Fenoterol: Difference between revisions

{{Short description|Chemical compound}}

{{distinguish|Formoterol}}

| Watchedfields = changed

| verifiedrevid = 443756837

| IUPAC_name = (''RR'',''SS'')-5-(1-hydroxy-2-<nowiki/>{[2-(4-hydroxyphenyl)-1-methylethyl]amino}ethyl)benzene-1,3-diol

| image = (RR)- and (SS)- fenoterol.svg

| width = 265

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

<!--Clinical data-->| tradename =

| Drugs.com = {{drugs.com|CONS|fenoterol}}

| pregnancy_AU = A

| pregnancy_US = B

| pregnancy_category =

| routes_of_administration = Inhalation ([[Metered-dose inhaler|MDI]])

<!--Legal status-->| legal_AU = S4

<!--Pharmacokinetic data-->| bioavailability =

| protein_bound =

| metabolism =

| elimination_half-life = 6.5 hours approximately <ref name="Drugs.com 1996">{{cite web | title=Fenoterol Hydrobromide Drug Information, Professional | website=Drugs.com | date=1996-01-01 | url=https://www.drugs.com/mmx/fenoterol-hydrobromide.html | access-date=2018-06-11 | archive-date=2019-08-25 | archive-url=https://web.archive.org/web/20190825002626/https://www.drugs.com/mmx/fenoterol-hydrobromide.html | url-status=dead }}</ref><ref name="DrugInfoSys.com 2016">{{cite web | title=Fenoterol - Drug Monograph | website=DrugInfoSys.com | date=2016-10-27 | url=http://www.druginfosys.com/drug.aspx?drugcode=303&type=1 | access-date=2018-06-11}}</ref><ref name="RxMed.com">{{cite web | title=Berotec Inhalation Solution (Fenoterol HBr) | website=RxMed.com | url=https://www.rxmed.com/b.main/b2.pharmaceutical/b2.1.monographs/cps-_monographs/CPS-_(General_Monographs-_B)/BEROTEC_INHALATION_SOLUTION.html | access-date=2018-06-11}}</ref><ref name="Svedmyr pp. 109–126">{{cite journal | vauthors = Svedmyr N | title=Fenoterol: A Beta2-adrenergic Agonist for Use in Asthma; Pharmacology, Pharmacokinetics, Clinical Efficacy and Adverse Effects | journal=Pharmacotherapy | publisher=Wiley | volume=5 | issue=3 | date=1985-05-06 | issn=0277-0008 | doi=10.1002/j.1875-9114.1985.tb03409.x | pmid=2991865 | pages=109–126| s2cid=189746 }}</ref>

| excretion = <!--Identifiers-->

| CAS_number_Ref =

| CAS_number = 13392-18-2

| ATC_prefix = R03

| ATC_suffix = AC04

| ATC_supplemental = {{ATC|G02|CA03}}

| PubChem = 3343

| IUPHAR_ligand = 557

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank = DB01288

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 3226

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 22M9P70OQ9

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D04157

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEBI = 149226

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 32800

<!--Chemical data-->| C = 17

| H = 21

| N = 1

| O = 4

| smiles = Oc1cc(cc(O)c1)C(O)CNC(C)Cc2ccc(O)cc2

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C17H21NO4/c1-11(6-12-2-4-14(19)5-3-12)18-10-17(22)13-7-15(20)9-16(21)8-13/h2-5,7-9,11,17-22H,6,10H2,1H3

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = LSLYOANBFKQKPT-UHFFFAOYSA-N

| drug_name =

| alt =

| caption =

| type =

| MedlinePlus =

| legal_status =

| licence_EU =

| licence_US =

}}

'''Fenoterol''' is a [[Beta-adrenergic agonist|β adrenoreceptor agonist]]. It is classed as [[sympathomimetic]] β₂ agonist and an inhaled bronchodilator asthma medication.

It was patented in 1962 and came into medical use in 1971<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 }}</ref> but, in the 1980s, concerns emerged about its safety and its use being associated with an increased risk of death (see below).

==Adverse effects and toxicity==

[[File:Berotec.jpg|thumb|upright=1|left|Fenoterol branded as Berotec]]

Fenoterol is a short-acting [[Beta2-adrenergic agonist|β₂ agonist]] that also stimulates [[Beta-1 adrenergic receptor|β₁ receptor]]s. Fenoterol has more cardiovascular toxicity than isoprenaline or salbutamol.<ref>{{cite journal | vauthors = Crane J, Burgess C, Beasley R | title = Cardiovascular and hypokalaemic effects of inhaled salbutamol, fenoterol, and isoprenaline | journal = Thorax | volume = 44 | issue = 2 | pages = 136–40 | date = February 1989 | pmid = 2928998 | pmc = 461717 | doi=10.1136/thx.44.2.136}}</ref><ref>{{cite journal | vauthors = Burgess CD, Windom HH, Pearce N, Marshall S, Beasley R, Siebers RW, Crane J | title = Lack of evidence for beta-2 receptor selectivity: a study of metaproterenol, fenoterol, isoproterenol, and epinephrine in patients with asthma | journal = The American Review of Respiratory Disease | volume = 143 | issue = 2 | pages = 444–6 | date = February 1991 | pmid = 1671326 | doi = 10.1164/ajrccm/143.2.444 }}</ref> Fenoterol was widely used in [[New Zealand]] in the late 1970s and the 1980s until it was removed from the New Zealand drug tariff in 1989 because its introduction and widespread use was associated with an epidemic of asthma deaths.<ref>{{cite journal | vauthors = Beasley R, Pearce N, Crane J, Burgess C | title = Withdrawal of fenoterol and the end of the New Zealand asthma mortality epidemic | journal = International Archives of Allergy and Immunology | volume = 107 | issue = 1–3 | pages = 325–7 | date = 1995 | pmid = 7613161 | doi = 10.1159/000237016 }}</ref> A series of case-control studies demonstrated that asthmatics using fenoterol were more likely to die of asthma compared with controls treated with alternative beta agonists; this risk of asthma deaths was particularly high in severe asthmatics.<ref>{{cite journal | vauthors = Crane J, Pearce N, Flatt A, Burgess C, Jackson R, Kwong T, Ball M, Beasley R | title = Prescribed fenoterol and death from asthma in New Zealand, 1981-83: case-control study | journal = Lancet | volume = 1 | issue = 8644 | pages = 917–22 | date = April 1989 | pmid = 2565417 | doi=10.1016/s0140-6736(89)92505-1| s2cid = 22765551 }}</ref><ref>{{cite journal | vauthors = Pearce N, Grainger J, Atkinson M, Crane J, Burgess C, Culling C, Windom H, Beasley R | title = Case-control study of prescribed fenoterol and death from asthma in New Zealand, 1977-81 | journal = Thorax | volume = 45 | issue = 3 | pages = 170–5 | date = March 1990 | pmid = 2330548 | pmc = 462377 | doi = 10.1136/thx.45.3.170 }}</ref> The mortality rate declined following withdrawal of fenoterol<ref>{{cite journal | vauthors = Beasley R, Pearce N, Crane J, Burgess C | title = Withdrawal of fenoterol and the end of the New Zealand asthma mortality epidemic | journal = International Archives of Allergy and Immunology | volume = 107 | issue = 1–3 | pages = 325–7 | date = 1995 | pmid = 7613161 | doi = 10.1159/000237016 }}</ref> without evidence supporting an alternative explanation for the abrupt rise and fall in asthma deaths.<ref>{{cite journal | vauthors = Pearce N, Beasley R, Crane J, Burgess C, Jackson R | title = End of the New Zealand asthma mortality epidemic | language = English | journal = Lancet | volume = 345 | issue = 8941 | pages = 41–4 | date = January 1995 | pmid = 7799709 | doi = 10.1016/s0140-6736(95)91159-6 | s2cid = 13287788 | url = https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(95)91159-6/abstract }}</ref> Data did not support [[confounding]] by severity as the explanation for the [[excess mortality]].<ref>{{cite journal | vauthors = Beasley R, Burgess C, Pearce N, Woodman K, Crane J | title = Confounding by severity does not explain the association between fenoterol and asthma death | journal = Clinical and Experimental Allergy | volume = 24 | issue = 7 | pages = 660–8 | date = July 1994 | pmid = 7953948 | doi = 10.1111/j.1365-2222.1994.tb00970.x | s2cid = 24043007 }}</ref> There are alternative short-acting beta agonists that have not been associated with increased mortality e.g. [[salbutamol]].

5-(1-Hydroxy-2-<nowiki/>{[2-(4-hydroxyphenyl)-1-methylethyl]amino}ethyl)benzene-1,3-diol is a molecule with two different stereogenic centers. Thus, four [[stereoisomer]]s may exist, the (''R'',''R'')-, (''R'',''S'')-, (''S'',''R'')- and (''S'',''S'')-stereoisomers (see the figure below). Fenoterol is a [[racemate]] of the (''R'',''R'')- and the (''S'',''S'')-[[enantiomer]]s. This racemate is 9 to 20 times more effective, as compared to the racemate of the (''R'',''S'')- and (''S'',''R'')-enantiomers.<ref name="Beale und Stephenson">{{cite journal | vauthors = Beale JP, Stephenson NC | date = April 1972 | title = X-ray analysis of Th 1165a* and salbutamol | journal = Journal of Pharmacy and Pharmacology | volume = 24 | issue = 4 | pages = 277–280 | doi=10.1111/j.2042-7158.1972.tb08986.x| pmid = 4402834 | s2cid = 42668199 }}</ref>

[[File:Fenoterol stereoisomers.svg|thumb|left|Four stereoisomers of 5-(1-hydroxy-2-<nowiki/>{[2-(4-hydroxyphenyl)-1-methylethyl]amino}ethyl)benzene-1,3-diol]]{{clear}}

== References ==

{{Other gynecologicals}}

{{Adrenergic agonists}}

[[Category:Beta2-adrenergic agonists]]

[[Category:Substituted amphetamines]]

[[Category:Phenylethanolamines]]

[[Category:Tocolytics]]