Possible site of bronchodilation due to inhaled procaterol aerosol in asthmatic patients

Summary We studied the effective site of an inhaled aerosol of procaterol, a ₂-selective adrenergic bronchodilator, in 8 asthmatic patients whose basal lung functions are almost within the normal range in both slow vital capacity (VC) and forced expiratory volume in one second (FEV_1.0), and are free from asthmatic attack. In patients who had received procaterol 30 min after inhalation of aerosol, there was no significant change in VC, although FEV_1.0, maximal expiratory flow at 50% VC , maximal expiratory flow at 25% VC and maximal expiratory flow at 30% VC of partial maximal expiratory flow volume curve improved significantly. On the other hand, in those who had received placebo, none of the parameters changed. Furthermore, Rl decreased and C_0.5 increased significantly during the first 5 min after inhalation of procaterol aerosol. After an interval of 5 min, Rl did not change any further, while C_0.5 continued to improve until 30 min after inhalation of procaterol. These results suggest that procaterol may first dilate the large airway and then may gradually dilate the small airway in bronchial asthma.     

Long-acting muscarinic M3 receptor antagonists

Two applications claim a novel class of muscarinic M₃ receptor antagonists and their use as long-acting agents for the treatment of chronic obstructive pulmonary disease. The two applications claim closely related structures with one claiming quaternary amine salts of the tertiary amines claimed in the other. The claimed compounds comprise a biarylmethylamine core with the amino group modified by acylation or sulfonation and a tertiary or quaternary amine coupled to the distal ring of the biaryl system.     

A clinical trial of oral clenbuterol (NAB 365) in chronic airways obstruction

Summary

A new oral bronchodilator, clenbuterol, was compared with terbutaline during a 5-week single-blind crossover study in 16 patients with chronic airways obstruction and with cough and sputum production. After a run-in period (I week), the study was performed in two separated 2-week periods (Phase II and Phase IV), separated by a I-week drug-free period. Oral clenbuterol was administered at 20 to 30 μg 3-times daily, oral terbutaline at 2.5 to 5?mg 3-times daily. The forced expiratory volume in 1 second (FEV₁) was measured at the beginning and end of Phase II and Phase IV under baseline conditions, and 1 hour after an oral dose of clenbuterol or terbutaline. Patients recorded subjective and objective information in a daily diary and used no bronchodilator therapy for 12 hours before each visit. Clenbuterol and terbutaline significantly improved baseline FEV₁ and the bronchodilator effects of single oral doses were similar. The mean dyspnoea, cough and sputum score values after treatments were lower than during the wash-out period(p <0.05). Tremors were noted in 6 patients on clenbuterol and 5 on terbutaline. It is suggested that clenbuterol is a good alternative oral drug for treatment of chronic airways obstruction.     

The effects of ‘Nethaprin’ Syrup in chronic asthmatic children

Summary

In an open study using ‘Nethapriri’ Syrup in 20 children with chronic asthma there was considerable improvement in average PEFR and FEV₁ values which were statistically significant at the p < 0.01 level. A maximal rise in these levels occurred within the second and third hours, with residual bronchodilator effects still present at the sixth hour. Only a slight rise in pulse rate was noted.     

A simple model for understanding the causes of paediatric wheeze

Wheeze is one of the most common paediatric presentations. While there are only a few possible reasons for a child to develop wheeze, there is often diagnostic uncertainty between common causes such as bronchiolitis, viral wheeze and asthma. The evidence shows that these conditions respond differently to the treatments available. This means that better differentiation should have a beneficial effect through more appropriate and targeted disease management. This article describes my personal model for understanding why these three conditions occur at different ages and respond to different treatments. The model is also used to give practical advice regarding the differentiation of bronchiolitis, viral wheeze and asthma in children and young people.     

Pfizer's dual-acting β2 agonists/muscarinic M3 antagonists

Bifunctional aromatic compounds that contain both β₂ agonist and muscarinic antagonist pharmacophores linked by a flexible lipophilic spacer are claimed. The compounds display nanomolar potency with respect to both activities and appear designed to provide a long duration of action. The compounds are claimed to be useful in the treatment of both asthma and chronic obstructive pulmonary disease.     

Aclidinium bromide and formoterol fumarate for the maintenance treatment of chronic obstructive pulmonary disease

ABSTRACT

Introduction: Treatment options for COPD have evolved rapidly in the last decade and inhaled bronchodilators have largely supplanted the use of oral bronchodilators because of their increased efficacy and excellent safety with topical delivery to the lung. Recently added to the therapeutic armamentarium are fixed-dose combinations (FDC) of two long acting bronchodilators. LAMAs (long acting muscarinic antagonists) and LABAs (long acting beta agonists) are the main classes available and use different pathways to effectively produce bronchial smooth muscle relaxation.

Areas covered: The most recent inhaled FDC LAMA/LABA to come to market is Aclidinium Bromide and Formoterol Fumarate. We searched databases of PubMed, Cochrane Library, and manufacturers’ websites and retrieved all the randomized-controlled trials (RCTs) conducted with these drugs up to September 2019.

Expert opinion: It is likely that FDCs will become the core of our COPD pharmacotherapy for all but the mildest COPD patients. These individual drugs have excellent efficacy and safety records for the maintenance treatment of COPD. Studies have demonstrated that twice daily treatment with aclidinium/formoterol resulted in significant improvement in lung function and an improved exercise tolerance when compared to placebo. Adverse effects are within the range of what is seen with other LAMA/LABA combinations.