The bronchodilating effect of fenoterol is produced primarily by stimulation of b2 receptors in the bronchial smooth muscles. The effect has been measured by means of spirometry (FEV1, FVC, MMFR), peak flow rates, flow volume curves, airway resistance (plethysmography) and oscillation mechanics.Fenoterol
Fenoterol, when administered by inhalation, exerts a significant increase in pulmonary function 5 minutes after administration and maximal effect in 30 to 60 minutes. This effect remains at the same level for 2 to 3 hours before gradually declining. A significant degree of bronchodilation has been detected in some studies for 6 to 8 hours.
Pharmacokinetics: In man, fenoterol is rapidly absorbed from the gastrointestinal tract, with an absorption level of 60%. After administration of tritium labelled fenoterol, peak plasma levels (2.5% of the oral dose) are reached in 2 hours, the half-life of radioactivity being 6 to 7 hours. When given from a pressurized container, absorption proceeds in 2 phases: the first one is essentially independent of the dose and apparently takes place between the first and fourth subdivision of the bronchial tree. A second phase appears to be identical to oral absorption. After inhalation, blood levels remain almost unchanged for 7 hours (0.3 to 0.4 ng/mL fenoterol).
Following i.v. administration, fenoterol is very rapidly taken up by the tissues where it is conjugated to the extent of 99% (as sulfates). Unlike isoproterenol, fenoterol is not metabolized by catechol-O-methyl transferase. The resulting metabolites are excreted via the kidneys (40% within 48 hours after oral administration) and the bile (fecal excretion: 40% of the oral dose).
Autoradiographic studies in gravid rats showed no detectable amounts of fenoterol in the fetus. Direct blood and tissue studies in several animal species and in man showed that the levels of fenoterol and its conjugates were 10 to 20 times lower in the fetus than in the maternal tissues.Indications And Clinical Uses: For the symptomatic relief and acute prophylaxis of bronchial obstruction in asthma and other conditions in which reversible bronchospasm is a complicating factor, such as chronic bronchitis or emphysema.
Contra-Indications: Like other sympathomimetic amines, fenoterol inhalation aerosols should not be used in patients with tachyarrhythmias, hypertrophic obstructive cardiomyopathy or in patients with known hypersensitivity to fenoterol or to any of the product components (see Supplied).Manufacturers’ Warnings In Clinical States: Like other b2 agonists inhalers, fenoterol should not be used on a regular basis without appropriate concomitant anti-inflammatory therapy (see Dosage).
Children: Not currently indicated for use in children under 12 years of age as the dosing regimen and evidence concerning its safety in this age group have not been established.Pregnancy and Lactation: The safety of fenoterol in pregnancy and lactation has not been established. b2 agonists should be used with caution before childbirth in view of their inhibiting effect on uterine contractions.
General: Care should be taken in patients suffering from myocardial insufficiency, cardiac arrhythmias, recent myocardial infarction, severe organic heart and/or other vascular disorders, hypertension, hyperthyroidism or diabetes mellitus.Fatalities, the exact cause of which is unknown, have been reported following excessive use of sympathomimetic amines by inhalation. Cardiac arrest was noticed in several instances.
Some patients receiving inhaled b-adrenergic agonists have developed severe paradoxical bronchospasm, which has been life-threatening. The cause of this refractory state is unknown. If it occurs, the preparation should be discontinued immediately and alternative therapy instituted.In common with other b-adrenergic agents, fenoterol can induce reversible metabolic changes. These are most pronounced during infusions of the drug and include hyperglycemia and hypokalemia.
Potentially serious hypokalemia may result from b2-agonist therapy, mainly from parenteral and nebulized administration. Particular caution is advised in acute severe asthma as hypokalemia may be potentiated by concomitant treatment with xanthine derivatives, steroids and diuretics; the adverse effects of hypokalemia may be exacerbated by hypoxia. It is recommended that serum potassium levels be monitored in such situations. Hypokalemia will increase the susceptibility of digitalis-treated patients to cardiac arrhythmias.
The bronchodilating action of sympathomimetic drugs may be antagonized by b-adrenergic blocking agents with the result that the respiratory status of patients may worsen when the 2 drugs are used concomitantly. In patients requiring concomitant treatment with fenoterol inhalation aerosols and a b-adrenergic blocking agent, the use of a relatively cardioselective b-blocker (e.g., metoprolol, atenolol, acebutolol) must be considered. During concomitant treatment, patients must be monitored carefully for possible deterioration in pulmonary function or for the need to adjust the dosage of either drug.
