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Current Urology Reports Oct 2020This paper discusses the recent evidence supporting beta 3 adrenergic agonists as the preferred pharmacological management of overactive bladder syndrome. (Review)
Review
PURPOSE OF THE REVIEW
This paper discusses the recent evidence supporting beta 3 adrenergic agonists as the preferred pharmacological management of overactive bladder syndrome.
RECENT FINDINGS
Mirabegron has a similar efficacy profile to first-line antimuscarinics with favorable adverse effects profile. Treatment of OAB with beta-3 adrenergic agonist should be favored in patients at higher risk of anticholinergic adverse events. The efficacy and tolerability of beta-3 adrenergic agonists are consistently reported in older OAB patients, whether used alone or with other antimuscarinics. Mirabegron is cost-effective in treating OAB unless the symptoms were severe or refractory. Combination therapy of mirabegron and other pharmacotherapy has proven to be efficient in controlling OAB symptoms without inducing serious add-on adverse effects. While beta-3 adrenergic agonists bear favorable advantages in OAB treatment, physicians should perform a thorough and careful pre-treatment planning to optimize treatment benefits and adherence.
Topics: Acetanilides; Adrenergic alpha-1 Receptor Antagonists; Adrenergic beta-3 Receptor Agonists; Cholinergic Antagonists; Cost-Benefit Analysis; Humans; Muscarinic Antagonists; Phosphodiesterase Inhibitors; Pyrimidinones; Pyrrolidines; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents
PubMed: 33090278
DOI: 10.1007/s11934-020-01003-z -
Journal of Neuroimmune Pharmacology :... Mar 2020Evidence supporting the use of β2AR agonists in synucleinopathies is rapidly growing. Findings come from different scientific approaches. Molecular and immunological... (Review)
Review
Evidence supporting the use of β2AR agonists in synucleinopathies is rapidly growing. Findings come from different scientific approaches. Molecular and immunological data suggest that adrenergic stimulation may decrease both α-synuclein (α-syn) deposition and pro-inflammatory/neurotoxic molecules release. Small open label clinical trials including a total number of 25 Parkinson's disease (PD) patients, in which the β2AR agonist salbutamol was added to levodopa, suggest a promising symptomatic benefit. In line with these findings, epidemiological studies investigating the risk of PD development suggest that long term exposure to the agonist salbutamol might be protective, while the antagonist propranolol possibly detrimental. Nonetheless, in both lines of investigation the studies performed so far present important limitations. On the clinical side, large randomized controlled trials are lacking, whereas on the epidemiological side the presence of co-morbid conditions (i.e. smoking and essential tremor) potentially influencing PD risk should taken into consideration. In summary, it is our opinion that β2AR stimulation in synucleinopathies has a rationale and therefore merits further investigation. Graphical Abstract.
Topics: Adrenergic beta-2 Receptor Agonists; Animals; Catecholamines; Clinical Trials as Topic; Humans; Parkinson Disease; Receptors, Adrenergic, beta-2; Synucleinopathies; T-Lymphocytes
PubMed: 30617750
DOI: 10.1007/s11481-018-09831-0 -
JAMA May 2021Attention-deficit/hyperactivity disorder (ADHD) is diagnosed in approximately 2.4% of preschool-age children. Stimulants are recommended as first-line medication...
IMPORTANCE
Attention-deficit/hyperactivity disorder (ADHD) is diagnosed in approximately 2.4% of preschool-age children. Stimulants are recommended as first-line medication treatment. However, up to 25% of preschool-age children with ADHD are treated with α2-adrenergic agonist medications, despite minimal evidence about their efficacy or adverse effects in this age range.
OBJECTIVE
To determine the frequency of reported improvement in ADHD symptoms and adverse effects associated with α2-adrenergic agonists and stimulant medication for initial ADHD medication treatment in preschool-age children.
DESIGN, SETTING, AND PARTICIPANTS
Retrospective electronic health record review. Data were obtained from health records of children seen at 7 outpatient developmental-behavioral pediatric practices in the Developmental Behavioral Pediatrics Research Network in the US. Data were abstracted for 497 consecutive children who were younger than 72 months when treatment with an α2-adrenergic agonist or stimulant medication was initiated by a developmental-behavioral pediatrician for ADHD and were treated between January 1, 2013, and July 1, 2017. Follow-up was complete on February 27, 2019.
EXPOSURES
α2-Adrenergic agonist vs stimulant medication as initial ADHD medication treatment.
MAIN OUTCOMES AND MEASURES
Reported improvement in ADHD symptoms and adverse effects.
RESULTS
Data were abstracted from electronic health records of 497 preschool-age children with ADHD receiving α2-adrenergic agonists or stimulants. Median child age was 62 months at ADHD medication initiation, and 409 children (82%) were males. For initial ADHD medication treatment, α2-adrenergic agonists were prescribed to 175 children (35%; median length of α2-adrenergic agonist use, 136 days) and stimulants were prescribed to 322 children (65%; median length of stimulant use, 133 days). Improvement was reported in 66% (95% CI, 57.5%-73.9%) of children who initiated α2-adrenergic agonists and 78% (95% CI, 72.4%-83.4%) of children who initiated stimulants. Only daytime sleepiness was more common for those receiving α2-adrenergic agonists vs stimulants (38% vs 3%); several adverse effects were reported more commonly for those receiving stimulants vs α2-adrenergic agonists, including moodiness/irritability (50% vs 29%), appetite suppression (38% vs 7%), and difficulty sleeping (21% vs 11%).
CONCLUSIONS AND RELEVANCE
In this retrospective review of health records of preschool-age children with ADHD treated in developmental-behavioral pediatric practices, improvement was noted in the majority of children who received α2-adrenergic agonists or stimulants, with differing adverse effect profiles between medication classes. Further research, including from randomized clinical trials, is needed to assess comparative effectiveness of α2-adrenergic agonists vs stimulants.
Topics: Adrenergic alpha-2 Receptor Agonists; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child, Preschool; Disorders of Excessive Somnolence; Electronic Health Records; Feeding and Eating Disorders; Female; Guanfacine; Humans; Irritable Mood; Male; Methylphenidate; Retrospective Studies
PubMed: 33946100
DOI: 10.1001/jama.2021.6118 -
Scandinavian Journal of Medicine &... Dec 2019While beta -adrenoceptor stimulation has been shown to increase lean mass and to alter metabolic properties of skeletal muscle, adaptations in muscle oxidative enzymes... (Randomized Controlled Trial)
Randomized Controlled Trial
While beta -adrenoceptor stimulation has been shown to increase lean mass and to alter metabolic properties of skeletal muscle, adaptations in muscle oxidative enzymes and maximal oxygen uptake ( O ) in response to beta -adrenergic agonist treatment are inadequately explored in humans, particularly in association with resistance training. Herein, we investigated beta -adrenergic-induced changes in O , leg and arm composition, and muscle content of oxidative enzymes in response to treatment with the selective beta -adrenergic agonist terbutaline with and without concurrent resistance training in young men. Forty-six subjects were randomized to 4 weeks of lifestyle maintenance (n = 23) or resistance training (n = 23). Within the lifestyle maintenance and resistance training group, subjects received daily terbutaline (8 × 0.5 mg) (n = 13) or placebo (n = 10) treatment. No apparent treatment by training interactions was observed during the study period. Terbutaline increased leg and arm lean mass with the intervention, whereas no treatment differences were observed in absolute O and incremental peak power output (iPPO). Treatment main effects were observed for O -reserve (P < .05), O relative to body mass (P < .05), O relative to leg lean mass (P < .01), and iPPO relative to leg lean mass, in which terbutaline had a negative effect compared with placebo. Furthermore, content of electron transport chain complex I-V decreased by 11% (P < .05) for terbutaline compared with placebo. Accordingly, chronic treatment with the selective beta -adrenergic agonist terbutaline may negatively affect O and iPPO in relative terms, but not in absolute.
Topics: Adaptation, Physiological; Adrenergic beta-2 Receptor Agonists; Adult; Body Composition; Humans; Male; Muscle, Skeletal; Oxygen Consumption; Resistance Training; Terbutaline; Young Adult
PubMed: 31442335
DOI: 10.1111/sms.13544 -
Pharmacological Research Jan 2023Activation of brown adipose tissue (BAT) with the β3-adrenergic receptor agonist CL316,243 protects mice from atherosclerosis development, and the presence of...
Activation of brown adipose tissue (BAT) with the β3-adrenergic receptor agonist CL316,243 protects mice from atherosclerosis development, and the presence of metabolically active BAT is associated with cardiometabolic health in humans. In contrast, exposure to cold or treatment with the clinically used β3-adrenergic receptor agonist mirabegron to activate BAT exacerbates atherosclerosis in apolipoprotein E (ApoE)- and low-density lipoprotein receptor (LDLR)-deficient mice, both lacking a functional ApoE-LDLR pathway crucial for lipoprotein remnant clearance. We, therefore, investigated the effects of mirabegron treatment on dyslipidemia and atherosclerosis development in APOE*3-Leiden.CETP mice, a humanized lipoprotein metabolism model with a functional ApoE-LDLR clearance pathway. Mirabegron activated BAT and induced white adipose tissue (WAT) browning, accompanied by selectively increased fat oxidation and attenuated fat mass gain. Mirabegron increased the uptake of fatty acids derived from triglyceride (TG)-rich lipoproteins by BAT and WAT, which was coupled to increased hepatic uptake of the generated cholesterol-enriched core remnants. Mirabegron also promoted hepatic very low-density lipoprotein (VLDL) production, likely due to an increased flux of fatty acids from WAT to the liver, and resulted in transient elevation in plasma TG levels followed by a substantial decrease in plasma TGs. These effects led to a trend toward lower plasma cholesterol levels and reduced atherosclerosis. We conclude that BAT activation by mirabegron leads to substantial metabolic benefits in APOE*3-Leiden.CETP mice, and mirabegron treatment is certainly not atherogenic. These data underscore the importance of the choice of experimental models when investigating the effect of BAT activation on lipoprotein metabolism and atherosclerosis.
Topics: Animals; Humans; Mice; Adipose Tissue, Brown; Adrenergic Agonists; Apolipoproteins E; Atherosclerosis; Cholesterol; Fatty Acids; Lipoproteins, LDL; Liver; Triglycerides; Receptors, LDL
PubMed: 36574856
DOI: 10.1016/j.phrs.2022.106634 -
The Cochrane Database of Systematic... May 2017Managed withdrawal is a necessary step prior to drug-free treatment or as the endpoint of long-term substitution treatment. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Managed withdrawal is a necessary step prior to drug-free treatment or as the endpoint of long-term substitution treatment.
OBJECTIVES
To assess the effects of opioid antagonists plus minimal sedation for opioid withdrawal. Comparators were placebo as well as more established approaches to detoxification, such as tapered doses of methadone, adrenergic agonists, buprenorphine and symptomatic medications.
SEARCH METHODS
We updated our searches of the following databases to December 2016: CENTRAL, MEDLINE, Embase, PsycINFO and Web of Science. We also searched two trials registers and checked the reference lists of included studies for further references to relevant studies.
SELECTION CRITERIA
We included randomised and quasi-randomised controlled clinical trials along with prospective controlled cohort studies comparing opioid antagonists plus minimal sedation versus other approaches or different opioid antagonist regimens for withdrawal in opioid-dependent participants.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
Ten studies (6 randomised controlled trials and 4 prospective cohort studies, involving 955 participants) met the inclusion criteria for the review. We considered 7 of the 10 studies to be at high risk of bias in at least one of the domains we assessed.Nine studies compared an opioid antagonist-adrenergic agonist combination versus a treatment regimen based primarily on an alpha-adrenergic agonist (clonidine or lofexidine). Other comparisons (placebo, tapered doses of methadone, buprenorphine) made by included studies were too diverse for any meaningful analysis. This review therefore focuses on the nine studies comparing an opioid antagonist (naltrexone or naloxone) plus clonidine or lofexidine versus treatment primarily based on clonidine or lofexidine.Five studies took place in an inpatient setting, two studies were in outpatients with day care, two used day care only for the first day of opioid antagonist administration, and one study described the setting as outpatient without indicating the level of care provided.The included studies were heterogeneous in terms of the type of opioid antagonist treatment regimen, the comparator, the outcome measures assessed, and the means of assessing outcomes. As a result, the validity of any estimates of overall effect is doubtful, therefore we did not calculate pooled results for any of the analyses.The quality of the evidence for treatment with an opioid antagonist-adrenergic agonist combination versus an alpha-adrenergic agonist is very low. Two studies reported data on peak withdrawal severity, and four studies reported data on the average severity over the period of withdrawal. Peak withdrawal induced by opioid antagonists in combination with an adrenergic agonist appears to be more severe than withdrawal managed with clonidine or lofexidine alone, but the average severity over the withdrawal period is less. In some situations antagonist-induced withdrawal may be associated with significantly higher rates of treatment completion compared to withdrawal managed with adrenergic agonists. However, this result was not consistent across studies, and the extent of any benefit is highly uncertain.We could not extract any data on the occurrence of adverse events, but two studies reported delirium or confusion following the first dose of naltrexone. Delirium may be more likely with higher initial doses and with naltrexone rather than naloxone (which has a shorter half-life), but we could not confirm this from the available evidence.Insufficient data were available to make any conclusions on the best duration of treatment.
AUTHORS' CONCLUSIONS
Using opioid antagonists plus alpha-adrenergic agonists is a feasible approach for managing opioid withdrawal. However, it is unclear whether this approach reduces the duration of withdrawal or facilitates transfer to naltrexone treatment to a greater extent than withdrawal managed primarily with an adrenergic agonist.A high level of monitoring and support is desirable for several hours following administration of opioid antagonists because of the possibility of vomiting, diarrhoea and delirium.Using opioid antagonists to induce and accelerate opioid withdrawal is not currently an active area of research or clinical practice, and the research community should give greater priority to investigating approaches, such as those based on buprenorphine, that facilitate the transition to sustained-release preparations of naltrexone.
Topics: Adrenergic alpha-Agonists; Clonidine; Humans; Naloxone; Naltrexone; Narcotic Antagonists; Non-Randomized Controlled Trials as Topic; Opioid-Related Disorders; Prospective Studies; Randomized Controlled Trials as Topic; Severity of Illness Index; Substance Withdrawal Syndrome
PubMed: 28553701
DOI: 10.1002/14651858.CD002021.pub4 -
Journal of Animal Physiology and Animal... May 2021The objective was to conduct a systematic review to evaluate the effects of dietary supplementation with beta-adrenergic agonists on calpains and calpastatin activity in...
The objective was to conduct a systematic review to evaluate the effects of dietary supplementation with beta-adrenergic agonists on calpains and calpastatin activity in bovine muscle and changes in meat tenderness. A survey was conducted in June 2019 on Science Direct, Web of Science, Scopus, PubMed and Capes Periodicals, using four keyword combinations: agonist and calpain and cattle; agonist and calpain and bovine; agonist and calpain and heifers; agonist and calpain and steers. Thirteen studies were selected, 54% concluded that supplementation with beta-adrenergic agonists increases calpastatin activity, 23% observed increase in their gene expression and 23% reported no effect on activity or expression of this enzyme. Nine studies evaluated the influence of beta-adrenergic agonists supplementation on meat texture and all found an increase in shear force values. There is strong evidence that beta-adrenergic agonists may increase calpastatin activity in the muscle, causing damage to meat tenderness.
Topics: Adrenergic beta-Agonists; Animals; Calpain; Cattle; Female; Meat; Muscle, Skeletal; Muscles; Proteolysis
PubMed: 33452737
DOI: 10.1111/jpn.13479 -
Endocrine, Metabolic & Immune Disorders... 2020Mirabegron is a β3-agonist drug approved by the FDA for use in 2012 and administered in overactive bladder. Activating of adrenergic receptors leads to the relaxation... (Review)
Review
Mirabegron is a β3-agonist drug approved by the FDA for use in 2012 and administered in overactive bladder. Activating of adrenergic receptors leads to the relaxation of the detrusor muscle. According to the latest research and reports, it also has lipolytic activity, affecting the reduction of mainly brown adipose tissue (BAT) but also of white adipose tissue (WAT). This results in a decrease in body weight and triglyceride concentration and an increase in lipoprotein lipase activity, as well as in the level of free fatty acids or adipokines in the plasma. The drug indirectly participates in the regulation of carbohydrate metabolism, influencing the increase in insulin sensitivity, supporting cellular uptake of glucose. However, due to the elevation of blood pressure and pulse, as a supplement, the drug should be taken with care to avoid cardiovascular complications. In our review, below, we present a description and discussion of available studies in terms of mirabegron action on the exercise capacity of the body in the context of its potential use as a doping agent.
Topics: Acetanilides; Adipose Tissue; Adipose Tissue, Brown; Adipose Tissue, White; Adrenergic beta-3 Receptor Agonists; Animals; Exercise Tolerance; Humans; Lipolysis; Thiazoles; Urinary Bladder, Overactive
PubMed: 32416711
DOI: 10.2174/1871530320666200516164434 -
Psychopharmacology Bulletin Oct 2020This evidence-based systematic review will focus on the use of dexmedetomidine and its role as adjuvant anesthetics in regional blocks to help better guide physicians in... (Review)
Review
PURPOSE OF REVIEW
This evidence-based systematic review will focus on the use of dexmedetomidine and its role as adjuvant anesthetics in regional blocks to help better guide physicians in their practice. This review will cover background and mechanism of dexmedetomidine as well as the use in various regional blocks.
RECENT FINDINGS
Local anesthetics are preferred for nerve blocks over opioids; however, both due come with its own side effects. Local anesthetics may be toxic as they disrupt cell membrane and proteins, but by using adjuvants such as dexmedetomidine, that can prolong sensory and motor blocks can reduce total amount of local anesthetics needed. Dexmedetomidine is an alpha-2-adrenergic agonist used as additive for regional nerve block. It has a relatively low side effect profile and have been researched in various regional blocks (intrathecal, paravertebral, axillary, infraclavicular brachial plexus, interscalene). Dexmedetomidine shows promising results as adjuvant anesthetics in most regional blocks.
SUMMARY
Many studies have been done and many show promising results for the use of dexmedetomidine in regional blocks. It may significantly increase in duration of sensory and motor blocks that correlates with lower pain scores and less need of morphine in various regional blocks.
Topics: Adrenergic alpha-2 Receptor Agonists; Anesthesia, Conduction; Anesthetics, Local; Brachial Plexus Block; Dexmedetomidine
PubMed: 33633422
DOI: No ID Found -
The contribution of autonomic mechanisms to pain in temporomandibular disorders: A narrative review.Journal of Oral Rehabilitation Nov 2022Temporomandibular disorders (TMD) are diagnosed based on symptom presentation and, like other functional pain disorders, often lack definitive pathology. There is a... (Review)
Review
BACKGROUND
Temporomandibular disorders (TMD) are diagnosed based on symptom presentation and, like other functional pain disorders, often lack definitive pathology. There is a strong association between elevated stress levels and the severity of TMD-related pain, which suggests that alterations in autonomic tone may contribute to this pain condition.
OBJECTIVES
This narrative review examines the association between altered autonomic function and pain in TMD.
METHODS
Relevant articles were identified by searching PubMed and through the reference list of those studies.
RESULTS
TMD sufferers report an increased incidence of orthostatic hypotension. As in other chronic musculoskeletal pain conditions, TMD is associated with increased sympathetic tone, diminished baroreceptor reflex sensitivity and decreased parasympathetic tone. It remains to be determined whether ongoing pain drives these autonomic changes and/or is exacerbated by them. To examine whether increased sympathetic tone contributes to TMD-related pain through β adrenergic receptor activation, clinical trials with the beta blocker propranolol have been undertaken. Although evidence from small studies suggested propranolol reduced TMD-related pain, a larger clinical trial did not find a significant effect of propranolol treatment. This is consistent with human experimental pain studies that were unable to demonstrate an effect of β adrenergic receptor activation or inhibition on masticatory muscle pain. In preclinical models of temporomandibular joint arthritis, β adrenergic receptor activation appears to contribute to inflammation and nociception, whereas in masticatory muscle, α adrenergic receptor activation has been found to induce mechanical sensitisation. Some agents used to treat TMD, such as botulinum neurotoxin A, antidepressants and α adrenergic receptor agonists, may interact with the autonomic nervous system as part of their analgesic mechanism.
CONCLUSION
Even if dysautonomia turns out to be a consequence rather than a causative factor of painful TMD, the study of its role has opened up a greater understanding of the pathogenesis of this condition.
Topics: Adrenergic Agonists; Analgesics; Antidepressive Agents; Autonomic Nervous System; Botulinum Toxins, Type A; Clinical Trials as Topic; Humans; Pain; Propranolol; Receptors, Adrenergic; Temporomandibular Joint Disorders
PubMed: 36098708
DOI: 10.1111/joor.13370