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Current Neuropharmacology 2021New psychoactive substances (NPS) constitute a group of psychotropic substances, designed to mimic the effects of traditional substances like cannabis, cocaine, MDMA,...
New psychoactive substances (NPS) constitute a group of psychotropic substances, designed to mimic the effects of traditional substances like cannabis, cocaine, MDMA, khat, which was not regulated by the 1961 United Nations Convention on Narcotics or the 1971 United Nations Convention on Psychotropic Substances. Illegal laboratories responsible for their production regularly developed new substances and placed them on the market to replace the ones that have been banned; for this reason, during the last decade this class of substances has represented a great challenge for the public health and forensic toxicologists. The spectrum of side effects caused by the intake of these drugs of abuse is very wide since they act on different systems with various mechanisms of action. To date most studies have focused on the neurotoxic effects, very few works focus on cardiotoxicity. Specifically, both synthetic cannabinoids and synthetic cathinones appear to be involved in different cardiac events, including myocardial infarction and sudden cardiac death due to fatal arrhythmias. Synthetic cannabinoids and cathinones cardiotoxicity are mainly mediated through activation of the CB1 receptor present on cardiomyocyte and involved with reactive oxygen species production, ATP depletion and cell death. Concerns with the adrenergic over-stimulation induced by this class of substances and increasing oxidative stress are mainly reported. In this systematic review we aim to summarize the data from all the works analyzing the possible mechanisms through which synthetic cannabinoids and synthetic cathinones damage the myocardial tissue.
Topics: Alkaloids; Cannabinoids; Humans; Illicit Drugs; Psychotropic Drugs
PubMed: 33845747
DOI: 10.2174/1570159X19666210412101929 -
Iranian Journal of Kidney Diseases Jul 2020Carvedilol, the third generation of vasodilators; serves as the blocker of non-selective beta-adrenergic receptor and alpha1 adrenergic receptor. It could protect the... (Meta-Analysis)
Meta-Analysis
Carvedilol, the third generation of vasodilators; serves as the blocker of non-selective beta-adrenergic receptor and alpha1 adrenergic receptor. It could protect the cardiovascular system of patients receiving dialysis treatment. However, current clinical trials discussing the therapeutic benefit of carvedilol on patients receiving dialysis treatment remain inconsistent. Consequently, we decided to perform a meta-analysis to evaluate the clinical efficacy of carvedilol on patients receiving dialysis treatment. A search was conducted using EMBASE, Pubmed, Cochrane Central Register of Controlled Trials, Wanfang database, Chinese National Knowledge Infrastructure (CNKI), and VIP information database up to February 2020. We research publications (include English and Chinese language) that discuss the effects of carvedilol on cardiovascular events, all-cause mortality, hospitalizations or left ventricular ejection fraction (LVEF) in dialysis population. Our analysis included 4 randomized control trials and 2 observational studies. We discussed the therapeutical effects of carvedilol on all-cause mortality, cardiovascular events, hospitalizations, and LVEF of patients receiving dialysis treatment. Totally, this analysis reported 2998 hemodialysis (HD) patients. We found a significant association between carvedilol and reduced incidence of all-cause mortality, cardiovascular events and hospitalizations in HD patients. In addition, carvedilol significantly improves LVEF (n = 241; WMD = 6.95; 95% CI, 0.54 to 13.36; I2 = 90%) in HD population. Our systematic review and meta-analysis demonstrates that carvedilol is associated with a reduced incidence of cardiovascular events, all-cause mortality and hospitalizations in patients on HD. Besides; carvedilol significantly improves LVEF in HD population. Nevertheless, high-quality and well-powered evidence is still needed, so as to further confirm the impacts of carvedilol on HD patients.
Topics: Cardiovascular Diseases; Carvedilol; Humans; Observational Studies as Topic; Renal Dialysis; Stroke Volume; Ventricular Function, Left
PubMed: 32655020
DOI: No ID Found -
The Cochrane Database of Systematic... Feb 2021Transient tachypnea of the newborn is characterized by tachypnea and signs of respiratory distress. Transient tachypnea typically appears within the first two hours of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Transient tachypnea of the newborn is characterized by tachypnea and signs of respiratory distress. Transient tachypnea typically appears within the first two hours of life in term and late preterm newborns. Although transient tachypnea of the newborn is usually a self-limited condition, it is associated with wheezing syndromes in late childhood. The rationale for the use of salbutamol (albuterol) for transient tachypnea of the newborn is based on studies showing that β-agonists can accelerate the rate of alveolar fluid clearance. This review was originally published in 2016 and updated in 2020.
OBJECTIVES
To assess whether salbutamol compared to placebo, no treatment or any other drugs administered to treat transient tachypnea of the newborn, is effective and safe for infants born at 34 weeks' gestational age with this diagnosis.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL, 2020, Issue 4) in the Cochrane Library; PubMed (1996 to April 2020), Embase (1980 to April 2020); and CINAHL (1982 to April 2020). We applied no language restrictions. We searched the abstracts of the major congresses in the field (Perinatal Society of Australia New Zealand and Pediatric Academic Societies) from 2000 to 2020 and clinical trial registries.
SELECTION CRITERIA
Randomized controlled trials, quasi-randomized controlled trials and cluster trials comparing salbutamol versus placebo or no treatment or any other drugs administered to infants born at 34 weeks' gestational age or more and less than three days of age with transient tachypnea of the newborn.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology for data collection and analysis. The primary outcomes considered in this review were duration of oxygen therapy, need for continuous positive airway pressure and need for mechanical ventilation. We used the GRADE approach to assess the certainty of evidence.
MAIN RESULTS
Seven trials, which included 498 infants, met the inclusion criteria. All trials compared a nebulized dose of salbutamol with normal saline. Four studies used one single dose of salbutamol; in two studies, three to four doses were provided; in one study, additional doses were administered if needed. The certainty of the evidence was low for duration of hospital stay and very low for the other outcomes. Among the primary outcomes of this review, four trials (338 infants) reported the duration of oxygen therapy, (mean difference (MD) -19.24 hours, 95% confidence interval (CI) -23.76 to -14.72); one trial (46 infants) reported the need for continuous positive airway pressure (risk ratio (RR) 0.73, 95% CI 0.38 to 1.39; risk difference (RD) -0.15, 95% CI -0.45 to 0.16), and three trials (254 infants) reported the need for mechanical ventilation (RR 0.60, 95% CI 0.13 to 2.86; RD -0.01, 95% CI -0.05 to 0.03). Both duration of hospital stay (4 trials; 338 infants) and duration of respiratory support (2 trials, 228 infants) were shorter in the salbutamol group (MD -1.48, 95% CI -1.8 to -1.16; MD -9.24, 95% CI -14.24 to -4.23, respectively). One trial (80 infants) reported duration of mechanical ventilation and pneumothorax but data could not be extracted due to the reporting of these outcomes (type of units of effect measure and unclear number of events, respectively). Five trials are ongoing.
AUTHORS' CONCLUSIONS
There was limited evidence to establish the benefits and harms of salbutamol in the management of transient tachypnea of the newborn. We are uncertain whether salbutamol administration reduces the duration of oxygen therapy, duration of tachypnea, need for continuous positive airway pressure and for mechanical ventilation. Salbutamol may slightly reduce hospital stay. Five trials are ongoing. Given the limited and low certainty of the evidence available, we could not determine whether salbutamol was safe or effective for the treatment of transient tachypnea of the newborn.
Topics: Adrenergic beta-2 Receptor Agonists; Albuterol; Continuous Positive Airway Pressure; Humans; Infant, Newborn; Intermittent Positive-Pressure Ventilation; Length of Stay; Nebulizers and Vaporizers; Oxygen Inhalation Therapy; Randomized Controlled Trials as Topic; Time Factors; Transient Tachypnea of the Newborn
PubMed: 33543473
DOI: 10.1002/14651858.CD011878.pub3 -
Minerva Urologica E Nefrologica = the... Dec 2020The pathophysiology and management of male patients with lower urinary tract symptoms (LUTS) is still a matter of debate. In the past few years, the urothelium and the...
INTRODUCTION
The pathophysiology and management of male patients with lower urinary tract symptoms (LUTS) is still a matter of debate. In the past few years, the urothelium and the urinary microbiota represented important areas of research to improve the understanding and management of these patients. Aim of the present review was to summarize the available data on the urothelium and the microbiota related to male LUTS.
EVIDENCE ACQUISITION
A National Center for Biotechnology Information (NCBI) PubMed search for relevant articles published between January 2000 and December 2019 was performed using the medical subjects heading "urothelium," "microbioma," "microbiota," "urobioma," "urobiota," "benign prostatic hyperplasia," "benign prostatic enlargement," "lower urinary tract symptoms," "lower urinary tract dysfunction," "men," "male," "overactive bladder," "receptors." Exclusion criteria included: animal studies and studies on muscarinic and adrenergic pathways.
EVIDENCE SYNTHESIS
The urothelium has been recently evaluated in humans to evaluate new possible markers and pathways. New possible targets for the treatment of male LUTS include the neural growth factor, the cannabinoid, the vanilloid and the ATP pathways. However, studies in humans are still needed to elucidate the exact role of these pathways in the management of male patients with LUTS. The available evidence on the urinary microbioma in male is poor. Standing to the available, urinary microbioma is evident in healthy urine in males. Moreover, the urinary microbioma varies depending on the method of collection, sexually transmitted disease status, inflammation and urinary symptoms. A possible role of probiotics in the management of LUTS in women has been proposed and may have a role in male patients as well.
CONCLUSIONS
The urothelium and the urinary microbiota are still poorly studied in men with LUTS. Most of the evidence and the hypothesis on the relationship between urothelium/urinary microbiota and LUTS comes from animal/in-vitro evidence while clinical trials are lacking. These pathways seem interesting even in LUTS pathogenesis in men but their possible role as a new therapeutic target is still an open debate.
Topics: Animals; Humans; Lower Urinary Tract Symptoms; Male; Prostatic Hyperplasia; Urinary Bladder, Overactive; Urothelium
PubMed: 32550631
DOI: 10.23736/S0393-2249.20.03762-5 -
The International Journal of... Jul 2021Hyponatremia associated with antipsychotic drugs is a rare but potentially life-threatening adverse drug reaction; the underlying pharmacological mechanism has not yet...
Hyponatremia Following Antipsychotic Treatment: In Silico Pharmacodynamics Analysis of Spontaneous Reports From the US Food and Drug Administration Adverse Event Reporting System Database and an Updated Systematic Review.
BACKGROUND
Hyponatremia associated with antipsychotic drugs is a rare but potentially life-threatening adverse drug reaction; the underlying pharmacological mechanism has not yet been explained.
METHODS
We investigated the relationship between pharmacological targets of antipsychotic drugs and the occurrence of hyponatremia by conducting a nested case-control study using the Food and Drug Administration Adverse Event Reporting System database. Multiple logistic regression was used to determine the associations between antipsychotics receptor occupancy and hyponatremia. We also performed a systematic review of clinical studies on this association.
RESULTS
Of 139 816 reports involving at least 1 antipsychotic, 1.1% reported hyponatremia. Olanzapine was the most frequently suspected drug (27%). A significant positive association was found between dopamine D3, D4, and hyponatremia, while adrenergic α 1, serotonin 5-HT1A, and 5-HT2A receptor occupancies were negatively associated. A multivariable stepwise regression model showed that dopamine D3 (adj. odds ratio = 1.21; 95% CI = 1.09-1.34; P < .05) predicted the risk for hyponatremia (P < .05), while serotonin 5-HT2A occupancy (Adj. odds ratio = 0.78; 95% CI = 0.68-0.90; P < .01) exhibited a protective effect against hyponatremia. Among the 11 studies included in the systematic review, incidence rates of hyponatremia diverged between 0.003% and 86%, whereas the odds of developing hyponatremia from effect studies ranged between 0.83 and 3.47.
CONCLUSIONS
Antipsychotic drugs having a combined modest occupancy for D3 and 5-HT2A receptors and higher levels of D3 receptor occupancy correspond to different degrees of risk for hyponatremia. Based on the few, relatively large-scale available studies, atypical antipsychotics have a more attenuated risk profile for hyponatremia.
Topics: Antipsychotic Agents; Databases, Factual; Drug-Related Side Effects and Adverse Reactions; Humans; Hyponatremia; Pharmacovigilance; United States; United States Food and Drug Administration
PubMed: 33575781
DOI: 10.1093/ijnp/pyab005 -
Frontiers in Pharmacology 2020Pain is considered an unpleasant sensory and emotional experience, being considered as one of the most important causes of human suffering. Computational chemistry...
INTRODUCTION
Pain is considered an unpleasant sensory and emotional experience, being considered as one of the most important causes of human suffering. Computational chemistry associated with bioinformatics has stood out in the process of developing new drugs, through natural products, to manage this condition.
OBJECTIVE
To analyze, through literature data, recent molecular coupling studies on the antinociceptive activity of essential oils and monoterpenes.
DATA SOURCE
Systematic search of the literature considering the years of publications between 2005 and December 2019, in the electronic databases PubMed and .
ELIGIBILITY CRITERIA
Were considered as criteria of 1) Biological activity: non-clinical effects of an OE and/or monoterpenes on antinociceptive activity based on animal models and analysis, 2) studies with plant material: chemically characterized essential oils and/or their constituents isolated, 3) clinical and non-clinical studies with analysis to assess antinociceptive activity, 4) articles published in English. Exclusion criteria were literature review, report or case series, meta-analysis, theses, dissertations, and book chapter.
RESULTS
Of 16,006 articles, 16 articles fulfilled all the criteria. All selected studies were non-clinical. The most prominent plant families used were Asteraceae, Euphorbiaceae, Verbenaceae, Lamiaceae, and Lauraceae. Among the phytochemicals studied were α-Terpineol, 3-(5-substituted-1,3,4-oxadiazol-2-yl)-N'-[2-oxo-1,2-dihydro-3H-indol-3-ylidene] propane hydrazide, β-cyclodextrin complexed with citronellal, (-)-α-bisabolol, β-cyclodextrin complexed with farnesol, and p-Cymene. The softwares used for docking studies were Molegro Virtual Docker, SybylX, Vlife MDS, AutoDock Vina, Hex Protein Docking, and AutoDock 4.2 in PyRx 0.9. The molecular targets/complexes used were Nitric Oxide Synthase, COX-2, GluR2-S1S2, TRPV1, β-CD complex, CaV, CaV, CaV, and CaV, 5-HT receptor, delta receptor, kappa receptor, and MU (μ) receptor, alpha adrenergic, opioid, and serotonergic receptors, muscarinic receptors and GABA opioid and serotonin receptors, 5-HT and M receptors. Many of the covered studies used molecular coupling to investigate the mechanism of action of various compounds, as well as molecular dynamics to investigate the stability of protein-ligand complexes.
CONCLUSIONS
The studies revealed that through the advancement of more robust computational techniques that complement the experimental studies, they may allow some notes on the identification of a new candidate molecule for therapeutic use.
PubMed: 32547391
DOI: 10.3389/fphar.2020.00777 -
Cureus Jul 2022The renin-angiotensin-aldosterone system (RAAS) plays a vital role in cardiovascular homeostasis by regulating blood pressure, salt, and water balance. The kidneys... (Review)
Review
Effects of Renin-Angiotensin-Aldosterone System Inhibition on Left Ventricular Hypertrophy, Diastolic Function, and Functional Status in Patients With Hypertrophic Cardiomyopathy: A Systematic Review.
The renin-angiotensin-aldosterone system (RAAS) plays a vital role in cardiovascular homeostasis by regulating blood pressure, salt, and water balance. The kidneys produce renin which converts angiotensinogen to angiotensin-1 (AT-I) and angiotensin-converting enzyme (ACE) to angiotensin-II (AT-II). AT-II binds to receptors in the adrenal cortex to release aldosterone. AT-II and aldosterone promote water and salt retention, vascular tone, and myocardial contractility. These physiological changes raise blood pressure and circulation. Reduced renal perfusion pressure sensed by baroreceptors and the sympathetic nervous system's β-adrenergic receptors trigger renin release and RAAS activation. RAAS restores hemodynamic stability in pathological states associated with low perfusion. This adaptive response is important for restoring perfusion and hemodynamic stability, but prolonged RAAS activation has deleterious effects on the cardiovascular system. Long-term mineralocorticoid exposure has been linked to left ventricular hypertrophy (LVH) and remodeling. AT-II activates fibroblasts and cardiac myocytes to promote cardiac remodeling. Blocking RAAS can eliminate the long-term negative effects of RAAS activation. Direct renin inhibitors, ACE inhibitors, angiotensin receptor blockers, and aldosterone antagonists are RAAS blockers. RAAS blockade improves mortality and hospitalization in systolic heart failure and acute myocardial infarction. RAAS blockade has not demonstrated the same benefits in other cardiac populations, such as those with preserved ejection fraction. Hypertrophic cardiomyopathy (HCM) causes LVH and asymmetric septal hypertrophy. When the outflow tract gradient exceeds 30 mmHg and is associated with septal hypertrophy, it is known as obstructive HCM. Dyspnea on exertion, syncope, and exertional angina are symptoms of HCM. RAAS activation worsens LVH by increasing blood pressure and by directly affecting cardiac myocytes with AT-II and aldosterone. RAAS blockade reverses myocardial fibrosis and slows HCM progression in animal models. We performed a meta-analysis of randomized clinical trials to further investigate the potential benefit of RAAS blockade in HCM patients. Although our findings included significant results for some of the RAAS blockade agents, these findings were not consistent throughout all the studies. Mavacamten, one of the newest treatments, has shown promising outcomes.
PubMed: 35949750
DOI: 10.7759/cureus.26642 -
Medicine Feb 2021Vibegron is a new β3-adrenergic receptor agonist which has been demonstrated for the treatment of overactive bladder (OAB). We carried out meta-analysis to evaluate the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vibegron is a new β3-adrenergic receptor agonist which has been demonstrated for the treatment of overactive bladder (OAB). We carried out meta-analysis to evaluate the efficiency of vibegron vs antimuscarinic monotherapy for treating OAB.
METHODS
Randomized controlled trials (RCTs) of Vibegron vs antimuscarinic monotherapy for OAB were searched systematically by using EMBASE, MEDLINE, and the Cochrane Controlled Trials Register. The RevMan version 5.3.0. was used to analysis the data.
RESULTS
Three RCTs involving a total of 1751 patients were studied in the Systematic review and Meta-analysis. Efficacy end points: the mean number of micturitions episodes/d (P = .16); the mean number of urgency episodes/d (P = .05); mean number of urgency incontinence episodes/d (P = .11) and mean number of incontinence episodes/d (P = .14) indicated that vibegron and antimuscarinic had no significant differences in terms of OAB treatment. Mean volume voided/micturition showed a distinct difference in the two groups (P = .009). With regard to dry mouth and drug related treatment-emergent adverse event (TEAE), vibegron showed better tolerance than antimuscarinic. Serious adverse event (SAE) and discontinuations due to adverse event (AE) did not show a significant difference between the two groups.
CONCLUSIONS
The therapeutic effect of vibegron is similar to that of antimuscarinic, but vibegron does not increase the risk of AE.
Topics: Adrenergic beta-3 Receptor Agonists; Humans; Muscarinic Antagonists; Pyrimidinones; Pyrrolidines; Randomized Controlled Trials as Topic; Urinary Bladder, Overactive
PubMed: 33592817
DOI: 10.1097/MD.0000000000023171 -
Medicine Aug 2021Dexmedetomidine (Dexm), a selective alpha-2 adrenoceptor agonist, and dexamethasone (Dexa), a very potent and highly selective glucocorticoid, have both been proven... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dexmedetomidine (Dexm), a selective alpha-2 adrenoceptor agonist, and dexamethasone (Dexa), a very potent and highly selective glucocorticoid, have both been proven effectively to prolong the duration of local anesthetics (LA) in regional anesthesia. However, data comparing the efficacy of Dexm and Dexa as perineural adjuvants are inconsistent. Therefore, this systematic review and meta-analysis of randomized and quasi-randomized controlled trials (RCTs) was conducted to compare the effects of Dexm and Dexa when used as LA adjuvants on peripheral nerve block (PNB).
METHODS
We systematically searched PubMed, Cochrane Library, EMBASE, Web of Science, and ScienceDirect databases up to October, 2020. The primary outcome was the duration of analgesia. Secondary outcomes included incidence of rescue analgesia, cumulative opioid consumption, time required for onset of sensory and motor blockades, duration of sensory and motor blockades, incidence of postoperative nausea and vomiting (PONV), and side effect-associated outcomes (e.g., bradycardia, sedation, hypotension, rates of infection, and neurological complications). The study was registered on PROSPERO, number CRD42020188796.
RESULTS
After screening of full-text relevant articles, 13 RCTs that met the inclusion criteria were retrieved for this systematic review. It was revealed that perineural Dexm provided equivalent analgesic duration to perineural Dexa. Besides, the intake of Dexm increased the incidence of rescue analgesia in limbs surgery, as well as the cumulative opioid consumption, and decreased the time required for onset of sensory and motor blockades for long-acting LA (all P < .05). Other analysis revealed insignificant difference between the 2 groups in terms of the incidence of PONV (P > .05). Additionally, 2 studies demonstrated that Dexm possesses more sedative properties than Dexa (P < .05).
CONCLUSIONS
This meta-analysis indicated that the analgesic duration of Dexm and Dexa as LA adjuvants in PNB is the same. Meanwhile, the effects of perineural Dexm and Dexa on some secondary outcomes, including the incidence of rescue analgesia, cumulative opioid consumption, and time required for onset of sensory and motor blockades, are associated with the surgical site and type of LA.
Topics: Adjuvants, Anesthesia; Adrenergic alpha-2 Receptor Agonists; Anesthesia, Local; Dexamethasone; Dexmedetomidine; Glucocorticoids; Humans; Nerve Block; Peripheral Nerves; Randomized Controlled Trials as Topic
PubMed: 34449500
DOI: 10.1097/MD.0000000000027064 -
Neuroscience and Biobehavioral Reviews Sep 2021Activation of the HPA-axis and SNS are widely accepted to link chronic stress with elevated levels of peripheral pro-inflammatory markers in blood. Yet, empirical...
Glucocorticoid resistance and β2-adrenergic receptor signaling pathways promote peripheral pro-inflammatory conditions associated with chronic psychological stress: A systematic review across species.
Activation of the HPA-axis and SNS are widely accepted to link chronic stress with elevated levels of peripheral pro-inflammatory markers in blood. Yet, empirical evidence showing that peripheral levels of glucocorticoids and/or catecholamines mediate this effect is equivocal. Recent attention has turned to the possibility that cellular sensitivity to these ligands may contribute to inflammatory mediators that accompany chronic stress. We review current evidence for the association of chronic stress with glucocorticoid receptor (GR) and β-adrenergic receptor (β-AR) signaling sensitivity. Across 15 mouse, 7 primate, and 19 human studies, we found that chronic stress reliably associates with downregulation in cellular GR sensitivity, alterations in intracellular β-AR signaling, and upregulation in pro-inflammatory biomarkers in peripheral blood. We also present evidence that alterations in GR and β-AR signaling may be specific to myeloid progenitor cells such that stress-related signaling promotes release of cells that are inherently less sensitive to glucocorticoids and differentially sensitive to catecholamines. Our findings have broad implications for understanding mechanisms by which chronic stress may contribute to pro-inflammatory phenotypes.
Topics: Animals; Glucocorticoids; Hypothalamo-Hypophyseal System; Mice; Pituitary-Adrenal System; Receptors, Adrenergic; Receptors, Glucocorticoid; Stress, Psychological
PubMed: 34116126
DOI: 10.1016/j.neubiorev.2021.06.013