Abstract “Death rattle” is a term used to describe the noisy sound produced by dying patients caused by the oscillatory movements of secretions in the upper airways. Antimuscarinic drugs, including atropine, scopolamine (hyoscine hydrobromide), hyoscine butylbromide, and glycopyrronium, have been used to diminish the noisy sound by reducing airway secretions. We report on the effectiveness of sublingual atropine eyedrops in alleviating death rattle in a terminal cancer patient. We present a 58-year-old man with pancreatic cancer who was admitted to our hospital because of severe dyspnea, cough, and death rattle with excessive bronchial secretion as a result of multiple lung metastases. We administered 1% atropine eyedrops sublingually to obviate the need for subcutaneous infusions and to prevent somnolence. On the basis of our experience, we conclude that atropine eyedrops, administered sublingually for distressing upper respiratory secretions, may be an effective alternative to the injection of antimuscarinic drugs, or as an option when other antimuscarinic formulations are not available.
The effects of antihistamines with varying anticholinergic properties on voluntary and involuntary movement
- Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology
- Published over 5 years ago
OBJECTIVE: Recent evidence indicates that antihistamines can affect movement, which is most likely due to altered neurotransmission in cholinergic and histaminergic pathways. The purpose of this study was to determine if antihistamines with varying anticholinergic properties differentially affect voluntary and involuntary movement control. METHODS: Eleven healthy subjects were enlisted into a human double blind, placebo-controlled, five-way crossover study. Drowsiness, reaction time, and physiological tremor were examined 1-, 2-, and 3-hr post-ingestion of antihistamines with known anticholinergic profiles. These were the first-generation promethazine, and second-generation loratadine, desloratadine, and fexofenadine. Hyoscine butylbromide was used in an additional experiment to determine how a peripheral antimuscarinic drug influenced neuromotor function. RESULTS: Promethazine, desloratadine and fexofenadine increased drowsiness. Promethazine increased simple and choice reaction time and reduced tremor. Desloratadine increased choice reaction time and tremor, while loratadine slowed simple and choice reaction time. CONCLUSION: Central anticholinergic and antihistaminergic properties of antihistamines potentially contribute to movement dysfunction. SIGNIFICANCE: Second-generation antihistamines have provided the consumer with a safer alternative to the first-generation sedating antihistamine. However, the results of this study suggest that loratadine and desloratadine have the potential to affect movement control, and further research is warranted to understand the clinical relevance of these findings.
Persons with Alzheimer’s disease (AD) commonly present with chronic non-malignant pain, but long-term use of opioids among this population has not been studied previously. Our aim was to investigate the prevalence of long-term (≥180 days) use of opioids for non-malignant pain and associated factors among community-dwelling persons with AD and to compare the prevalence to a matched cohort without AD.Medication use and Alzheimer’s disease (MEDALZ) cohort was utilized for this study, comprising all community-dwelling persons diagnosed with AD in Finland during 2005-2011 and their matched comparison persons without AD. After exclusion of persons with active cancer treatment, 62,074 persons with and 62,074 persons without AD were included in this study. Data were collected from nationwide registers.Opioids were used by 13,111 persons with and by 16,659 without AD. Overall long-term opioid use was more common among persons without AD (8.7%) compared to persons with AD (7.2%, p<0.0001). However, among opioid users, prevalence of long-term opioid use was slightly higher among persons with AD compared to those without AD (34.2% vs. 32.3%, respectively, p=0.0004). Long-term use of transdermal opioids was more than two-fold among opioid users with AD (13.2%) compared to users without AD (5.5%). Factors associated with long-term opioid use included AD, ≥80 years of age, female gender, rheumatoid arthritis, osteoporosis, low socioeconomic position, history of substance abuse and long-term benzodiazepine use.Prevalence of long-term opioid use was somewhat similar among both groups. Among persons with AD, long-term opioid use was strongly associated with transdermal opioids.
- European respiratory review : an official journal of the European Respiratory Society
- Published over 2 years ago
Asthma is a chronic inflammatory disorder of the airways that is a major global burden on both individuals and healthcare systems. Despite guideline-directed treatment, a significant proportion of patients with asthma do not achieve control. This review focuses on the potential use of long-acting anticholinergics as bronchodilators in the treatment of asthma, with results published from clinical trials of glycopyrrolate, umeclidinium and tiotropium. The tiotropium clinical trial programme is the most advanced, with data available from a number of phase II and III studies of tiotropium as an add-on to inhaled corticosteroid maintenance therapy, with or without a long-acting β2-agonist, in patients across asthma severities. Recent studies using the Respimat Soft Mist inhaler have identified 5 µg once daily as the preferred dosing regimen, which has shown promising results in adults, adolescents and children with asthma. Tiotropium Respimat has recently been incorporated into the Global Initiative for Asthma 2015 treatment strategy as a recommended alternative therapy at steps 4 and 5 in adult patients with a history of exacerbations. The increasing availability of evidence from ongoing and future clinical trials will be beneficial in determining where long-acting anticholinergic agents fit in future treatment guidelines across a variety of patient populations and disease severities.
The aim of this study was to compare the effects of the selective M3 muscarinic acetylcholine receptor antagonist Darifenacin, oral Hyoscine hydrobromide and Placebo on motion sickness induced by cross-coupled stimulation.
In this work, the enantiomeric separation of ten anticholinergic drugs was first examined on two derivative polysaccharide chiral stationary phases (CSPs), i.e., Chiralpak ID and Chiralpak IA in the normal phase mode. Except for scopolamine hydrobromide, the remaining nine analytes could be completely separated with good resolutions using both columns under the optimized mobile phase conditions. And the enantiomeric discrimination ability of the studied CSPs towards nine analytes was in the order of Chiralpak ID > Chiralpak IA. The influences of organic modifier types, alcohol content, and base/acid additives on the enantiomeric separation were evaluated and optimized. According to the experimental results, the effect of the structures of analytes on enantiomeric separation was discussed. Additionally, the chiral recognition mechanisms were proposed based on the thermodynamic analysis of the experimental data. This article is protected by copyright. All rights reserved.
Comparison of two hyoscyamine 6β-hydroxylases in engineering scopolamine biosynthesis in root cultures of Scopolia lurida
- Biochemical and biophysical research communications
- Published 8 months ago
Scopolia lurida, a medicinal plant native to the Tibetan Plateau, is among the most effective producers of pharmaceutical tropane alkaloids (TAs). The hyoscyamine 6β-hydroxylase genes of Hyoscyamus niger (HnH6H) and S. lurida (SlH6H) were cloned and respectively overexpressed in hairy root cultures of S. lurida, to compare their effects on promoting the production of TAs, especially the high-value scopolamine. Root cultures with SlH6H/HnH6H overexpression were confirmed by PCR and real-time quantitative PCR, suggesting that the enzymatic steps defined by H6H were strongly elevated at the transcriptional level. Tropane alkaloids, including hyoscyamine, anisodamine and scopolamine, were analyzed by HPLC. Scopolamine and anisodamine contents were remarkably elevated in the root cultures overexpressing SlH6H/HnH6H, whereas that of hyoscyamine was more or less reduced, when compared with those of the control. These results also indicated that SlH6H and HnH6H promoted anisodamine production at similar levels in S. lurida root cultures. More importantly, HnH6H-overexpressing root cultures had more scopolamine in them that did SlH6H-overexpressing root cultures. This study not only provides a feasible way of overexpressing H6H to produce high-value scopolamine in engineered root cultures of S. lurida but also found that HnH6H was better than SlH6H for engineering scopolamine production.
- The British journal of oral & maxillofacial surgery
- Published 8 months ago
Our aim was to investigate whether perioperative transdermal application of scopolamine could help to prevent fistulas after parotidectomy, and to this end we retrospectively studied the records of all patients (n=645) who had benign parotid tumours treated by partial parotidectomy between 2011 and 2016. We found that scopolamine led to a significant decrease in the incidence of salivary fistulas from 54/371(15%) in the group not given it to 10/274 (4%) in the group given it (p<0.0001). The "number needed to treat" was 9.17. There was a relatively low incidence of all adverse effects after scopolamine. Our results are encouraging. Thorough consideration of the contraindications and a knowledge of the potential adverse effects are crucial for its successful implementation.
Plants have evolved many defenses against insect herbivores, including numerous chemicals that can reduce herbivore growth, performance, and fitness. One group of chemicals, the tropane alkaloids, is commonly found in the nightshade family (Solanaceae) and has been thought to reduce performance and fitness in insects. We examined the effects of the tropane alkaloid scopolamine, the alkaloid constituent of Datura wrightii, which is the most frequent host plant for the abundant and widespread insect herbivore Manduca sexta in the southwestern United States. We exposed caterpillars of two different species to scopolamine: M. sexta, which has a shared evolutionary history with Datura and other solanceous plants, and Galleria mellonella, which does not. We showed that the addition of ecologically-realistic levels of scopolamine to both the diet and the hemolymph of these two caterpillar species (M. sexta and G. mellonella) had no effect on the growth of either species. We also showed that M. sexta has no behavioral preference for or against scopolamine incorporated into an artificial diet. These results are contrary to other work showing marked differences in performance for other insect species when exposed to scopolamine, and provide evidence that scopolamine might not provide the broad-spectrum herbivore resistance typically attributed to it. It also helps to clarify the coevolutionary relationship between M. sexta and one of its main host plants, as well as the physiological mechanism of resistance against scopolamine.
Effectiveness of the repeated administration of scopolamine ointment on clozapine-induced hypersalivation in patients with treatment-resistant schizophrenia: A preliminary study
- Asia-Pacific psychiatry : official journal of the Pacific Rim College of Psychiatrists
- Published 10 months ago
This study investigated the efficacy of scopolamine (an anticholinergic agent) ointment against clozapine-induced hypersalivation.