Fenoterol

Adverse effects

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

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.

References

References

1. (1996-01-01). "Fenoterol Hydrobromide Drug Information, Professional".
2. (2016-10-27). "Fenoterol - Drug Monograph".
3. "Berotec Inhalation Solution (Fenoterol HBr)".
4. (1985-05-06). "Fenoterol: A Beta2-adrenergic Agonist for Use in Asthma; Pharmacology, Pharmacokinetics, Clinical Efficacy and Adverse Effects". Wiley.
5. (2006). "Analogue-based Drug Discovery". John Wiley & Sons.
6. (February 1989). "Cardiovascular and hypokalaemic effects of inhaled salbutamol, fenoterol, and isoprenaline". Thorax.
7. (February 1991). "Lack of evidence for beta-2 receptor selectivity: a study of metaproterenol, fenoterol, isoproterenol, and epinephrine in patients with asthma". The American Review of Respiratory Disease.
8. (1995). "Withdrawal of fenoterol and the end of the New Zealand asthma mortality epidemic". International Archives of Allergy and Immunology.
9. (April 1989). "Prescribed fenoterol and death from asthma in New Zealand, 1981-83: case-control study". Lancet.
10. (March 1990). "Case-control study of prescribed fenoterol and death from asthma in New Zealand, 1977-81". Thorax.
11. (1995). "Withdrawal of fenoterol and the end of the New Zealand asthma mortality epidemic". International Archives of Allergy and Immunology.
12. (January 1995). "End of the New Zealand asthma mortality epidemic". Lancet.
13. (July 1994). "Confounding by severity does not explain the association between fenoterol and asthma death". Clinical and Experimental Allergy.
14. (April 1972). "X-ray analysis of Th 1165a* and salbutamol". Journal of Pharmacy and Pharmacology.