The prevention of and the controlling of symptoms, reductions in the frequency of exacerbations, and disease severity are central to the pharmacologic therapy of chronic obstructive pulmonary disease (COPD). COPD patients are inclined to be older, have more comorbidities, and use polypharmacy as a result. Long-acting inhaled muscarinic antagonists (LAMAs) is a preferred treatment modality. However, the cardiovascular (CV) safety of anti-cholinergics, including LAMA, has been an issue. In contrast, the results of the UPLIFT trial and a pooled analysis of data from 30 trials of tiotropium illustrates the association of tiotropium with reductions in the risk of all cause mortality, CV mortality and CV events. And, the UPLIFT trial provides clues regarding the additive advantages of tiotropium in COPD patients who already are using long-acting inhaled beta2 agonists and inhaled corticosteroids. Following the contribution of tiotropium as a first LAMA, new LAMAs such as aclidinium and glycopyrrolate (NVA-237) seem to be emerging.
Adrenal Cortex Hormones ; Cholinergic Antagonists ; Comorbidity ; Glycopyrrolate ; Humans ; Muscarinic Antagonists ; Polypharmacy ; Pulmonary Disease, Chronic Obstructive ; Scopolamine Derivatives ; Tiotropium Bromide

OBJECTIVE: The study aimed to evaluate efficacy of tiotropium as add-on therapy on top of standard regimens for uncontrolled asthma, specifically in terms of FEV1, morning and evening PEF, reduction in exacerbations, rescue medication use, and quality of life improvement.
METHODS: A search was done for eligible trials after which validity screen and data extraction was performed. Results were presented as mean differences, standard errors, and 95% confidence intervals, and graphically as forest plots. Estimates were pooled using the random effects model with I2 and Chi2 tests used to assess heterogeneity. Adverse events were reported as dichotomous variables.
RESULTS: Four studies were included totaling 1617 participants. The tiotropium group had statistically significant improvement in FEV1 (95% Cl, 0.14 [0.09, 0.19], p<0.00001), morning (95% Cl, 20.03 [11.71, 28.35], p<0.00001) with trend towards benefit in reduction of rescue medications (95% Cl, 0.12 [-0.17,0.4],p=0.42) and quality of life improvements (95% Cl, 0.1 [-0.05,0.25], p=0.20). Homogeneity (I2= 0%, Chi2= 0.47-3.22) was found across studies.
CONCLUSION: Tiotropium is associated with significant improvement in pulmonary function among patients with uncontrolled asthma, with possible benefit in reduction of rescue medications and quality of life improvement.

Human ; Male ; Female ; Adult ; Asthma ; Bronchodilator Agents ; Confidence Intervals ; Quality Of Life ; Respiratory Physiological Phenomena ; Scopolamine Derivatives ; Tiotropium Bromide ; Meta-analysis

Airway Remodeling ; drug effects ; Cholinergic Antagonists ; therapeutic use ; Humans ; Pulmonary Disease, Chronic Obstructive ; drug therapy ; immunology ; metabolism ; Scopolamine Derivatives ; therapeutic use ; Tiotropium Bromide

Adrenergic beta-Agonists ; therapeutic use ; Aged ; Androstadienes ; therapeutic use ; Cholinergic Antagonists ; therapeutic use ; Fluticasone ; Humans ; Male ; Middle Aged ; Scopolamine Derivatives ; therapeutic use ; Silicosis ; drug therapy ; Tiotropium Bromide

BACKGROUND: A combination of salmeterol and fluticasone propionate (SFC) and tiotropium bromide (TIO) is commonly prescribed for COPD patients but there is little data on their effectiveness, particularly in COPD patients with bronchial hyperresponsiveness. This study compared the spirometric improvement based on the change in FEV1, FEV1/FVC, and IC as well as the clinical outcomes of the therapeutic strategies with SFC and TIO versus the individual components in patients with severe COPD and bronchial hyperresponsiveness. METHODS: This study examined the spirometric data and clinical outcomes of 214 patients with COPD and hyperresponsiveness, who were divided into three groups according to the therapeutic regimen (TIO only, SFC only, and a triple therapy regimen). RESULTS: All regimen groups showed early improvement in the FEV1 and IC (at 3- and 6 months after treatment). However, long-term beneficial effects were observed only in the SFC group (at 24 months after treatment). However, these beneficial effects decreased after a 36-month follow up. In all spirometric results, the 12-, 24-, and 36-months data showed a similar degree of improvement in the three groups. The triple therapy group showed higher St. George's Respiratory Questionnaire scores and lower acute exacerbations and hospitalization. CONCLUSION: SFC can be a more important component in the pharmacological treatment of severe COPD patients with hyperresponsiveness than TIO, particularly in the spirometric and clinical outcomes.
Albuterol ; Androstadienes ; Diethylpropion ; Drug Therapy, Combination ; Follow-Up Studies ; Hospitalization ; Humans ; Pulmonary Disease, Chronic Obstructive ; Surveys and Questionnaires ; Scopolamine Derivatives ; Treatment Outcome ; Fluticasone ; Tiotropium Bromide ; Salmeterol Xinafoate

OBJECTIVETo observe the therapeutic effect of tiotropium bromide powder inhalation on stable bronchiectasis.

METHODSTwenty-two patients with stable bronchiectasis received inhalation of totropium bromide powder at the daily dose of 18 microg, and on days 1 and 28, the patients were examined for forced expiratory volume in one second (FEVl), predicted value [FEVl(%)], forced expiratory volume (FEV), and FEVl/FVC. The symptom score and BODE index were also recorded.

RESULTSAfter 1 month of inhalation therapy, the FEV1% of the patients showed a moderate increase but the increment was not statistically significant (t=-1.875, P>0.05); the symptom score and BODE index decreased significantly after the therapy (t=7.091, P<0.001; t=2.982, P<0.05).

CONCLUSIONLong-term inhalation of tiotropium bromide powder can improve the clinical symptoms and BODE index and enhance the exercise tolerance and quality of life of the patients with bronchiectasis.

Administration, Inhalation ; Adult ; Aged ; Bronchiectasis ; drug therapy ; Female ; Forced Expiratory Volume ; Humans ; Male ; Middle Aged ; Powders ; Receptor, Muscarinic M3 ; antagonists & inhibitors ; Scopolamine Derivatives ; administration & dosage ; Tiotropium Bromide

BACKGROUNDA pharmacokinetic study in an Asian population showed that tiotropium 5 µg via Respimat leads to the same plasma levels compared to 18 µg via HandiHaler. The objective of the trial was to compare the efficacy and safety of longterm treatment (1 year) with tiotropium bromide (5 µg) via Respimat® with placebo in patients with chronic obstructive pulmonary disease (COPD).

METHODSA total of 3991 patients were randomized in this double-blind, placebo controlled, parallel group study, while in China 338 patients (309 males, 29 females) received either tiotropium bromide (n = 167) or placebo (n = 171). Tiotropium bromide solution or matching placebo was delivered via Respimat® at a dosage of 5 µg (2×2.5 µg/puff) once daily for 48 weeks. Co-primary endpoints were trough forced expiratory volume in one second (FEV1) and the time to first exacerbation.

RESULTSStatistically significant improvements in trough FEV1 and trough forced vital capacity (FVC) in the tiotropium group were achieved at weeks 4, 24, and 48 compared with those in the placebo group. A statistically significant difference (P = 0.0027) in favour of tiotropium was also observed for the time to first exacerbation. The total numbers of exacerbations during treatment were 90 and 128 in the tiotropium and placebo groups, respectively, with a rate ratio of 0.69 (P = 0.0164). The difference between the treatment groups in the adjusted mean changes from baseline of St. George Respiratory Questionnaire (SGRQ) total score was -3.9 (95% CI: -7.5, -0.2) and was of statistical significance (P = 0.0367). The incidences of serious adverse events (SAEs) in the tiotropium and placebo groups were 16.2% and 17.0%, respectively. Seven deaths occurred whilst patients were on treatment, four in the tiotropium group and three in the placebo group, all of which were assessed as non-related study drugs by the investigators.

CONCLUSIONSTiotropium significantly improved lung function and quality of life, delayed the time to first exacerbation, reduced the number of exacerbations. Overall, tiotropium was well tolerated.

Administration, Inhalation ; Aged ; Bronchodilator Agents ; adverse effects ; therapeutic use ; Cholinergic Antagonists ; adverse effects ; therapeutic use ; Double-Blind Method ; Female ; Forced Expiratory Volume ; Humans ; Male ; Middle Aged ; Pulmonary Disease, Chronic Obstructive ; drug therapy ; physiopathology ; Scopolamine Derivatives ; adverse effects ; therapeutic use ; Tiotropium Bromide

BACKGROUND/AIMS: Cimetropium bromide has been used widely as a premedication for endoscopy; however, there are no subjective data pertaining to the effects of cimetropum bromide as a premedication. Thus, the current study was undertaken to compare the effects of cimetropum bromide with placebo as a premedication for esophagogastroduodenoscopy (EGD). METHODS: Two hundred ninety-nine consecutive outpatients who had undergone EGD were enrolled in this study. Thirty minutes before EGD, the patients were randomly given an intramuscular injection of cimetropium bromide (5 mg) or saline using a placebo-controlled, double-blind, randomized technique. Immediately after EGD, all the patients and endoscopists were requested to fill out the questionnaire form. RESULTS: One-hundred patients were injected with cimetropium bromide and 150 patients were injected with placebo. There was no statistically significant difference in the degree of residual gastric secretions, the peristaltic activity detected by endoscopists, and the comfort experienced by the patients in each study group. CONCLUSIONS: The intramuscular injection of cimetropium bromide (5 mg) as a premedication for EGD was not significantly superior to placebo, at least with respect to subjective parameters, in spite of its broad use.
Endoscopy, Digestive System ; Humans ; Injections, Intramuscular ; Outpatients ; Parasympatholytics ; Premedication ; Scopolamine Derivatives ; Surveys and Questionnaires

OBJECTIVETo evaluate the therapeutic effect of compound anisodine (CA) for patients with primary open angle glaucoma (POAG).

METHODSAccording to the modified Hodapp-Parrish-Anderson Visual Fields Grading System, 46 patients with moderate stage POAG were randomized to receive compound anisodine injection (CA group) or venoruton tablets (control group). Visual acuity (VA), IOP, fundus, visual fields (VF) and the blood flow of optic nerve were observed.

RESULTSThe mean of defect (MD) was decreased in CA group after treatment. The PSV and EDV of ophthalmic artery were remarkably improved in both groups, as well as the PSV, EDV and RI of retinal central artery. Compound anisodine was superior in improving hemodynamics of ophthalmic artery and retinal central artery to venoruton.

CONCLUSIONCompound anisodine can protect optic nerve of POAG through improving the visual function and blood supply of optic nerve.

Adult ; Female ; Glaucoma, Open-Angle ; drug therapy ; Humans ; Male ; Middle Aged ; Scopolamine Derivatives ; therapeutic use ; Treatment Outcome

AIMTo identify anisodine and its metabolites in rat plasma after ingestion of anisodine by combining liquid chromatography and tandem mass spectrometry (LC-MS(n)).

METHODSPlasma samples from rats after a single orally administration of 20 mg anisodine were added with methanol to precipitate protein. Then, it was analyzed by LC-MS(n). Identification and structural elucidation of the metabolites were performed by comparing their changes in molecular masses, retention-times and full scan MS(n) spectra with those of the parent drug and blank plasma.

RESULTSThe results revealed that the parent drug and its four metabolites (norscopine, scopine, hydroxyanisodine, N-oxide anisodine) existed in rat plasma.

CONCLUSIONThis method is sensitive, rapid, simple, and it is suitable for the rapid identification of drug and its metabolits.

Administration, Oral ; Animals ; Chromatography, Liquid ; methods ; Plants, Medicinal ; chemistry ; Rats ; Rats, Wistar ; Scopolamine Derivatives ; isolation & purification ; metabolism ; Sensitivity and Specificity ; Solanaceae ; chemistry ; Tandem Mass Spectrometry ; methods