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Respiratory Medicine 2019Tiotropium is a long-acting muscarinic antagonist approved for maintenance treatment of asthma in children, adolescents, and adults in the United States, and recommended... (Review)
Review
OBJECTIVE
Tiotropium is a long-acting muscarinic antagonist approved for maintenance treatment of asthma in children, adolescents, and adults in the United States, and recommended as add-on treatment for uncontrolled asthma despite treatment with inhaled corticosteroids and/or long-acting beta-2 agonists. This review traces the journey of tiotropium from its historical origins through early preclinical testing to human clinical trials and real-life studies.
DATA SOURCES
A search was performed in PubMed using search terms 'tiotropium' and 'asthma.' Relevant references cited in those articles were reviewed.
STUDY SELECTIONS
English language articles published from December 2008-December 2018 were screened. Articles evaluating the efficacy, cost-effectiveness, real-life evidence, and steroid-sparing effect of tiotropium with inadequately controlled asthma were included.
RESULTS
Anticholinergics have a long history of use in the treatment of obstructive airway diseases. Evidence indicates that tiotropium's mechanism of action consists of bronchodilation and diminished mucus secretion, with preclinical evidence suggesting an anti-inflammatory effect as well. Phase 2 and 3 clinical trials have demonstrated that tiotropium is efficacious and safe, resulting in significant improvements in lung function in adults, adolescents, and children across asthma severities. Emerging evidence suggests that add-on tiotropium might potentially enable reductions in inhaled corticosteroid dose in patients with uncontrolled asthma. Further, tiotropium is a cost-effective treatment option that is also effective in the clinical practice setting.
CONCLUSIONS
An increasing body of evidence indicates that tiotropium can play a significant role in the treatment of patients with uncontrolled asthma.
Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Asthma; Bronchodilator Agents; Child; Cholinergic Antagonists; Clinical Trials as Topic; Cost-Benefit Analysis; Expectorants; Humans; Muscarinic Antagonists; Prevalence; Tiotropium Bromide; Treatment Outcome; United States; Young Adult
PubMed: 31212121
DOI: 10.1016/j.rmed.2019.06.008 -
Pharmacological Research Jan 2021The use of anticholinergic drugs and other drugs with anticholinergic activity is highly prevalent in older people. Cumulative anticholinergic effects, known as... (Review)
Review
The use of anticholinergic drugs and other drugs with anticholinergic activity is highly prevalent in older people. Cumulative anticholinergic effects, known as anticholinergic burden, are associated with important peripheral and central adverse effects and outcomes. Several methods have been developed to quantify anticholinergic burden and to estimate the risk of adverse anticholinergic effects. Serum anticholinergic activity (SAA) and anticholinergic burden scoring systems are the most commonly used methods to predict the occurrence of important negative outcomes. These tools could guide clinicians in making more rational prescriptions to enhance patient safety, especially in older people. However, the literature has reported conflicting results about the predictive ability of these tools. The majority of these instruments ignore relevant pharmacologic aspects such as the doses used, differential muscarinic receptor subtype affinities, and blood-brain barrier permeability. To increase the clinical relevance of these tools, mechanistic and clinical pharmacology should collaborate. This narrative review describes the rational and pharmacological basis of anticholinergic burden tools and provides insight about their predictive value for adverse outcomes.
Topics: Aged; Cholinergic Antagonists; Drug Utilization; Humans
PubMed: 33248197
DOI: 10.1016/j.phrs.2020.105306 -
Journal of Comparative Effectiveness... Dec 2022To determine the economic burden associated with anticholinergic medication use in adults with overactive bladder (OAB) in the USA. A systematic literature review was... (Review)
Review
To determine the economic burden associated with anticholinergic medication use in adults with overactive bladder (OAB) in the USA. A systematic literature review was conducted to identify articles assessing healthcare resource utilization (HCRU) and costs associated with anticholinergic use in adults with OAB. From the 34 articles identified, increased anticholinergic burden, switching anticholinergic treatments and potentially inappropriate anticholinergic use were associated with increased HCRU and/or costs. However, studies comparing patients with OAB receiving anticholinergics to individuals with untreated OAB or without OAB reported a mix of increases and decreases in HCRU and costs. Additional controlled studies assessing the economic impact of anticholinergics in OAB are needed and may enable optimization of economic and potentially patient outcomes.
Topics: Humans; Adult; Urinary Bladder, Overactive; Cholinergic Antagonists; Financial Stress; Costs and Cost Analysis; Patient Acceptance of Health Care
PubMed: 36354285
DOI: 10.2217/cer-2022-0160 -
Current Allergy and Asthma Reports Dec 2014Anticholinergic alkaloids have been used for thousands of years for the relief of bronchoconstriction and other respiratory symptoms, and their use in the treatment of... (Review)
Review
Anticholinergic alkaloids have been used for thousands of years for the relief of bronchoconstriction and other respiratory symptoms, and their use in the treatment of chronic obstructive pulmonary disease is well established. Acetylcholine, acting through muscarinic receptor (M) receptor, modulates multiple physiologic functions pertinent to asthma including airway muscle tone, mucus gland secretion, and various parameters of inflammation and remodeling. In addition, activation of M receptors may inhibit beta2 adrenoreceptor. These observations offer the rationale for the use of M receptors antagonists in the treatment of asthma. Short-acting antimuscarinic agents may be effective alone or in combination with short-acting beta agonists for the relief of acute symptoms. Long-acting antimuscarinic agents have emerged as potentially useful in the long-term treatment of difficult-to-control asthma. This review will analyze the mechanisms of action and therapeutic role of antimuscarinic agents on asthma including current guidelines regarding antimuscarinic drugs, recent studies in asthma, special populations to consider, and possible predictors of response.
Topics: Asthma; Cholinergic Antagonists; Humans; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive
PubMed: 25283149
DOI: 10.1007/s11882-014-0484-y -
Archives of Gerontology and Geriatrics 2020Available metrics for characterizing cumulative anticholinergic exposure over time may not be well suited for use across all US data sources. In this review, the...
BACKGROUND/OBJECTIVES
Available metrics for characterizing cumulative anticholinergic exposure over time may not be well suited for use across all US data sources. In this review, the properties of existing anticholinergic scales and measures were evaluated to determine their suitability for implementation in observational studies relying on administrative data.
METHODS
A targeted literature review was conducted to identify available anticholinergic scales and measures. Suitability of the identified scales and measures for quantification of anticholinergic exposure was evaluated based on pre-defined criteria. Agreement between selected scales was characterized by the percentage overlap of included drugs and inter-scale Spearman's correlation of scores.
RESULTS
Sixteen scales were identified; six were relevant and suitable for the quantification of anticholinergic exposure. When implemented on administrative data the Anticholinergic Drug Scale and Anticholinergic Cognitive Burden scale demonstrated the most agreement, with an inter-scale correlation coefficient of 0.82. Scale performance varied by outcome of interest, and underlying disease profile of the population of interest. Variability across the two measures ("average daily dose" and "cumulative dose") was observed, with neither considering both dose and anticholinergic potency in score calculations.
CONCLUSIONS
Accurate quantification of anticholinergic burden is important in assessing relative risks versus benefits of prescribing anticholinergic medications. In this review, the Anticholinergic Drug Scale and the Anticholinergic Cognitive Burden scale and the average daily dose and cumulative dose measures, were determined to be well suited for the quantification of anticholinergic exposure, particularly in the context of administrative data analyses; however, methods to characterize anticholinergic burden through consideration of both anticholinergic dose and potency are needed.
Topics: Aged; Aged, 80 and over; Cholinergic Antagonists; Cognition; Cognition Disorders; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Parkinson Disease; Risk; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 31155228
DOI: 10.1016/j.archger.2019.05.010 -
Journal of the American Academy of... Sep 2018
Topics: Cholinergic Antagonists; Dementia; Humans; Hyperhidrosis; Patient Participation; Time Factors
PubMed: 30119867
DOI: 10.1016/j.jaad.2018.03.016 -
Chest May 2015
Topics: Asthma; Cholinergic Antagonists; Humans; Scopolamine Derivatives
PubMed: 25940271
DOI: 10.1378/chest.15-0194 -
Oral Surgery, Oral Medicine, Oral... Dec 2021Salivary glands are among the most sensitive target organs of medications with anticholinergic (AC) properties, interrupting the neural stimulation of saliva secretion... (Review)
Review
OBJECTIVE
Salivary glands are among the most sensitive target organs of medications with anticholinergic (AC) properties, interrupting the neural stimulation of saliva secretion and reducing saliva flow. Hyposalivation results in dry mouth, leading to dental caries, intraoral infection, orofacial pain, problems with speaking and swallowing, and diminished oral health--related quality of life. Current understanding of the pharmacokinetics of AC medications and their effect on muscarinic receptors in the salivary glands were reviewed to assist clinicians in predicting salivary damage in patients with AC medication-induced dry mouth.
STUDY DESIGN
We summarized the literature related to the mechanisms and properties of AC medications, anticholinergic adverse effects, and their effect on salivary function and management strategies to prevent oral health damage.
RESULTS
Although a large number of studies reported on the frequencies of medication-induced dry mouth, we found very limited data on predicting individual susceptibility to AC medication--caused hyposalivation and no prospective clinical studies addressing this issue.
CONCLUSION
Dry mouth is most frequently caused by medications with AC properties, which interrupt the neural stimulation of saliva secretion. Interdisciplinary care should guide pharmacotherapeutics and dental interventions should aim in preventing AC salivary adverse effects and reducing the oral health burden from AC medication-induced dry mouth.
Topics: Cholinergic Antagonists; Dental Caries; Humans; Quality of Life; Saliva; Salivary Glands; Xerostomia
PubMed: 34593340
DOI: 10.1016/j.oooo.2021.08.015 -
Current Topics in Behavioral... 2023Acetylcholine (ACh) signaling is critical for central nervous function and is known to be abnormal in schizophrenia (SZ), a chronic neuropsychiatric disorder in which... (Review)
Review
Acetylcholine (ACh) signaling is critical for central nervous function and is known to be abnormal in schizophrenia (SZ), a chronic neuropsychiatric disorder in which cognitive deficits persist, despite treatment. This review provides a summary of the clinical evidence linking ACh abnormalities to SZ-associated cognitive deficits, an overview of ACh-based pro-cognitive strategies attempted in SZ, and a survey of recent studies that describe the impact of anticholinergic medication burden on cognitive outcomes in SZ. Methodological challenges that currently limit more substantial investigation of ACh in SZ patients and future directions are also discussed.
Topics: Humans; Schizophrenia; Cholinergic Antagonists; Cognitive Dysfunction; Cognition; Cognition Disorders; Acetylcholine
PubMed: 36441495
DOI: 10.1007/7854_2022_400 -
Archives of Gerontology and Geriatrics 2016Anticholinergic drugs may increase the risk of cognitive and functional disorders in older patients. There are anticholinergic scales on which said risk is estimated.... (Review)
Review
PURPOSE
Anticholinergic drugs may increase the risk of cognitive and functional disorders in older patients. There are anticholinergic scales on which said risk is estimated. The objectives of this study are: to identify the scales described in literature that are applicable to polypathological patients and analyze their clinical outcomes.
MATERIAL AND METHODS
A systematic review was performed. Data sources were MEDLINE, EMBASE and Web of Science which were consulted until August 2014.
INCLUSION CRITERIA
(1) studies that specify the list of drugs, describe the methodology for their elaboration and how they calibrate the anticholinergic potential and (2) studies that use the scales identified as a tool to measure exposure to anticholinergic drugs in polypathological patients or those with similar characteristics. The main differences between the scales and main results on cognitive, functional and mortality status were collected.
RESULTS
25 articles were included. 10 scales were identified. For their preparation, 8 were based on literature about drugs with anticholinergic activity and/or previously published scales as well as expert opinions. Exposure to anticholinergic drugs has been linked to cognitive disorders (basically measured with Anticholinergic Risk Scale (ARS), Anticholinergic Cognitive Burden Scale (ACB) and Drug Burden Index (DBI)) and functional scale (with ARS and DBI). However, there is no clear relationship with mortality. The Anticholinergic Drug Scale was the only one that obtained no association with any of the variables studied.
CONCLUSIONS
There is a great variety of scales published and applied to older patients. The clinical results are different depending on the scale used which is probably due to the different methodology in their elaboration.
Topics: Aged; Cholinergic Antagonists; Cognition; Cognition Disorders; Humans; Male; Risk; Risk Assessment
PubMed: 26518612
DOI: 10.1016/j.archger.2015.10.002