“Fenoterol”的意思、由来-开放百科全书

Fenoterol is a β adrenoreceptor agonist. It is classed as sympathomimetic β₂ agonist and an inhaled bronchodilator asthma medication.

Fenoterol is produced and sold by Boehringer Ingelheim as Berotec N and in combination with ipratropium as Berodual N.

It was patented in 1962 and came into medical use in 1971^[5] 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

Fenoterol is a short-acting β₂ agonist that also stimulates β₁ receptors. Fenoterol has more cardiovascular toxicity than isoprenaline or salbutamol.^[6]^[7] 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.^[8] 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.^[9]^[10] The mortality rate declined following withdrawal of fenoterol ^[11] without evidence supporting an alternative explanation for the abrupt rise and fall in asthma deaths.^[12] Data did not support confounding by severity as the explanation for the excess mortality.^[13] There are alternative short-acting beta agonists that have not been associated with increased mortality e.g. salbutamol.

Stereoisomers

5-(1-Hydroxy-2-{[2-(4-hydroxyphenyl)-1-methylethyl]amino}ethyl)benzene-1,3-diol is a molecule with two different stereogenic centers. Thus, four stereoisomers 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)-enantiomers. This racemate is 9 to 20 times more effective, as compared to the racemate of the (R,S)- and (S,R)-enantiomers.^[14]

References

1. ^{{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}}
2. ^{{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}}
3. ^{{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}}
4. ^{{cite journal | last=Svedmyr | first=Nils | name-list-format = vanc | 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 | pages=109–126}}
5. ^{{cite book |last1=Fischer |first1=Jnos |last2=Ganellin |first2=C. Robin |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=542 |url=https://books.google.ca/books?id=FjKfqkaKkAAC&pg=PA542 }}
6. ^{{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 }}
7. ^{{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 }}
8. ^{{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 }}
9. ^{{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 }}
10. ^{{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 }}
11. ^{{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 }}
12. ^{{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 = 10.5555/uri:pii:S0140673695911596 | url = https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(95)91159-6/abstract | doi-broken-date = 2019-03-05 }}
13. ^{{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 }}
14. ^{{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 }}

词条	Fenoterol
释义	Adverse effects and toxicity Stereoisomers References {{distinguish\|Formoterol}}{{Drugbox \| Watchedfields = changed \| verifiedrevid = 443756837 \| IUPAC_name = (RR,SS)-5-(1-hydroxy-2-{[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 \| tradename = \| Drugs.com = {{drugs.com\|CONS\|fenoterol}} \| pregnancy_AU = \| pregnancy_US = B \| pregnancy_category = \| routes_of_administration = Inhalation (MDI) \| bioavailability = \| protein_bound = \| metabolism = \| elimination_half-life = 6.5 hours approximately ^[1]^[2]^[3]^[4] \| excretion = \| CAS_number_Ref = {{cascite\|correct\|??}} \| 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 \| C=17 \| H=21 \| N=1 \| O=4 \| molecular_weight = 303.35 g/mol \| 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 β adrenoreceptor agonist. It is classed as sympathomimetic β₂ agonist and an inhaled bronchodilator asthma medication. Fenoterol is produced and sold by Boehringer Ingelheim as Berotec N and in combination with ipratropium as Berodual N. It was patented in 1962 and came into medical use in 1971^[5] 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 Fenoterol is a short-acting β₂ agonist that also stimulates β₁ receptors. Fenoterol has more cardiovascular toxicity than isoprenaline or salbutamol.^[6]^[7] 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.^[8] 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.^[9]^[10] The mortality rate declined following withdrawal of fenoterol ^[11] without evidence supporting an alternative explanation for the abrupt rise and fall in asthma deaths.^[12] Data did not support confounding by severity as the explanation for the excess mortality.^[13] There are alternative short-acting beta agonists that have not been associated with increased mortality e.g. salbutamol. Stereoisomers 5-(1-Hydroxy-2-{[2-(4-hydroxyphenyl)-1-methylethyl]amino}ethyl)benzene-1,3-diol is a molecule with two different stereogenic centers. Thus, four stereoisomers 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)-enantiomers. This racemate is 9 to 20 times more effective, as compared to the racemate of the (R,S)- and (S,R)-enantiomers.^[14] {{clear}} References 1. ^{{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}} 2. ^{{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}} 3. ^{{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}} 4. ^{{cite journal \| last=Svedmyr \| first=Nils \| name-list-format = vanc \| 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 \| pages=109–126}} 5. ^{{cite book \|last1=Fischer \|first1=Jnos \|last2=Ganellin \|first2=C. Robin \|title=Analogue-based Drug Discovery \|date=2006 \|publisher=John Wiley & Sons \|isbn=9783527607495 \|page=542 \|url=https://books.google.ca/books?id=FjKfqkaKkAAC&pg=PA542 }} 6. ^{{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 }} 7. ^{{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 }} 8. ^{{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 }} 9. ^{{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 }} 10. ^{{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 }} 11. ^{{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 }} 12. ^{{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 = 10.5555/uri:pii:S0140673695911596 \| url = https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(95)91159-6/abstract \| doi-broken-date = 2019-03-05 }} 13. ^{{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 }} 14. ^{{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 }} {{Drugs for obstructive airway diseases}}{{Other gynecologicals}}{{Adrenergic agonists}} 3 : Beta2-adrenergic agonists\|Resorcinols\|Substituted amphetamines
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