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Ugeskrift For Laeger Mar 2019
Topics: Adrenergic beta-Antagonists; Anxiety Disorders; Humans; Propranolol
PubMed: 30931879
DOI: No ID Found -
JAMA Otolaryngology-- Head & Neck... Jul 2021Propranolol has become the first-line therapy for problematic infantile hemangiomas (IHs) that require systemic therapy. However, different adverse events have been... (Comparative Study)
Comparative Study Randomized Controlled Trial
IMPORTANCE
Propranolol has become the first-line therapy for problematic infantile hemangiomas (IHs) that require systemic therapy. However, different adverse events have been reported during propranolol treatment. The positive efficacy and safety of atenolol raise the question of whether it could be used as a promising therapy for IH.
OBJECTIVE
To compare the efficacy and safety of propranolol vs atenolol in infants (between age 5 and 20 weeks) with problematic IHs who required systemic therapy.
DESIGN, SETTING, AND PARTICIPANTS
This was a prospective, multicenter, randomized, controlled, open-label clinical trial conducted in collaboration among 6 separate investigation sites in China from February 1, 2015, to December 31, 2018. A total of 377 patients met the criteria for inclusion and were randomized to the propranolol (190 [50.4%]) and atenolol (187 [49.6%]) groups. Data were analyzed in June 2020.
INTERVENTIONS
Participants were randomized to receive either propranolol or atenolol for at least 6 months. They completed efficacy assessments at 2 years after the initial treatment.
MAIN OUTCOMES AND MEASURES
The primary outcome was any response or nonresponse at 6 months. The key secondary outcome was changes in the hemangioma activity score.
RESULTS
Of 377 participants, 287 (76.1%) were female, and the mean (SD) age was 10.2 (4.0) weeks in the propranolol group and 9.8 (4.1) weeks in the atenolol group. After 6 months of treatment, in the propranolol and atenolol groups, the overall response rates were 93.7% and 92.5%, respectively (difference, 1.2%; 95% CI, -4.1% to 6.6%). At 1 and 4 weeks after treatment, and thereafter, the hemangioma activity score in the atenolol group aligned with the propranolol group (odds ratio, 1.034; 95% CI, 0.886-1.206). No differences between the propranolol group and atenolol group were observed in successful initial responses, quality of life scores, complete ulceration healing times, or the rebound rate. Both groups presented a similar percentage of complete/nearly complete responses at 2 years (82.1% vs 79.7%; difference, 2.4%; 95% CI, -5.9% to 10.7%). Adverse events were more common in the propranolol group (70.0% vs 44.4%; difference, 25.6%; 95% CI, 15.7%-34.8%), but the frequency of severe adverse events did not differ meaningfully between the groups.
CONCLUSIONS AND RELEVANCE
In this randomized clinical trial, when compared with propranolol, atenolol had similar efficacy and fewer adverse events in the treatment of infants with problematic IHs. The results suggest that oral atenolol can be used as an alternative treatment option for patients with IH who require systemic therapy.
TRIAL REGISTRATION
ClinicalTrial.gov Identifier: NCT02342275.
Topics: Adrenergic beta-1 Receptor Antagonists; Adrenergic beta-Antagonists; Atenolol; China; Female; Hemangioma, Capillary; Humans; Infant; Male; Propranolol; Prospective Studies
PubMed: 33856430
DOI: 10.1001/jamaoto.2021.0454 -
Nature Feb 2020The solid tumour microenvironment includes nerve fibres that arise from the peripheral nervous system. Recent work indicates that newly formed adrenergic nerve fibres...
The solid tumour microenvironment includes nerve fibres that arise from the peripheral nervous system. Recent work indicates that newly formed adrenergic nerve fibres promote tumour growth, but the origin of these nerves and the mechanism of their inception are unknown. Here, by comparing the transcriptomes of cancer-associated trigeminal sensory neurons with those of endogenous neurons in mouse models of oral cancer, we identified an adrenergic differentiation signature. We show that loss of TP53 leads to adrenergic transdifferentiation of tumour-associated sensory nerves through loss of the microRNA miR-34a. Tumour growth was inhibited by sensory denervation or pharmacological blockade of adrenergic receptors, but not by chemical sympathectomy of pre-existing adrenergic nerves. A retrospective analysis of samples from oral cancer revealed that p53 status was associated with nerve density, which was in turn associated with poor clinical outcomes. This crosstalk between cancer cells and neurons represents mechanism by which tumour-associated neurons are reprogrammed towards an adrenergic phenotype that can stimulate tumour progression, and is a potential target for anticancer therapy.
Topics: Adrenergic Antagonists; Adrenergic Neurons; Animals; Cell Division; Cell Transdifferentiation; Cellular Reprogramming; Disease Models, Animal; Disease Progression; Female; Humans; Male; Mice; Mice, Inbred BALB C; MicroRNAs; Mouth Neoplasms; Nerve Fibers; Neurites; Receptors, Adrenergic; Retrospective Studies; Sensory Receptor Cells; Tumor Microenvironment; Tumor Suppressor Protein p53; Xenograft Model Antitumor Assays
PubMed: 32051587
DOI: 10.1038/s41586-020-1996-3 -
Communications Biology Nov 2022Vesicular monoamine transporter 2 (VMAT2) is responsible for packing monoamine neurotransmitters into synaptic vesicles for storage and subsequent neurotransmission....
Vesicular monoamine transporter 2 (VMAT2) is responsible for packing monoamine neurotransmitters into synaptic vesicles for storage and subsequent neurotransmission. VMAT2 inhibitors are approved for symptomatic treatment of tardive dyskinesia and Huntington's chorea, but despite being much-studied inhibitors their exact binding site and mechanism behind binding and inhibition of monoamine transport are not known. Here we report the identification of several approved drugs, notably β2-adrenergic agonists salmeterol, vilanterol and formoterol, β2-adrenergic antagonist carvedilol and the atypical antipsychotic ziprasidone as inhibitors of rat VMAT2. Further, plausible binding modes of the established VMAT2 inhibitors reserpine and tetrabenazine and hit compounds salmeterol and ziprasidone were identified using molecular dynamics simulations and functional assays using VMAT2 wild-type and mutants. Our findings show VMAT2 as a potential off-target of treatments with several approved drugs in use today and can also provide important first steps in both drug repurposing and therapy development targeting VMAT2 function.
Topics: Animals; Rats; Adrenergic Agonists; Antipsychotic Agents; Piperazines; Vesicular Monoamine Transport Proteins; Adrenergic Antagonists
PubMed: 36418492
DOI: 10.1038/s42003-022-04121-1 -
Critical Care (London, England) Jun 2021β-adrenergic antagonists (BAAs) are used to treat cardiovascular disease such as ischemic heart disease, congestive heart failure, dysrhythmias, and hypertension....
BACKGROUND
β-adrenergic antagonists (BAAs) are used to treat cardiovascular disease such as ischemic heart disease, congestive heart failure, dysrhythmias, and hypertension. Poisoning from BAAs can lead to severe morbidity and mortality. We aimed to determine the utility of extracorporeal treatments (ECTRs) in BAAs poisoning.
METHODS
We conducted systematic reviews of the literature, screened studies, extracted data, and summarized findings following published EXTRIP methods.
RESULTS
A total of 76 studies (4 in vitro and 2 animal experiments, 1 pharmacokinetic simulation study, 37 pharmacokinetic studies on patients with end-stage kidney disease, and 32 case reports or case series) met inclusion criteria. Toxicokinetic or pharmacokinetic data were available on 334 patients (including 73 for atenolol, 54 for propranolol, and 17 for sotalol). For intermittent hemodialysis, atenolol, nadolol, practolol, and sotalol were assessed as dialyzable; acebutolol, bisoprolol, and metipranolol were assessed as moderately dialyzable; metoprolol and talinolol were considered slightly dialyzable; and betaxolol, carvedilol, labetalol, mepindolol, propranolol, and timolol were considered not dialyzable. Data were available for clinical analysis on 37 BAA poisoned patients (including 9 patients for atenolol, 9 for propranolol, and 9 for sotalol), and no reliable comparison between the ECTR cohort and historical controls treated with standard care alone could be performed. The EXTRIP workgroup recommends against using ECTR for patients severely poisoned with propranolol (strong recommendation, very low quality evidence). The workgroup offered no recommendation for ECTR in patients severely poisoned with atenolol or sotalol because of apparent balance of risks and benefits, except for impaired kidney function in which ECTR is suggested (weak recommendation, very low quality of evidence). Indications for ECTR in patients with impaired kidney function include refractory bradycardia and hypotension for atenolol or sotalol poisoning, and recurrent torsade de pointes for sotalol. Although other BAAs were considered dialyzable, clinical data were too limited to develop recommendations.
CONCLUSIONS
BAAs have different properties affecting their removal by ECTR. The EXTRIP workgroup assessed propranolol as non-dialyzable. Atenolol and sotalol were assessed as dialyzable in patients with kidney impairment, and the workgroup suggests ECTR in patients severely poisoned with these drugs when aforementioned indications are present.
Topics: Adrenergic beta-Antagonists; Consensus; Drug Overdose; Extracorporeal Membrane Oxygenation; Humans
PubMed: 34112223
DOI: 10.1186/s13054-021-03585-7 -
Archives of Razi Institute Feb 2022The current study was conducted to investigate the interaction between the central adrenergic and histaminergic systems and the broiler chick's feed intake. In the first...
The current study was conducted to investigate the interaction between the central adrenergic and histaminergic systems and the broiler chick's feed intake. In the first experiment, the intracerebroventricular (ICV) injection of solutions was conducted which included 10 nmol of prazosin (an α-receptor antagonist), 300 nmol of histamine, co-injection of prazosin and histamine. Experiments two to five were conducted similarly the same as the first experiment, in which chickens were ICV injected with 13 nmol of yohimbine (an α-receptor antagonist), 24 nmol of metoprolol (a β adrenergic receptor antagonist), 5 nmol of ICI 118,551 (a β adrenergic receptor antagonist), and 20 nmol of SR 59230R (a β adrenergic receptor antagonist). The injected solutions in the sixth experiment included 300 nmol of noradrenaline, 250 nmol of α-FMH (an alpha fluoromethyl histidine), noradrenaline, and α-FMH. Seventh to ninth experiments were similar to the sixth experiment, except that the chickens were ICV injected with 300 nmol of chlorpheniramine (a histamine H receptors antagonist), 82 nmol of famotidine (a histamine H receptors antagonist), and 300 nmol of thioperamide (a histamine H receptors antagonist), rather than α-FMH. Afterward, the cumulative food intake was measured 120 min after injection. Based on the obtained results, both histamine ICV injection and noradrenaline injection reduced food intake (<0.05). Moreover, co-injection of histamine and ICI 118,551 (<0.05), and co-injection of noradrenaline and Chlorpheniramine reduced food intake (<0.05). In addition, noradrenaline and Thioperamide co-injection improved hypophagic effect of noradrenaline in neonatal chicken (<0.05). These findings suggested the effect of interconnection between adrenergic and histaminergic systems, which may be mediated by H and H histaminergic and β adrenergic receptors, on the regulation of food intake in the neonatal broiler chicken.
Topics: Adrenergic Agents; Adrenergic Antagonists; Animals; Animals, Newborn; Appetite; Chickens; Chlorpheniramine; Feeding Behavior; Histamine; Norepinephrine; Prazosin; Receptors, Adrenergic; Receptors, Histamine
PubMed: 35891757
DOI: 10.22092/ARI.2021.354450.1638 -
International Braz J Urol : Official... 2021To describe the otorhinolaryngological adverse effects of the main drugs used in urological practice. (Review)
Review
PURPOSE
To describe the otorhinolaryngological adverse effects of the main drugs used in urological practice.
MATERIALS AND METHODS
A review of the scientific literature was performed using a combination of specific descriptors (side effect, adverse effect, scopolamine, sildenafil, tadalafil, vardenafil, oxybutynin, tolterodine, spironolactone, furosemide, hydrochlorothiazide, doxazosin, alfuzosin, terazosin, prazosin, tamsulosin, desmopressin) contained in publications until April 2020. Manuscripts written in English, Portuguese, and Spanish were manually selected from the title and abstract. The main drugs used in Urology were divided into five groups to describe their possible adverse effects: alpha-blockers, anticholinergics, diuretics, hormones, and phosphodiesterase inhibitors.
RESULTS
The main drugs used in Urology may cause several otorhinolaryngological adverse effects. Dizziness was most common, but dry mouth, rhinitis, nasal congestion, epistaxis, hearing loss, tinnitus, and rhinorrhea were also reported and varies among drug classes.
CONCLUSIONS
Most of the drugs used in urological practice have otorhinolaryngological adverse effects. Dizziness was most common, but dry mouth, rhinitis, nasal congestion, epistaxis, hearing loss, tinnitus, and rhinorrhea were also reported. Therefore, doctors must be aware of these adverse effects to improve adherence to the treatment and to minimize damage to the health of patients.
Topics: Adrenergic alpha-Antagonists; Doxazosin; Humans; Male; Pharmaceutical Preparations; Prazosin; Prostatic Hyperplasia; Tadalafil; Tamsulosin
PubMed: 33566468
DOI: 10.1590/S1677-5538.IBJU.2021.99.06 -
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 -
JACC. Heart Failure Nov 2018
Topics: Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Heart Failure; Humans
PubMed: 30316937
DOI: 10.1016/j.jchf.2018.07.013 -
Molecules (Basel, Switzerland) Jan 2021β-adrenergic antagonists (β-blockers) with at least one chiral center are an exceedingly important class of drugs used mostly to treat cardiovascular diseases. At... (Review)
Review
β-adrenergic antagonists (β-blockers) with at least one chiral center are an exceedingly important class of drugs used mostly to treat cardiovascular diseases. At least 70 β-blockers have been investigated in history. However, only a few β-blockers, e.g., timolol, are clinically marketed as an optically pure enantiomer. Therefore, the separation of racemates of β-blockers is essential both in the laboratory and industry. Many approaches have been explored to obtain the single enantiomeric β-blocker, including high performance liquid chromatography, supercritical fluid chromatography and simulated moving bed chromatography. In this article, a review is presented on different chromatographic methods applied for the enantioseparation of β-blockers, covering high performance liquid chromatography (HPLC), supercritical fluid chromatography (SFC) and simulated moving bed chromatography (SMB).
Topics: Adrenergic beta-Antagonists; Chromatography, High Pressure Liquid; Chromatography, Supercritical Fluid; Stereoisomerism
PubMed: 33477385
DOI: 10.3390/molecules26020468