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.     

支气管扩张剂对老年阻塞性气道疾病的治疗现状

 阻塞性气道疾病（如COPD、哮喘）是老年人的常见病,随增龄出现的解剖、心理和生理上的一些变化会对这类疾病的治疗产生影响,而同时伴有的其他系统的慢性疾病也会对这类疾病的药物治疗产生影响。支气管扩张剂是治疗这类疾病的基本药物,但即便是吸入剂型也会出现局部甚至全身的不良反应。由于增龄而出现的药物吸收、代谢、分布、排泄方面的改变会导致老年阻塞性气道疾病患者出现与年轻患者不同的药物反应。文中从老年人药动学特点、常见支气管扩张剂包括β2受体激动剂、抗胆碱药、磷酸二酯酶抑制剂的作用机制、体内外活性、安全性等方面综述支气管扩张剂对老年阻塞性气道疾病的治疗进展。     

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.     

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.     

Acute Bronchodilator Response Has Limited Value in Differentiating Bronchial Asthma from COPD

Background. Acute responsiveness to inhaled bronchodilators is often used to differentiate between bronchial asthma and chronic obstructive pulmonary disease (COPD). The response can be expressed in terms of a change in FEV₁ and FVC in several ways—as absolute change, change as percent of baseline value, or as percent of predicted value with different thresholds for a positive test. A comprehensive evaluation of the diagnostic value of these different methods of expressing the acute bronchodilator response has not been carried out. Methodology. Response to inhaled salbutamol was measured by spirometry in 200 asthmatics and 154 patients with COPD. The sensitivity, specificity, and positive and negative predictive values of different methods of expressing responsiveness were calculated. Receiver operative characteristic curves were obtained. Results. None of the expressions of response gave a clear-cut separation between the two diseases. A ΔFEV₁≥ 0.2 L gave the most satisfactory combination of sensitivity (73%) and specificity (80%) and the highest positive (82%) and negative predictive values (69%) for diagnosing asthma. These values were superior to those obtained for the ERS or the ATS criteria for reversibility (ΔFEV₁%predicted ≥ 9% and ΔFEV₁ of ≥ than 12% and 0.2 L over the baseline, respectively), which had almost similar diagnostic characteristics. This was confirmed by the area under curve of the ROC plots. Expressions of response in terms of changes in FVC were unsatisfactory in separating the two diseases. Conclusions. It was concluded that the test of acute bronchodilator responsiveness has limited diagnostic value in separating asthma and COPD.     

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.