lorazepam lorazepam lorazepam, sold under the brand name ativan among others, is a benzodiazepine medication. it is used to treat anxiety disorders, trouble sleeping, severe agitation, active seizures including status epilepticus, alcohol withdrawal, and chemotherapy-induced nausea and vomiting. it is also used during surgery to interfere with memory formation and to sedate those who are being mechanically ventilated. it is also used, along with other treatments, for acute coronary syndrome due to cocaine use. it can be given by mouth or as an injection into a muscle or vein. when given by injection onset of effects is between one and thirty minutes and effects last for up to a day. not to be confused with loprazolam or lormetazepam. lorazepamclinical datatrade namesativan, tavor, temesta, othersother nameso-chloroxazepam, l-lorazepam acetateahfs/drugs.commonographmedlineplusa682053license data us dailymed: lorazepam pregnancycategory au: c dependenceliabilityvery highaddictionliabilitymoderate - highroutes ofadministrationby mouth, intramuscular, intravenous, transdermalatc coden05ba06 (who) legal statuslegal status au: s4 (prescription only) ca: schedule iv de: prescription only (anlage iii for higher doses) uk: controlled drug (benz) pom us: schedule iv pharmacokinetic databioavailability85% when taken by mouthmetabolismliver glucuronidationonset of action1–5 min (iv), 15–30 min (im)elimination half-life10–20 hoursduration of action12–24 hours (iv, im)excretionkidneyidentifiers iupac name 7-chloro-5-(2-chlorophenyl)-3-hydroxy-1,3-dihydro-1,4-benzodiazepin-2-one cas number846-49-1 ypubchem cid3958drugbankdb00186 nchemspider3821 yuniio26fzp769lkeggd00365 ychebichebi:6539chemblchembl580 ycomptox dashboard (epa)dtxsid7023225 echa infocard100.011.534 chemical and physical dataformulac15h10cl2n2o2molar mass321.16 g·mol−13d model (jsmol)interactive image smiles o=c1nc2ccc(cl)cc2c(c2ccccc2cl)=nc1o inchi inchi=1s/c15h10cl2n2o2/c16-8-5-6-12-10(7-8)13(19-15(21)14(20)18-12)9-3-1-2-4-11(9)17/h1-7,15,21h,(h,18,20) ykey:diwrorzwfloclc-uhfffaoysa-n y ny (what is this?) (verify) common side effects include weakness, sleepiness, low blood pressure, and a decreased effort to breathe. when given intravenously, the person should be closely monitored. among those who are depressed, there may be an increased risk of suicide. with long-term use, larger doses may be required for the same effect. physical dependence and psychological dependence may also occur. if stopped suddenly after long-term use, benzodiazepine withdrawal syndrome may occur. older people more often develop adverse effects. in this age group, lorazepam is associated with falls and hip fractures. due to these concerns, lorazepam use is generally only recommended for up to two to four weeks. lorazepam was initially patented in 1963 and went on sale in the united states in 1977. it is on the world health organization's list of essential medicines. it is available as a generic medication. in 2020, it was the 65th most commonly prescribed medication in the united states, with more than 10 million prescriptions. medical uses anxiety lorazepam is used in the short-term management of severe anxiety. in the us, the fda advises against use of benzodiazepines such as lorazepam for longer than four weeks. it is fast acting, and useful in treating fast onset panic anxiety. lorazepam can effectively reduce agitation and induce sleep, and the duration of effects from a single dose makes it an appropriate choice for the short-term treatment of insomnia, especially in the presence of severe anxiety or night terrors. it has a fairly short duration of action. withdrawal symptoms, including rebound insomnia and rebound anxiety, may occur after seven days' use of lorazepam. seizures intravenous diazepam or lorazepam are first-line treatments for convulsive status epilepticus. lorazepam is more effective than diazepam and intravenous phenytoin in the treatment of status epilepticus and has a lower risk of continuing seizures that might require additional medication. however, phenobarbital has a superior success rate compared to lorazepam and other drugs, at least in the elderly. lorazepam's anticonvulsant properties and pharmacokinetic profile make intravenous use reliable for terminating acute seizures, but induce prolonged sedation. oral benzodiazepines, including lorazepam, are occasionally used as long-term prophylactic treatment of resistant absence seizures; because of gradual tolerance to their anti-seizure effects, benzodiazepines such as lorazepam are not considered first-line therapies. lorazepam's anticonvulsant and cns depressant properties are useful for the treatment and prevention of alcohol withdrawal syndrome. in this setting, impaired liver function is not a hazard with lorazepam, since lorazepam does not require oxidation, in the liver or otherwise, for its metabolism. sedation lorazepam is sometimes used for individuals receiving mechanical ventilation. however, in critically ill people, propofol has been found to be superior to lorazepam both in effectiveness and overall cost; as a result, the use of propofol for this indication is now encouraged, whereas the use of lorazepam is discouraged. its relative effectiveness in preventing new memory formation, along with its ability to reduce agitation and anxiety, makes lorazepam useful as premedication. it is given before a general anesthetic to reduce the amount of anesthetic required, or before unpleasant awake procedures, such as in dentistry or endoscopies, to reduce anxiety, to increase compliance, and to induce amnesia for the procedure. lorazepam by mouth is given 90 to 120 minutes before procedures, and intravenous lorazepam as late as 10 minutes before procedures. lorazepam is sometimes used as an alternative to midazolam in palliative sedation. in intensive care units lorazepam is sometimes used to produce anxiolysis, hypnosis, and amnesia. agitation lorazepam is sometimes used as an alternative to haloperidol when there is the need for rapid sedation of violent or agitated individuals, but haloperidol plus promethazine is preferred due to better effectiveness and due to lorazepam's adverse effects on respiratory function. however, adverse effects such as behavioral disinhibition may make benzodiazepines inappropriate for some people who are acutely psychotic . acute delirium is sometimes treated with lorazepam, but as it can cause paradoxical effects, it is preferably given together with haloperidol. lorazepam is absorbed relatively slowly if given intramuscularly, a common route in restraint situations. other catatonia with inability to speak is responsive to lorazepam. symptoms may recur and treatment for some days may be necessary. catatonia due to abrupt or overly rapid withdrawal from benzodiazepines, as part of the benzodiazepine withdrawal syndrome, should also respond to lorazepam treatment. as lorazepam can have paradoxical effects, haloperidol is sometimes given at the same time. it is sometimes used in chemotherapy in addition to medications used to treat nausea and vomiting, i.e. nausea and vomiting caused or worsened by psychological sensitization to the thought of being sick. adverse effects many beneficial effects of lorazepam (e.g., sedative, muscle relaxant, anti-anxiety, and amnesic effects) may become adverse effects when unwanted. adverse effects can include sedation and low blood pressure; the effects of lorazepam are increased in combination with other cns depressant drugs. other adverse effects include confusion, ataxia, inhibiting the formation of new memories, pupil constriction and hangover effects. with long-term benzodiazepine use it is unclear whether cognitive impairments fully return to normal after stopping lorazepam use; cognitive deficits persist for at least six months after withdrawal, but longer than six months may be required for recovery of cognitive function. lorazepam appears to have more profound adverse effects on memory than other benzodiazepines; it impairs both explicit and implicit memory. in the elderly, falls may occur as a result of benzodiazepines. adverse effects are more common in the elderly, and they appear at lower doses than in younger people. benzodiazepines can cause or worsen depression. paradoxical effects can also occur, such as worsening of seizures, or paradoxical excitement; paradoxical excitement is more likely to occur in the elderly, children, those with a history of alcohol abuse, and in people with a history of aggression or anger problems. lorazepam's effects are dose-dependent, meaning the higher the dose, the stronger the effects (and side effects) will be. using the smallest dose needed to achieve desired effects lessens the risk of adverse effects. sedative drugs and sleeping pills, including lorazepam, have been associated with an increased risk of death. sedation is the side effect people taking lorazepam most frequently report. in a group of around 3,500 people treated for anxiety, the most common side effects complained of from lorazepam were sedation (15.9%), dizziness (6.9%), weakness (4.2%), and unsteadiness (3.4%). side effects such as sedation and unsteadiness increased with age. cognitive impairment, behavioural disinhibition and respiratory depression as well as hypotension may also occur. paradoxical effects: in some cases, paradoxical effects can occur with benzodiazepines, such as increased hostility, aggression, angry outbursts, and psychomotor agitation. these effects are seen more commonly with lorazepam than with other benzodiazepines. paradoxical effects are more likely to occur with higher doses, in people with pre-existing personality disorders and those with a psychiatric illness. frustrating stimuli may trigger such reactions, though the drug may have been prescribed to help the person cope with such stress and frustration in the first place. as paradoxical effects appear to be dose-related, they usually subside on dose reduction or on complete withdrawal of lorazepam. suicidality: benzodiazepines are associated with increased risk of suicide, possibly due to disinhibition. higher dosages appear to confer greater risk. amnesic effects: among benzodiazepines, lorazepam has relatively strong amnesic effects, but people soon develop tolerance to this with regular use. to avoid amnesia (or excess sedation) being a problem, the initial total daily lorazepam dose should not exceed 2 mg. this also applies to use for night sedation. five participants in a sleep study were prescribed lorazepam 4 mg at night, and the next evening, three subjects unexpectedly volunteered memory gaps for parts of that day, an effect that subsided completely after two to three days' use. amnesic effects cannot be estimated from the degree of sedation present, since the two effects are unrelated. high-dose or prolonged parenterally administered lorazepam with its associated solvent can cause propylene glycol intoxication and poisoning. 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. contraindications lorazepam should be avoided in people with: allergy or hypersensitivity – past hypersensitivity or allergy to lorazepam, to any benzodiazepine, or to any of the ingredients in lorazepam tablets or injections respiratory failure – benzodiazepines, including lorazepam, may depress central nervous system respiratory drive and are contraindicated in severe respiratory failure. an example would be the inappropriate use to relieve anxiety associated with acute severe asthma. the anxiolytic effects may also be detrimental to a person's willingness and ability to fight for breath. however, if mechanical ventilation becomes necessary, lorazepam may be used to facilitate deep sedation. acute intoxication – lorazepam may interact synergistically with the effects of alcohol, narcotics, or other psychoactive substances. it should, therefore, not be administered to a drunk or intoxicated person. ataxia – this is a neurological clinical sign, consisting of unsteady and clumsy motion of the limbs and torso, due to the failure of gross muscle movement coordination, most evident on standing and walking. it is the classic way in which acute alcohol intoxication may affect a person. benzodiazepines should not be administered to people already-ataxic. acute narrow-angle glaucoma – lorazepam has pupil-dilating effects, which may further interfere with the drainage of aqueous humor from the anterior chamber of the eye, thus worsening narrow-angle glaucoma. sleep apnea – sleep apnea may be worsened by lorazepam's central nervous system depressant effects. it may further reduce the person's ability to protect his or her airway during sleep. myasthenia gravis – this condition is characterized by muscle weakness, so a muscle relaxant such as lorazepam may exacerbate symptoms. pregnancy and breastfeeding – lorazepam belongs to the food and drug administration (fda) pregnancy category d, which means it is likely to cause harm to the developing baby if taken during the first trimester of pregnancy. the evidence is inconclusive whether lorazepam if taken early in pregnancy results in reduced intelligence, neurodevelopmental problems, physical malformations in cardiac or facial structure, or other malformations in some newborns. lorazepam given to pregnant women antenatally may cause floppy infant syndrome in the neonate, or respiratory depression necessitating ventilation. regular lorazepam use during late pregnancy (the third trimester), carries a definite risk of benzodiazepine withdrawal syndrome in the neonate. neonatal benzodiazepine withdrawal may include hypotonia, reluctance to suck, apneic spells, cyanosis, and impaired metabolic responses to cold stress. symptoms of floppy infant syndrome and the neonatal benzodiazepine withdrawal syndrome have been reported to persist from hours to months after birth. lorazepam may also inhibit fetal liver bilirubin glucuronidation, leading to neonatal jaundice. lorazepam is present in breast milk, so caution must be exercised about breastfeeding. specific groups children and the elderly – the safety and effectiveness of lorazepam is not well determined in children under 18 years of age, but it is used to treat acute seizures. dose requirements have to be