diazepam diazepam diazepam, first marketed as valium, is a medicine of the benzodiazepine family that acts as an anxiolytic. it is commonly 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 by mouth, inserted into the rectum, injected into muscle, injected into a vein or used as a nasal spray. when given into a vein, effects begin in one to five minutes and last up to an hour. by mouth, effects begin after 15 to 60 minutes. diazepamclinical datapronunciation/daɪˈæzɪpæm/ dy-az-ip-am trade namesvalium, vazepam, valtoco, othersahfs/drugs.commonographmedlineplusa682047license data us dailymed: diazepam us fda: diazepam pregnancycategory au: c dependenceliabilityhighaddictionliabilitymoderateroutes ofadministrationby mouth, intramuscular, intravenous, rectal, nasalatc coden05ba01 (who) legal statuslegal status au: s4 (prescription only) br: class b1 (psychoactive drugs) ca: schedule iv de: prescription only (anlage iii for higher doses) nz: class c uk: class c us: schedule iv un: psychotropic schedule iv in general: ℞ (prescription only) pharmacokinetic databioavailability76% (64–97%) by mouth, 81% (62–98%) rectalmetabolismliver – cyp2b6 (minor route) to desmethyldiazepam, cyp2c19 (major route) to inactive metabolites, cyp3a4 (major route) to desmethyldiazepamelimination half-life(50 hours); 20–100 hours (36–200 hours for main active metabolite desmethyldiazepam)excretionkidneyidentifiers iupac name 7-chloro-1,3-dihydro-1-methyl-5-phenyl-3h-1,4-benzodiazepin-2-one cas number439-14-5 ypubchem cid3016iuphar/bps3364drugbankdb00829 nchemspider2908 yuniiq3jtx2q7tukeggd00293 ychebichebi:49575 ychemblchembl12 ycomptox dashboard (epa)dtxsid4020406 echa infocard100.006.476 chemical and physical dataformulac16h13cln2omolar mass284.74 g·mol−13d model (jsmol)interactive image smiles c1ccccc1c2=ncc(=o)n(c)c3ccc(cl)cc23 inchi inchi=1s/c16h13cln2o/c1-19-14-8-7-12(17)9-13(14)16(18-10-15(19)20)11-5-3-2-4-6-11/h2-9h,10h2,1h3 ykey:aaovkjbebidnhe-uhfffaoysa-n y ny (what is this?) (verify) 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 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 2020, it was the 128th most commonly prescribed medication in the united states, with more than 4 million prescriptions. in 1985 the patent ended, and there are now more than 500 brands available on the market. it is on the world health organization's list of essential medicines. medical uses diazepam tablets (10, 5, and 2 mg) 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 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: treatment of anxiety, panic attacks, and states of agitation treatment of neurovegetative symptoms associated with vertigo treatment of the symptoms of alcohol, opiate, and benzodiazepine withdrawal short-term treatment of insomnia treatment of muscle spasms treatment of tetanus, together with other measures of intensive treatment adjunctive treatment of spastic muscular paresis (paraplegia/tetraplegia) caused by cerebral or spinal cord conditions such as stroke, multiple sclerosis, or spinal cord injury (long-term treatment is coupled with other rehabilitative measures) palliative treatment of stiff person syndrome pre- or postoperative sedation, anxiolysis or amnesia (e.g., before endoscopic or surgical procedures) treatment of complications with stimulant overdoses and psychosis, such as cocaine or methamphetamine used in treatment of organophosphate poisoning and reduces the risk of seizure induced brain and cardiac damage. preventive treatment of oxygen toxicity during hyperbaric oxygen therapy 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. seizures intravenous diazepam or lorazepam are first-line treatments for status epilepticus. however, intravenous lorazepam has advantages over intravenous diazepam, including 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 12 months of treatment, effectively rendering it useless for that purpose. the anticonvulsant effects of diazepam can help in 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 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 the anticonvulsant effects. alcohol withdrawal 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. other diazepam is used for 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 the muscle relaxant effects of benzodiazepines such as diazepam. baclofen is sometimes used as an alternative to diazepam. availability 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 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. contraindications use of diazepam should be avoided, when possible, in individuals with: ataxia severe hypoventilation acute narrow-angle glaucoma severe hepatic deficiencies (hepatitis and liver cirrhosis decrease elimination by a factor of two) severe renal deficiencies (for example, patients on dialysis) liver disorders severe sleep apnea severe depression, particularly when accompanied by suicidal tendencies psychosis pregnancy or breast feeding caution required in elderly or debilitated patients coma or shock abrupt discontinuation of therapy acute intoxication with alcohol, narcotics, or other psychoactive substances (with the exception of hallucinogens or some stimulants, where it is occasionally used as a treatment for overdose) history of alcohol or drug dependence myasthenia gravis, an autoimmune disorder causing marked fatiguability hypersensitivity or allergy to any drug in the benzodiazepine class caution benzodiazepine abuse and misuse should be guarded against when prescribed to those with alcohol or drug dependencies or who have psychiatric disorders. pediatric patients less than 18 years of age, this treatment is usually not indicated, except for treatment of epilepsy, and pre- or postoperative treatment. the smallest possible effective dose should be used for this group of patients. under 6 months of age, safety and effectiveness have not been established; diazepam should not be given to those in this age group. elderly and very ill patients can possibly experience apnea or cardiac arrest. concomitant use of other central nervous system depressants increases this risk. the smallest possible effective dose should be used for this group of people. the elderly metabolise benzodiazepines much more slowly than younger adults, and are also more sensitive to the effects of benzodiazepines, even at similar blood plasma levels. doses of diazepam are recommended to be about half of those given to younger people, and treatment limited to a maximum of two weeks. long-acting benzodiazepines such as diazepam are not recommended for the elderly. diazepam can also be dangerous in geriatric patients owing to a significant increased risk of falls. intravenous or intramuscular injections in hypotensive people or those in shock should be administered carefully and vital signs should be monitored. benzodiazepines such as diazepam are lipophilic and rapidly penetrate membranes, so rapidly cross over into the placenta with significant uptake of the drug. use of benzodiazepines including diazepam in late pregnancy, especially high doses, can result in floppy infant syndrome. diazepam when taken late in pregnancy, during the third trimester, causes a definite risk of a severe benzodiazepine withdrawal syndrome in the neonate with symptoms including hypotonia, and reluctance to suck, to apnoeic spells, cyanosis, and impaired metabolic responses to cold stress. floppy infant syndrome and sedation in the newborn may also occur. symptoms of floppy infant syndrome and the neonatal benzodiazepine withdrawal syndrome have been reported to persist from hours to months after birth. adverse effects 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 is not impaired. long-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 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 the medicines in the class. diazepam has a range of side effects common to most benzodiazepines, including: suppression of rem sleep and slow wave sleep impaired motor function impaired coordination impaired balance dizziness reflex tachycardia less commonly, paradoxical side effects 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 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 behaviors 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 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. tolerance and withdrawal