Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Terbutaline: Difference between pages

{{Short description|Chemical compound}}

{{For|the UK-based company|Marex Spectron}}

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 470602258

| IUPAC_name = (''RS'')-5-[2-(''tert''-Butylamino)-1-hydroxyethyl]benzene-1,3-diol

| image = Terbutaline.svg

| width = 200

| chirality = [[Racemic mixture]]

| image2 = Terbutaline ball-and-stick model.png

| caption = Terbutaline (top),<br />and (''R'')-(−)-terbutaline (bottom)

<!--Clinical data-->

| MedlinePlus = a682144

| pregnancy_AU = A

| pregnancy_category =

| legal_AU =

| legal_CA =

| legal_UK = POM

| legal_US =

| legal_status =

| routes_of_administration = Oral ([[Tablet (pharmacy)|tablets]], oral [[Solution (chemistry)|solution]]), inhalational ([[Dry powder inhaler|DPI]], [[nebulizer]] solution), [[Subcutaneous injection|SQ]]

<!--Pharmacokinetic data-->

| protein_bound = 25%

| metabolism = GI tract (oral), liver; CYP450: unknown

| elimination_half-life = 11–16 hours

| excretion = urine 90% (60% unchanged), bile/faeces

<!--Identifiers-->

| CAS_number = 23031-25-6

| ATC_prefix = R03

| ATC_suffix = AC03

| = R03

| PubChem = 5403

| IUPHAR_ligand = 560

| DrugBank_Ref = {{drugbankcite|changed|drugbank}}

| DrugBank = DB00871

| = {{|changed|}}

| ChemSpiderID = 5210

| ChEBI_Ref = {{ebicite|changed|EBI}}

| ChEBI = 9449

| UNII_Ref = {{fdacite||FDA}}

| UNII = N8ONU3L3PG

| KEGG_Ref = {{keggcite||kegg}}

| KEGG = D08570

| ChEMBL_Ref = {{ebicite||EBI}}

| ChEMBL = 1760

<!--Chemical data-->

| =

| N = 1

| O = 3

| smiles = Oc1cc(cc(O)c1)C(O)CNC(C)(C)C

| StdInChI_Ref = {{stdinchicite||chemspider}}

| StdInChI = 1S/C12H19NO3/c1-12(2,3)13-7-11(16)8-4-9(14)6-10(15)5-8/h4-6,11,13-16H,7H2,1-3H3

| StdInChIKey_Ref = {{stdinchicite||chemspider}}

| StdInChIKey = XWTYSIMOBUGWOL-UHFFFAOYSA-N

<!-- Definition and medical uses -->

'''Terbutaline''', sold under the brand names '''Bricanyl''' and '''Marex''' among others, is a [[beta2-adrenergic receptor agonist|β₂ adrenergic receptor agonist]], used as a "reliever" inhaler in the management of [[asthma]] symptoms and as a [[tocolytic]] (anti-[[Uterine contraction|contraction]] medication) to delay [[preterm labor]] for up to 48 hours. This time can then be used to administer steroid injections to the mother which help fetal lung maturity and reduce complications of prematurity.<ref>{{cite web|last=WHO|title=Antenatal administration of corticosteroids for women at risk of preterm birth|url=http://apps.who.int/rhl/pregnancy_childbirth/complications/preterm_birth/cd004454_hofmeyrgj_com/en/index.html|archive-url=https://web.archive.org/web/20090724135016/http://apps.who.int/rhl/pregnancy_childbirth/complications/preterm_birth/cd004454_hofmeyrgj_com/en/index.html|url-status=dead|archive-date=July 24, 2009|publisher=WHO|access-date=2013-03-25}}</ref> It should not be used to prevent preterm labor or delay labor more than 48–72 hours. In February 2011, the [[Food and Drug Administration]] began requiring a black box warning on the drug's label. Pregnant women should not be given injections of the drug terbutaline for the prevention of preterm labor or for long-term (beyond 48–72 hours) management of preterm labor, and should not be given oral terbutaline for any type of prevention or treatment of preterm labor "due to the potential for serious maternal heart problems and death."<ref>{{cite news | url=http://yourlife.usatoday.com/parenting-family/pregnancy/story/2011/02/FDA-flags-risks-on-popular-drug-used-during-pregnancy/43875986/1?csp=34news | work=USA Today | title=Most Popular E-mail Newsletter | date=18 February 2011 }}{{Dead link|date=March 2022 |bot=InternetArchiveBot |fix-attempted=yes }}</ref><ref>{{cite web |url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm243840.htm |title=FDA warns against certain uses of asthma drug terbutaline for preterm labor |website=[[Food and Drug Administration]] |access-date=2015-09-13 |url-status=dead |archive-url=https://web.archive.org/web/20150921130836/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm243840.htm |archive-date=2015-09-21 }} </ref>

<!-- Society and culture -->

It was patented in 1966 and came into medical use in 1970.<ref name=Fis2006>{{cite book | vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=542 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA542 |language=en}}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO22nd">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 22nd list (2021) | year = 2021 | hdl = 10665/345533 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2021.02 | hdl-access=free }}</ref>

==Medical uses==

Terbutaline is used as a fast-acting [[bronchodilator]] (often used as a short-term asthma treatment) and as a [[tocolytic]]<ref name="pmid18554601">{{cite journal | vauthors = Mohamed Ismail NA, Ibrahim M, Mohd Naim N, Mahdy ZA, Jamil MA, Mohd Razi ZR | title = Nifedipine versus terbutaline for tocolysis in external cephalic version | journal = International Journal of Gynaecology and Obstetrics | volume = 102 | issue = 3 | pages = 263–266 | date = September 2008 | pmid = 18554601 | doi = 10.1016/j.ijgo.2008.04.010 | s2cid = 20258298 }}</ref> to delay [[premature labor]].

As an asthma treatment, the inhaled form of terbutaline, starts working within 15 minutes and can last up to 6 hours. It is also sold as an injectable solution, an oral tablet, and as a syrup (in combination with [[guaifenesin]]).

Terbutaline is a [[pregnancy category]] C medication and is prescribed to stop contractions. After successful intravenous tocolysis, little evidence exists that oral terbutaline is effective.<ref>{{cite journal | vauthors = Goldenberg RL | title = The management of preterm labor | journal = Obstetrics and Gynecology | volume = 100 | issue = 5 Pt 1 | pages = 1020–1037 | date = November 2002 | pmid = 12423870 | doi = 10.1016/S0029-7844(02)02212-3 | url = http://www.acog.org/from_home/publications/green_journal/2002/ong13732fla.htm | url-status = dead | archive-url = https://web.archive.org/web/20110720084331/http://www.acog.org/from_home/publications/green_journal/2002/ong13732fla.htm | archive-date = 2011-07-20 }}</ref> Terbutaline as a treatment for premature labor is an [[off-label use]] not approved by the US [[Food and Drug Administration|FDA]], who have warned that oral terbutaline is not effective and can cause severe heart problems or death, and while injectable terbutaline can be used for premature labor in emergency situations in a hospital setting, it should only be used for short periods of time.<ref name="fdawarning">{{cite web |title=FDA Drug Safety Communication: New warnings against use of terbutaline to treat preterm labor |url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-new-warnings-against-use-terbutaline-treat-preterm-labor |website=Center for Drug Evaluation and Research |publisher=FDA |access-date=11 May 2021 |language=en |date=17 February 2011}}</ref>

==Side effects==

* Adult — [[tachycardia]], [[anxiety]], [[wikt:nervousness|nervousness]], [[tremor]]s, [[headache]], [[hyperglycemia]], [[hypokalemia]], [[hypotension]] and, rarely, [[pulmonary edema]].<ref name=pharmnemonics>{{Cite book | vauthors = Shen H | title=Illustrated Pharmacology Memory Cards: PharMnemonics | year=2008 | publisher=Minireview | isbn=978-1-59541-101-3 | page=7}}</ref>

* Fetal — [[tachycardia]] and [[hypoglycemia]].<ref name="5 Minute Consult (Original source: UpToDate)">{{cite web | url = http://5minuteconsult.com/printDrugMonograph.aspx?MonoId=3764085 | via = 5 Minute Consult | work = Original Source: UpToDate | title = Terbutaline: Drug information | access-date = 2021-11-25 | archive-date = 2013-06-28 | archive-url = https://archive.today/20130628091017/http://5minuteconsult.com/printDrugMonograph.aspx?MonoId=3764085 | url-status = dead }}</ref>

== Pharmacology==

The tertiary butyl group in terbutaline makes it more selective for [[Beta-2 adrenergic receptor|β₂ receptors]]. Since there is no hydroxy group on position 4 of the benzene ring, the molecule is less susceptible to metabolism by the enzyme [[Catechol-O-methyl transferase|catechol-''O''-methyl transferase]].<ref>{{cite web | vauthors = Mehta A | title = Medicinal Chemistry of the Peripheral Nervous System–Adrenergics and Cholinergics their Biosynthesis, Metabolism, and Structure Activity Relationships | veditors = Melloni B, Germouty J | date = 1992 | pages = 503–507 | publisher = PharmaXChange |url=http://pharmaxchange.info/notes/medicinal_chemistry/adrenergics_cholinergics.html |url-status=dead |archive-url= https://web.archive.org/web/20101104022742/http://pharmaxchange.info/notes/medicinal_chemistry/adrenergics_cholinergics.html |archive-date=2010-11-04}}</ref>

==Chemistry==

Terbutaline is synthesized by brominating 3,5-dibenzyloxy[[acetophenone]] into 3,5-dibenzyloxybromoacetophenone, which is reacted with ''N''-[[benzyl]]-''N''-''tert''-butylamine, giving a ketone intermediate. Reduction of this product with H₂ over [[Pd/C]] leads to terbutaline.<ref>{{Cite patent|country=GB|number=1199630 | title = Phenylethanolamine Derivatives Effective in the Treatment of Bronchospastic Conditions |assign1 = Draco Lunds Farmacevtiska Aktiebolag | gdate = 1967}}</ref><ref>{{Cite patent|country=BE|number=704932 | title = 1-3,5-dihydroxyphenyl-2-alkylaminoethanols | assign= Draco Lunds Farmacevtiska Aktiebolag | gdate = 1968}}</ref><ref>{{cite patent | inventor = Svensson LA, Wetterlin ID | title = Orally Active Bronchospasmolytic Compounds and Their Preparation | country = US | number = 3937838 | gdate = 1976}}</ref><br />

:[[File:Terbutaline synthesis.png|800px]]

=== Stereochemistry ===

Terbutaline contains a stereocenter and consists of two enantiomers. This is a [[racemate]], ie a 1: 1 mixture of (R) - and the (S) - form:<ref name="Hager">{{cite book | veditors = Hager H, von Bruchhausen F, Dannhard G, Ebel S, Frahm AW, Hackenthal E, Holzgrabe U | title = Hagers Handbuch der Pharmazeutischen Praxis Band 9: Stoffe P-Z | publisher = Springer Verlag | location = Berlin | volume = 5 | date = 2014 | page = 804 | isbn = 978-3-642-63389-8}}</ref>

{| class="wikitable" style="text-align:center"

|- class="hintergrundfarbe6"

! colspan="2"| Enantiomers of terbutaline

|-

| [[File:(R)-Terbutalin Structural Formula V1.svg|200 px]]<br /><small>(R)-Terbutaline</small>

| [[File:(S)-Terbutalin Structural Formula V1.svg|200 px]]<br /><small>(S)-Terbutaline</small>

|}

==Society and culture==

===Athletics===

As with all β2-adrenergic receptor agonists, terbutaline is on the [[World Anti-Doping Agency]]'s list of prohibited drugs, except when administered by inhalation and a Therapeutic Use Exemption (TUE) has been obtained in advance.

===Brand names===

Brand names include Astherin, Bronclyn, Brethine, Bricanyl, Brethaire, Marex, Terasma, and Terbulin.

== References ==

{{reflist}}

{{Asthma and copd rx}}

{{Other gynecologicals}}

{{Adrenergic agonists}}

[[Category:Beta2-adrenergic agonists]]

[[Category:Chemical substances for emergency medicine]]

[[Category:Resorcinols]]

[[Category:Drugs developed by AstraZeneca]]

[[Category:Tocolytics]]

[[Category:Tert-butyl compounds]]

[[Category:Phenylethanolamines]]