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International Journal of Molecular... Nov 2022Asthma is a common inflammatory disease of the lungs. The prevalence of asthma is increasing worldwide, and the tendency indicates that the number of asthma sufferers... (Review)
Review
Asthma is a common inflammatory disease of the lungs. The prevalence of asthma is increasing worldwide, and the tendency indicates that the number of asthma sufferers will soar in the coming years for several reasons, in particular, the lifestyles we have adopted that expose us to risk factors. Salbutamol is the first selective short-acting β-agonist (SABA) used as an alternative reliever in the treatment of asthma. Its therapeutic effect is based on its potent smooth muscle relaxant properties, which allow the inhibition of bronchial smooth muscle contraction and subsequent bronchodilation. Salbutamol can be administered orally, intravenously (IV), intramuscularly (IM), subcutaneously, or by inhalation. For this reason, the pharmacokinetic (PK) parameters-absorption, distribution, metabolism, and elimination-are highly diverse and, consequently, the efficacy and adverse effects also differ between each formulation. Here, we review the pharmacological profile of different salbutamol formulations, focusing on their efficacy and adverse effects for its original application, asthma.
Topics: Humans; Albuterol; Asthma; Bronchi; Drug-Related Side Effects and Adverse Reactions; Risk Factors
PubMed: 36430683
DOI: 10.3390/ijms232214207 -
Italian Journal of Pediatrics Feb 2023Bronchiolitis is an acute respiratory illness that is the leading cause of hospitalization in young children. This document aims to update the consensus document... (Review)
Review
Bronchiolitis is an acute respiratory illness that is the leading cause of hospitalization in young children. This document aims to update the consensus document published in 2014 to provide guidance on the current best practices for managing bronchiolitis in infants. The document addresses care in both hospitals and primary care. The diagnosis of bronchiolitis is based on the clinical history and physical examination. The mainstays of management are largely supportive, consisting of fluid management and respiratory support. Evidence suggests no benefit with the use of salbutamol, glucocorticosteroids and antibiotics with potential risk of harm. Because of the lack of effective treatment, the reduction of morbidity must rely on preventive measures. De-implementation of non-evidence-based interventions is a major goal, and educational interventions for clinicians should be carried out to promote high-value care of infants with bronchiolitis. Well-prepared implementation strategies to standardize care and improve the quality of care are needed to promote adherence to guidelines and discourage non-evidence-based attitudes. In parallel, parents' education will help reduce patient pressure and contribute to inappropriate prescriptions. Infants with pre-existing risk factors (i.e., prematurity, bronchopulmonary dysplasia, congenital heart diseases, immunodeficiency, neuromuscular diseases, cystic fibrosis, Down syndrome) present a significant risk of severe bronchiolitis and should be carefully assessed. This revised document, based on international and national scientific evidence, reinforces the current recommendations and integrates the recent advances for optimal care and prevention of acute bronchiolitis.
Topics: Infant, Newborn; Child; Infant; Humans; Child, Preschool; Bronchiolitis; Hospitalization; Risk Factors; Albuterol; Respiratory Syncytial Virus Infections
PubMed: 36765418
DOI: 10.1186/s13052-022-01392-6 -
Chest Sep 2023In the phase 3 MANDALA trial, as-needed albuterol-budesonide pressurized metered-dose inhaler significantly reduced severe exacerbation risk vs as-needed albuterol in... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
In the phase 3 MANDALA trial, as-needed albuterol-budesonide pressurized metered-dose inhaler significantly reduced severe exacerbation risk vs as-needed albuterol in patients with moderate-to-severe asthma receiving inhaled corticosteroid-containing maintenance therapy. This study (DENALI) was conducted to address the US Food and Drug Administration combination rule, which requires a combination product to demonstrate that each component contributes to its efficacy.
RESEARCH QUESTION
Do both albuterol and budesonide contribute to the efficacy of the albuterol-budesonide combination pressurized metered-dose inhaler in patients with asthma?
STUDY DESIGN AND METHODS
This phase 3 double-blind trial randomized patients aged ≥ 12 years with mild-to-moderate asthma 1:1:1:1:1 to four-times-daily albuterol-budesonide 180/160 μg or 180/80 μg, albuterol 180 μg, budesonide 160 μg, or placebo for 12 weeks. Dual-primary efficacy end points included change from baseline in FEV area under the curve from 0 to 6 h (FEV AUC) over 12 weeks (assessing albuterol effect) and trough FEV at week 12 (assessing budesonide effect).
RESULTS
Of 1,001 patients randomized, 989 were ≥ 12 years old and evaluable for efficacy. Change from baseline in FEV AUC over 12 weeks was greater with albuterol-budesonide 180/160 μg vs budesonide 160 μg (least-squares mean [LSM] difference, 80.7 [95% CI, 28.4-132.9] mL; P = .003). Change in trough FEV at week 12 was greater with albuterol-budesonide 180/160 and 180/80 μg vs albuterol 180 μg (LSM difference, 132.8 [95% CI, 63.6-201.9] mL and 120.8 [95% CI, 51.5-190.1] mL, respectively; both P < .001). Day 1 time to onset and duration of bronchodilation with albuterol-budesonide were similar to those with albuterol. The albuterol-budesonide adverse event profile was similar to that of the monocomponents.
INTERPRETATION
Both monocomponents contributed to albuterol-budesonide lung function efficacy. Albuterol-budesonide was well tolerated, even at regular, relatively high daily doses for 12 weeks, with no new safety findings, supporting its use as a novel rescue therapy.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov; No.: NCT03847896; URL: www.
CLINICALTRIALS
gov.
Topics: Humans; Child; Budesonide; Formoterol Fumarate; Metered Dose Inhalers; Administration, Inhalation; Asthma; Albuterol; Double-Blind Method; Bronchodilator Agents; Treatment Outcome
PubMed: 37003355
DOI: 10.1016/j.chest.2023.03.035 -
International Journal of Molecular... Feb 2023Congenital myasthenic syndromes (CMS) are a heterogeneous group of disorders characterized by impaired neuromuscular signal transmission due to germline pathogenic... (Review)
Review
Congenital myasthenic syndromes (CMS) are a heterogeneous group of disorders characterized by impaired neuromuscular signal transmission due to germline pathogenic variants in genes expressed at the neuromuscular junction (NMJ). A total of 35 genes have been reported in CMS (). The 35 genes can be classified into 14 groups according to the pathomechanical, clinical, and therapeutic features of CMS patients. Measurement of compound muscle action potentials elicited by repetitive nerve stimulation is required to diagnose CMS. Clinical and electrophysiological features are not sufficient to identify a defective molecule, and genetic studies are always required for accurate diagnosis. From a pharmacological point of view, cholinesterase inhibitors are effective in most groups of CMS, but are contraindicated in some groups of CMS. Similarly, ephedrine, salbutamol (albuterol), amifampridine are effective in most but not all groups of CMS. This review extensively covers pathomechanical and clinical features of CMS by citing 442 relevant articles.
Topics: Humans; Albuterol; Amifampridine; Cholinesterase Inhibitors; Mitochondrial Proteins; Mutation; Myasthenic Syndromes, Congenital; NAV1.4 Voltage-Gated Sodium Channel; Neuromuscular Junction; Receptors, Cholinergic; Symporters; Synaptic Transmission
PubMed: 36835142
DOI: 10.3390/ijms24043730 -
Archivos Argentinos de Pediatria Aug 2021In 1995, the first Guideline on Diagnosis and Treatment for Childhood Asthma was published in Archivos Argentinos de Pediatría. Updates were made in 2007 and 2016....
In 1995, the first Guideline on Diagnosis and Treatment for Childhood Asthma was published in Archivos Argentinos de Pediatría. Updates were made in 2007 and 2016. After 5 years, the new contents are presented. The most relevant modifications, although not the only ones, are observed in therapeutic strategies. In this version, treatment is stratified into "levels" (1 to 5). The current paradigm of change in chronic asthma treatment consists in eradicating the prescription of bronchodilators (salbutamol) on demand. Besides that, the option of intermittent treatment with inhaled corticosteroids plus long-acting bronchodilators (LABA) appears for milder forms (levels 1 and 2) in children > 12 years old. There is still not enough evidence to support these options in<12 years old maintaining the previous recommendations in this group. For more details we suggest reading the full document.
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Albuterol; Asthma; Bronchodilator Agents; Child; Humans
PubMed: 34309325
DOI: 10.5546/aap.2021.S123 -
American Family Physician Nov 2020Drugs are being prescribed with more frequency and in higher quantities. A serious adverse drug event from prescribed medications constitutes 2.4% to 16.2% of all...
Drugs are being prescribed with more frequency and in higher quantities. A serious adverse drug event from prescribed medications constitutes 2.4% to 16.2% of all hospital admissions. Many of the adverse drug events present intraorally or periorally in isolation or as a clinical symptom of a systemic effect. Clinical recognition and treatment of adverse drug events are important to increase patient adherence, manage drug therapy, or detect early signs of potentially serious outcomes. Oral manifestations of commonly prescribed medications include gingival enlargement, oral hyperpigmentation, oral hypersensitivity reaction, medication-related osteonecrosis, xerostomia, and other oral or perioral conditions. To prevent dose-dependent adverse drug reactions, physicians should prescribe medications judiciously using the lowest effective dose with minimal duration. Alternatively, for oral hypersensitivity reactions that are not dose dependent, quick recognition of clinical symptoms associated with time-dependent drug onset can allow for immediate discontinuation of the medication without discontinuation of other medications. Physicians can manage oral adverse drug events in the office through oral hygiene instructions for gingival enlargement, medication discontinuation for oral pigmentation, and prescription of higher fluoride toothpastes for xerostomia.
Topics: Albuterol; Amlodipine; Anticonvulsants; Antihypertensive Agents; Atorvastatin; Bisphosphonate-Associated Osteonecrosis of the Jaw; Bronchodilator Agents; Deprescriptions; Drug Hypersensitivity; Fluorides; Gingival Overgrowth; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperpigmentation; Hypoglycemic Agents; Lisinopril; Losartan; Metformin; Metoprolol; Mouth Diseases; Omeprazole; Oral Hygiene; Proton Pump Inhibitors; Simvastatin; Thyroxine; Toothpastes; Xerostomia
PubMed: 33179891
DOI: No ID Found -
British Journal of Clinical Pharmacology Jul 2022The propellants in metered-dose inhalers (MDIs) are powerful greenhouse gases, which account for approximately 13% of the NHS's carbon footprint related to the delivery... (Review)
Review
The propellants in metered-dose inhalers (MDIs) are powerful greenhouse gases, which account for approximately 13% of the NHS's carbon footprint related to the delivery of care. Most MDI use is in salbutamol relievers in patients with poorly controlled disease. The UK lags behind Europe in this regard, with greater reliance on salbutamol MDI and correspondingly greater greenhouse gas emissions, roughly treble that of our European neighbours. There has been a broad switch towards MDIs in asthma treatment in the UK over the last 20 years to reduce financial costs, such that the treatment for two-thirds of asthma patients in the UK is dominated by salbutamol MDI. Strategies that replace overuse of reliever MDIs with regimes emphasising inhaled corticosteroids have the potential to improve asthma control alongside significant reductions in greenhouse gas emissions. Real-world evidence shows that once-daily long-acting combination dry-powder inhalers (DPIs) can improve compliance and asthma control, and reduce the carbon footprint of care. Similarly, maintenance and reliever therapy (MART), which uses combination reliever and inhaled steroids in one device (usually a DPI), can simplify therapy, improve asthma control and reduce greenhouse gas emissions. Both treatment strategies are popular with patients, most of whom would be willing to change treatment to reduce their carbon footprint. By focussing on patients who are currently using high amounts of salbutamol MDI and prioritising inhaled steroids via DPIs, there are golden opportunities to make asthma care in the UK more effective, safer and greener.
Topics: Administration, Inhalation; Albuterol; Asthma; Dry Powder Inhalers; Environment; Greenhouse Gases; Humans; Metered Dose Inhalers
PubMed: 34719810
DOI: 10.1111/bcp.15135 -
BMJ Open Respiratory Research Dec 2021Uncontrolled asthma is associated with substantial morbidity. While fast-acting bronchodilators provide quick relief from asthma symptoms, their use as rescue fails to... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and safety of as-needed albuterol/budesonide versus albuterol in adults and children aged ≥4 years with moderate-to-severe asthma: rationale and design of the randomised, double-blind, active-controlled MANDALA study.
INTRODUCTION
Uncontrolled asthma is associated with substantial morbidity. While fast-acting bronchodilators provide quick relief from asthma symptoms, their use as rescue fails to address the underlying inflammation. Combining a short-acting beta-agonist, such as albuterol (salbutamol), with an inhaled corticosteroid, such as budesonide, in a single inhaler as rescue therapy could help control both bronchoconstriction and inflammation, and reduce the risk of asthma exacerbations.
METHODS AND ANALYSIS
The Phase 3 MANDALA study was designed to determine the efficacy of albuterol in combination with budesonide (albuterol/budesonide 180/160 µg or 180/80 µg, two actuations of 90/80 µg or 90/40 µg, respectively) versus albuterol (180 µg, two actuations of 90 µg) as rescue therapy in adult, adolescent and paediatric patients with moderate-to-severe asthma. This event-driven study enrolled symptomatic patients (3000 adults/adolescents and 100 children aged 4-11 years) who experienced ≥1 severe asthma exacerbation in the previous year and were receiving maintenance therapy for ≥3 months prior to study entry. The primary efficacy endpoint was time-to-first severe asthma exacerbation.
ETHICS AND DISSEMINATION
The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki, and that are consistent with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use and Good Clinical Practice and the applicable regulatory requirements.
TRIAL REGISTRATION
NCT03769090.
Topics: Administration, Inhalation; Adolescent; Adult; Albuterol; Asthma; Budesonide; Child; Drug Combinations; Ethanolamines; Formoterol Fumarate; Humans
PubMed: 34887317
DOI: 10.1136/bmjresp-2021-001077