Norepinephrine (medication)

{{Short description|Therapeutic use of norepinephrine}} {{About|the medication|this substance as a naturally occurring hormone|Norepinephrine}} {{Infobox drug | verifiedrevid = 595681188 | drug_name = Norepinephrine | INN = | type = <!-- empty --> | image = Norepinephrine.svg | image_class = skin-invert-image | width = 180 | alt = | caption = Skeletal formula of noradrenaline | image2 = Noradrenaline-from-xtal-view-1-3D-bs-17.png | image_class2 = bg-transparent | width2 = | alt2 = | caption2 = Ball-and-stick model of the zwitterionic form of noradrenaline found in the crystal structure<ref>{{cite journal | vauthors = Andersen AM | title = Structural studies of metabolic products of dopamine. IV. Crystal and molecular structure of (-)-noradrenaline | journal = Acta Chemica Scandinavica B | volume = 29 | issue = 8 | pages = 871–876 | year = 1975 | pmid = 1202890 | doi = 10.3891/acta.chem.scand.29b-0871 | doi-access = free }}</ref>

<!-- Clinical data --> | pronounce = | tradename = Levarterenol, Levophed, Norepin, other | Drugs.com = {{drugs.com|monograph|norepinephrine-bitartrate}} | MedlinePlus = | licence_EU = <!-- EMA uses INN (or special INN_EMA) --> | DailyMedID = Norepinephrine | licence_US = Norepinephrine | pregnancy_AU = B3 | pregnancy_AU_comment = | pregnancy_US = C | pregnancy_US_comment = | pregnancy_category = | dependency_liability = | addiction_liability = | class = Adrenergic receptor agonist; Sympathomimetic | routes_of_administration = Intravenous | ATCvet = | ATC_prefix = C01 | ATC_suffix = CA03 | ATC_supplemental =

<!--Physiological data--> | source_tissues = Locus coeruleus; sympathetic nervous system; adrenal medulla | target_tissues = System-wide | receptors = α₁, α₂, β₁, β₃ | agonists = Sympathomimetic drugs, clonidine, isoprenaline | antagonists = Tricyclic antidepressants, Beta blockers, antipsychotics | precursor = | biosynthesis =

<!-- Legal status --> | legal_AU = S4 | legal_AU_comment = | legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F --> | legal_BR_comment = | legal_CA = OTC | legal_CA_comment = | legal_DE = <!-- Anlage I, II, III or Unscheduled --> | legal_DE_comment = | legal_NZ = <!-- Class A, B, C --> | legal_NZ_comment = | legal_UK = POM | legal_UK_comment = | legal_US = Rx-only | legal_US_comment = | legal_EU = | legal_EU_comment = | legal_UN = <!-- N I, II, III, IV / P I, II, III, IV --> | legal_UN_comment = | legal_status = <!-- For countries not listed above -->

<!-- Pharmacokinetic data --> | bioavailability = | protein_bound = | metabolism = MAO-A; COMT | metabolites = | onset = | elimination_half-life = | duration_of_action = | excretion = Urine (84–96%)

<!-- Identifiers --> | index2_label = as salt | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 51-41-2 | CAS_supplemental = | PubChem = 439260 | IUPHAR_ligand = 505 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB00368 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 388394 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = X4W3ENH1CV | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D00076 | KEGG2_Ref = {{keggcite|correct|kegg}} | KEGG2 = D05206 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 18357 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 1437 | NIAID_ChemDB = | PDB_ligand = | synonyms = Noradrenaline<br />(''R'')-(–)-Norepinephrine<br />''l''-1-(3,4-Dihydroxyphenyl)-2-aminoethanol<br />3,4,β-Trihydroxyphenethylamine

<!-- Chemical data --> | IUPAC_name = 4-[(1''R'')-2-amino-1-hydroxyethyl]benzene-1,2-diol | C=8 | H=11 | N=1 | O=3 | SMILES = Oc1ccc(cc1O)[C@@H](O)CN | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C8H11NO3/c9-4-8(12)5-1-2-6(10)7(11)3-5/h1-3,8,10-12H,4,9H2/t8-/m0/s1 | StdInChI_comment = | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = SFLSHLFXELFNJZ-QMMMGPOBSA-N

<!-- Physical data --> | density = 1.397±0.06 | density_notes = | melting_point = 217 | melting_high = | melting_notes = (''decomposes'') | boiling_point = 442.6 | boiling_notes = ±40.0°C | solubility = | sol_units = | specific_rotation = }} <!-- Definition and medical uses --> '''Norepinephrine''', also known as '''noradrenaline''' and sold under the brand name '''Levophed''' among others, is a medication used to treat people with very low blood pressure.<ref name=AHFS2017/> It is the typical medication used in sepsis if low blood pressure does not improve following intravenous fluids.<ref>{{cite book | vauthors = Latifi R |title= Surgical Decision Making: Beyond the Evidence Based Surgery|date=2016|publisher=Springer|isbn=9783319298245|page=67|url=https://books.google.com/books?id=2Z8YDAAAQBAJ&pg=PA67|language=en|url-status=live|archive-url=https://web.archive.org/web/20170327165820/https://books.google.ca/books?id=2Z8YDAAAQBAJ&pg=PA67|archive-date=2017-03-27}}</ref> It is the same molecule as the hormone and neurotransmitter norepinephrine.<ref name=AHFS2017/> It is given by slow injection into a vein.<ref name=AHFS2017>{{cite web|title=Norepinephrine Bitartrate|url=https://www.drugs.com/monograph/norepinephrine-bitartrate.html|publisher=The American Society of Health-System Pharmacists|access-date=26 March 2017|url-status=live|archive-url=https://web.archive.org/web/20170326230032/https://www.drugs.com/monograph/norepinephrine-bitartrate.html|archive-date=26 March 2017}}</ref>

<!-- Side effects and mechanism --> Common side effects include headache, slow heart rate, and anxiety.<ref name=AHFS2017/> Other side effects include an irregular heartbeat.<ref name=AHFS2017/> If it leaks out of the vein at the site it is being given, norepinephrine can result in limb ischemia.<ref name=AHFS2017/> If leakage occurs the use of phentolamine in the area affected may improve outcomes.<ref name=AHFS2017/> Norepinephrine works by binding and activating alpha adrenergic receptors.<ref name=AHFS2017/>

<!-- History and culture --> Norepinephrine was discovered in 1946 and was approved for medical use in the United States in 1950.<ref name=AHFS2017/><ref>{{cite book|title=Encyclopedia of the Neurological Sciences|date=2014|publisher=Academic Press|isbn=9780123851581|page=224|url=https://books.google.com/books?id=hfjSVIWViRUC&pg=RA1-PA224|language=en|url-status=live|archive-url=https://web.archive.org/web/20170327165724/https://books.google.ca/books?id=hfjSVIWViRUC&pg=RA1-PA224|archive-date=2017-03-27}}</ref> It is available as a generic medication.<ref name=AHFS2017/>

==Medical uses== Norepinephrine is used mainly as a sympathomimetic drug to treat people in vasodilatory shock states such as septic shock and neurogenic shock, while showing fewer adverse side-effects compared to dopamine treatment.<ref>{{cite journal | vauthors = Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, Rochwerg B, Rubenfeld GD, Angus DC, Annane D, Beale RJ, Bellinghan GJ, Bernard GR, Chiche JD, Coopersmith C, De Backer DP, French CJ, Fujishima S, Gerlach H, Hidalgo JL, Hollenberg SM, Jones AE, Karnad DR, Kleinpell RM, Koh Y, Lisboa TC, Machado FR, Marini JJ, Marshall JC, Mazuski JE, McIntyre LA, McLean AS, Mehta S, Moreno RP, Myburgh J, Navalesi P, Nishida O, Osborn TM, Perner A, Plunkett CM, Ranieri M, Schorr CA, Seckel MA, Seymour CW, Shieh L, Shukri KA, Simpson SQ, Singer M, Thompson BT, Townsend SR, Van der Poll T, Vincent JL, Wiersinga WJ, Zimmerman JL, Dellinger RP | display-authors = 6 | title = Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016 | journal = Critical Care Medicine | volume = 45 | issue = 3 | pages = 486–552 | date = March 2017 | pmid = 28098591 | doi = 10.1097/CCM.0000000000002255 | hdl-access = free | quote = We recommend norepinephrine as the first-choice vasopressor (strong recommendation, moderate quality of evidence). | s2cid = 52827184 | hdl = 10281/267577 | url = https://archive.lstmed.ac.uk/19349/1/0.%20SSC%202020%20main%20paper%20ICM%20Revisions%20FINAL%20CLEAN%20copy.docx }}{{Dead link|date=February 2026 |bot=InternetArchiveBot }}</ref><ref>{{cite journal | vauthors = De Backer D, Biston P, Devriendt J, Madl C, Chochrad D, Aldecoa C, Brasseur A, Defrance P, Gottignies P, Vincent JL | display-authors = 6 | title = Comparison of dopamine and norepinephrine in the treatment of shock | journal = The New England Journal of Medicine | volume = 362 | issue = 9 | pages = 779–789 | date = March 2010 | pmid = 20200382 | doi = 10.1056/nejmoa0907118 | doi-access = free }}</ref>

==Pharmacology== ===Mechanism of action=== It stimulates α₁ and α₂ adrenergic receptors to cause blood vessel contraction, thus increases peripheral vascular resistance and resulted in increased blood pressure. This effect also reduces the blood supply to gastrointestinal tract and kidneys. Norepinephrine acts on beta-1 adrenergic receptors, causing increase in heart rate and cardiac output.<ref>{{cite book| vauthors = Moore JI | title=Pharmacology|date=6 December 2012|publisher=Springer Science and Business Media|isbn=9781468405248|page=39|edition=3rd |url=https://books.google.com/books?id=r2ArBgAAQBAJ&pg=PA39|access-date=19 November 2017}}</ref> However, the elevation in heart rate is only transient, as baroreceptor response to the rise in blood pressure as well as enhanced vagal tone ultimately result in a sustained decrease in heart rate.<ref>{{Cite web | vauthors = Klabunde RE | date = 7 December 2022 |url= https://cvphysiology.com/Blood%20Pressure/BP018| work = CV Physiology | title = Circulating Catecholamines |access-date=2019-02-27}}</ref> Norepinephrine acts more on alpha receptors than the beta receptors.<ref>{{cite journal | vauthors = Pollard S, Edwin SB, Alaniz C | title = Vasopressor and Inotropic Management Of Patients With Septic Shock | journal = P & T | volume = 40 | issue = 7 | pages = 438–450 | date = July 2015 | pmid = 26185405 | pmc = 4495871 }}</ref>

===Pharmacokinetics=== Norepinephrine does not cross the blood–brain barrier under normal circumstances and hence is a peripherally selective drug.<ref name="FroeseDianGomez2020">{{cite journal | vauthors = Froese L, Dian J, Gomez A, Unger B, Zeiler FA | title = The cerebrovascular response to norepinephrine: A scoping systematic review of the animal and human literature | journal = Pharmacol Res Perspect | volume = 8 | issue = 5 | article-number = e00655 | date = October 2020 | pmid = 32965778 | doi = 10.1002/prp2.655 | pmc = 7510331 | url = }}</ref>

==Chemistry== Norepinephrine, or noradrenaline, also known as 3,4,β-trihydroxyphenethylamine, is a substituted phenethylamine and catecholamine. It is the ''N''-demethylated analogue of epinephrine (adrenaline; 3,4,β-trihydroxy-''N''-methylphenethylamine) and the β-hydroxylated analogue of dopamine (3,4-dihydroxyphenethylamine).

==Society and culture== ===Names=== ''Norepinephrine'' is the generic name of the drug and its {{Abbrlink|INN|International Nonproprietary Name}}, while ''noradrenaline'' is its {{Abbrlink|BAN|British Approved Name}}.<ref name="Elks2014">{{cite book | last=Elks | first=J. | title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies | publisher=Springer US | year=2014 | isbn=978-1-4757-2085-3 | url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA885 | access-date=31 August 2024 | page=885}}</ref><ref name="IndexNominum2004">{{cite book | author=Schweizerischer Apotheker-Verein | title=Index Nominum: International Drug Directory | publisher=Medpharm Scientific Publishers | year=2004 | isbn=978-3-88763-101-7 | url=https://books.google.com/books?id=EgeuA47Ocm4C&pg=PA874 | access-date=31 August 2024 | page=874}}</ref> It is often referred to as simply "levo" in clinical settings in the United States, an abbreviation of the trade name Levophed.

== References == {{Reflist}}

== External links == * {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/rn/51-41-2 | archive-url = https://web.archive.org/web/20170212020153/https://druginfo.nlm.nih.gov/drugportal/rn/51-41-2 | url-status = dead | archive-date = February 12, 2017 | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Norepinephrine }} * {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/rn/108341-18-0 | archive-url = https://web.archive.org/web/20201022142638/https://druginfo.nlm.nih.gov/drugportal/rn/108341-18-0 | url-status = dead | archive-date = October 22, 2020 | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Norepinephrine bitartrate }}

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Category:Antihypotensive agents Category:Cardiac stimulants Category:Inotropic agents Category:Intensive care medicine Category:Norepinephrine Category:Peripherally selective drugs Category:Sympathomimetics Category:Wikipedia medicine articles ready to translate