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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 -
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 -
Clinical and Translational Science Dec 2023Lidocaine is classified as a class Ib anti-arrhythmic that blocks voltage- and pH-dependent sodium channels. It exhibits well investigated anti-arrhythmic effects and... (Review)
Review
Lidocaine is classified as a class Ib anti-arrhythmic that blocks voltage- and pH-dependent sodium channels. It exhibits well investigated anti-arrhythmic effects and has been the anti-arrhythmic of choice for the treatment of ventricular arrhythmias for several decades. Lidocaine binds primarily to inactivated sodium channels, decreases the action potential duration, and increases the refractory period. It increases the ventricular fibrillatory threshold and can interrupt life-threatening tachycardias caused by re-entrant mechanisms, especially in ischemic tissue. Its use was pushed into the background in the era of amiodarone and modern electric device therapy. Recently, lidocaine has come back into focus for the treatment of acute sustained ventricular tachyarrhythmias. In this brief overview, we review the clinical pharmacology including possible side effects, the historical course, possible indications, and current Guideline recommendations for the use of lidocaine.
Topics: Humans; Lidocaine; Anti-Arrhythmia Agents; Amiodarone; Arrhythmias, Cardiac; Sodium Channels
PubMed: 37781966
DOI: 10.1111/cts.13650 -
Pharmaceutics Aug 2023Amiodarone is underutilized due to significant off-target toxicities. We hypothesized that targeted delivery to the heart would lead to the lowering of the dose by...
BACKGROUND
Amiodarone is underutilized due to significant off-target toxicities. We hypothesized that targeted delivery to the heart would lead to the lowering of the dose by utilizing a cardiomyocyte-targeting peptide (CTP), a cell-penetrating peptide identified by our prior phage display work.
METHODS
CTP was synthesized thiolated at the N-terminus, conjugated to amiodarone via Schiff base chemistry, HPLC purified, and confirmed with MALDI/TOF. The stability of the conjugate was assessed using serial HPLCs. Guinea pigs (GP) were injected intraperitoneally daily with vehicle (7 days), amiodarone (7 days; 80 mg/kg), CTP-amiodarone (5 days; 26.3 mg/kg), or CTP (5 days; 17.8 mg/kg), after which the GPs were euthanized, and the hearts were excised and perfused on a Langendorff apparatus with Tyrode's solution and blebbistatin (5 µM) to minimize the contractions. Voltage (RH237) and Ca-indicator dye (Rhod-2/AM) were injected, and fluorescence from the epicardium split and was captured by two cameras at 570-595 nm for the cytosolic Ca and 610-750 nm wavelengths for the voltage. Subsequently, the hearts were paced at 250 ms with programmed stimulation to measure the changes in the conduction velocities (CV), action potential duration (APD), and Ca transient durations at 90% recovery (CaTD). mRNA was extracted from all hearts, and RNA sequencing was performed with results compared to the control hearts.
RESULTS
The CTP-amiodarone remained stable for up to 21 days at 37 °C. At ~1/15th of the dose of amiodarone, the CTP-amiodarone decreased the CV in hearts significantly compared to the control GPs (0.92 ± 0.05 vs. 1.00 ± 0.03 ms, = 0.0007), equivalent to amiodarone alone (0.87 ± 0.08 ms, = 0.0003). Amiodarone increased the APD (192 ± 5 ms vs. 175 ± 8 ms for vehicle, = 0.0025), while CTP-amiodarone decreased it significantly (157 ± 16 ms, = 0.0136), similar to CTP alone (155 ± 13 ms, = 0.0039). Both amiodarone and CTP-amiodarone significantly decreased the calcium transients compared to the controls. CTP-amiodarone and CTP decreased the CaTD to an extent greater than amiodarone alone ( < 0.001). RNA-seq showed that CTP alone increased the expression of DHPR and SERCA2a, while it decreased the expression of the proinflammatory genes, NF-kappa B, TNF-α, IL-1β, and IL-6.
CONCLUSIONS
Our data suggest that CTP can deliver amiodarone to cardiomyocytes at ~1/15th the total molar dose of the amiodarone needed to produce a comparable slowing of CVs. The ability of CTP to decrease the AP durations and CaTD may be related to its increase in the expression of Ca-handling genes, which merits further study.
PubMed: 37631321
DOI: 10.3390/pharmaceutics15082107 -
Cureus Nov 2023A review of the literature was made to find and choose research papers, on drugs (amiodarone and adenosine) used for managing supraventricular tachycardia (SVT) in... (Review)
Review
A review of the literature was made to find and choose research papers, on drugs (amiodarone and adenosine) used for managing supraventricular tachycardia (SVT) in children and infants (one hour to 17 years of age) with no structural heart disease by PRISMA guideline. Our team conducted an exhaustive systematic literature review (SLR), utilizing an extensive search methodology across recognized databases like PubMed, PubMed Central, Google Scholar, Web of Science, and The Cochrane Library. We included 10 scholarly articles that satisfied our rigorous selection criteria including systematic reviews/meta-analysis, and randomized control trials, shedding light on treatment with amiodarone and adenosine for SVT in pediatric patients. There is no first- or second-line treatment for SVT in pediatrics, and drug effectiveness can vary significantly between patients. Adenosine has a shorter half-life than other drugs, instead, it is safer and more valuable when an electrocardiogram is uncertain, it is recommended as an acute management, and it continues as the first-line option for paroxysmal SVT. Amiodarone management patients with acute STV within, its use showed better results when administered 48 hours after diagnosis. Furthermore, it is recommended to reduce the incidence of junctional ectopic tachycardia (JET), by pre-operative prophylaxis, also for chronic control in this and other types of SVT. In none of the evaluated studies were documented significant adverse effects in pediatric patients. Side effects that did occur were mild and easily managed. The studies also emphasize that although both amiodarone and adenosine can successfully convert SVT to sinus rhythm, better results have been observed when using combined therapies of each recommended medication. Therefore, more randomized clinical trials, meta-analyses, and systematic reviews are needed to solidify and possibly standardize an effective and safe pharmacological treatment for SVT and its types in pediatric patients.
PubMed: 38073952
DOI: 10.7759/cureus.48507