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Biomedicine & Pharmacotherapy =... Jul 2023Torsemide is commonly used to relieve edema during the treatment of acute promyelocytic leukemia (APL) with arsenic trioxide (ATO). We explored the effect of torsemide...
Torsemide is commonly used to relieve edema during the treatment of acute promyelocytic leukemia (APL) with arsenic trioxide (ATO). We explored the effect of torsemide on the plasma concentrations of inorganic arsenic (iAs), monomethylarsonic acid (MMA) and dimethyarsinic acid (DMA) in APL patients treated with ATO and clarified its molecular mechanism in rats and cells. The study included 146 APL patients treated with ATO. 60(41.1 %) of these 146 patients were co-administered with torsemide. The treatment of torsemide increased plasma concentrations of iAs (P < 0.05) and DMA (P < 0.05) in APL patients. The single co-administration of ATO and torsemide in rats significantly increased the plasma concentrations and AUC of iAs (P < 0.05) and MMA (P < 0.05), decreased the urinary excretion rates and the urine concentrations of iAs (P < 0.05) and DMA (P < 0.05), and enhanced iAs (P < 0.05) and MMA (P < 0.05) concentrations in the kidneys of rats. In addition, torsemide decreased the expression of multidrug resistance protein 4 (MRP4) in rat kidneys after 7 days of continuous co-administration (P < 0.05). We also treated MRP4-overexpressing HEK293T cells with ATO and different concentrations of torsemide. Torsemide markedly increased the concentrations of iAs, MMA and DMA by inhibiting MRP4 compared with ATO alone (P < 0.05). In conclusion, torsemide increased the plasma concentrations of arsenic metabolites in APL patients treated with ATO by inhibiting the transporter MRP4 in a dose-dependent manner.
Topics: Animals; Humans; Rats; Antineoplastic Agents; Arsenic; Arsenic Trioxide; Arsenicals; Drug Resistance, Multiple; HEK293 Cells; Leukemia, Promyelocytic, Acute; Multidrug Resistance-Associated Proteins; Oxides; Torsemide
PubMed: 37172335
DOI: 10.1016/j.biopha.2023.114858 -
Cureus Jul 2023Heart failure is associated with an increased frequency of hospitalization, reduced life span, and greater risk to public health, thus posing a challenge. In India,... (Review)
Review
Heart failure is associated with an increased frequency of hospitalization, reduced life span, and greater risk to public health, thus posing a challenge. In India, torsemide is one of the commonly used loop diuretics for decongestion in heart failure. However, this use of torsemide, including its dosing, and up/down titration, is based on practical experience. Loop diuretic therapy for heart failure patients poses several dilemmas due to the lack of robust evidence based on which treatment decisions can be made. To guide physicians on the optimal use of torsemide in heart failure patients with or without renal impairment, a panel of expert cardiologists and nephrologists from India convened to develop this expert opinion document for the use of torsemide. This expert opinion on torsemide will pave the way for optimal management with loop diuretic therapy in real-world heart failure patients.
PubMed: 37588313
DOI: 10.7759/cureus.41957 -
Clinical Cardiology Jan 2024
Topics: Humans; Furosemide; Torsemide; Randomized Controlled Trials as Topic; Heart Failure; Sulfonamides; Diuretics
PubMed: 37608566
DOI: 10.1002/clc.24088 -
BMC Cardiovascular Disorders Sep 2023Older adults with heart failure often experience adverse drug events with high doses of heart failure medications. Recognizing whether a patient is on a high or low dose... (Review)
Review
BACKGROUND
Older adults with heart failure often experience adverse drug events with high doses of heart failure medications. Recognizing whether a patient is on a high or low dose intensity heart failure medication can be helpful for daily practice, since it could potentially guide the physician on which symptoms to look for, whether from overdosing or underdosing. However, the current guideline does not provide sufficient information about the dose intensity below the target dose. Furthermore, the definition of high or low-intensity heart failure medication is unclear, and there is no consensus.
METHODS
To close the knowledge gap, we conducted a scoping review of the current literature to identify the most frequently used definition of high versus low doses of heart failure medications. We searched Pubmed, Embase, CINAHL, and Cochrane Library using comprehensive search terms that can capture the intensity of heart failure medications.
RESULTS
We reviewed 464 articles, including 144 articles that had information about beta-blockers (BB), 179 articles about angiotensin-converting enzyme inhibitors (ACEi), 75 articles about angiotensin receptor blockers (ARB), 80 articles about diuretics, 37 articles about mineralocorticoid receptor antagonists (MRA), and 33 articles about angiotensin receptor-neprilysin inhibitor (ARNI). For hydralazine with isosorbide dinitrate or ivabradine, we could not identify any eligible articles. We identified 40 medications with most frequently used definitions of dose intensity. Four medications (nadolol, pindolol, cilazapril, and torsemide) did not reach consensus in definitions. Most of the BBs, ACEis, or ARBs used the definition of low being < 50% of the target dose and high being ≥ 50% of the target dose from the guideline. However, for lisinopril and losartan, the most commonly used definitions of high or low were from pivotal clinical trials with a pre-defined definition of high or low.
CONCLUSION
Our comprehensive scoping review studies identified the most frequently used definition of dose intensity for 40 medications but could not identify the definitions for 4 medications. The results of the current scoping review will be helpful for clinicians to have awareness whether the currently prescribed dose is considered high - requiring close monitoring of side effects, or low - requiring more aggressive up-titration.
Topics: Humans; Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Heart Failure; Isosorbide Dinitrate; Adrenergic beta-Antagonists; Stroke Volume
PubMed: 37759279
DOI: 10.1186/s12872-023-03514-2 -
Drugs in Context 2023Diuresis with loop diuretics is the mainstay treatment for volume optimization in patients with congestive heart failure, in which perfusion and volume expansion play a... (Review)
Review
Diuresis with loop diuretics is the mainstay treatment for volume optimization in patients with congestive heart failure, in which perfusion and volume expansion play a crucial role. There are robust guidelines with extensive evidence for the management of heart failure; however, clear guidance is needed for patients who do not respond to standard diuretic treatment. Diuretic resistance (DR) can be defined as an insufficient quantity of natriuresis with proper diuretic therapy. A combination of diuretic regimens is used to overcome DR and, more recently, SGLT2 inhibitors have been shown to improve diuresis. Despite DR being relatively common, it is challenging to treat and there remains a notable lack of substantial data guiding its management. Moreover, DR has been linked with poor prognosis. This review aims to expose the multiple approaches for treatment of patients with DR and the importance of intravascular volume expansion in the response to therapy.
PubMed: 38188263
DOI: 10.7573/dic.2023-6-5 -
Veterinary Medicine and Science Jul 2023Two loop diuretics, torsemide and frusemide, can affect the urinary system and consequently the cardiordiovascular haemodynamics in different ways.
BACKGROUND
Two loop diuretics, torsemide and frusemide, can affect the urinary system and consequently the cardiordiovascular haemodynamics in different ways.
OBJECTIVES
This study compared a number of echocardiographic parameters and systemic arterial blood pressure (ABP) changes following administration of furosemide or torsemide.
METHODS
Five shelter dogs underwent transthoracic two-dimensional M-mode echocardiography to obtain the following measurements: left ventricular internal dimension at end-systole (LVIDs), left ventricular internal dimension at end-diastole (LVIDd), fractional shortening (FS), heart rate (HR) and the distance between the mitral valve socket and the ventricle wall (septal to E Point, SEP). Arterial blood pressure was measured using the oscillometric method. Measurements recorded before treatment (baseline data) were compared to those after the dogs received furosemide (5 mg/kg) or torsemide (0.5 mg/kg).
RESULTS
Torsemide significantly reduced blood pressure 1 h after administration, but this was not seen with furosemide. Fractional shortening, LVIDd and SEP decreased following both treatments, but there were no significant differences between the treatment groups. Torsemide increased heart rate above that seen in the furosemide groups.
CONCLUSIONS
The results of this study indicate that 1 h after administration, torsemide increases heart rate and decreases blood pressure when compared to furosemide, but both drugs have similar effects on measured cardiovascular indices.
Topics: Dogs; Animals; Furosemide; Torsemide; Sodium Potassium Chloride Symporter Inhibitors; Sulfonamides; Diuretics; Echocardiography
PubMed: 37249046
DOI: 10.1002/vms3.1129 -
Journal of Pharmaceutical and... May 2024Free radical formation in two diuretics: indapamide and torasemide was examined during UV irradiation and storage at higher temperatures using X-band (9.3 GHz)...
Application of electron paramagnetic resonance spectroscopy to examine free radicals formed in indapamide and torasemide storage under UV irradiation and at the higher temperatures which appear under light exposition.
Free radical formation in two diuretics: indapamide and torasemide was examined during UV irradiation and storage at higher temperatures using X-band (9.3 GHz) electron paramagnetic resonance spectroscopy (EPR). The aim of this study was to investigate the possibility of storing indapamide and torasemide under UV irradiation and at higher temperatures, which may occur during exposure to light. The diuretic samples were exposed to UVA irradiation for 15, 30 and 45 minutes, and stored at temperatures of 40 C and 50 C by 30 minutes. The EPR spectra were analyzed to determine the amplitudes (A), linewidths (ΔB), and integral intensities (I) and g factors. The concentrations of free radical (N) in the diuretic samples were also determined. The influence of microwave power on amplitudes, linewidths and the asymmetry parameter were evaluated. The result showed that the tested indapamide and torasemide samples exhibited high free radical concentrations in the range of 10-10 spin/g after UV irradiation and heat treatment. Therefore, due to the significant free radical formation indapamide and torasemide should not be stored under UV light and at temperatures of 40 C and 50 C. The complex character of free radical systems in the diuretic samples was proved as evidenced by the changes of the asymmetry parameters of the EPR lines with increasing microwave power. Fast spin-lattice relaxation processes were observed in all tested diuretic samples, regardless of the storage conditions. Electron paramagnetic resonance spectroscopy is proposed as a useful method in pharmacy to determine the appropriate storage conditions for diuretics.
Topics: Hot Temperature; Indapamide; Torsemide; Temperature; Electron Spin Resonance Spectroscopy; Ultraviolet Rays; Free Radicals; Diuretics
PubMed: 38422674
DOI: 10.1016/j.jpba.2024.116057 -
BMJ Open Feb 2024The current guidelines strongly recommend early initiation of multiple classes of cardioprotective drugs for patients with heart failure with reduced ejection fraction...
Rationale and protocol of the LAQUA-HF trial: a factorial randomised controlled trial evaluating the effects of neurohormonal and diuretic agents on health-status reported outcomes in heart failure patients.
INTRODUCTION
The current guidelines strongly recommend early initiation of multiple classes of cardioprotective drugs for patients with heart failure with reduced ejection fraction to improve prognosis and health status. However, evidence on the optimal sequencing of approved drugs is scarce, highlighting the importance of individualised treatment plans. Registry data indicate that only a portion of these patients can tolerate all four recommended classes, underscoring the need to establish the favoured sequence when using these drugs. Additionally, the choice between long-acting and short-acting loop diuretics in the present era remains uncertain. This is particularly relevant given the frequent use of angiotensin receptor-neprilysin inhibitor and sodium-glucose cotransporter 2 inhibitor, both of which potentiate natriuretic effects.
METHODS AND ANALYSIS
In a prospective, randomised, open-label, blinded endpoint method, LAQUA-HF (Long-acting vs short-acting diuretics and neurohormonal Agents on patients' QUAlity-of-life in Heart Failure patients) will be a 2×2 factorial design, with a total of 240 patients randomised to sacubitril/valsartan versus dapagliflozin and torsemide versus furosemide in a 1:1 ratio. Most enrolment sites have participated in an ongoing observational registry for consecutive patients hospitalised for heart failure involved dedicated study coordinators, and used the same framework to enrol patients. The primary endpoint is the change in patients' health status over 6 months, defined by the Kansas City Cardiomyopathy Questionnaire. Additionally, clinical benefit at 6 months defined as a hierarchical composite endpoint will be assessed by the win ratio as the secondary endpoint.
ETHICS AND DISSEMINATION
The medical ethics committee Keio University in Japan has approved this trial. All participants provide written informed consent prior to study entry. The results of this trial will be disseminated in one main paper and additional papers on secondary endpoints and subgroup analyses.
TRIAL REGISTRATION NUMBER
UMIN000045229.
Topics: Humans; Prospective Studies; Angiotensin Receptor Antagonists; Stroke Volume; Heart Failure; Valsartan; Sodium Potassium Chloride Symporter Inhibitors; Drug Combinations; Aminobutyrates; Patient Reported Outcome Measures; Randomized Controlled Trials as Topic
PubMed: 38355194
DOI: 10.1136/bmjopen-2023-076519 -
Pakistan Journal of Medical Sciences 2023To investigate the efficacy of metoprolol combined with torasemide in elderly patients with degenerative valvular heart disease (DVHD) and heart failure and its...
OBJECTIVE
To investigate the efficacy of metoprolol combined with torasemide in elderly patients with degenerative valvular heart disease (DVHD) and heart failure and its influence on N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations.
METHODS
The records of 129 DVHD patients ≥60 years old with heart failure diagnosed and treated in our hospital from January 2020 to February 2022 were retrospectively selected. According to the treatment records, 62 patients received metoprolol treatment (Control-group), and 67 patients received metoprolol combined with torasemide treatment (Observation-group). The changes in cardiac function, NT-proBNP and inflammatory factor concentrations and clinical efficacy were analyzed and compared between the two groups before and after treatment.
RESULTS
After treatment, left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD) and the mitral ratio of peak early to late diastolic filling velocity (E/A) were lower, with a greater decrease in the Observation-group compared to the Control-group (<0.05). After treatment, NT-proBNP and interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6) concentrations were lower in both groups, with a greater decrease in the Observation-group compared to the Control-group (<0.05). The total clinical efficacy of the Observation-group was significantly higher than the Control-group (<0.05). There was no significant difference in the total incidence of adverse drug reactions between the two groups (>0.05).
CONCLUSION
Metoprolol combined with torasemide has a significant therapeutic effect on DVHD patients with heart failure. This drug combination improved cardiac function, reduced NT-proBNP concentrations and has good safety.
PubMed: 37492298
DOI: 10.12669/pjms.39.4.7465