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Journal of Veterinary Internal Medicine 2023Erroneous thyroid function test results can occur because of drugs that alter thyroid hormone physiology in one or more aspects, including synthesis, secretion,... (Review)
Review
Erroneous thyroid function test results can occur because of drugs that alter thyroid hormone physiology in one or more aspects, including synthesis, secretion, distribution, and metabolism. Research since publication of the last review in the Journal of Veterinary Internal Medicine (JVIM) 20 years ago has evaluated the effects of amiodarone, zonisamide, inhalant anesthetics, clomipramine, trilostane, and toceranib on thyroid function tests in the dog. In addition, recent work on the effects of glucocorticoids, sulfonamides, phenobarbital, and nonsteroidal anti-inflammatory drugs will be reviewed. Awareness of these effects is necessary to avoid misdiagnosis of hypothyroidism and unnecessary treatment.
Topics: Dogs; Animals; Thyroid Function Tests; Hypothyroidism; Thyroid Hormones; Amiodarone; Anti-Arrhythmia Agents; Dog Diseases
PubMed: 37498128
DOI: 10.1111/jvim.16823 -
Intensive Care Medicine Nov 2023Acute onset supraventricular arrhythmias can contribute to haemodynamic compromise in septic shock. Both amiodarone and propafenone are available interventions, but... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Acute onset supraventricular arrhythmias can contribute to haemodynamic compromise in septic shock. Both amiodarone and propafenone are available interventions, but their clinical effects have not yet been directly compared.
METHODS
In this two-centre, prospective controlled parallel group double blind trial we recruited 209 septic shock patients with new-onset arrhythmia and a left ventricular ejection fraction above 35%. The patients were randomised in a 1:1 ratio to receive either intravenous propafenone (70 mg bolus followed by 400-840 mg/24 h) or amiodarone (300 mg bolus followed by 600-1800 mg/24 h). The primary outcomes were the proportion of patients who had sinus rhythm 24 h after the start of the infusion, time to restoration of the first sinus rhythm and the proportion of patients with arrhythmia recurrence.
RESULTS
Out of 209 randomized patients, 200 (96%) received the study drug. After 24 h, 77 (72.8%) and 71 (67.3%) were in sinus rhythm (p = 0.4), restored after a median of 3.7 h (95% CI 2.3-6.8) and 7.3 h (95% CI 5-11), p = 0.02, with propafenone and amiodarone, respectively. The arrhythmia recurred in 54 (52%) patients treated with propafenone and in 80 (76%) with amiodarone, p < 0.001. Patients with a dilated left atrium had better rhythm control with amiodarone (6.4 h (95% CI 3.5; 14.1) until cardioversion vs 18 h (95% CI 2.8; 24.7) in propafenone, p = 0.05).
CONCLUSION
Propafenone does not provide better rhythm control at 24 h yet offers faster cardioversion with fewer arrhythmia recurrences than with amiodarone, especially in patients with a non-dilated left atrium. No differences between propafenone and amiodarone on the prespecified short- and long-term outcomes were observed.
Topics: Humans; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Propafenone; Prospective Studies; Shock, Septic; Stroke Volume; Ventricular Function, Left
PubMed: 37698594
DOI: 10.1007/s00134-023-07208-3 -
Phytomedicine : International Journal... Oct 2023Atrial fibrillation (AF) is one of the most common arrhythmias encountered in clinical settings. Currently, the pathophysiology of AF remains unclear, which severely...
BACKGROUND
Atrial fibrillation (AF) is one of the most common arrhythmias encountered in clinical settings. Currently, the pathophysiology of AF remains unclear, which severely limits the effectiveness and safety of medical therapies. The Chinese herbal formula Qi-Po-Sheng-Mai Granule (QPSM) has been widely used in China to treat AF. However, its pharmacological and molecular mechanisms remain unknown.
PURPOSE
The purpose of this study was to investigate the molecular mechanisms and potential targets of QPSM for AF.
STUDY DESIGN AND METHODS
The AF model was induced by Ach (66 μg/ml) and CaCl (10 mg/kg), and the dose of 0.1 ml/100 g was injected into the tail vein for 5 weeks. QPSM was administered daily at doses of 4.42 and 8.84 g/kg, and amiodarone (0.18 g/kg) was used as the positive control. The effect of QPSM on AF was assessed by electrocardiogram, echocardiography, and histopathological analysis. Then, we employed network pharmacology with single nucleus RNA sequencing (snRNA-Seq) to investigate the molecular mechanisms and potential targets of QPSM for AF. Furthermore, high performance liquid chromatography (HPLC) method was used for component analysis of QPSM, and molecular docking was used to verify the potential targets. Using the IonOptix single cell contraction and ion synchronization test equipment, single myocyte length and calcium ion variations were observed in real time. The expression levels of calcium Transporter-related proteins were detected by western blot and immunohistochemistry.
RESULTS
Based on an Ach-CaCl-induced AF model, we found that QPSM treatment significantly reduced atrial electrical remodeling-related markers, such as AF inducibility and duration, and attenuated atrial dilation and fibrosis. Network pharmacology identified 52 active ingredients and 119 potential targets for QPSM in the treatment of AF, and 45 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were enriched, among which calcium pathway had the greatest impact. Using single nucleus sequencing (snRNA-seq), we identified cardiomyocytes as the most differentially expressed in response to drug treatment, with nine differentially expressed genes enriched in calcium signaling pathways. High performance liquid chromatography and molecular docking confirmed that the core components of QPSM strongly bind to the key factors in the calcium signaling pathway. Additional experiments have shown that QPSM increases calcium transients (CaT) and contractility in the individual cardiomyocyte. This was accomplished by increasing the expression of CACNA1C and SERCA2a and decreasing the expression of CAMK2B and NCX1.
CONCLUSION
The present study has systematically elucidated the role of QPSM in maintaining calcium homeostasis in cardiomyocytes through the regulation of calcium transporters, which could lead to new drug development ideas for AF.
Topics: Humans; Atrial Fibrillation; Myocytes, Cardiac; Calcium; Calcium Chloride; Molecular Docking Simulation; Qi; Bone Density Conservation Agents; Amino Acids; Homeostasis
PubMed: 37597360
DOI: 10.1016/j.phymed.2023.155017 -
Cell Nov 2023Ca1.2 channels play crucial roles in various neuronal and physiological processes. Here, we present cryo-EM structures of human Ca1.2, both in its apo form and in...
Ca1.2 channels play crucial roles in various neuronal and physiological processes. Here, we present cryo-EM structures of human Ca1.2, both in its apo form and in complex with several drugs, as well as the peptide neurotoxin calciseptine. Most structures, apo or bound to calciseptine, amlodipine, or a combination of amiodarone and sofosbuvir, exhibit a consistent inactivated conformation with a sealed gate, three up voltage-sensing domains (VSDs), and a down VSD. Calciseptine sits on the shoulder of the pore domain, away from the permeation path. In contrast, when pinaverium bromide, an antispasmodic drug, is inserted into a cavity reminiscent of the IFM-binding site in Na channels, a series of structural changes occur, including upward movement of VSD coupled with dilation of the selectivity filter and its surrounding segments in repeat III. Meanwhile, S4-5 merges with S5 to become a single helix, resulting in a widened but still non-conductive intracellular gate.
Topics: Humans; Calcium Channels, L-Type; Elapid Venoms; Neurotoxins; Protein Domains; Cryoelectron Microscopy
PubMed: 37972591
DOI: 10.1016/j.cell.2023.10.007 -
Emergency Medicine Clinics of North... Aug 2023The effectiveness of pharmacologic management of cardiac arrest patients is widely debated; however, several studies published in the past 5 years have begun to clarify... (Review)
Review
The effectiveness of pharmacologic management of cardiac arrest patients is widely debated; however, several studies published in the past 5 years have begun to clarify some of these issues. This article covers the current state of evidence for the effectiveness of the vasopressor epinephrine and the combination of vasopressin-steroids-epinephrine and antiarrhythmic medications amiodarone and lidocaine and reviews the role of other medications such as calcium, sodium bicarbonate, magnesium, and atropine in cardiac arrest care. We additionally review the role of β-blockers for refractory pulseless ventricular tachycardia/ventricular fibrillation and thrombolytics in undifferentiated cardiac arrest and suspected fatal pulmonary embolism.
Topics: Humans; Heart Arrest; Epinephrine; Atropine; Sodium Bicarbonate; Anti-Arrhythmia Agents
PubMed: 37391250
DOI: 10.1016/j.emc.2023.03.010 -
American Journal of Health-system... Aug 2023This article, the first in a 2-part review, aims to reinforce current literature on the pathophysiology of cardiac arrhythmias and various evidence-based treatment...
PURPOSE
This article, the first in a 2-part review, aims to reinforce current literature on the pathophysiology of cardiac arrhythmias and various evidence-based treatment approaches and clinical considerations in the acute care setting. Part 1 of this series focuses on atrial arrhythmias.
SUMMARY
Arrhythmias are prevalent throughout the world and a common presenting condition in the emergency department (ED) setting. Atrial fibrillation (AF) is the most common arrhythmia worldwide and expected to increase in prevalence. Treatment approaches have evolved over time with advances in catheter-directed ablation. Based on historic trials, heart rate control has been the long-standing accepted outpatient treatment modality for AF, but the use of antiarrhythmics is often still indicated for AF in the acute setting, and ED pharmacists should be prepared and poised to help in AF management. Other atrial arrhythmias include atrial flutter (AFL), atrioventricular nodal reentry tachycardia (AVNRT), and atrioventricular reentrant tachycardia (AVRT), which warrant distinction due to their unique pathophysiology and because each requires a different approach to utilization of antiarrhythmics. Atrial arrhythmias are typically associated with greater hemodynamic stability than ventricular arrhythmias but still require nuanced management according to patient subset and risk factors. Since antiarrhythmics can also be proarrhythmic, they may destabilize the patient due to adverse effects, many of which are the focus of black-box label warnings that can be overreaching and limit treatment options. Electrical cardioversion for atrial arrhythmias is generally successful and, depending on the setting and/or hemodynamics, often indicated.
CONCLUSION
Atrial arrhythmias arise from a variety of mechanisms, and appropriate treatment depends on various factors. A firm understanding of physiological and pharmacological concepts serves as a foundation for exploring evidence supporting agents, indications, and adverse effects in order to provide appropriate care for patients.
Topics: Humans; Adult; Atrial Fibrillation; Tachycardia, Supraventricular; Atrial Flutter; Tachycardia, Atrioventricular Nodal Reentry; Anti-Arrhythmia Agents
PubMed: 37227130
DOI: 10.1093/ajhp/zxad108 -
Heart (British Cardiac Society) Jan 2024Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disease characterised by fibrofatty replacement of the ventricular myocardium due to specific mutations,... (Review)
Review
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disease characterised by fibrofatty replacement of the ventricular myocardium due to specific mutations, leading to ventricular arrhythmias and sudden cardiac death. Treating this condition can be challenging due to progressive fibrosis, phenotypic variations and small patient cohorts limiting the feasibility of conducting meaningful clinical trials. Although widely used, the evidence base for anti-arrhythmic drugs is limited. Beta-blockers are theoretically sound, yet their efficacy in reducing arrhythmic risk is not robust. Additionally, the impact of sotalol and amiodarone is inconsistent with studies reporting contradictory results. Emerging evidence suggests that combining flecainide and bisoprolol may be efficacious.Radiofrequency ablation has shown some potential in disrupting ventricular tachycardia circuits, with combined endo and epicardial ablation yielding better results which could be considered at the index procedure. In addition, stereotactic radiotherapy may be a future option that can decrease arrhythmias beyond simple scar formation by altering levels of Nav1.5 channels, Connexin 43 and Wnt signalling, potentially modifying myocardial fibrosis.Future therapies, such as adenoviruses and GSk3b modulation, are still in early-stage research. While implantable cardioverter-defibrillator implantation is a key intervention for reducing arrhythmic death, the risks of inappropriate shocks and device complications must be carefully considered.
Topics: Humans; Arrhythmogenic Right Ventricular Dysplasia; Arrhythmias, Cardiac; Anti-Arrhythmia Agents; Death, Sudden, Cardiac; Sotalol; Tachycardia, Ventricular; Defibrillators, Implantable
PubMed: 37433658
DOI: 10.1136/heartjnl-2023-322612