Pharmacologic Management of Chronic Obstructive Pulmonary Disease. An Official American Thoracic Society Clinical Practice Guideline.

Background: This document provides clinical recommendations for the pharmacologic treatment of chronic obstructive pulmonary disease (COPD). It represents a collaborative effort on the part of a panel of expert COPD clinicians and researchers along with a team of methodologists under the guidance of the American Thoracic Society.Methods: Comprehensive evidence syntheses were performed on all relevant studies that addressed the clinical questions and critical patient-centered outcomes agreed upon by the panel of experts. The evidence was appraised, rated, and graded, and recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluation approach.Results: After weighing the quality of evidence and balancing the desirable and undesirable effects, the guideline panel made the following recommendations: 1) a strong recommendation for the use of long-acting ß2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) combination therapy over LABA or LAMA monotherapy in patients with COPD and dyspnea or exercise intolerance; 2) a conditional recommendation for the use of triple therapy with inhaled corticosteroids (ICS)/LABA/LAMA over dual therapy with LABA/LAMA in patients with COPD and dyspnea or exercise intolerance who have experienced one or more exacerbations in the past year; 3) a conditional recommendation for ICS withdrawal for patients with COPD receiving triple therapy (ICS/LABA/LAMA) if the patient has had no exacerbations in the past year; 4) no recommendation for or against ICS as an additive therapy to long-acting bronchodilators in patients with COPD and blood eosinophilia, except for those patients with a history of one or more exacerbations in the past year requiring antibiotics or oral steroids or hospitalization, for whom ICS is conditionally recommended as an additive therapy; 5) a conditional recommendation against the use of maintenance oral corticosteroids in patients with COPD and a history of severe and frequent exacerbations; and 6) a conditional recommendation for opioid-based therapy in patients with COPD who experience advanced refractory dyspnea despite otherwise optimal therapy.Conclusions: The task force made recommendations regarding the pharmacologic treatment of COPD based on currently available evidence. Additional research in populations that are underrepresented in clinical trials is needed, including studies in patients with COPD 80 years of age and older, those with multiple chronic health conditions, and those with a codiagnosis of COPD and asthma.

Seventeen-Year Nationwide Trends in Use of Long-acting Bronchodilators and Inhaled Corticosteroids among Adults - A Danish Drug Utilization Study.

Long-acting bronchodilators and inhaled corticosteroids (ICS) are the cornerstones in treatment of chronic obstructive and inflammatory pulmonary diseases. However, non-adherence to guidelines is widespread. Detailed information on real-life treatment patterns is needed to promote rational use. We aimed to investigate nationwide time trends in individual-level treatment patterns of long-acting bronchodilators and ICS. Using nationwide Danish health registries, we identified all Danish adults with a prescription for long-acting bronchodilators and/or ICS from 2000 to 2016. We investigated the total use of long-acting bronchodilators and ICS, the proportion of current users and the rate of new users over time. Finally, we assessed treatment persistence. We included 23,061,681 prescriptions for long-acting bronchodilators and ICS issued to 805,860 individuals from 2000 to 2016. Over this period, the total annual amount of prescribed long-acting bronchodilators and ICS increased by 39%. Similarly, the proportion of adult users increased from 2.6% to 4.5%, mainly driven by the introduction of combination therapy and long-acting muscarinic antagonist (LAMA). Although the rate of new users of fixed-dose combination drugs increased substantially over time, the overall rate of new users was stable. In general, the proportion of patients on therapy after 1 year was low (25-53%), especially among young individuals and users of ICS. We document a pronounced increase in the total use of long-acting bronchodilators and ICS over time, mainly driven by the introduction of combination drugs and LAMA. Special attention should be paid to the low level of persistence, especially among young individuals and users of ICS.

Isolation, identification and characterization of degradant impurities in Tolterodine tartrate formulation.

During the stability study of Tolterodine tartrate drug product, two unknown impurities (Impurities I and II) were detected by ultra performance liquid chromatography (UPLC). Both impurities were isolated by preparative liquid chromatography and were subjected to mass and NMR spectral studies. Based on the spectral data, the Impurities I and II were characterized as N-(3-(2-hydroxy-5-methylphenyl)-3-phenylpropyl)-N,N-diisopropyl hydroxyl ammonium trifluoro acetate and 3-(2-hydroxy-5-methylphenyl)-N-isopropyl-3-phenylpropane-1-amine oxide respectively.

The influence of anticholinergic drug selection on the efficacy of antidotal treatment of soman-poisoned rats.

The influence of some anticholinergic drugs (atropine, benactyzine, biperiden, scopolamine) on the efficacy of antidotal treatment to eliminate soman (O-pinacolyl methylphosphonofluoridate)-induced disturbance of respiration and circulation and to protect experimental animals poisoned with supralethal dose of soman (1.5 x LD(50)) was investigated in a rat model with on-line monitoring of respiratory and circulatory parameters. While the oxime HI-6 in combination with atropine prevented soman-induced changes in monitored physiological parameters insufficiently and very shortly, the combination of HI-6 with benactyzine or biperiden is able to prevent soman-induced alteration of respiration and circulation much more longer. Nevertheless, only rats treated with HI-6 in combination with scopolamine were fully protected against the lethal toxic effects of soman within 2 h following soman challenge. Our findings confirm that anticholinergic drugs with the strong central antimuscarinic activity, such as benactyzine, biperiden and especially scopolamine, seem to be more effective adjuncts to HI-6 treatment of severe acute soman-induced poisoning than atropine.