Fenoterol, asthma

Poole C, Lanes SF, Walker AM. (1990) Fenoterol and fatal asthma. Lancet. 335, 920. 

Bronchodilation. P2-Adrenocep-tor-mediated bronchodilation (e.g., with terbutaline, fenoterol, or salbutamol) plays an essential part in the treatment of bronchial asthma (p. 328). 

Kassner, F., Hodder, R., and Bateman, E. D. (2004), A review of ipratropium bromide/fenoterol hydrobromide (berodual) delivered via respimat soft mist inhaler in patients with asthma and chronic obstructive pulmonary disease, Drugs, 64, 1671-1682. 

Vincken, W., Dewberry, H., and Moonen, D. (2003), Fenoterol delivery by respimat soft mist inhaler versus CFC metered dose inhaler Cumulative dose-response study in asthma patients, J. Asthma, 40, 721-730. 

Pj effects, used in asthma, or to relax the uterus, include salbutamol, terbutaline, fenoterol, pirbuterol, reproterol, rimiterol, isoxsuprine, orciprenaline, rit-odrine. 

Salbutamol, fenoterol, rimiterol, reproterol, pir-buterol, salmeterol, ritodrine and terbutaline are P-adrenoceptor agonists that are relatively selective for p2-receptors, so that cardiac (chiefly p -receptor) effects are less prominent. Tachycardia still occurs because of atrial (sinus node) p -receptor stimulation the P2-adrenoceptors are less numerous in the ventricle and there is probably less risk of serious ventricular arrhythmias than with the use of nonselective catecholamines. The synthetic agonists are also longer-acting than isoprenaline because they are not substrates for catechol-O-methyltransferase, which methylates catecholamines in the liver. They are used principally in asthma, and to reduce uterine contractions in premature labour. 

Like other betaz-agonists fenoterol has been used in premature labor as well as in asthma. 

In a report the manufacturers have discussed the epidemiological data linking the use of fenoterol to asthma mortahty in New Zealand. They pointed out that asthma mortahty started to fall in 1979 while fenoterol sales were stiU increasing. Sales of fenoterol in Austria, Belgium, and Germany were similar to those in New Zealand at the peak of the New Zealand asthma death epidemic, but asthma mortality in the other countries did not rise. The confounding problem that fenoterol was preferentially prescribed for the more severe cases of asthma was... 

The cardiovascular safety of high doses of inhaled fenoterol and salbutamol has been compared in acute severe asthma (SEDA-21, 183). It was concluded that in adequately oxygenated patients a total dose of 3.2 mg of fenoterol or 1.6 mg of salbutamol given over 60 minutes was safe in terms of cardiovascular effects in acute severe asthma. 

Simi WW, Miller WC. Clinical investigation of fenoterol, a new bronchodilator, in asthma. J Allergy Clin Immunol 1977 59(2) 178—181. 

Eggleston PA, and McMahan S. A. The effects of fenoterol, ephedrine and placebo on exercise-induced asthma. Chest 1978 73(6 Suppl) 1006-1008. 

Crane J, Pearce N, Flatt A, et al. Prescribed fenoterol and death from asthma in New Zealand, 1981-83 case-control study. Lancet 1989 1 917-22. 

Fenoterol (200 to 400 meg by inhalation), a beta2-adrenergic receptor agonist, is being used in patients with moderate to severe asthma, with chronic obstructive pulmonary disease, in protection against exercise-induced asthma, and for acute treatment of asthma attack. However, no apparent advantage of fenoterol over equipotent doses of albuterol or terbutaline has been demonstrated in clinical trials (see also Figure 94). 

J -selective (intermediate- acting) Albuterol Bitolterol Fenoterol Isoetharine Metaproterenol Procaterol Terbutaline Ritodrine Relaxation of bronchial smooth muscle Relaxation of uterine smooth muscle Activation of other receptors after systemic administration Bronchodilators for treatment of asthma and COPD Short/intermediate-acting drugs for acute bronchospasm Skeletal muscle tremor Tachycardia and other cardiac effects seen after systemic administration (much less with inhalational use) Use with caution in patients with CV disease (reduced by inhalational administration) Minimal side effects... 

Combination bronchodilator therapy - This topic has been recently reviewed In chronic asthma, the combination of IB and fenoterol was more effective administered by a metered dose inhaler than salbutamol. Aerosol IB when administered concurrently with Inhaled fenoterol and oral oxtriphylline increased bronchodllation with no detectable additional side effects. Inhalation of IB followed by metaproterenol resulted in additive bronchodllation that was greater and longer lasting than IB alone, metaproterenol alone or metaproterenol followed by IB. ° Neither Inhaled terbutallne nor DSCG were very effective in cold air-induced bronchoconstriction whereas both drugs in combination were much more effective. The interaction of methylxanthlnes and B-agonists continues to be a subject of interest. An Increased Incidence of... 

Another example of marked B-adrenoreceptor potency enhancement by N-substltution is illustrated by fenoterol (60a). which is strikingly more potent than its N-tert-butyl counterpart, ter-butallne (6. Fenoterol is a clinically effective bronchodilator by either oral or aerosol administration however, some cardiac stimulation and tremors are noted (136, 137). Cat soleus muscle, bronchial and heart rate experiments indicate selective B2 adrenoreceptor potency for 60b (138). Another resorcinol, one of a series of xanthine derivatives, is reproterol (60c). Repro-terol is clinically effective in bronchial asthma it causes minimum CNS and cardiovascular side effects upon administration orally or by inhalation, and tachyphylaxis is not observed (139). 

Some Pj-agonists, such as isoprenaline and fenoterol, behave as full agonists of the Pj-receptor, whereas salbutamol and terbutaline are partial antagonists. Moreover, fenoterol is less selective than salbutamol or terbutaline for Pj-receptors (35). These differences have important clinical consequences. For example, fenoterol has greater cardiovascular effects than salbutamol and greater intrinsic myocardial effects than terbutaline in healthy volunteers and in patients with asthma (32). It also appears that the maximum response elicited by fenoterol in terms of reduction in plasma potassium, increase in heart rate and inotropy is greater than that by salbutamol, and that the dose required to reach 50% of maximum response is substantially lower for fenoterol than for salbutamol (35). 

Physicians often overlook pharmacodynamic and pharmacokinetic properties of aerosolized drugs. Differences in Pj-selectivity and the presence of a partial antagonistic activity make that salbutamol and terbutaline, are thought to be less associated with disturbing side effects and asthma mortality than fenoterol (54). 

Wong CS, Pavord ID, WUhams J, Britton JR, Tattersfield AE. Bronchodilator, cardiovascular, and hypokalaemic effects of fenoterol, salbutamol, and terbutaline in asthma (see comments). Lancet 1990 336 1396-1399. 

Kunkel G, Magnussen H, Bergmann K-C, Juergens U, De May C, Freund E, Hinz-mann R, Jahnel B. Cumulative dose response study comparing a new soft mist inhaler with a conventional MDI for dehvery of fenoterol/ipratropium bromide combination in patients with asthma. Eur Respir J 1997 10(suppl 25) 104s. 

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