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Journal of Veterinary Internal Medicine Jul 2018Diuretic treatment is the mainstay for management of congestive heart failure in horses, and its use has been restricted to injectable medications because no currently...
BACKGROUND
Diuretic treatment is the mainstay for management of congestive heart failure in horses, and its use has been restricted to injectable medications because no currently data supports the use of PO administered loop diuretics.
OBJECTIVES
To determine the pharmacokinetic and pharmacodynamic properties of PO administered torsemide and, determine if PO administered torsemide, could be used as an alternative to injectable diuretics in the horse.
ANIMALS
Six healthy adult mares.
METHODS
A 2-phase, prospective study, that consisted of pharmacokinetic profiling of a single dose (6 mg/kg PO) and pharmacodynamic effects of long-term torsemide administration (2 mg/kg PO q12h) for 6 days in healthy horses.
RESULTS
Pharmacokinetic analysis identified a peak concentration (C ) of 10.14 µg/mL (range, 6.79-14.69 µg/mL) and elimination half-life (T ) 9.2 hours (range, 8.4-10.4 hours). The area under the plasma drug concentration over time curve (AUC) was 80.7 µg × h/mL (range, 56.5-117.2 µg × h/mL). A statistically significant increase in urine volume and decrease in urine specific gravity were found from day 0 (baseline) to day 6 (P < .0001). Significant alterations in biochemical variables included hyponatremia, hypokalemia, hypochloremia, and increased serum creatinine concentration. Mean arterial blood pressure significantly decreased on day 6 (57.7 ± 8.8 mm Hg, P = .001) as compared with baseline (78 ± 6.1 mm Hg). Serum aldosterone concentrations significantly increased after 6 days of torsemide administration (P = .0006).
CONCLUSIONS AND CLINICAL IMPORTANCE
PO administered torsemide (4 mg/kg/day) successfully reached therapeutic concentrations in blood, induced clinically relevant diuresis, and resulted in moderate pre-renal azotemia and electrolyte disturbances.
Topics: Administration, Oral; Animals; Chlorides; Creatinine; Diuretics; Female; Half-Life; Horse Diseases; Horses; Hypokalemia; Hyponatremia; Sulfonamides; Torsemide
PubMed: 29770976
DOI: 10.1111/jvim.15213 -
British Journal of Clinical Pharmacology Sep 2006To investigate the association between torsemide renal clearance and genetic variation in the basolaterally expressed renal organic anion transporters OAT1 and OAT3 and...
AIMS
To investigate the association between torsemide renal clearance and genetic variation in the basolaterally expressed renal organic anion transporters OAT1 and OAT3 and in the luminally situated OAT4.
METHODS
We analysed 22 polymorphisms in the OAT coding genes SLC22A6, SLC22A8 and SLC22A11 and their haplotypes and measured torsemide renal clearance in 95 healthy men. In addition, the effect of torsemide on the OAT-mediated transport was studied in vitro.
RESULTS
In stably transfected HEK293 cells torsemide (100 microm) inhibited the uptake by human OAT1, OAT3 and OAT4 by 63.1, 58.1 and 68.0%, respectively. Torsemide renal clearance ranged from 6.5 to 43.1 ml min(-1) with a log-normal distribution and a geometric mean of 15.6 ml min(-1) (15.0-16.1 +/- SEM). No clear outlier group was observed. AA carriers of the polymorphism rs11231809 in SLC22A11 had a torsemide renal clearance of 13.3 ml min(-1) (12.7-13.9) compared with 15.1 ml min(-1) (14.5-15.8) in AT and 18.0 ml min(-1) (16.7-19.5) in TT carriers (P = 0.002). The two most frequent haplotypes at SLC22A11 showed an association with torsemide renal clearance. Homozygous carriage of these two haplotypes resulted in renal clearances of 21.2 ml min(-1) (19.0-23.7) and 11.8 ml min(-1) (10.5-13.5), respectively. No association between reanl clearance and genetic variation in SLC22A6 or SLC22A8 was observed.
CONCLUSIONS
Genetic variation in the gene encoding the luminally expressed OAT4 rather than in the basolaterally expressed OATs may affect the renal clearance of torsemide.
Topics: Adult; Diuretics; Genetic Linkage; Genetic Variation; Haplotypes; Humans; Kidney; Male; Middle Aged; Organic Anion Transporters; Polymerase Chain Reaction; Polymorphism, Genetic; Sulfonamides; Torsemide
PubMed: 16934049
DOI: 10.1111/j.1365-2125.2006.02655.x -
International Heart Journal Jul 2018The aim of this study was to investigate the effect on mortality of torsemide and a combination of loop diuretics (furosemide + torsemide) in contemporary practice in...
The aim of this study was to investigate the effect on mortality of torsemide and a combination of loop diuretics (furosemide + torsemide) in contemporary practice in patients with chronic heart failure (HF).We investigated patients with HF in the Heart Failure Center of Fuwai Hospital from 2009 to 2013 who were discharged on furosemide, torsemide, or a combination of the 2 drugs. Using inverse probability weighting (IPW) to account for nonrandom selection of diuretic strategies, we assessed the association between different diuretic strategies and mortality.Among 956 patients, 19.7% (n = 188) received furosemide, 36.6% (n = 350) torsemide, and 43.7% (n = 418) the combination therapy. The torsemide-treated and combination-treated patients had worse heart function and higher furosemide equivalent. Univariable Cox proportional hazards models showed that the combination group had worse outcomes (all-cause HR = 2.044, P = 0.008; CV HR = 1.988, P = 0.011), while torsemide was associated with an outcome (all-cause HR = 1.640, P = 0.078; CV HR = 1.509, P = 0.147) similar to that of furosemide. After IPW, torsemide was associated with a nominally lower mortality compared with furosemide (all-cause HR = 0.738, P = 0.222; CV HR = 0.667, P = 0.110), and the association between the combination treatment and increased mortality was no longer statistically significant (all-cause HR = 1.207, P = 0.470;CV HR = 1.174, P = 0.540).We found that torsemide and the combination strategy had similar outcomes when compared with furosemide. However, considering the lack of diuretic randomized clinical trials (RCTs) conducted with the aim of exploring the effect on mortality of different diuretic treatments, prospective trials are needed to investigate the effect of different diuretic strategies in chronic HF.
Topics: Aged; China; Diuretics; Drug Therapy, Combination; Female; Furosemide; Heart Failure; Humans; Male; Middle Aged; Proportional Hazards Models; Sulfonamides; Torsemide
PubMed: 29877310
DOI: 10.1536/ihj.17-522 -
Case Reports in Obstetrics and... 2021Lower extremity edema is one of the most common complaints among pregnant patients. However, there is no literature mentioning weeping edema (i.e., lymphorrhea) in a...
INTRODUCTION
Lower extremity edema is one of the most common complaints among pregnant patients. However, there is no literature mentioning weeping edema (i.e., lymphorrhea) in a pregnant woman who has no concordant underlying renal and/or cardiac pathology. There is also a lack of evidence and recommendations regarding the therapeutic benefit and safety profile of diuretic use to treat profound pregnancy-associated edema. Herein, we present the case of 32-year-old female who presented with a significant lymphorrhea during the third trimester without cardiac or renal comorbidity and was successfully treated with torsemide. . We report a case of a 32-year-old multigravida patient pregnant with her third child and has two living full-term children (G3P2003). Her pregnancy was complicated by obesity, smoking (vape), and previous history of fetal growth restriction. The patient presented for routine prenatal care at 9-week gestation. She was diagnosed with chronic hypertension at 19 weeks of pregnancy based upon systolic blood pressure > 140. Lifestyle modifications were recommended, but the patient did not comply. At her 31-week office visit, the patient presented with anasarca and clear, slightly viscous fluid seeping through the atraumatic skin of her lower extremities. Preeclampsia, renal, cardiac, vascular, and infectious complications were all ruled out. The patient responded positively to loop diuretic therapy. Torsemide was found to be far more beneficial than furosemide. The patient was induced at 37 weeks secondary to chronic hypertension requiring antihypertensive therapy. Delivery was uncomplicated. The patient gave birth to a healthy male with birth weight of 2,920 g via spontaneous vaginal delivery. . Pitting edema of lower limbs frequently occurs as a result of fluid overload and chronic venous insufficiency, and pregnancy is one of the known risk factors. Additionally, the blockage of lymphatic channel with the gravida uterus likely was the main contributing factor for her lymphorrhea. In this patient, the capillary hydrostatic pressure was likely accentuated due to hypertension, obesity, and vaping. Furosemide was minimally effective to alleviate her symptoms. Torsemide provided much more effective diuresis and symptom control. However, her symptoms persisted until delivery.
CONCLUSION
Torsemide provided significant therapeutic benefit over furosemide in this patient without adverse maternal, fetal, or neonatal outcomes. Further study is needed to assess the safe use of loop diuretics in the pregnant population who suffers from significant lower extremity edema.
PubMed: 34877022
DOI: 10.1155/2021/3594923 -
American Heart Journal Mar 2015The health and economic burden of heart failure is significant and continues to grow each year. Loop diuretics are an integral part of symptom management in heart... (Review)
Review
The health and economic burden of heart failure is significant and continues to grow each year. Loop diuretics are an integral part of symptom management in heart failure. Furosemide is used disproportionately compared with other loop diuretics, and there is currently no guidance for physicians regarding which agent to choose. However, there exist pharmacologic differences as well as other mechanistic differences that appear to favor torsemide use over furosemide. Compared with furosemide, torsemide improves surrogate markers of heart failure severity such as left ventricular function, plasma brain natriuretic peptide levels, and New York Heart Association functional class and may also reduce hospitalizations, readmissions, and mortality. Data suggest that these benefits could be mediated through torsemide's ability to positively affect the renin-angiotensin-aldosterone system. Specifically, torsemide has been shown to inhibit aldosterone secretion, synthesis, and receptor binding in vitro, as well as decrease transcardiac extraction of aldosterone, myocardial collagen production, and cardiac fibrosis in patients with heart failure. We identified pertinent literature using keyword MEDLINE searches and cross-referencing prior bibliographies. We summarize the available data suggesting potential benefits with torsemide over furosemide, and call attention to the need for a reappraisal of diuretic use in heart failure patients and also for a well-powered, randomized control trial assessing torsemide versus furosemide use.
Topics: Choice Behavior; Fibrosis; Furosemide; Heart; Heart Failure; Humans; Myocardium; Practice Patterns, Physicians'; Renin-Angiotensin System; Sodium Potassium Chloride Symporter Inhibitors; Sulfonamides; Torsemide; Up-Regulation; Ventricular Dysfunction, Left
PubMed: 25728721
DOI: 10.1016/j.ahj.2014.12.009 -
Journal of Veterinary Internal Medicine Nov 2017Torsemide use for congestive heart failure (CHF) has been reported, but prescription frequency is unknown. Commercially available tablet sizes in North America limit...
BACKGROUND
Torsemide use for congestive heart failure (CHF) has been reported, but prescription frequency is unknown. Commercially available tablet sizes in North America limit dosing precision, indicating a need to evaluate its strength and stability in suspension.
OBJECTIVES
To determine the frequency of torsemide prescriptions and to determine a beyond use date (BUD) of a compounded suspension of torsemide for oral administration stored under 2 temperature conditions for 90 days.
ANIMALS
No animals used.
METHODS
Pharmacy records were retrospectively reviewed for torsemide and furosemide prescriptions from 2008 to 2015 at 2 veterinary referral centers. After preliminary strength testing, compounded torsemide suspension (5 mg/mL) for oral administration was prepared using torsemide tablets suspended in OraPlus:OraSweet 1:1, buffered to a pH of 8.3 and stored at refrigeration (2-8°C) and room temperature (20-25°C) in 2 oz amber plastic bottles. Samples were analyzed by reverse phase high-performance liquid chromatography (RP-HPLC) on days 0, 14, 30, 60, and 90.
RESULTS
Prescriptions for torsemide increased from 2008 to 2015. Analysis of the torsemide 5 mg/mL suspension for oral administration at each time point met United States Pharmacopeia (USP) requirements for torsemide content of 90-110% of label claim. The average strength at 90 days decreased to 92 ± 3% at 2-8°C and 95 ± 2% at 20-25°C. Stability testing did not detect unknown impurities.
CONCLUSIONS
Increasing torsemide use warrants availability of a validated and stable compounded formulation. Our results support the assignment of a 90-day BUD for torsemide 5 mg/mL suspension for oral administration compounded in OraPlus:Sweet 1:1 buffered to a pH of 8.3.
Topics: Administration, Oral; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Drug Compounding; Drug Stability; Drug Storage; Furosemide; Pharmaceutical Solutions; Pharmaceutical Vehicles; Refrigeration; Sulfonamides; Suspensions; Temperature; Torsemide
PubMed: 28913839
DOI: 10.1111/jvim.14819 -
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 -
BMC Cardiovascular Disorders May 2019Loop diuretics are recommended by clinical practice guidelines to treat volume overload in acute decompensated heart failure (ADHF). The effectiveness of switching... (Comparative Study)
Comparative Study Observational Study
BACKGROUND
Loop diuretics are recommended by clinical practice guidelines to treat volume overload in acute decompensated heart failure (ADHF). The effectiveness of switching furosemide to torsemide versus optimizing the furosemide dose following ADHF has not yet been evaluated.
METHODS
This retrospective observational study aimed to assess the impact of switching furosemide to torsemide versus optimizing the furosemide dose after ADHF on HF-related hospitalization within 1 month and 6 months of discharge. The study included patients previously on furosemide admitted with ADHF to the Heart Hospital in Qatar between January 1, 2016 and June 30, 2017. The study included 2 groups: (1) patients discharged on torsemide; and (2) patients discharged on an optimized furosemide dose. Cox proportional hazard regression analysis was used to determine the association between diuretic use and hospitalization.
RESULTS
Of the 232 patients included, 45 received torsemide and 187 received an optimized furosemide dose upon discharge. The majority of patients included were males (54%) with a mean age of 67 ± 12 years, and presented with HF with reduced ejection fraction (57%) and had a history of coronary artery disease (68%). The 1-month and 6-month HF-related hospitalization did not differ between the torsemide and optimized furosemide groups (aHR = 0.72; 95% CI 0.23-2.3, p = 0.57; aHR = 0.94, 95% CI 0.45-1.8, p = 0.87), respectively.
CONCLUSION
Switching furosemide to torsemide after ADHF was not associated with reduced HF-related hospitalization compared to receiving an optimized furosemide dose. Larger prospective clinical trials are needed to confirm the findings of this study.
Topics: Aged; Drug Substitution; Female; Furosemide; Heart Failure; Humans; Male; Middle Aged; Patient Readmission; Qatar; Retrospective Studies; Sodium Potassium Chloride Symporter Inhibitors; Time Factors; Torsemide; Treatment Outcome
PubMed: 31138146
DOI: 10.1186/s12872-019-1112-5 -
Clinical Cardiology Mar 2022Loop diuretics are commonly used for patients with heart failure (HF) but it remains unknown if one loop diuretic is clinically superior.
BACKGROUND
Loop diuretics are commonly used for patients with heart failure (HF) but it remains unknown if one loop diuretic is clinically superior.
HYPOTHESIS
Biomarkers and proteomics provide insight to how different loop diuretics may differentially affect outcomes.
METHODS
Blood and urine were collected from outpatients with HF who were taking torsemide or furosemide for >30 days. Differences were assessed in cardiac, renal, and inflammatory biomarkers and soluble protein panels using the Olink Cardiovascular III and inflammation panels.
RESULTS
Of 78 subjects, 55 (71%) were treated with furosemide and 23 (29%) with torsemide, and 25 provided a urine sample (15 treated with furosemide, 10 with torsemide). Patients taking torsemide were older (68 vs 64 years) with a lower mean eGFR (46 vs 54 ml/min/1.73 m ), a higher proportion were women (39% vs 24%) and Black (43% vs 27%). In plasma, levels of hs-cTnT, NT-proBNP, and hsCRP were not significantly different between groups. In urine, there were significant differences in urinary albumin, β-2M, and NGAL, with higher levels in the torsemide-treated patients. Of 184 proteins testing in Olink panels, in plasma, 156 (85%) were higher in patients taking torsemide but none were significantly different after correcting for false discovery.
CONCLUSIONS
We show differences in urinary biomarkers but few differences in plasma biomarkers among HF patients on different loop diuretics. Olink technology can detect differences in plasma protein levels from multiple biologic domains. These findings raise the importance of defining differences in mechanisms of action of each diuretic in an appropriately powered study.
Topics: Diuretics; Female; Furosemide; Heart Failure; Humans; Proteomics; Torsemide
PubMed: 35014074
DOI: 10.1002/clc.23733