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Medicina (Kaunas, Lithuania) 2006Epinephrine is an adrenergic agonist used to treat bronchospasm, anaphylactic reactions, bradycardia, cardiac arrest, and hypotension. Its toxicity is usually caused by... (Review)
Review
Epinephrine is an adrenergic agonist used to treat bronchospasm, anaphylactic reactions, bradycardia, cardiac arrest, and hypotension. Its toxicity is usually caused by iatrogenic errors. In overdose there is a typical rapid onset of agitation, hypertension, tachycardia, and dysrhythmias. This review article focuses on the causes of overdose, signs and symptoms, treatment and expected course, and prognosis of this iatrogenic pathology.
Topics: Adrenergic Agonists; Anaphylaxis; Arrhythmias, Cardiac; Bradycardia; Bronchial Spasm; Drug Overdose; Epinephrine; Heart Arrest; Humans; Hypertension; Hypotension; Iatrogenic Disease; Prognosis; Pulmonary Edema; Shock, Cardiogenic; Tachycardia
PubMed: 16861845
DOI: No ID Found -
Handbook of Experimental Pharmacology 2017History suggests β agonists, the cognate ligand of the β adrenoceptor, have been used as bronchodilators for around 5,000 years, and β agonists remain today the... (Review)
Review
History suggests β agonists, the cognate ligand of the β adrenoceptor, have been used as bronchodilators for around 5,000 years, and β agonists remain today the frontline treatment for asthma and chronic obstructive pulmonary disease (COPD). The β agonists used clinically today are the products of significant expenditure and over 100 year's intensive research aimed at minimizing side effects and enhancing therapeutic usefulness. The respiratory physician now has a therapeutic toolbox of long acting β agonists to prophylactically manage bronchoconstriction, and short acting β agonists to relieve acute exacerbations. Despite constituting the cornerstone of asthma and COPD therapy, these drugs are not perfect; significant safety issues have led to a black box warning advising that long acting β agonists should not be used alone in patients with asthma. In addition there are a significant proportion of patients whose asthma remains uncontrolled. In this chapter we discuss the evolution of β agonist use and how the understanding of β agonist actions on their principal target tissue, airway smooth muscle, has led to greater understanding of how these drugs can be further modified and improved in the future. Research into the genetics of the β adrenoceptor will also be discussed, as will the implications of individual DNA profiles on the clinical outcomes of β agonist use (pharmacogenetics). Finally we comment on what the future may hold for the use of β agonists in respiratory disease.
Topics: Adrenergic beta-2 Receptor Agonists; Animals; Asthma; Bronchodilator Agents; Humans; Pharmacogenetics; Polymorphism, Single Nucleotide; Pulmonary Disease, Chronic Obstructive
PubMed: 27878470
DOI: 10.1007/164_2016_64 -
ELife Aug 2020How the brain dynamics change during anesthetic-induced altered states of consciousness is not completely understood. The α2-adrenergic agonists are unique. They...
How the brain dynamics change during anesthetic-induced altered states of consciousness is not completely understood. The α2-adrenergic agonists are unique. They generate unconsciousness selectively through α2-adrenergic receptors and related circuits. We studied intracortical neuronal dynamics during transitions of loss of consciousness (LOC) with the α2-adrenergic agonist dexmedetomidine and return of consciousness (ROC) in a functionally interconnecting somatosensory and ventral premotor network in non-human primates. LOC, ROC and full task performance recovery were all associated with distinct neural changes. The early recovery demonstrated characteristic intermediate dynamics distinguished by sustained high spindle activities. Awakening by the α2-adrenergic antagonist completely eliminated this intermediate state and instantaneously restored awake dynamics and the top task performance while the anesthetic was still being infused. The results suggest that instantaneous functional recovery is possible following anesthetic-induced unconsciousness and the intermediate recovery state is not a necessary path for the brain recovery.
Topics: Adrenergic alpha-Agonists; Adrenergic alpha-Antagonists; Animals; Brain; Consciousness; Dexmedetomidine; Electroencephalography; Humans; Hypnotics and Sedatives; Imidazoles; Macaca; Male; Unconsciousness; Wakefulness
PubMed: 32857037
DOI: 10.7554/eLife.57670 -
Biosensors Jul 2022The illegal use of β-adrenergic agonists during livestock growth poses a threat to public health; the long-term intake of this medication can cause serious... (Review)
Review
The illegal use of β-adrenergic agonists during livestock growth poses a threat to public health; the long-term intake of this medication can cause serious physiological side effects and even death. Therefore, rapid detection methods for β-adrenergic agonist residues on-site are required. Traditional detection methods such as liquid chromatography have limitations in terms of expensive instruments and complex operations. In contrast, paper methods are low cost, ubiquitous, and portable, which has led to them becoming the preferred detection method in recent years. Various paper-based fluidic devices have been developed to detect β-adrenergic agonist residues, including lateral flow immunoassays (LFAs) and microfluidic paper-based analytical devices (μPADs). In this review, the application of LFAs for the detection of β-agonists is summarized comprehensively, focusing on the latest advances in novel labeling and detection strategies. The use of μPADs as an analytical platform has attracted interest over the past decade due to their unique advantages and application for detecting β-adrenergic agonists, which are introduced here. Vertical flow immunoassays are also discussed for their shorter assay time and stronger multiplexing capabilities compared with LFAs. Furthermore, the development direction and prospects for the commercialization of paper-based devices are considered, shedding light on the development of point-of-care testing devices for β-adrenergic agonist residue detection.
Topics: Adrenergic beta-Agonists; Immunoassay; Lab-On-A-Chip Devices; Microfluidic Analytical Techniques; Paper; Point-of-Care Systems; Point-of-Care Testing
PubMed: 35884321
DOI: 10.3390/bios12070518 -
Drug Testing and Analysis Feb 2021Higenamine was included in the World Anti-Doping Agency (WADA) Prohibited Substances and Methods List as a β -adrenoceptor agonist in 2017, thereby resulting in its... (Review)
Review
Higenamine was included in the World Anti-Doping Agency (WADA) Prohibited Substances and Methods List as a β -adrenoceptor agonist in 2017, thereby resulting in its prohibition both in and out of competition. The present mini review describes the physiology and pharmacology of adrenoceptors, summarizes the literature addressing the mechanism of action of higenamine and extends these findings with previously unpublished in silico and in vitro work. Studies conducted in isolated in vitro systems, whole-animal preparations and a small number of clinical studies suggest that higenamine acts in part as a β -adrenoceptor agonist. In silico predictive tools indicated that higenamine and possibly a metabolite have a high probability of interacting with the β -receptor as an agonist. Stable expression of human β -receptors in Chinese hamster ovary (CHO) cells to measure agonist activity not only confirmed the activity of higenamine at β but also closely agreed with the in silico prediction of potency for this compound. These data confirm and extend literature findings supporting the inclusion of higenamine in the Prohibited List.
Topics: Adrenergic beta-Agonists; Alkaloids; Animals; Athletic Performance; Doping in Sports; Humans; Performance-Enhancing Substances; Receptors, Adrenergic, beta-2; Tetrahydroisoquinolines
PubMed: 33369180
DOI: 10.1002/dta.2992 -
Biomolecules Jun 2021Adrenergic receptors are G protein-coupled receptors for epinephrine and norepinephrine. They are targets of many drugs for various conditions, including treatment of... (Review)
Review
Adrenergic receptors are G protein-coupled receptors for epinephrine and norepinephrine. They are targets of many drugs for various conditions, including treatment of hypertension, hypotension, and asthma. Adrenergic receptors are intensively studied in structural biology, displayed for binding poses of different types of ligands. Here, we summarized molecular mechanisms of ligand recognition and receptor activation exhibited by structure. We also reviewed recent advances in structure-based ligand discovery against adrenergic receptors.
Topics: Adrenergic Agonists; Adrenergic Antagonists; Amino Acid Sequence; Animals; Crystallography, X-Ray; Epinephrine; Humans; Ligands; Norepinephrine; Protein Binding; Protein Conformation; Protein Structure, Secondary; Protein Structure, Tertiary; Receptors, Adrenergic
PubMed: 34202543
DOI: 10.3390/biom11070936 -
Current Neuropharmacology 2023Congenital myasthenic syndromes (CMS) refer to a series of inherited disorders caused by defects in various proteins. Mutation in the collagen-like tail subunit of... (Review)
Review Meta-Analysis
BACKGROUND
Congenital myasthenic syndromes (CMS) refer to a series of inherited disorders caused by defects in various proteins. Mutation in the collagen-like tail subunit of asymmetric acetylcholinesterase () is the second-most common cause of CMS. However, data on pharmacological treatments are limited.
OBJECTIVE
In this study, we reviewed related reports to determine the most appropriate pharmacological strategy for CMS caused by mutations. A literature review and meta-analysis were also performed. PubMed, MEDLINE, Web of Science, and Cochrane Library databases were searched to identify studies published in English before July 22, 2022.
RESULTS
A total of 42 studies including 164 patients with CMS due to 72 different mutations were selected for evaluation. Most studies were case reports, and none were randomized clinical trials. Our meta-analysis revealed evidence that β-adrenergic agonists, including salbutamol and ephedrine, can be used as first-line pharmacological treatments for CMS patients with mutations, as 98.7% of patients (74/75) treated with β-adrenergic agonists showed positive effects. In addition, AChEIs should be avoided in CMS patients with mutations, as 90.5% (105/116) of patients treated with AChEIs showed either no or negative effects.
CONCLUSION
(1) β-adrenergic agonist therapy is the first pharmacological strategy for treating CMS with mutations. (2) AChEIs should be avoided in patients with CMS with mutations.
Topics: Humans; Myasthenic Syndromes, Congenital; Acetylcholinesterase; Muscle Proteins; Mutation; Adrenergic beta-Agonists; Collagen
PubMed: 36703579
DOI: 10.2174/1570159X21666230126145652 -
The Journal of Allergy and Clinical... Feb 2022Administering allergens in increasing doses can temporarily suppress IgE-mediated allergy and anaphylaxis by desensitizing mast cells and basophils; however, allergen...
BACKGROUND
Administering allergens in increasing doses can temporarily suppress IgE-mediated allergy and anaphylaxis by desensitizing mast cells and basophils; however, allergen administration during desensitization therapy can itself induce allergic responses. Several small molecule drugs and nutraceuticals have been used clinically and experimentally to suppress these allergic responses.
OBJECTIVES
This study sought to optimize drug inhibition of IgE-mediated anaphylaxis.
METHODS
Several agents were tested individually and in combination for ability to suppress IgE-mediated anaphylaxis in conventional mice, FcεRIα-humanized mice, and reconstituted immunodeficient mice that have human mast cells and basophils. Hypothermia was the readout for anaphylaxis; therapeutic efficacy was measured by degree of inhibition of hypothermia. Serum mouse mast cell protease 1 level was used to measure extent of mast cell degranulation.
RESULTS
Histamine receptor 1 (HR1) antagonists, β-adrenergic agonists, and a spleen tyrosine kinase (Syk) inhibitor were best at individually inhibiting IgE-mediated anaphylaxis. A Bruton's tyrosine kinase (BTK) inhibitor, administered alone, only inhibited hypothermia when FcεRI signaling was suboptimal. Combinations of these agents could completely or nearly completely inhibit IgE-mediated hypothermia in these models. Both Syk and BTK inhibition decreased mast cell degranulation, but only Syk inhibition also blocked desensitization. Many other agents that are used clinically and experimentally had little or no beneficial effect.
CONCLUSIONS
Combinations of an HR1 antagonist, a β-adrenergic agonist, and a Syk or a BTK inhibitor protect best against IgE-mediated anaphylaxis, while an HR1 antagonist plus a β-adrenergic agonist ± a BTK antagonist is optimal for inhibiting IgE-mediated anaphylaxis without suppressing desensitization.
Topics: Adrenergic beta-Agonists; Anaphylaxis; Animals; Drug Therapy, Combination; Histamine Antagonists; Immunoglobulin E; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Protein Kinase Inhibitors; Protein-Tyrosine Kinases
PubMed: 34186142
DOI: 10.1016/j.jaci.2021.06.022 -
The Cochrane Database of Systematic... May 2016Withdrawal is a necessary step prior to drug-free treatment or as the endpoint of long-term substitution treatment. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Withdrawal is a necessary step prior to drug-free treatment or as the endpoint of long-term substitution treatment.
OBJECTIVES
To assess the effectiveness of interventions involving the use of alpha2-adrenergic agonists compared with placebo, reducing doses of methadone, symptomatic medications, or an alpha2-adrenergic agonist regimen different to the experimental intervention, for the management of the acute phase of opioid withdrawal. Outcomes included the withdrawal syndrome experienced, duration of treatment, occurrence of adverse effects, and completion of treatment.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1946 to November week 2, 2015), EMBASE (January 1985 to November week 2, 2015), PsycINFO (1806 to November week 2, 2015), Web of Science, and reference lists of articles.
SELECTION CRITERIA
Randomised controlled trials comparing alpha2-adrenergic agonists (clonidine, lofexidine, guanfacine, tizanidine) with reducing doses of methadone, symptomatic medications or placebo, or comparing different alpha2-adrenergic agonists to modify the signs and symptoms of withdrawal in participants who were opioid dependent.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by The Cochrane Collaboration.
MAIN RESULTS
We included 26 randomised controlled trials involving 1728 participants. Six studies compared an alpha2-adrenergic agonist with placebo, 12 with reducing doses of methadone, four with symptomatic medications, and five compared different alpha2-adrenergic agonists. We assessed 10 studies as having a high risk of bias in at least one of the methodological domains that were considered.We found moderate-quality evidence that alpha2-adrenergic agonists were more effective than placebo in ameliorating withdrawal in terms of the likelihood of severe withdrawal (risk ratio (RR) 0.32, 95% confidence interval (CI) 0.18 to 0.57; 3 studies; 148 participants). We found moderate-quality evidence that completion of treatment was significantly more likely with alpha2-adrenergic agonists compared with placebo (RR 1.95, 95% CI 1.34 to 2.84; 3 studies; 148 participants).Peak withdrawal severity may be greater with alpha2-adrenergic agonists than with reducing doses of methadone, as measured by the likelihood of severe withdrawal (RR 1.18, 95% CI 0.81 to 1.73; 5 studies; 340 participants; low quality), and peak withdrawal score (standardised mean difference (SMD) 0.22, 95% CI -0.02 to 0.46; 2 studies; 263 participants; moderate quality), but these differences were not significant and there is no significant difference in severity when considered over the entire duration of the withdrawal episode (SMD 0.13, 95% CI -0.24 to 0.49; 3 studies; 119 participants; moderate quality). The signs and symptoms of withdrawal occurred and resolved earlier with alpha2-adrenergic agonists. The duration of treatment was significantly longer with reducing doses of methadone (SMD -1.07, 95% CI -1.31 to -0.83; 3 studies; 310 participants; low quality). Hypotensive or other adverse effects were significantly more likely with alpha2-adrenergic agonists (RR 1.92, 95% CI 1.19 to 3.10; 6 studies; 464 participants; low quality), but there was no significant difference in rates of completion of withdrawal treatment (RR 0.85, 95% CI 0.69 to 1.05; 9 studies; 659 participants; low quality).There were insufficient data for quantitative comparison of different alpha2-adrenergic agonists. Available data suggest that lofexidine does not reduce blood pressure to the same extent as clonidine, but is otherwise similar to clonidine.
AUTHORS' CONCLUSIONS
Clonidine and lofexidine are more effective than placebo for the management of withdrawal from heroin or methadone. We detected no significant difference in efficacy between treatment regimens based on clonidine or lofexidine and those based on reducing doses of methadone over a period of around 10 days, but methadone was associated with fewer adverse effects than clonidine, and lofexidine has a better safety profile than clonidine.
Topics: Acute Disease; Adrenergic alpha-2 Receptor Agonists; Clonidine; Controlled Clinical Trials as Topic; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome
PubMed: 27140827
DOI: 10.1002/14651858.CD002024.pub5 -
Allergology International : Official... Jun 2012Tulobuterol patch (HokunalinTM Tape), which contains a β(2)-adrenergic agonist, is the first bronchodilator to be available as a transdermal patch. This drug delivery... (Review)
Review
Tulobuterol patch (HokunalinTM Tape), which contains a β(2)-adrenergic agonist, is the first bronchodilator to be available as a transdermal patch. This drug delivery system ensures that the time at which the peak drug concentration in the blood is reached coincides with the morning dip in respiratory function. The use of the patch also prevents excessive increase in blood drug concentrations, thereby reducing the incidence of systemic adverse reactions. Since 1998, when it was first approved in Japan and worldwide, the tulobuterol patch has been used widely in the treatment of bronchial asthma and chronic obstructive pulmonary disease (COPD), and evidence collected since it was approved has confirmed its clinical efficacy and safety. Because the patch is easy to use and requires only once-daily application, treatment adherence of patients using the patch is good. In this article, we discuss the rationale behind the development of the tulobuterol patch, evaluate data on its clinical efficacy and safety in the treatment of asthma and COPD, and examine the treatment adherence in individuals using the patch.
Topics: Adrenergic beta-Agonists; Asthma; Bronchodilator Agents; Drug Approval; Evidence-Based Medicine; Humans; Patient Compliance; Pulmonary Disease, Chronic Obstructive; Terbutaline; Transdermal Patch
PubMed: 22270072
DOI: 10.2332/allergolint.11-RA-0358