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| {{Drugbox|
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| | IUPAC_name = 8-chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5-a][1,4]benzodiazepine
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| | image = Midazolam.svg
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| | width = 140
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| | image2 = Midazolam3d.png
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| | CAS_number = 59467-70-8
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| | ATC_prefix = N05
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| | ATC_suffix = CD08
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| | ATC_supplemental =
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| | PubChem = 4192
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| | DrugBank = APRD00680
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| | C = 18 | H = 13 | Cl = 1 | F = 1 | N = 3
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| | molecular_weight = 325.78
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| | bioavailability = Oral ~36% <br>I.M. 90%+
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| | metabolism = [[Liver|Hepatic]]
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| | elimination_half-life = 1.8-6.4 hours
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| | excretion = [[Kidney|Renal]]
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| | pregnancy_category = D ([[United States|USA]])<br> C ([[Australia|Aus]])
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| | legal_status = [[Schedule IV controlled substance|Schedule IV]](US)
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| | routes_of_administration = Oral, I.M., I.V., parenteral
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| }}
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| '''Midazolam''' (marketed under brand names '''Versed®''', '''Hypnovel®''', '''Dormicum®''' and '''Dormonid®''', pronounced <span class="IPA">mɪˈdæzəlæm</span>) is a drug which is a [[benzodiazepine]] [[derivative (chemistry)|derivative]]. It has powerful [[anxiolytic]], [[amnestic]], [[hypnotic]], [[anticonvulsant]], [[skeletal muscle relaxant]] and [[sedative]] properties. It is considered a fast-acting benzodiazepine, with a short elimination half-life. It is therefore a very useful drug to use for short minor procedures such as [[dental extraction]].
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| Midazolam was first synthesized in 1976 by Fryer and Walser.
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| ==Mechanism of action==
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| Like other benzodiazepines, midazolam acts on benzodiazepine receptors which enhance the binding of [[GABA]] to the GABA<sub>A</sub> receptor which results in inhibitory effects on the [[central nervous system]].<ref>{{cite journal | author = Skerritt JH | coauthors = Johnston GA. | year = 1983 | month = May | date = 6 | title = Enhancement of GABA binding by benzodiazepines and related anxiolytics. | journal = Eur J Pharmacol. | volume = 89 | issue = 3-4 | pages = 193-8 | pmid = 6135616 }}</ref>
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| ==Indications==
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| Midazolam is indicated for the acute management of [[aggressive]] or [[delirium|delirious]] patients and also is sometimes used for the acute management of seizures such as [[status epilepticus]]. Long term use for the management of epilepsy is not recommended however, due to the significant risk of tolerance which renders midazolam and other benzodiazepines ineffective and as well the significant side effect of sedation.<ref>{{cite journal | last = Isojärvi | first = JI | coauthors = Tokola RA. | year = 1998 | month = Dec | title = Benzodiazepines in the treatment of epilepsy in people with intellectual disability. | journal = J Intellect Disabil Res. | volume = 42 | issue = 1 | pages = 80-92 | pmid = 10030438 }}</ref>
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| In mice given chronic midazolam a slowly evolving tolerance developed to the anticonvulsant properties of midazolam over 15 days, although some anticonvulsant effects were still apparent after 15 days of continued administration.<ref>{{cite journal | author = Garratt JC | coauthors = Gent JP, Feely M, Haigh JR. | year = 1988 | month = Jan | date = 5 | title = Can benzodiazepines be classified by characterising their anticonvulsant tolerance-inducing potential? | journal = Eur J Pharmacol. | volume = 145 | issue = 1 | pages = 75-80 | pmid = 2894998 }}</ref>
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| Midazolam is occasionally used as a hypnotic, especially in hospitals. Like other benzodiazepines, it produces a decrease in delta activity, though the effect of benzodiazepines on delta may not be mediated via benzodiazepine receptors. Delta activity is an indicator of depth of sleep within non-REM sleep; it is thought to reflect sleep quality, with lower levels of delta sleep reflecting poorer sleep. Thus midazolam and other benzodiazepines cause a deterioration in sleep quality. [[Cyproheptadine]] may be superior to [[nitrazepam]] in the treatment of insomnia as it enhances sleep quality based on [[EEG]] studies.<ref>{{cite journal | author = Tokunaga S | coauthors = Takeda Y, Shinomiya K, Hirase M, Kamei C. | year = 2007 | month = Feb | title = Effects of some H1-antagonists on the sleep-wake cycle in sleep-disturbed rats. | journal = J Pharmacol Sci. | volume = 103 | issue = 2 | pages = 201-6 | pmid = 17287588 | url = http://www.jstage.jst.go.jp/article/jphs/103/2/201/_pdf | format = pdf }}</ref>
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| ==Interactions==
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| Midazolam is metabolized almost completely by [[CYP3A4|cytochrome P450-3A4]]. Grapefruit juice reduces intestinal 3A4 and results in less metabolism and higher plasma concentrations, which could result in overdose.
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| ==Contraindications==
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| Hypersensitivity, acute narrow angle glaucoma, shock, hypotension, head injury, and drug or alcohol use. Most are relative contraindications.
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| ==Side Effects==
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| Residual 'hangover' effects after nighttime administration of midazolam such as sleepiness, impaired psychomotor and [[cognitive]] functions may persist into the next day which may impair the ability of users to drive safely and increase risks of falls and [[hip fractures]].<ref>{{cite journal | author = Vermeeren A. | coauthors = | year = 2004 | month = | title = Residual effects of hypnotics: epidemiology and clinical implications. | journal = CNS Drugs. | volume = 18 | issue = 5 | pages = 297-328 | pmid = 15089115 }}</ref>
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| ==Pregnancy==
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| Midazolam (as with other [[central nervous system]] [[depressants]], if taken regularly in pregnancy, may result in reduced IQ, developmental problems, physical malformations--however this data is inconclusive. Midazolam when taken during the [[third trimester]] of pregnancy may cause severe risk to the neonate, including [[benzodiazepine withdrawal syndrome]] with possible symptoms including [[hypotonia]], [[apnoeic]] spells, [[cyanosis]], and impaired [[metabolic]] responses to cold stress. Symptoms of hypotonia and the neonatal benzodiazepine withdrawal syndrome have been reported to persist from hours to months after birth.<ref>{{cite journal | author = McElhatton PR. | coauthors = | year = 1994 | month = Nov-Dec | title = The effects of benzodiazepine use during pregnancy and lactation. | journal = Reprod Toxicol. | volume = 8 | issue = 6 | pages = 461-75 | pmid = 7881198 }}</ref>
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| ==Overdose==
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| Symptoms of midazolam overdose include:
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| *[[Somnolence]] (difficulty staying awake)
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| *Mental confusion
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| *[[Hypotension]]
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| *Impaired motor functions
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| ** Impaired reflexes
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| ** Impaired coordination
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| ** Impaired balance
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| ** Dizziness
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| *[[Coma]]
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| In animal models, the oral LD<sub>50</sub> of midazolam is 825 mg/kg<!--In what animal??-->.
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| Midazolam overdose is considered a medical emergency and generally requires the immediate attention of medical personnel. The [[antidote]] for an overdose of midazolam (or any other benzodiazepine) is [[flumazenil]] (Anexate®).
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| The risk of midazolam overdose is increased significantly if midazolam is abused in conjunction with opiates as was highlighted in a review of deaths of users of the opiate buprenorphine in Singapore.<ref>{{cite journal | last = Lai | first = SH | coauthors = Yao YJ, Lo DS. | year = 2006 | month = Oct | title = A survey of buprenorphine related deaths in Singapore. | journal = Forensic Sci Int. | volume = 162(1-3) | pages = 80-6 | pmid = 16879940 }}</ref>
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| ==Legal status==
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| Midazolam is a Schedule IV drug under the [[Convention on Psychotropic Substances]].<ref name="ScheduleIV">[http://www.incb.org/pdf/e/list/green.pdf List of psychotropic substances under international control]</ref>
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| ==Popular Culture==
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| Midazolam is offered to death row inmates before execution in the [[United States]], according to the film ''The Missouri Protocol'' (1990). A [[Missouri]] prison doctor interviewed in the film said virtually no prisoners turned down the drug when it was offered a few hours prior to execution.
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| Prolonged after-effects of midazolam dosing after dental surgery inspired [[Duran Duran]] vocalist [[Simon Le Bon]] to entitle the group's 1997 album ''[[Medazzaland]]'', likely in reference to [[psychotropic]] effects he experienced.
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| Used by [[Alexander Mahone]] in the show [[Prison Break]], under the alias "Veritril."
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| ==See also==
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| *[[Benzodiazepine]]s
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| *[[Triazolam]]
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| *[[Brotizolam]]
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| *[[Estazolam]]
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| ==External links==
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| *[http://www.rxlist.com/cgi/generic2/versedinj.htm Rx-List - Midazolam (Versed)]
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| *[http://www.inchem.org/documents/pims/pharm/pim674.htm Inchem - Midazolam]
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| ==Notes==
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| {{reflist|2}}
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| ==References==
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| * [[European Medicines Agency|EMEA]] [http://www.emea.europa.eu/pdfs/human/referral/462002en.pdf Summary of Product Characteristics: Hypnovel and associated names].
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| * [http://mars.bbraun.de/mars/docman/delivery?contextName=CW_COM_VIEW_CONTEXT&documentId=BPB0000000000000001000001106--000 Clinical Use of Midazolam] by John Shou.
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| *{{cite journal
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| | author = Brevoord J, Joosten K, Arts W, van Rooij R, de Hoog M
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| | title = Status epilepticus: clinical analysis of a treatment protocol based on midazolam and phenytoin.
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| | journal = J Child Neurol
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| | volume = 20
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| | issue = 6
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| | pages = 476-81
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| | year = 2005
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| | id = PMID 15996395
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| }}
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| *{{cite journal
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| | author = Wolfe T, Macfarlane T
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| | title = Intranasal midazolam therapy for pediatric status epilepticus.
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| | journal = Am J Emerg Med
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| | volume = 24
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| | issue = 3
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| | pages = 343-6
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| | year = 2006
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| | id = PMID 16635708
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| }}
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| *{{cite journal
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| | author = Johnson T, Rostami-Hodjegan A, Goddard J, Tanner M, Tucker G
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| | title = Contribution of midazolam and its 1-hydroxy metabolite to preoperative sedation in children: a pharmacokinetic-pharmacodynamic analysis.
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| | journal = Br J Anaesth
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| | volume = 89
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| | issue = 3
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| | pages = 428-37
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| | year = 2002
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| | id = PMID 12402721
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| | url = http://bja.oxfordjournals.org/cgi/content/full/89/3/428
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| }}
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| *''Prediction of the disposition of midazolam in surgical patients by a physiologically based pharmacokinetic model'', Bjorkman, S et al, J Pharm Sci 2001:90(9)1226-1241.
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| *{{cite journal
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| | author = Merritt P, Hirshman E, Hsu J, Berrigan M
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| | title = Metamemory without the memory: are people aware of midazolam-induced amnesia?
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| | journal = Psychopharmacology (Berl)
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| | volume = 177
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| | issue = 3
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| | pages = 336-43
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| | year = 2005
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| | id = PMID 15290003
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| }}
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| {{Benzodiazepines}}
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| {{Anticonvulsants}}
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| {{Hypnotics and sedatives}}
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| [[Category:Anticonvulsants]]
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| [[Category:Anxiolytics]]
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| [[Category:Benzodiazepines]]
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| [[Category:Hypnotics]]
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| [[Category:Imidazoles]]
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| [[Category:Muscle relaxants]]
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| [[Category:Sedatives]]
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| [[de:Midazolam]]
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| [[es:Midazolam]]
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| [[fr:Midazolam]]
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| [[it:Midazolam]]
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| [[nl:Midazolam]]
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| [[pl:Midazolam]]
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| [[pt:Midazolam]]
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| [[fi:Midatsolaami]]
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| [[sv:Midazolam]]
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| {{WikiDoc Sources}}
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