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Dual therapy: Pharmacologic management in pulmonary rehabilitation
Published in Claudio F. Donner, Nicolino Ambrosino, Roger S. Goldstein, Pulmonary Rehabilitation, 2020
J. Michael Nicholson, Richard Casaburi
Multiple newer inhaled bronchodilator combinations of LABA and LAMA (for example umeclidinium + vilanterol or glycopyrronium + indacaterol) (36) have confirmed improvements in exercise tolerance. The existence of a ceiling effect when adding bronchodilators will need to be determined, as many existing studies were not powered to detect differences between two bronchodilator regimens (36).
Inhaled therapeutics in chronic obstructive pulmonary disease
Published in Anthony J. Hickey, Heidi M. Mansour, Inhalation Aerosols, 2019
Tejas Sinha, Paul Dejulio, Philip Diaz
Generally, LAMAs have a limited side effect profile with a very low risk for adverse effects as the majority of the drug is active only in the respiratory tract. However, the M3 receptor is also present on a variety of extrapulmonary tissue, including the myocardium, salivary glands, gastrointestinal tract, bladder, and the eye. When systemically available, LAMA agents can subsequently cause tachycardia/tachyarrhythmia, dry mouth from inhibition of salivary secretion, constipation, urinary retention, and increased intraocular pressure with blurry vision. Fortunately, the LAMA agents are quaternary ammonium compounds with low lipid solubility (37). The low lipid solubility prevents absorption across lipid membranes, thereby reducing systemic bioavailability (37). A pooled safety analysis of studies involving LAMAs did show an increased risk of classic anticholinergic effects, including dry mouth, constipation, and urinary retention, but did not show an increased risk of serious adverse events, major adverse events, or fatal events, regardless of inhaler type (38). The safety of glycopyrronium was studied in the GLOW1 and GLOW2 trials. There was no increased risk of significant adverse effects or mortality in either study. Umeclidinium and its combination LABA agent umeclidinium/vilanterol did not show an increased risk for major adverse events or fatal events relative to placebo in a phase IIIb trial (39). Anticholinergic symptoms were present in less than 1%–2% of patients, and the most common side effects noted were headaches and nasopharyngitis (39). Similarly multiple clinical trials have shown that aclidinum bromide is generally well tolerated with no increased incidence of serious adverse effects relative to placebo and minimal anticholinergic side effects (<1%–2%). The most common side effects were headaches and nasopharyngitis (40).
Drugs and Therapeutics
Published in James Sherifi, General Practice Under the NHS, 2023
The main side effect of salbutamol, although not as severe as isoprenaline, remained tachycardia, but this did not lead to increased morbidity or, specifically, life-threatening arrhythmias. In short, it was magnificent! Yet, despite its increasing use in the community and theoretically improved management in primary care dedicated asthma clinics, hospital admissions and mortality remained inexplicably high.16Ipratropium—1966COPD/COAD. AsthmaPrior to the introduction of more recent muscarinic acetylcholine receptor blockers, such as tiotropium and ipratropium, Atrovent, as an inhaler, was the sole agent for reducing symptoms of chronic obstructive airways disease, or ‘chronic bronchitis,’ as it was known at that time. Ipratropium was moderately effective and had a good safety profile but was hindered by a short plasma half-life, requiring four-times-a-day dosing. It was eventually replaced by more convenient, long-acting muscarinic antagonists (LAMA), tiotropium (1989), glycopyrronium (2005), and umeclidinium (2013). LAMAs are an integral part of the GOLD (Global Initiative for Chronic Obstructive Lung Disease) guidance17 on managing patients with COPD. Aminophylline—1950s This dramatic intravenous remedy for acute severe asthma served doctors well in the 1970s and 1980s, but it fell out of favour through its small therapeutic window and tendency to cause cardiac arrhythmia. Although it required slow injection over ten minutes, a luxury of time never afforded to a GP in an emergency setting, it rarely caused any problems in practice. Less effective oral formulations were used as an adjunct to salbutamol and inhaled steroids. PholcodineCough Perhaps an unusual addition to any list of essential medications, pholcodine was the linctus of choice for any patient initially presenting with an acute cough of unknown aetiology. It was cheap, soothing, generally harmless, and, unlike codeine, non-addictive. It was a useful placebo, tidying patients over until symptoms had run their course. For all these reasons it is rarely prescribed nowadays.
The discovery and development of aclidinium bromide for the treatment of chronic obstructive pulmonary disease
Published in Expert Opinion on Drug Discovery, 2018
Mario Malerba, Alessandro Radaeli, Giuseppe Santini, Jaymin Morjaria, Nadia Mores, Chiara Mondino, Giuseppe Macis, Paolo Montuschi
Tiotropium bromide, the first-in-class LAMA, is available as hard capsules, inhalation powder delivered through a DPI at a dose of 18 μg once daily (first authorization in the EU in 2002) [15] and as a fixed-dose soft mist inhaler at a dose of two puffs of 2.5 μg each once daily (first authorization in the EU in 2012) [16]. A single soft mist inhaler containing tiotropium bromide and olodaterol, a LABA, at a dose of two puffs of 2.5/2.5μg each once daily is also available for COPD patients requiring two bronchodilators [17]. Glycopyrronium bromide is available as once-daily monotherapy for COPD in 63 μg capsules, inhalation powder delivered through a DPI equivalent to 50 μg of glycopyrronium [18]. In a single inhaler FDC with indacaterol maleate, a LABA, glycopyrronium bromide is available in capsules for inhalation through a DPI with a delivered dose of 85 μg of indacaterol and 43 μg of glycopyrronium once daily [19]. First authorization for glycopyrronium bromide in the EU was released in 2012 [18]. Once-daily umeclidinium is marketed for COPD as a multi-dose DPI [20]. Each single inhalation provides a delivered dose of umeclidinium of 55 μg corresponding to a pre-dispensed dose of 62.5 μg [20]. For dual once-daily LAMA/LABA therapy, umeclidinium at a delivered dose of 55 μg is combined with vilanterol, a LABA, at a delivered dose of 22 μg in a pre-dispensed DPI [21]. First authorization for umeclidinium bromide in the EU was released in 2014 [20].
Improving the risk-to-benefit ratio of inhaled corticosteroids through delivery and dose: current progress and future directions
Published in Expert Opinion on Drug Safety, 2022
Piotr Damiański, Grzegorz Kardas, Michał Panek, Piotr Kuna, Maciej Kupczyk
Interestingly, the novel combination of FF/umeclidinium(UMEC)/VI (ICS/LAMA/LABA) with the convenience of once-daily administration via a single inhaler is widely approved as a treatment for COPD but is now also being extensively studied in patients with uncontrolled asthma. Indeed, results from the CAPTAIN trial revealed that the addition of the second long-acting bronchodilator UMEC has the potential to offer better treatment outcomes in regard to improved symptoms, asthma control and lung function compared with the respective FF/VI dose in patients with moderate or severe asthma uncontrolled on ICS/LABA. However, FF/UMEC/VI did not show superiority in reducing moderate and/or severe exacerbations compared to FF/VI therapy [109].
Current pharmacogenomic recommendations in chronic respiratory diseases: Is there a biomarker ready for clinical implementation?
Published in Expert Review of Respiratory Medicine, 2022
Ingrid Fricke-Galindo, Ramcés Falfán-Valencia
Umeclidinium is an effective and well-tolerated long-acting muscarinic receptor antagonist (LAMA) for COPD treatment [36]. Currently, the information indicates that CYP2D6 variants do not affect the exposure of LAMA [37] and that it is also a substrate of P-glycoprotein and CYP3A4. However, there are no significant variations in umeclidinium treatment due to these gene–drug interactions [38]. Moreover, two pharmacogenetic studies found a lack of association of genetic variants with the umeclidinium response as monotherapy or combination in patients with COPD [39,40]. According to this information, umeclidinium will not be a drug with an effective genotype-guided prescription.