Comparative study of the effects of intravenous administration of aminophylline, salbutamol and terbutaline in patients suffering from reversible airways obstruction.

A study was carried out in 20 patients with reversible airways obstruction to compare the bronchodilator potency of salbutamol (250 micrograms), terbutaline (500 micrograms) and aminophylline (250 mg), given by slow intravenous injection. Patients received each of the three treatments, on separate days, in random order using a double-blind design. Measurements were made of pulmonary function, pulse rate and blood pressure and side-effects were recorded before and at intervals up to 4 hours after drug administration. All three drugs improved pulmonary function to a significant degree and this effect was observed at 5 minutes post-treatment and lasted for 3 hours. Terbutaline and salbutamol had a significantly greater effect than aminophylline, but there was no difference between salbutamol and terbutaline. Both salbutamol and terbutaline produced tachycardia of a similar magnitude, and which returned to initial values within 90 minutes post-injection. Aminophylline did not cause tachycardia and this difference compared with the beta-agonists on pulse rate was statistically significant (p less than 0.001). Salbutamol caused a significantly greater incidence of palpitations than did either aminophylline (p less than 0.01) or terbutaline (p less than 0.05). No other differences between treatments were observed.

A 21-day double-blind study of the effect of adding sustained-release theophylline (Nuelin SA) to inhaled salbutamol in patients with asthma.

The effect of adding sustained-release theophylline tablets (Nuelin SA) in a dose of 350 and 700 mg daily to regular treatment with inhaled salbutamol was assessed in a double-blind cross-over study in 19 patients with reversible airways obstruction. In this combination, oral theophylline, even in the relatively low dose of 350 mg a day, produced a significant additional improvement in lung function. Subjectively, patients showed a preference for the combination of theophylline and inhaled salbutamol compared with the beta-stimulant alone.

A therapeutic comparison of ipratropium bromide and salbutamol in asthmatic patients.

A single-blind, crossover study was carried out in 43 asthmatic patients to compare the efficacy and tolerance of inhaled ipratropium bromide with inhaled salbutamol. One or other drug was given 3-times daily (0.04 mg ipratropium bromide or 0.2 mg salbutamol per dose) over a period of 4 weeks. Patients were then crossed over to the alternative medication for a further 4 weeks. The results of lung function tests performed at routine clinic visits and by the patients at home showed similar increases in peak flow and spirometry recordings, although more patients expressed a preference for salbutamol. Unwanted effects were minor with both drugs. It is suggested, therefore, that ipratropium bromide may be a useful alternative to beta-stimulants in some asthmatics.

Asthma and beta-blockers.

In a randomized, blind crossover study in 14 hypertensive patients with asthma, involving placebo and chronically administered (3 weeks) equipotent beta1-blocking doses of atenolol 100 mg once daily and metoprolol 100 mg bid, atenolol and metoprolol produced a similar fall in blood pressure. Atenolol caused significantly (p less than 0.05) less bronchospasm in terms of fewer asthmatic attacks, more asthma-free days, less frequent sensations of moderate to very severe, wheeziness and less effect on the evening peak flow rate. It was concluded that, in patients with asthma who require beta blockade, atenolol is the preferred agent, co-prescribed with a beta2 stimulant.

Cardioselectivity of atenolol in asthmatic patients.

This double-blind, randomised, within patient, placebo-controlled study set out to investigate the effect of a cardioselective beta-blocker, atenolol, at different oral doses (50, 100 and 200 mg) and a non-selective agent, propranolol (40 mg), upon 1. airways resistance (forced expiratory volume at one second = FEV1) and 2. the bronchodilator action of increasing doses of inhaled isoprenaline, in patients with co-existent hypertension and reversible airways obstruction. In 10 patients, two hours after drug administration, the 3 doses of atenolol caused a significantly greater (P less than 0.05) degree of B1-blockade than propranolol. In contrast the 3 doses of atenolol caused significantly less (P less than 0.05 to 0.01) B2-blockade as evidenced by a smaller fall in FEV1. The isoprenaline FEV1 dose response curves were displaced progressively to the right of the placebo curve with increasing doses of atenolol, but the greatest displacement was with propranolol. It was concluded that patients with reversible airways obstruction who require beta-blockade should be given a low dose of a cardioselective agent in conjunction with, if required, a beta 2 stimulant such as isoprenaline. Such a treatment will be less likely to cause a troublesome increase in airways resistance and the bronchodilator action of the beta 2 stimulant will be almost fully preserved.

Efficacy of nifedipine in the treatment of angina pectoris and chronic airways obstruction.

Twenty patients suffering from angina pectoris with co-existing fixed or labile airways obstruction, were administered fortnightly treatment periods of nifedipine or matching placebo over an 8-week period. Maintenance treatment for their airways obstruction continued throughout this period. Nifedipine was found to be an effective drug in controlling their angina, and did not have an adverse effect on the airways obstruction. Both systolic and diastolic BP was reduced over a 90-min period after administration of a single dose of nifedipine.

Long-term study of flunisolide treatment in perennial rhinitis with special reference to nasal mucosal histology and morphology.

Ten patients with allergic perennial rhinitis completed a 3-month course of reatment with flunisolide nasal spray. Biopsy of the nasal mucosa was carried out before the initiation of treatment and at the end of the treatment period. The flunisolilde was administered as a 0.025% solution twice daily at a total daily dose of 200 micrograms. No histological abnormalities which could have been attributed to the effects of the drug were found in the post-treatment biopsies. Comparison of the pre- and post-treatment histological features showed either that there had been no apparent changes or that there had been a reduction in the oedema and/or cellular infiltration which had been present initially. All except one patient improved clinically and in this case the pre-treatment nasal biopsy demonstrated features of atrophic rhinitis.

A comparative trial of flunisolide and beclomethasone dipropionate in the treatment of perennial allergic rhinitis.

An open, parallel comparison of flunisolide and beclomethasone dipropionate nasal sprays is described. Sixty patients entered the study of whom fifty-six completed the full 4 weeks' therapy. The dosage of flunisolide was two actuations (25 micrograms/actuation) into each nostril twice a day (total 200 micrograms). The dosage of beclomethasone dipropionate was one actuation (50 micrograms) in each nostril four times a day (total 400 micrograms). Both drugs produced statistically significant improvements compared with admission values in sneezing, stuffiness, runny nose, nose blowing and post-nasal drip. Both drug significantly decreased the interference by symptoms with routine life and sleep. At the end of the trial both treatment groups showed total or good control of symptoms in the majority of patients. No statistically significant difference was shown between the effects of the two drugs. Side-effects did not cause withdrawal from the trial in any patient and were mostly confined to minor headache and nose and throat complaints. In neither treatment group was there any evidence of adrenal suppression or growths of Candida from nasal swabs.

A comparative trial of combination therapy in obstructive airways disease.

Eleven patients suffering from chronic reversible airways obstruction completed a comparative crossover trial of two combinations of a controlled-release aminophylline formulation and inhaled salbutamol, and two combinations of oral and inhaled salbutamol. Assessment was by FEV1, which was measured at the end of each 2-week treatment period. The highest mean FEV1 was recorded in patients using controlled-release aminophylline plus routine inhaled salbutamol. The only treatment which gave a significant (p < 0.05) increase over baseline was a combination of controlled-release aminophylline and inhaled salbutamol on demand. The combination of controlled-release aminophylline plus inhaled salbutamol on need was significantly more effective than the combination of oral salbutamol plus routinely inhaled salbutamol.

Inhaled corticosteroid aerosols and candidiasis.

A three-month controlled study was performed to assess the cumulative incidence of oral Candida carriage and thrush in patients starting to take betamethasone valerate aerosol (800 microgram/day) for control of their asthma. Four of 41 patients on the corticosteroid aerosol developed thrush compared with none of 40 in the control group. However, the number of cumulative saliva culture positives for C. albicans rose by a similar amount (approximately 20%) in each group. A simple mouthwash procedure was shown to have no prophylactic benefit in the aerosol group. Oral candidiasis was not, however, clinically important.

Flunisolide--a new intranasal steroid for the treatment of allergic rhinitis.

A double-blind, cross-over comparison of flunisolide nasal spray and its inactive aqueous vehicle has been carried out in fifty patients suffering from perennial allergic rhinitis. Patients were randomly allocated to two groups; the first group (group I) received flunisolide for 3 weeks and then placebo for 3 weeks while the regimes were given in the reverse order to the second group (group II). Patients used two insufflations of 0.1 ml in each nostril twice daily. As the active spray was presented as a 0.025% solution of flunisolide, the total daily dosage was 200 microgram. Patients were assessed on admission and at the end of each 3 week period. The results show flunisolide to be significantly superior to placebo in relieving sneezing, nasal obstruction and postnasal drip, as well as improving the quality of sleep and everday life. At the end of the trial the preferences for treatment recorded by both doctors and patients were significantly in favour of the flunisolide spray. Side effects were minor and occurred during both placebo and active phases of the trial. A short Synacthen test performed at each visit showed no evidence of adrenal suppression.

A comparison of controlled-release aminophylline (Phyllocontin Continus tablets) and sympathomimetic bronchodilators.

In a crossover trial on twenty-four patients with reversible airways obstruction the rise in FEV1 on Phyllocontin Continus tablets (15%) was comparable to that achieved with Alupent tablets (14%). The usage of inhaled salbutamol and frequency of attacks of wheeziness were both greater when the patients were taking Alupent tablets. In a second study the effect of Phyllocontin tablets and Ventolin tablets both in combination with inhaled Ventolin and alone were examined. It was found that on Phyllocontin tablets alone patients showed a similar improvement (22%) in FEV1 to Ventolin tablets alone (19%). When inhaled Ventolin was added to Phyllocontin tablets a further rise in FEV1 was seen but not when inhaled Ventolin was added to Ventolin tablets.