Alupent (Orciprenaline Sulfate)
Orciprenaline powder is a bronchodilating agent. The bronchospasm associated with various pulmonary diseases – chronic bronchitis, pulmonary emphysema, bronchial asthma, silicosis, tuberculosis, sarcoidosis and carcinoma of the lung, has been successfully reversed by therapy with orciprenaline.
Orciprenaline has the following major characteristics: The action of orciprenaline is one of beta stimulation. Receptor sites in the bronchi and bronchioles are more sensitive to the drug than those in the heart and blood vessels, so that the ratio of bronchodilating to cardiovascular effects is favorable. Consequently, it is usually possible clinically to produce good bronchodilation at dosage levels which are unlikely to cause cardiovascular side effects.
The efficacy of the bronchodilator after both oral and inhalation administration has been demonstrated by pulmonary function studies (spirometry, and by measurements of airways resistance by body plethysmography).Rapid onset of action follows administration of orciprenaline inhalants, and the effect is usually noted immediately. Following oral administration, the effect is usually noted within 30 minutes.The peak effect of bronchodilator activity following orciprenaline generally occurs within 60 to 90 minutes, and this activity lasts for 3 to 6 hours.Orciprenaline taken orally potentiates the action of a bronchodilator inhalant administered 90 minutes later, whereas no additive effect occurs when the drugs are given in reverse order.
Patients have not developed tolerance to the drug during prolonged therapy.No toxic effects on the liver, kidneys or hematologic system have been reported in the long-term use of orciprenaline in man.Indications And Clinical Uses: Orciprenaline has been found useful in the following conditions: bronchial asthma, chronic bronchitis, pulmonary emphysema.Orciprenaline is also useful in sarcoidosis, silicosis, carcinoma of the lung and tuberculosis when bronchospasm contributes to the disability.
Patients with chronic airways obstructive disease require long-term therapy with bronchodilators as an essential part of overall management aimed at lowering airways resistance and facilitating bronchial drainage. Orciprenaline has been shown to fulfill the basic requirements of such continued therapy in that it is effective both orally and as an inhalant, has a rapid and prolonged action, and has a low incidence of side effects.
Inhalation Aerosol: The efficacy of orciprenaline administered as an aerosol has been demonstrated by increased flow rates (FEV1, MMFR, MEFR, MBC) decreased airways resistance (body plethysmography), and decreased functional residual capacity (body plethysmography).
In one study the effect of 4.5 mg of orciprenaline has been compared with the effect of 0.45 mg of isoproterenol each drug being given as an aerosol over a period of 8 minutes. Although the improvement in pulmonary function was consistently better with orciprenaline, 1 hour, 3 hours, and 6 hours following inhalation, changes in pulse rate and blood pressure were less pronounced with orciprenaline. This indicated a more favorable ratio of bronchodilating to cardiovascular effects for orciprenaline.
In another study, orciprenaline 2% solution, racemic epinephrine 2.25% and isoproterenol 1% were each administered as aerosols on separate days. The aerosols were administered by hand nebulizer for 30 minutes or until cardiovascular side effects appeared.
The immediate effect of orciprenaline on airways resistance in this study was similar to that produced by isoproterenol and by racemic epinephrine. However, the reduction in airways resistance after orciprenaline was significantly greater than that seen with isoproterenol in 30 minutes after inhalation, and after 90 minutes the effect of orciprenaline was superior to both isoproterenol and racemic epinephrine.
Whereas isoproterenol aerosol and epinephrine aerosol produced only transient reductions in the functional residual capacity of less than 30 minutes duration, the effect of orciprenaline on this parameter remained significant up to 90 minutes after inhalation.
Syrup: The efficacy of orciprenaline has been demonstrated by improvement of flow rates (FEV1, MMFR, MEFR) and airways resistance measurements (body plethysmography). Repeated measurements of pulmonary function made over a 4-hour period show that orciprenaline 20 mg orally gives a generally better result regarding duration of action and magnitude of response than placebo, 100 mg methoxyphenamine, 30 mg ephedrine by mouth, or 10 mg isoproterenol sublingually.
The effect of an inhalant bronchodilator may be potentiated by oral administration of 20 mg of orciprenaline 90 minutes prior to use of the inhalant. No additive effect occurs when the drugs are given in reverse order. The probable reason for this is that a bronchodilator delivered to the lungs via the vascular system (i.v. or oral medication) acts upon bronchioles whether or not they are occluded. Such an effect causes a wider distribution in the lungs of a subsequently given drug, and consequently the bronchodilation is more intense. Knowledge of this interaction is of value when instructing patients in the combined use of oral and inhalant forms of orciprenaline.
Orciprenaline may be given orally in dosages ranging from 60 to 120 mg daily. An effective clinical response in adults and children above 12 years can be achieved by 20 mg orciprenaline 3 times daily, and at this dosage side effects are not significantly different from those following placebo. Orciprenaline at a dosage of 20 mg 4 times daily is well tolerated and side effects are usually mild. Only at dosages of 100 mg daily and above, do palpitations and tremulousness become troublesome. If high doses of orciprenaline are necessary, it may be possible to eliminate the side effects whilst continuing the same total daily dose, by administering 10 mg single doses at more frequent intervals.
General: The low incidence of side effects together with effective bronchodilation make orciprenaline acceptable to patients with chronic bronchial asthma for continuous use either alone or concurrently with corticosteroids. Some of these patients may be controlled with orciprenaline as the sole medication, and it may be possible to avoid the use of steroid therapy. In a proportion of individuals who are already taking corticosteroids, it may be possible to withdraw this medication and continue with orciprenaline alone. However, caution should be observed in this regard as many patients, particularly those with severe bronchial asthma, can be managed satisfactorily only if steroids and bronchodilators are given together.
Prolonged studies have shown that patients with bronchitis and emphysema respond to continuous therapy with orciprenaline. The frequency and severity of acute attacks decrease, and patients experience relief of wheezing, chest congestion and shortness of breath. A close association is apparent between objective measurements of pulmonary function and the subjective response.
Contra-Indications: Known sensitivity to the drug or other sympathomimetic amines. The use of orciprenaline and other beta stimulators is generally considered to be contraindicated in patients with cardiac arrhythmias associated with tachycardia.Beta blocking agents, (e.g. propranolol) effectively antagonize the action of orciprenaline. Their concomitant use, except in the treatment of accidental overdosage, is therefore contraindicated.