tiotropium-bromide and Respiratory-Tract-Diseases

Inhaled corticosteroids, anticholinergics and β₂-adrenoceptor agonists are frequently combined for treating chronic respiratory diseases. We examine the corticosteroid, budesonide, and novel NO-donating derivative, TPI 1020, against histamine- and methacholine-induced bronchoconstriction and whether they enhance the β₂-adrenoceptor agonist formoterol or muscarinic antagonist tiotropium in conscious guinea pigs.. Dunkin-Hartley guinea pigs received inhaled histamine (3 mM) or methacholine (1.5 mM) and specific airway conductance (sG(aw)) was measured before and 15 or 75 min after treatment with budesonide, TPI 1020, tiotropium or formoterol alone or in combinations.. Formoterol (0.7-10 µM) and budesonide (0.11-0.7 mM) inhibited histamine-induced bronchoconstriction and tiotropium (2-20 µM) inhibited methacholine-induced bronchoconstriction by up to 70.8 ± 16.6%, 34.9 ± 4.4% and 85.1 ± 14.3%, respectively. Formoterol (2.5 µM) or tiotropium (2 µM) alone exerted small non-significant bronchoprotection. However, when co-administered with TPI 1020 0.11 mM, which alone had no significant effect, there was significant inhibition of the bronchoconstriction (45.7 ± 12.2% and 79.7 ± 21.4%, respectively). Co-administering budesonide (0.11 mM) with tiotropium (2 µM), which alone had no effect, also significantly inhibited the methacholine bronchoconstriction (36.5 ± 13.0%), but there was no potentiation of formoterol against histamine. The NO scavenger, CPTIO, prevented the bronchoprotection by SNAPand TPI 1020.. TPI 1020 potentiated the bronchoprotection by formoterol and tiotropium. Budesonide also enhanced the effects of tiotropium but not formoterol. Combination of TPI 1020 with a long-acting β₂-adrenoceptor agonist or muscarinic receptor antagonist may therefore be a more potent therapeutic approach for treatment of chronic respiratory diseases.

Topics: Administration, Inhalation; Animals; Bronchoconstriction; Bronchodilator Agents; Budesonide; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination; Ethanolamines; Formoterol Fumarate; Guinea Pigs; Histamine; Male; Methacholine Chloride; Respiratory Tract Diseases; Scopolamine Derivatives; Time Factors; Tiotropium Bromide

Adverse drug reactions is an important healthcare issue, it causes excess morbidity and mortality. The aim of this study was to determine the adverse drug reactions in patients who admitted to the outpatient clinic of respiratory diseases and to improve some clinical strategies if they are preventable.. This study is a prospective observational study which was performed to determine adverse drug reaction in patients who admitted to the outpatient clinic of respiratory diseases.. During the 15 months of study period a total of 114 adverse reactions were reported in 92 out of 18.130 patients. Most of the adverse reactions were related with gastrointestinal system, central nervous system and cardiovascular system. The most of the adverse events were associated with fixed inhaled formoterol-budesonide combination and inhaled tiotropium. The most frequently reported reactions were hoarseness, xerostomia, headache and dizziness. Poliuri and cough were less frequently reported reactions.. Most of the adverse reactions were of limited intensity but some of these side effects might effect patients compliance. Serious adverse events were not detected.

Topics: Administration, Inhalation; Bronchodilator Agents; Budesonide; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Middle Aged; Outpatient Clinics, Hospital; Patient Compliance; Pharmacovigilance; Respiratory Tract Diseases; Scopolamine Derivatives; Tiotropium Bromide

Chronic obstructive pulmonary disease (COPD) exacerbations are associated with systemic consequences. Data from a 4-year trial (Understanding Potential Long-term Impacts on Function with Tiotropium [UPLIFT(®)], n = 5,992) were used to determine risk for nonlower respiratory serious adverse events (NRSAEs) following an exacerbation.. Patients with ≥ 1 exacerbation were analyzed. NRSAE incidence rates (incidence rate [IR], per 100 patient-years) were calculated for the 30 and 180 days before and after the first exacerbation. NRSAEs were classified by diagnostic terms and organ classes. Maentel-Haenszel rate ratios (RR) (pre- and postexacerbation onset) along with 95% confidence intervals (CI) were computed.. A total of 3,960 patients had an exacerbation. The mean age was 65 years, forced expiratory volume in 1 s (FEV(1)) was 38% predicted, and 74% were men. For all NRSAEs, the IRs 30 days before and after an exacerbation were 20.2 and 65.2 with RR (95% CI) = 3.22 (2.40-4.33). The IRs for the 180-day periods were 13.2 and 31.0 with RR (95% CI) = 2.36 (1.93-2.87). The most common NRSAEs by organ class for both time periods were cardiac, respiratory system (other), and gastrointestinal. All NRSAEs as well as cardiac events were more common after the first exacerbation, irrespective of whether the patient had cardiac disease at baseline.. The findings confirm that, after exacerbations, serious adverse events in other organ systems are more frequent, particularly those that are cardiac in nature.

Topics: Aged; Bronchodilator Agents; Disease Progression; Female; Forced Expiratory Volume; Gastrointestinal Diseases; Heart Diseases; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Quality of Life; Randomized Controlled Trials as Topic; Respiratory Tract Diseases; Risk; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome