effect on myocardial depression and respiratory drive, as well as its low cost and high therapeutic index allows it to see continued use in developing countries. Diethyl ether could also be mixed with other anesthetic agents such as chloroform to make C.E. mixture , or chloroform and alcohol to make A.C.E. mixture . In
6450-727: Is significant, and patients experience symptoms of benzodiazepine withdrawal syndrome if it is taken for six weeks or longer. In humans, tolerance to the anticonvulsant effects of diazepam occurs frequently. Improper or excessive use of diazepam can lead to dependence . At a particularly high risk for diazepam misuse, substance use disorder or dependence are: Patients from the aforementioned groups should be monitored very closely during therapy for signs of abuse and development of dependence. Therapy should be discontinued if any of these signs are noted, although if dependence has developed, therapy must still be discontinued gradually to avoid severe withdrawal symptoms. Long-term therapy in such instances
6579-433: Is sold and used in countries with cold climates, as it can help with cold starting an engine at sub-zero temperatures. For the same reason it is also used as a component of the fuel mixture for carbureted compression ignition model engines . Triethyloxonium tetrafluoroborate is prepared from boron trifluoride , diethyl ether, and epichlorohydrin : Diethyl ether is a common laboratory aprotic solvent . Diethyl ether
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#17327721027096708-414: Is susceptible to formation of hydroperoxides . A cytochrome P450 enzyme is proposed to metabolize diethyl ether. Diethyl ether inhibits alcohol dehydrogenase , and thus slows the metabolism of ethanol . It also inhibits metabolism of other drugs requiring oxidative metabolism . For example, diazepam requires hepatic oxidization whereas its oxidized metabolite oxazepam does not. Diethyl ether
6837-588: Is the most effective in preventing and controlling acute seizures. Benzodiazepines are often prescribed for a wide range of conditions: Benzodiazepines require special precaution if used in the elderly, during pregnancy, in children, alcohol or drug-dependent individuals and individuals with comorbid psychiatric disorders . 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
6966-1057: Is typically issued to service members, along with three Mark I NAAK kits, when operating in circumstances where chemical weapons in the form of nerve agents are considered a potential hazard. Both of these kits deliver drugs using autoinjectors . They are intended for use in "buddy aid" or "self aid" administration of the drugs in the field prior to decontamination and delivery of the patient to definitive medical care. Use of diazepam should be avoided, when possible, in individuals with: Benzodiazepines, such as diazepam, can cause anterograde amnesia , confusion, and sedation . The elderly are more prone to diazepam's confusion, amnesia, ataxia, hangover symptoms, and falls. Long-term use of benzodiazepines, such as diazepam, induces tolerance, dependency, and withdrawal syndrome. Like other benzodiazepines, diazepam impairs short-term memory and learning new information. Diazepam and other benzodiazepines can produce anterograde amnesia, but not retrograde amnesia . It means information learned before using benzodiazepines
7095-441: Is typically supplied with trace amounts of the antioxidant butylated hydroxytoluene (BHT), which reduces the formation of peroxides. Storage over sodium hydroxide precipitates the intermediate ether hydroperoxides. Water and peroxides can be removed by either distillation from sodium and benzophenone , or by passing through a column of activated alumina . Due to its application in the manufacturing of illicit substances, it
7224-488: The GABA A 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 , panic disorder , insomnia , agitation , seizures , muscle spasms , alcohol withdrawal and as
7353-516: The Government of Victoria 's (Australia) Department of Health , long-term use can cause "impaired thinking or memory loss, anxiety and depression, irritability, paranoia, aggression, etc." A minority of people have paradoxical reactions after taking benzodiazepines such as worsened agitation or panic. Benzodiazepines are associated with an increased risk of suicide due to aggression, impulsivity, and negative withdrawal effects. Long-term use
7482-619: The Lethe River (Λήθη, meaning "forgetfulness, oblivion"). However, Crawford Williamson Long is now known to have demonstrated its use privately as a general anesthetic in surgery to officials in Georgia, as early as March 30, 1842, and Long publicly demonstrated ether's use as a surgical anesthetic on six occasions before the Boston demonstration. British doctors were aware of the anesthetic properties of ether as early as 1840 where it
7611-586: 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 for toxicity and fatal overdose increases significantly. Benzodiazepines are commonly used recreationally and also often taken in combination with other addictive substances, and are controlled in most countries. Benzodiazepines possess psycholeptic , sedative , hypnotic , anxiolytic , anticonvulsant, muscle relaxant , and amnesic actions, which are useful in
7740-462: The first-line treatment options with the anticonvulsant drug pregabalin indicated as a second- or third-line treatment and suitable for long-term use. NICE stated that long-term use of benzodiazepines for panic disorder with or without agoraphobia is an unlicensed indication, does not have long-term efficacy, and is, therefore, not recommended by clinical guidelines. Psychological therapies such as cognitive behavioural therapy are recommended as
7869-422: The muscle relaxant effects of benzodiazepines such as diazepam. Baclofen is sometimes used as an alternative to diazepam. Diazepam is marketed in over 500 brands throughout the world. It is supplied in oral, injectable, inhalation, and rectal forms. The United States military employs a specialized diazepam preparation known as Convulsive Antidote, Nerve Agent ( CANA ), which contains diazepam. One CANA kit
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#17327721027097998-450: The 'P'-conformer and 'M'-conformer. Diazepam is an equimolar mixture and it was shown through CD spectra in serum protein solutions, that the 'P'-conformer is preferred by α1-acid glycoprotein binding. The drug diazepam occurs as a pale yellow-white crystalline powder without distinctive smell and has a low molecular weight (MW = 284.74 g/mol). This classic aryl 1,4-benzodiazepine possesses three acceptors and no hydrogen bond donors. Diazepam
8127-479: The 19th century called ether frolics , where guests were encouraged to inhale therapeutic amounts of diethyl ether or nitrous oxide , producing a state of excitation. Long, as well as fellow dentists Horace Wells , William Edward Clarke and William T. G. Morton observed that during these gatherings, people would often experience minor injuries but appear to show no reaction to the injury, nor memory that it had happened, demonstrating ether's anaesthetic effects. In
8256-487: The 21st century, ether is rarely used. The use of flammable ether was displaced by nonflammable fluorinated hydrocarbon anesthetics. Halothane was the first such anesthetic developed and other currently used inhaled anesthetics, such as isoflurane , desflurane , and sevoflurane , are halogenated ethers. Diethyl ether was found to have undesirable side effects, such as post-anesthetic nausea and vomiting. Modern anesthetic agents reduce these side effects. Prior to 2005, it
8385-480: The GABA type A receptors ( GABA A ). The GABA A receptors are ligand-gated chloride-selective ion channels that are activated by GABA , the major inhibitory neurotransmitter in the brain. Binding of benzodiazepines to this receptor complex promotes the binding of GABA, which in turn increases the total conduction of chloride ions across the neuronal cell membrane. This increased chloride ion influx hyperpolarizes
8514-541: The Netherlands, Belgium and France. Clobazam was approved for use in the United States in 2011. In the UK, both clobazam and clonazepam are second-line choices for treating many forms of epilepsy. Clobazam also has a useful role for very short-term seizure prophylaxis and in catamenial epilepsy . Discontinuation after long-term use in epilepsy requires additional caution because of the risks of rebound seizures. Therefore,
8643-523: The accuracy of studies that were not placebo-controlled. And, based on the findings of placebo-controlled studies , they do not recommend use of benzodiazepines beyond two to four weeks, as tolerance and physical dependence develop rapidly, with withdrawal symptoms including rebound anxiety occurring after six weeks or more of use. Nevertheless, benzodiazepines are still prescribed for long-term treatment of anxiety disorders , although specific antidepressants and psychological therapies are recommended as
8772-486: The acid ether synthesis. The dominant use of diethyl ether is as a solvent. One particular application is in the production of cellulose plastics such as cellulose acetate . It is a common solvent for the Grignard reaction in addition to other reactions involving organometallic reagents. These uses exploit its basicity. Diethyl ether is a popular non-polar solvent in liquid-liquid extraction . As an extractant, it
8901-507: The amnesic effects does not occur. However, controversy exists as to tolerance to the anxiolytic effects with some evidence that benzodiazepines retain efficacy and opposing evidence from a systematic review of the literature that tolerance frequently occurs and some evidence that anxiety may worsen with long-term use. The question of tolerance to the amnesic effects of benzodiazepines is, likewise, unclear. Some evidence suggests that partial tolerance does develop, and that, "memory impairment
9030-400: The anticonvulsant effects. Because of its relatively long duration of action, and evidence of safety and efficacy, diazepam is preferred over other benzodiazepines for treatment of persons experiencing moderate to severe alcohol withdrawal. An exception to this is when a medication is required intramuscular in which case either lorazepam or midazolam is recommended. Diazepam is used for
9159-642: The benefits of psychotherapy by inhibiting memory consolidation and reducing fear extinction, and reducing coping with trauma/stress and increasing vulnerability to future stress. The latter two explanations may be why benzodiazepines are ineffective and/or potentially harmful in PTSD and phobias . Anxiety, insomnia and irritability may be temporarily exacerbated during withdrawal, but psychiatric symptoms after discontinuation are usually less than even while taking benzodiazepines. Functioning significantly improves within 1 year of discontinuation. The main problem of
9288-476: The benzodiazepine medication itself. The benzodiazepines with a longer half-life make detoxification more tolerable, and dangerous (and potentially lethal) alcohol withdrawal effects are less likely to occur. On the other hand, short-acting benzodiazepines may lead to breakthrough seizures , and are, therefore, not recommended for detoxification in an outpatient setting. Oxazepam and lorazepam are often used in patients at risk of drug accumulation, in particular,
9417-453: The best choice of pharmacotherapy for many patients with panic disorder, but benzodiazepines are also often used, and some studies suggest that these medications are still used with greater frequency than the SSRIs. One advantage of benzodiazepines is that they alleviate the anxiety symptoms much faster than antidepressants, and therefore may be preferred in patients for whom rapid symptom control
9546-446: 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 effects develops more slowly with little evidence of continued effectiveness beyond four to six months of continued use. In general, tolerance to
9675-751: The course of therapy, tolerance to the sedative effects usually develops, but not to the anxiolytic and myorelaxant effects. Patients with severe attacks of apnea during sleep may experience respiratory depression (hypoventilation), leading to respiratory arrest and death. Diazepam in doses of 5 mg or more causes significant deterioration in alertness performance combined with increased feelings of sleepiness. Diazepam, as with other benzodiazepine drugs, can cause tolerance, physical dependence, substance use disorder , and benzodiazepine withdrawal syndrome . Withdrawal from diazepam or other benzodiazepines often leads to withdrawal symptoms similar to those seen during barbiturate or alcohol withdrawal. The higher
9804-413: The decision to treat febrile seizures (which are benign in nature) with medication should use this as part of the evaluation. Long-term use of diazepam for the management of epilepsy is not recommended; however, a subgroup of individuals with treatment-resistant epilepsy benefit from long-term benzodiazepines, and for such individuals, clorazepate has been recommended due to its slower onset of tolerance to
9933-589: The delivery may result in a floppy infant syndrome . Newborns with this condition tend to have hypotonia , hypothermia , lethargy , and breathing and feeding difficulties. Cases of neonatal withdrawal syndrome have been described in infants chronically exposed to benzodiazepines in utero . This syndrome may be hard to recognize, as it starts several days after delivery, for example, as late as 21 days for chlordiazepoxide. The symptoms include tremors , hypertonia , hyperreflexia , hyperactivity , and vomiting and may last for up to three to six months. Tapering down
10062-431: The development of diazepam (Valium) three years later, in 1963. By 1977, benzodiazepines were the most prescribed medications globally; the introduction of selective serotonin reuptake inhibitors (SSRIs), among other factors, decreased rates of prescription, but they remain frequently used worldwide. Benzodiazepines are depressants that enhance the effect of the neurotransmitter gamma-aminobutyric acid (GABA) at
10191-552: The dose and the longer the drug is taken, the greater the risk of experiencing unpleasant withdrawal symptoms. Withdrawal symptoms can occur from standard dosages and also after short-term use, and can range from insomnia and anxiety to more serious symptoms, including seizures and psychosis. Withdrawal symptoms can sometimes resemble pre-existing conditions and be misdiagnosed. Diazepam may produce less intense withdrawal symptoms due to its long elimination half-life . Benzodiazepine treatment should be discontinued as soon as possible by
10320-430: The dose during pregnancy may lessen its severity. If used in pregnancy, those benzodiazepines with a better and longer safety record, such as diazepam or chlordiazepoxide , are recommended over potentially more harmful benzodiazepines, such as temazepam or triazolam . Using the lowest effective dose for the shortest period of time minimizes the risks to the unborn child. The benefits of benzodiazepines are least and
10449-406: The dose is slowly tapered over a period of up to six months or longer. 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 dependence to
10578-481: The effect of GABA. About one-third of individuals who take benzodiazepines for longer than four weeks become dependent and experience withdrawal syndrome on cessation. Differences in rates of withdrawal (50–100%) vary depending on the patient sample. For example, a random sample of long-term benzodiazepine users typically finds around 50% experience few or no withdrawal symptoms, with the other 50% experiencing notable withdrawal symptoms. Certain select patient groups show
10707-425: The effects of long-term administration. One view is that many of the short-term effects continue into the long-term and may even worsen, and are not resolved after stopping benzodiazepine usage. Another view maintains that cognitive deficits in chronic benzodiazepine users occur only for a short period after the dose, or that the anxiety disorder is the cause of these deficits. While the definitive studies are lacking,
10836-440: The elderly and those with cirrhosis , because they are metabolized differently from other benzodiazepines, through conjugation . 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
10965-459: The elderly can also worsen dementia. 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 particularly in the elderly. Another result is impairment of driving skills and increased likelihood of road traffic accidents. Decreased libido and erection problems are
11094-468: The elderly can resemble dementia , depression, or anxiety syndromes , and progressively worsens over time. Adverse effects on cognition can be mistaken for the effects of old age. The benefits of withdrawal include improved cognition, alertness, mobility, reduced risk of incontinence, and a reduced risk of falls and fractures. The success of gradual-tapering benzodiazepines is as great in the elderly as in younger people. Benzodiazepines should be prescribed to
11223-535: The elderly only with caution and only for a short period at low doses. Short to intermediate-acting benzodiazepines are preferred in the elderly such as oxazepam and temazepam . The high potency benzodiazepines alprazolam and triazolam and long-acting benzodiazepines are not recommended in the elderly due to increased adverse effects. Nonbenzodiazepines such as zaleplon and zolpidem and low doses of sedating antidepressants are sometimes used as alternatives to benzodiazepines. Long-term use of benzodiazepines
11352-466: The emergency treatment of eclampsia , when IV magnesium sulfate and blood-pressure control measures have failed. Benzodiazepines do not have any pain-relieving properties themselves, and are generally recommended to avoid in individuals with pain. However, benzodiazepines such as diazepam can be used for their muscle-relaxant properties to alleviate pain caused by muscle spasms and various dystonias , including blepharospasm . Tolerance often develops to
11481-417: The first couple of months of withdrawal but usually are of a sub-acute level of severity. Such symptoms do gradually lessen over time, eventually disappearing altogether. 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
11610-448: The first loses effectiveness. Additionally, because tolerance to benzodiazepine sedating effects develops more quickly than does tolerance to brainstem depressant effects, those taking more benzodiazepines to achieve desired effects may experience sudden respiratory depression, hypotension or death. Most patients with anxiety disorders and PTSD have symptoms that persist for at least several months, making tolerance to therapeutic effects
11739-454: 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 detected impairment. Some of the other impairments reported were decreased IQ, visiomotor coordination, information processing, verbal learning and concentration. The authors of
11868-488: The hospital and as follow-up. Overdoses of diazepam with alcohol, opiates, or other depressants may be fatal. If diazepam is administered concomitantly with other drugs, attention should be paid to the possible pharmacological interactions. Particular care should be taken with drugs that potentiate the effects of diazepam, such as barbiturates, phenothiazines , opioids , and antidepressants . Diazepam does not increase or decrease hepatic enzyme activity, and does not alter
11997-522: 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 increased odds of a serious health outcome. In September 2020, the US Food and Drug Administration (FDA) required the boxed warning be updated for all benzodiazepine medicines to describe
12126-478: The hypnotic based on cost and the patient's preference. 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, and falls and hip fracture for older patients. Prolonged convulsive epileptic seizures are
12255-526: The idea was disproved in about 1800. The synthesis of diethyl ether by a reaction between ethanol and sulfuric acid has been known since the 13th century. William T. G. Morton participated in a public demonstration of ether anesthesia on October 16, 1846, at the Ether Dome in Boston, Massachusetts . Morton had called his ether preparation, with aromatic oils to conceal its smell, " Letheon " after
12384-428: The immediate management of GAD, if necessary. However, they should not usually be given for longer than 2–4 weeks. The only medications NICE recommends for the longer term management of GAD are antidepressants. 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
12513-524: 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 disorder treatments over another. The choice of treatment between benzodiazepines, SSRIs, serotonin–norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants , and psychotherapy should be based on the patient's history, preference, and other individual characteristics. Selective serotonin reuptake inhibitors are likely to be
12642-427: The lowest effective dose. They improve sleep-related problems by shortening the time spent in bed before falling asleep, prolonging the sleep time, and, in general, reducing wakefulness. However, they worsen sleep quality by increasing light sleep and decreasing deep sleep. Other drawbacks of hypnotics, including benzodiazepines, are possible tolerance to their effects, rebound insomnia , and reduced slow-wave sleep and
12771-414: The medicines in the class. Diazepam has a range of side effects common to most benzodiazepines, including: Less commonly, paradoxical reactions can occur, including nervousness, irritability, excitement, worsening of seizures, insomnia, muscle cramps, changes in libido , and in some cases, rage and violence. These adverse reactions are more likely to occur in children, the elderly, and individuals with
12900-584: The meta-analysis and a later reviewer noted that the applicability of this meta-analysis is limited because the subjects were taken mostly from withdrawal clinics; the coexisting drug, alcohol use, and psychiatric disorders were not defined; and several of the included studies conducted the cognitive measurements during the withdrawal period. 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
13029-1068: The metabolism of other compounds. No evidence would suggest diazepam alters its own metabolism with chronic administration. Agents with an effect on hepatic cytochrome P450 pathways or conjugation can alter the rate of diazepam metabolism. These interactions would be expected to be most significant with long-term diazepam therapy, and their clinical significance is variable. Diazepam is a long-acting "classical" benzodiazepine. Other classical benzodiazepines include chlordiazepoxide , clonazepam , lorazepam , oxazepam , nitrazepam , temazepam , flurazepam , bromazepam , and clorazepate . Diazepam has anticonvulsant properties. Benzodiazepines act via micromolar benzodiazepine binding sites as calcium channel blockers and significantly inhibit depolarization-sensitive calcium uptake in rat nerve cell preparations. Diazepam inhibits acetylcholine release in mouse hippocampal synaptosomes . This has been found by measuring sodium-dependent high-affinity choline uptake in mouse brain cells in vitro , after pretreatment of
13158-448: The mice with diazepam in vivo . This may play a role in explaining diazepam's anticonvulsant properties. Diazepam binds with high affinity to glial cells in animal cell cultures. Diazepam at high doses has been found to decrease histamine turnover in mouse brain via diazepam's action at the benzodiazepine-GABA receptor complex. Diazepam also decreases prolactin release in rats. Benzodiazepines are positive allosteric modulators of
13287-447: The most important risk factor for disinhibition; learning disabilities and neurological disorders are also significant risks. Most reports of disinhibition involve high doses of high-potency benzodiazepines. Paradoxical effects may also appear after chronic use of benzodiazepines. 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
13416-418: The name reflects the fact that it is obtained by distilling a mixture of ethanol and sulfuric acid (then known as oil of vitriol) – and noted some of its medicinal properties . At about the same time, Paracelsus discovered the analgesic properties of the molecule in dogs. The name ether was given to the substance in 1729 by August Sigmund Frobenius . It was considered to be a sulfur compound until
13545-486: The neuron's membrane potential . As a result, the difference between resting potential and threshold potential is increased and firing is less likely. As a result, the arousal of the cortical and limbic systems in the central nervous system is reduced. The GABA A receptor is a heteromer composed of five subunits, the most common ones being two αs, two βs, and one γ (α2β2γ). For each subunit, many subtypes exist (α1–6, β1–3, and γ1–3). GABA A receptors containing
13674-476: The new non benzodiazepine hypnotics (Z-drugs) are better than the short-acting benzodiazepines. The efficacy of these two groups of medications is similar. According to the US Agency for Healthcare Research and Quality , indirect comparison indicates that side-effects from benzodiazepines may be about twice as frequent as from nonbenzodiazepines. Some experts suggest using nonbenzodiazepines preferentially as
13803-414: The next day and are, in general, not recommended. Since the release of nonbenzodiazepines , also known as z-drugs, 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 as to whether
13932-574: The patient was treated but worse than before. Withdrawal symptoms are the new symptoms that occur when the benzodiazepine is stopped. They are the main sign of physical dependence . 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 delirium tremens . Severe symptoms usually occur as
14061-520: The plastic bags and tubing used for intravenous infusions. Absorption appears to depend on several factors, such as temperature, concentration, flow rates, and tube length. Diazepam should not be administered if a precipitate has formed and does not dissolve. Diazepam is mainly used to treat anxiety, insomnia, panic attacks and symptoms of acute alcohol withdrawal. It is also used as a premedication for inducing sedation, anxiolysis, or amnesia before certain medical procedures (e.g., endoscopy ). In 2020, it
14190-656: The result of suppression of withdrawal effects. 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, cancer, infections, pancreatitis and respiratory disease exacerbations. 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
14319-412: The risk of seizure induced brain and cardiac damage. Dosages should be determined on an individual basis, depending on the condition being treated, severity of symptoms, patient body weight, and any other conditions the person may have. Intravenous diazepam or lorazepam are first-line treatments for status epilepticus. However, intravenous lorazepam has advantages over intravenous diazepam, including
14448-584: 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, daytime sedation, impaired motor coordination, and increased risk of motor vehicle accidents and falls, and an increased risk of hip fractures . The long-term effects of benzodiazepines and benzodiazepine dependence in
14577-437: The risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions consistently across all the medicines in the class. 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
14706-432: 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 . In an overdose, benzodiazepines can cause dangerous deep unconsciousness , but are less toxic than their predecessors,
14835-411: The seizure threshold and can worsen withdrawal effects; if used extreme caution is required. 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
14964-544: The severity of the withdrawal syndrome and increases the failure rate. A slow and gradual withdrawal customised to the individual and, if indicated, psychological support is the most effective way of managing the withdrawal. Opinion as to the time needed to complete withdrawal ranges from four weeks to several years. A goal of less than six months has been suggested, but due to factors such as dosage and type of benzodiazepine, reasons for prescription, lifestyle, personality, environmental stresses , and amount of available support,
15093-429: The short and long term. 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 possible. It is preferred that benzodiazepines be taken intermittently and at
15222-453: The static electricity which can build up when ether is being poured from one vessel into another. The autoignition temperature of diethyl ether is 160 °C (320 °F). The diffusion of diethyl ether in air is 9.18 × 10 m /s (298 K, 101.325 kPa). Ether is sensitive to light and air, tending to form explosive peroxides . Ether peroxides have a higher boiling point than ether and are contact explosives when dry. Commercial diethyl ether
15351-714: The stomach following a diazepam overdose. Emesis is contraindicated. Dialysis is minimally effective. Hypotension may be treated with levarterenol or metaraminol . The oral LD 50 (lethal dose in 50% of the population) of diazepam is 720 mg/kg in mice and 1240 mg/kg in rats. D. J. Greenblatt and colleagues reported in 1978 on two patients who had taken 500 mg and 2000 mg of diazepam, respectively, went into moderately-deep comas, and were discharged within 48 hours without having experienced any important complications, in spite of having high concentrations of diazepam and its metabolites desmethyldiazepam , oxazepam, and temazepam, according to samples taken in
15480-408: The subsequent loss of control over socially unacceptable behavior. Paradoxical reactions are rare in the general population, with an incidence rate below 1% and similar to placebo. However, they occur with greater frequency in recreational abusers, individuals with borderline personality disorder , children, and patients on high-dosage regimes. In these groups, impulse control problems are perhaps
15609-640: 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 those holding benzodiazepines are not effective long-term and should be reserved for treatment-resistant cases to those holding they are as effective in the long term as selective serotonin reuptake inhibitors (SSRIs). American Psychiatric Association (APA) guidelines, published in January 2009, note that, in general, benzodiazepines are well tolerated, and their use for
15738-419: The treatment of seizures due to a drug overdose or chemical toxicity as a result of exposure to sarin , VX , or soman (or other organophosphate poisons), lindane , chloroquine , physostigmine , or pyrethroids . Diazepam is sometimes used intermittently for the prevention of febrile seizures that may occur in children under five years of age. Recurrence rates are reduced, but side effects are common so
15867-421: The usage of benzodiazepines in those on opioids and those who have used them long term. Benzodiazepines can have serious adverse health outcomes, and these findings support clinical and regulatory efforts to reduce usage, especially in combination with non-benzodiazepine receptor agonists. Because of their effectiveness, tolerability, and rapid onset of anxiolytic action, benzodiazepines are frequently used for
15996-467: The α1 subunit mediate the sedative, the anterograde amnesic, and partly the anticonvulsive effects of diazepam. GABA A receptors containing α2 mediate the anxiolytic actions and to a large degree the myorelaxant effects. GABA A receptors containing α3 and α5 also contribute to benzodiazepines myorelaxant actions, whereas GABA A receptors comprising the α5 subunit were shown to modulate the temporal and spatial memory effects of benzodiazepines. Diazepam
16125-465: Was approved for use in the United States as a nasal spray to interrupt seizure activity in people with epilepsy . Diazepam is the most commonly used benzodiazepine for "tapering" benzodiazepine dependence due to the drug's comparatively long half-life, allowing for more efficient dose reduction. Benzodiazepines have a relatively low toxicity in overdose. Diazepam has a number of uses, including: Used in treatment of organophosphate poisoning and reduces
16254-559: Was on the World Health Organization's List of Essential Medicines for use as an anesthetic. Ether was once used in pharmaceutical formulations. A mixture of alcohol and ether, one part of diethyl ether and three parts of ethanol, was known as "Spirit of ether" , Hoffman's Anodyne or Hoffman's Drops. In the United States this concoction was removed from the Pharmacopeia at some point prior to June 1917, as
16383-413: Was the 169th most commonly prescribed medication in the United States, with more than 3 million prescriptions. In 1985, the patent ended, and there are more than 500 brands available on the market. It is on the World Health Organization's List of Essential Medicines . Diazepam does not possess any chiral centers in its structure, but it does have two conformers . The two conformers mentioned were
16512-401: Was unsuccessful. Although they are second-line agents, benzodiazepines can be used for a limited time to relieve severe anxiety and agitation. CPA guidelines note that after 4–6 weeks the effect of benzodiazepines may decrease to the level of placebo, and that benzodiazepines are less effective than antidepressants in alleviating ruminative worry , the core symptom of GAD. However, in some cases,
16641-429: Was widely prescribed in conjunction with opium. Diethyl ether was preferred by some practitioners over chloroform as a general anesthetic due to ether's more favorable therapeutic index , that is, a greater difference between an effective dose and a potentially toxic dose. Diethyl ether does not depress the myocardium but rather it stimulates the sympathetic nervous system leading to hypertension and tachycardia. It
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