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

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

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

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

Atropa belladonna is a medicinal plant and main commercial source of tropane alkaloids (TAs) including scopolamine and hyoscyamine, which are anticholine drugs widely used clinically. Based on the high throughput transcriptome sequencing results, the digital expression patterns of UniGenes representing 9 structural genes (ODC, ADC, AIH, CPA, SPDS, PMT, CYP80F1, H6H, TRII) involved in TAs biosynthesis were constructed, and simultaneously expression analysis of 4 released genes in NCBI (PMT, CYP80F1, H6H, TRII) for verification was performed using qPCR, as well as the TAs contents detection in 8 different tissues. Digital expression patterns results suggested that the 4 genes including ODC, ADC, AIH and CPA involved in the upstream pathway of TAs, and the 2 branch pathway genes including SPDS and TRII were found to be expressed in all the detected tissues with high expression level in secondary root. While the 3 TAs-pathway-specific genes including PMT, CYP80F1, H6H were only expressed in secondary roots and primary roots, mainly in secondary roots. The qPCR detection results of PMT, CYP80F1 and H6H were consistent with the digital expression patterns, but their expression levels in primary root were too low to be detected. The highest content of hyoscyamine was found in tender stems (3.364 mg x g(-1)), followed by tender leaves (1.526 mg x g(-1)), roots (1.598 mg x g(-1)), young fruits (1.271 mg x g(-1)) and fruit sepals (1.413 mg x g(-1)). The highest content of scopolamine was detected in fruit sepals (1.003 mg x g(-1)), then followed by tender stems (0.600 mg x g(-1)) and tender leaves (0.601 mg x g(-1)). Both old stems and old leaves had the lowest content of hyoscyamine and scopolamine. The gene expression profile and TAs accumulation indicated that TAs in Atropa belladonna were mainly biosynthesized in secondary root, and then transported and deposited in tender aerial parts. Screening Atropa belladonna secondary root transcriptome database will facilitate unveiling the unknown enzymatic reactions and the mechanisms of transcriptional control.
Alkaloids ; biosynthesis ; genetics ; metabolism ; Atropa belladonna ; genetics ; metabolism ; Gene Expression Regulation, Plant ; genetics ; Hyoscyamine ; genetics ; metabolism ; Plants, Medicinal ; genetics ; metabolism ; Scopolamine Hydrobromide ; metabolism ; Tropanes ; metabolism

1) Atropine and scopolamine in doses of 0. 05, 0. 1, 0, 15, 0. 2 and 0. 25 mg produced bradycardia in humans. 2) The bradycardia induced by 0. 05 and 0, 1 mg of atropine was restored to normal rhythm by 0. 2 and 0. 15 mg of atropine, respectively. 3) The bradycardia induced by 0. 05 and 0. 1 mg of scopolamine was reversed to tachycardia by 0. 2 and 0. 15 mg of scopolamine, respectively. 4) The scopolamine(0.05mg) induced bradycardia was restored to normal rhythm by atropine 0.15 mg and reversed to tachycardia by atropine 0.2mg 5) The atropine(0.1 mg) induced bradycardia was partially restored by scopolamine 0.15 and 0. 2 mg. 6) It was argued that these results were not explainable by a central vagal effect of a direct effect of atropine and scopolamine on the heart but explainable by the blocking effect of these drugs to the sympathetic ganglia.
Atropine* ; Bradycardia* ; Ganglia, Sympathetic ; Heart ; Humans ; Scopolamine Hydrobromide* ; Tachycardia

In forensic toxicology analysis, various types of biological samples have their own special characteristics and scope of applications. In this article, the physiological structure of nails, methods for collecting and pre-processing samples, and for analyzing some poisons and drugs in the nails are reviewed with details. This paper introduces the influence factors of drug abuse of the nails. The prospects of its further applications are concluded based on the research results. Nails, as an unconventional bio-sample without general application, show great potential and advantages in forensic toxicology.
Alprazolam/analysis* ; Azabicyclo Compounds/analysis* ; Chromatography, High Pressure Liquid/methods* ; Cocaine/analysis* ; Diazepam/analysis* ; Eszopiclone ; Forensic Toxicology/methods* ; Gas Chromatography-Mass Spectrometry/methods* ; Hair/chemistry* ; Humans ; Illicit Drugs/analysis* ; Nails/physiology* ; Piperazines/analysis* ; Specimen Handling/methods* ; Substance Abuse Detection/methods*

It is well known that small dose of belladonna alkaloid(atropine, scopolarnine) has the effect of decreasing the heart rate in normal conscious subjects, but the mechanism involved in it remains still unanswered. Based on various lines of evidence, the most likely mechanism seems to be the blockade of sympathetic ganglion caused by the alkaloids and it is possible that the effect on the slower heart rate may differ in the depressed state of the sympathetic ganglion when under halothane anesthesia. The present study was undertaken, therefore, on comatose patients and halothane anesthetized patients with and without atropine premedication about 1 hour before anesthesia to observe the effect of a small dose of scopolamine(0.1 mg) which affects the heart rate more significantly than atropine in conscious subjects. The results were as follows: 1) In the comatose patients, scopolamine(0.1 mg) produced a significant decrease in heart rate. 2) During halothane anesthesia without atropine premedication, scopolamine produced a slight decrease in heart rate. 3) During halothane anesthesia with atropine premedication, scopolamine produced a significant increase in the heart rate. These results indicate that scopolamine can further affect the sympathetic ganglion already depressed by halothane, and it is suggested that scopolamine is more effective in blocking the sympathetic ganglion than halothane.
Alkaloids ; Anesthesia ; Atropa belladonna ; Atropine ; Coma ; Ganglia, Sympathetic ; Halothane* ; Heart Rate* ; Heart* ; Humans ; Premedication ; Scopolamine Hydrobromide*