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Psychiatry Research Nov 2022Algorithms for posttraumatic stress disorder were published by this team in 1999 and 2011. Developments since then warrant revision. New studies and review articles from... (Review)
Review
Algorithms for posttraumatic stress disorder were published by this team in 1999 and 2011. Developments since then warrant revision. New studies and review articles from January 2011 to November 2021 were identified via PubMed and analyzed for evidence supporting changes. Following consideration of variations required by special patient populations, treatment of sleep impairments remains as the first recommended step. Nightmares and non-nightmare disturbed awakenings are best addressed with the anti-adrenergic agent prazosin, with doxazosin and clonidine as alternatives. First choices for difficulty initiating sleep include hydroxyzine and trazodone. If significant non-sleep PTSD symptoms remain, an SSRI should be tried, followed by a second SSRI or venlafaxine as a third step. Second generation antipsychotics can be considered, particularly for SSRI augmentation when PTSD-associated psychotic symptoms are present, with the caveat that positive evidence is limited and side effects are considerable. Anti-adrenergic agents can also be considered for general PTSD symptoms if not already tried, though evidence for daytime use lags that available for sleep. Regarding other pharmacological and procedural options, e.g., transcranial magnetic stimulation, cannabinoids, ketamine, psychedelics, and stellate ganglion block, evidence does not yet support firm inclusion in the algorithm. An interactive version of this work can be found at www.psychopharm.mobi.
Topics: Humans; Stress Disorders, Post-Traumatic; Psychopharmacology; Prazosin; Dreams; Sleep Wake Disorders; Sleep Initiation and Maintenance Disorders; Adrenergic Antagonists
PubMed: 36162349
DOI: 10.1016/j.psychres.2022.114840 -
Profiles of Drug Substances,... 2017Clenbuterol (Broncodil and trade) is a direct-acting sympathomimetic agent with mainly beta-adrenergic activity and a selective action on β2 receptors (a β2 agonist)....
Clenbuterol (Broncodil and trade) is a direct-acting sympathomimetic agent with mainly beta-adrenergic activity and a selective action on β2 receptors (a β2 agonist). It has properties similar to those of salbutamol. It is used as a bronchodilator in the management of reversible airways obstruction, as in asthma and in certain patients with chronic obstructive pulmonary disease. The uses, applications, and the synthetic pathways of this drug are outlined. Physical characteristics including: ionization constant, solubility, X-ray powder diffraction pattern, thermal methods of analysis, UV spectrum, IR spectrum, mass spectrum are all produced. This profile also includes the monograph of British Pharmacopoeia, together with several reported analytical methods including spectrophotometric, electrochemical, chromatographic, immunochemical methods, and capillary electrophoretic methods. The stability, the pharmacokinetic behavior, and the pharmacology of the drug are also provided.
Topics: Adrenergic beta-Agonists; Animals; Asthma; Bronchodilator Agents; Clenbuterol; Humans; Molecular Structure; Pulmonary Disease, Chronic Obstructive; Sympathomimetics
PubMed: 28431781
DOI: 10.1016/bs.podrm.2017.02.002 -
Critical Care Medicine Sep 2022
Topics: Adrenergic Agents; Adrenergic beta-Antagonists
PubMed: 35984059
DOI: 10.1097/CCM.0000000000005524 -
Angewandte Chemie (International Ed. in... Feb 2021Adrenoceptors are ubiquitous and mediate important autonomic functions as well as modulating arousal, cognition, and pain on a central level. Understanding these...
Adrenoceptors are ubiquitous and mediate important autonomic functions as well as modulating arousal, cognition, and pain on a central level. Understanding these physiological processes and their underlying neural circuits requires manipulating adrenergic neurotransmission with high spatio-temporal precision. Here we present a first generation of photochromic ligands (adrenoswitches) obtained via azologization of a class of cyclic amidines related to the known ligand clonidine. Their pharmacology, photochromism, bioavailability, and lack of toxicity allow for broad biological applications, as demonstrated by controlling locomotion in zebrafish and pupillary responses in mice.
Topics: Adrenergic Agents; Animals; Chromogenic Compounds; Ligands; Mice; Mice, Nude; Molecular Structure; Receptors, Adrenergic; Zebrafish
PubMed: 33103317
DOI: 10.1002/anie.202010553 -
Journal of Neurochemistry May 2023Alzheimer's disease (AD) is a progressive neurodegenerative disease originating partly from amyloid β protein-induced synaptic failure. As damaging of noradrenergic... (Review)
Review
Alzheimer's disease (AD) is a progressive neurodegenerative disease originating partly from amyloid β protein-induced synaptic failure. As damaging of noradrenergic neurons in the locus coeruleus (LC) occurs at the prodromal stage of AD, activation of adrenergic receptors could serve as the first line of defense against the onset of the disease. Activation of β -ARs strengthens long-term potentiation (LTP) and synaptic activity, thus improving learning and memory. Physical stimulation of animals exposed to an enriched environment (EE) leads to the activation of β -ARs and prevents synaptic dysfunction. EE also suppresses neuroinflammation, suggesting that β -AR agonists may play a neuroprotective role. The β -AR agonists used for respiratory diseases have been shown to have an anti-inflammatory effect. Epidemiological studies further support the beneficial effects of β -AR agonists on several neurodegenerative diseases. Thus, I propose that β -AR agonists may provide therapeutic value in combination with novel treatments for AD.
Topics: Animals; Alzheimer Disease; Adrenergic Agents; Amyloid beta-Peptides; Microglia; Neurodegenerative Diseases
PubMed: 36799441
DOI: 10.1111/jnc.15782 -
Drug Metabolism Reviews 1997Summaries of the interactions caused by altering adrenoreceptor activity in conjunction with the administration of selected hepatotoxicants are provided in Table 2 and... (Review)
Review
Summaries of the interactions caused by altering adrenoreceptor activity in conjunction with the administration of selected hepatotoxicants are provided in Table 2 and Fig. 1. These hepatotoxicants can be divided into two groups, one whose toxicity is increased by adrenergic agonist drugs (group I) and the other whose toxicity is decreased by adrenergic antagonists (group II). Group I includes carbon tetrachloride, acetaminophen, and methylphenidate. Perhaps the most remarkable aspect these chemicals have in common is the striking potentiation that occurs with cotreatment with certain adrenergic agonist drugs. For each of these, cotreatment with the appropriate adrenergic agent can result in massive hepatocellular necrosis from an otherwise nontoxic dose. In terms of the specific adrenoreceptors involved and mechanisms of potentiation, however, they have little in common. Potentiation of carbon tetrachloride hepatotoxicity appears to be mediated by alpha(2)-adrenoceptor stimulation, acetaminophen is potentiated by alpha(1)-adrenoreceptor agonists, and methylphenidate responds to beta(2)-adrenoreceptor stimulation. Studies of the potentiation of carbon tetrachloride and acetaminophen agree that the timing of adrenergic stimulation relative to the hepatotoxicant dose is critically important to the interaction but markedly different for these two toxicants. Acetaminophen was potentiated only when the adrenergic drug was administered as a 3-h pretreatment. This is apparently a consequence of a mechanism of potentiation that involves adrenergic depression of hepatic glutathione content and a requirement that peak effects on glutathione of both the adrenergic agent and acetaminophen be coincident. The mechanism of potentiation of carbon tetrachloride hepatotoxicity is uncertain but clearly does not involve hepatic glutathione content. In contrast to acetaminophen, adrenergic effects must occur within a time window a few hours after the carbon tetrachloride dose for potentiation to occur. The importance of dose timing has not been evaluated for adrenergic potentiation of methylphenidate hepatotoxicity, but it is clear that this interaction is based on yet a third mechanism. While only three hepatotoxicants of the group I type have been examined in detail, the diversity of receptor types and mechanisms involved suggest that this phenomenon may be relevant for a wide variety of hepatotoxic drugs and chemicals. This interaction is also of interest because factors or events that lead to increased adrenergic stimulation are common in everyday life. Most over-the-counter cold and allergy preparations contain sympathomimetic drugs, and many prescription drugs produce adrenergic effects as either an extension of the intended therapeutic effect or as a side effect. Stress and some disease states can also lead to significant increases in peripheral adrenergic activity, creating the potential for increased susceptibility to hepatic injury from exposure to certain drugs or chemicals. Cocaine and bromobenzene represent group II, chemicals whose hepatotoxicity is diminished by cotreatment with adrenergic antagonist drugs. In the case of cocaine, adrenergic antagonist cotreatment was capable of reducing serum alanine aminotransferase activities by approximately 50%. For bromobenzene, the protection afforded by adrenergic antagonist cotreatment was more profound, with minimal hepatic lesions resulting from doses of bromobenzene that otherwise produced lethal hepatic necrosis. For the chemicals in group II, experimental observations are consistent with a phenomenon in which adrenergic potentiation of toxicity is supplied by the hepatotoxicant itself. Both cocaine and bromobenzene, in hepatotoxic doses increase endogenous catecholamine levels. When the effects of the elevated catecholamines are removed with the appropriate adrenergic antagonist, much lower toxicity (presumably due only to the direct hepatotoxic effects of the drug or chemical) is obse
Topics: Adrenergic alpha-Agonists; Adrenergic alpha-Antagonists; Adrenergic beta-Agonists; Animals; Chemical and Drug Induced Liver Injury; Drug Synergism; Receptors, Adrenergic
PubMed: 9187524
DOI: 10.3109/03602539709037587 -
Science China. Life Sciences May 2023Rapid over-activation of β-adrenergic receptors (β-AR) following acute stress initiates cardiac inflammation and injury by activating interleukin-18 (IL-18), however,...
Rapid over-activation of β-adrenergic receptors (β-AR) following acute stress initiates cardiac inflammation and injury by activating interleukin-18 (IL-18), however, the process of inflammation cascades has not been fully illustrated. The present study aimed to determine the mechanisms of cardiac inflammatory amplification following acute sympathetic activation. With bioinformatics analysis, galectin-3 was identified as a potential key downstream effector of β-AR and IL-18 activation. The serum level of galectin-3 was positively correlated with norepinephrine or IL-18 in patients with chest pain. In the heart of mice treated with β-AR agonist isoproterenol (ISO, 5 mg kg), galectin-3 expression was upregulated markedly later than IL-18 activation, and Nlrp3 and Il18 mice did not show ISO-induced galectin-3 upregulation. It was further revealed that cardiomyocyte-derived IL-18 induced galectin-3 expression in macrophages following ISO treatment. Moreover, galectin-3 deficiency suppressed ISO-induced cardiac inflammation and fibrosis without blocking ISO-induced IL-18 increase. Treatment with a galectin-3 inhibitor, but not a β-blocker, one day after ISO treatment effectively attenuated cardiac inflammation and injury. In conclusion, galectin-3 is upregulated to exaggerate cardiac inflammation and injury following acute β-AR activation, a galectin-3 inhibitor effectively blocks cardiac injury one day after β-AR insult.
Topics: Animals; Mice; Interleukin-18; Galectin 3; Adrenergic Agents; Myocytes, Cardiac; Receptors, Adrenergic, beta; Arrhythmias, Cardiac; Fibrosis; Inflammation
PubMed: 36449214
DOI: 10.1007/s11427-022-2189-x -
The Journal of Experimental Biology Mar 2018The enormous plasticity of adipose tissues, to rapidly adapt to altered physiological states of energy demand, is under neuronal and endocrine control. In energy... (Review)
Review
The enormous plasticity of adipose tissues, to rapidly adapt to altered physiological states of energy demand, is under neuronal and endocrine control. In energy balance, lipolysis of triacylglycerols and re-esterification of free fatty acids are opposing processes operating in parallel at identical rates, thus allowing a more dynamic transition from anabolism to catabolism, and vice versa. In response to alterations in the state of energy balance, one of the two processes predominates, enabling the efficient mobilization or storage of energy in a negative or positive energy balance, respectively. The release of noradrenaline from the sympathetic nervous system activates lipolysis in a depot-specific manner by initiating the canonical adrenergic receptor-G-protein-adenylyl cyclase-cyclic adenosine monophosphate-protein kinase A pathway, targeting proteins of the lipolytic machinery associated with the interface of the lipid droplets. In brown and brite adipocytes, lipolysis stimulated by this signaling pathway is a prerequisite for the activation of non-shivering thermogenesis. Free fatty acids released by lipolysis are direct activators of uncoupling protein 1-mediated leak respiration. Thus, pro- and anti-lipolytic mediators are bona fide modulators of thermogenesis in brown and brite adipocytes. In this Review, we discuss adrenergic and non-adrenergic mechanisms controlling lipolysis and thermogenesis and provide a comprehensive overview of pro- and anti-lipolytic mediators.
Topics: Adipose Tissue; Adrenergic Agents; Adrenergic Antagonists; Lipolysis; Thermogenesis
PubMed: 29514884
DOI: 10.1242/jeb.165381 -
The Pharmacogenomics Journal Apr 2021The emergence of genomic data in biobanks and health systems offers new ways to derive medically important phenotypes, including acute phenotypes occurring during...
The emergence of genomic data in biobanks and health systems offers new ways to derive medically important phenotypes, including acute phenotypes occurring during inpatient clinical care. Here we study the genetic underpinnings of the rapid response to phenylephrine, an α1-adrenergic receptor agonist commonly used to treat hypotension during anesthesia and surgery. We quantified this response by extracting blood pressure (BP) measurements 5 min before and after the administration of phenylephrine. Based on this derived phenotype, we show that systematic differences exist between self-reported ancestry groups: European-Americans (EA; n = 1387) have a significantly higher systolic response to phenylephrine than African-Americans (AA; n = 1217) and Hispanic/Latinos (HA; n = 1713) (31.3% increase, p value < 6e-08 and 22.9% increase, p value < 5e-05 respectively), after adjusting for genetic ancestry, demographics, and relevant clinical covariates. We performed a genome-wide association study to investigate genetic factors underlying individual differences in this derived phenotype. We discovered genome-wide significant association signals in loci and genes previously associated with BP measured in ambulatory settings, and a general enrichment of association in these genes. Finally, we discovered two low frequency variants, present at ~1% in EAs and AAs, respectively, where patients carrying one copy of these variants show no phenylephrine response. This work demonstrates our ability to derive a quantitative phenotype suited for comparative statistics and genome-wide association studies from dense clinical and physiological measures captured for managing patients during surgery. We identify genetic variants underlying non response to phenylephrine, with implications for preemptive pharmacogenomic screening to improve safety during surgery.
Topics: Adrenergic Agents; Black or African American; Blood Pressure; Female; Genome-Wide Association Study; Genomics; Humans; Male; Middle Aged; Perioperative Period; Phenotype; Phenylephrine; Polymorphism, Single Nucleotide; White People
PubMed: 33168928
DOI: 10.1038/s41397-020-00194-5 -
CNS & Neurological Disorders Drug... 2016The adrenergic system has an important role in normal central nervous system function as well as in brain disease. The locus coeruleus, the main source of norepinephrine... (Review)
Review
The adrenergic system has an important role in normal central nervous system function as well as in brain disease. The locus coeruleus, the main source of norepinephrine in brain, is involved in the regulation of learning and memory, reinforcement of sleep-wake cycle and synaptic plasticity. In Alzheimer's disease, locus coeruleus degeneration is observed early in the course of the disease, years before the onset of clinical cognitive signs, with neurofibrillary detected at the stage of mild cognitive impairment, preceding amyloid deposition. Thus, in the last years, a great interest has grown in evaluating the possibility of central adrenergic system modulation as a therapeutic tool in Alzheimer's disease. However, evidences do not show univocal results, with some studies suggesting that adrenergic stimulation might be beneficial in Alzheimer's Disease and some others favoring adrenergic blockade. In this review, we summarize data from both hypothesis and describe the pathophysiological role of the adrenergic system in neurodegeneration.
Topics: Adrenergic Agents; Alzheimer Disease; Animals; Brain; Cognitive Dysfunction; Humans; Nootropic Agents; Receptors, Adrenergic
PubMed: 27189470
DOI: 10.2174/1871527315666160518123201