Clinical Pharmacology of Loop Diuretics

  title={Clinical Pharmacology of Loop Diuretics},
  author={Dr D. Craig Brater},
  • D. Brater
  • Published 2012
  • Biology, Medicine
  • Drugs
SummaryThe clinical pharmacology of torasemide, bumetanide, piretanide and furosemide (frusemide) is discussed. These drugs share a similar mechanism of action in inhibiting Na+-K+-2Cl− reabsorption at the thick ascending limb of the loop of Henle. They differ in their routes of metabolism, pharmacokinetics, and potency. Whether such differences are clinically important requires further study. Bumetanide and torasemide are metabolised by cytochrome P450 pathways, whereas furosemide is… 
Clinical Pharmacology of the Loop Diuretics Furosemide and Bumetanide in Neonates and Infants
Comparison of continuous infusion versus intermittent infusion of furosemide showed that the diuresis is more controlled with fewer hemodynamic and electrolytic variations during continuous infusion, and the risk of failure of patent ductus arteriosus closure when indomethacin or ibuprofen have been co-administered is reduced.
Torsemide: a pyridine-sulfonylurea loop diuretic.
Torsemide is characterized by good bioavailability and once-daily dosing and, compared with furosemide, provides generally equivalent therapeutic efficacy.
Loop Diuretics in the Treatment of Hypertension
Loop diuretics appear to have a preferable side effect profile (less hyponatremia, hypokalemia, and possibly less glucose intolerance) and their rightful place in the antihypertensive arsenal is yet to be determined.
Hydrochlorothiazide does not increase furosemide's effects in end-stage renal disease
In patients with ESRD and severe proteinuria, the combination of hydrochlorothiazide with furosemide therapy did not increase the diuretic effect of furoSemide, and hydrochlorothsiazide was not a significant covariate in the furo Semide effect for the pharmacodynamic model.
Use of Diuretics in Chronic Kidney Disease Patients
Interaction Between the Sodium‐Glucose–Linked Transporter 2 Inhibitor Dapagliflozin and the Loop Diuretic Bumetanide in Normal Human Subjects
First‐dose Na+ excretion with bumetanide and dapagliflozin is not additive, but the weekly administration of one diuretic enhances the initial Na+excretion with the other, thereby demonstrating mutual adaptive natriuretic synergy.
Sodium and Fluid Excretion With Torsemide in Healthy Subjects is Limited by the Short Duration of Diuretic Action
Torsemide ER prolongs urine drug levels, thereby increasing the time spent with effective drug concentrations, reduces postdiuretic Na+ retention, and moderates a fall in glomerular filtration rate, which limits salt loss with loop diuretics.
Population Pharmacokinetic (Pop-PK) Analysis of Torsemide in Healthy Korean Males Considering CYP2C9 and OATP1B1 Genetic Polymorphisms
The torsemide PK variability between individuals was largely explained and, in the future, individualized effective drug therapy of torSemide taking individual patient’s genotypes into account might become possible.
Safety and Efficacy of Adding Dapagliflozin to Furosemide in Type 2 Diabetic Patients With Decompensated Heart Failure and Reduced Ejection Fraction
Dapagliflozin may provide a new drug option in the treatment of heart failure especially among vulnerable group of diabetics as it had no remarkable effects on serum potassium level and kidney functions.


Comparison of loop diuretics in patients with chronic renal insufficiency.
Assessing the pharmacokinetic and pharmacodynamic characteristics of intravenously administered furosemide and bumetanide in ten adult patients with stable, chronic renal insufficiency in a randomized, cross-over study during controlled sodium intake found differences in diuretic effectiveness.
Clinical pharmacology of torasemide, a new loop diuretic
Urinary dose‐response curves showed torasemide to be five times as potent as furosemide, implying that delivery of drug to the urinary side of the nephron is the major determinant of response.
Comparative pharmacodynamics of torasemide and furosemide in patients with oedema.
Torasemide was about 8 times more potent, exerted a longer lasting diuretic effect and was more potassium sparing than furosemide and was well tolerated and efficient in the treatment of oedema due to congestive heart failure and hepatic cirrhosis.
Furosemide: A Clinical Evaluation of Its Diuretic Action
The physiological effects of furosemide, a new diuretic agent chemically related to thiazide diuretics, have been evaluated in seven normal subjects and in 39 patients with edema of varied origin.The
Comparison of the pharmacokinetics and pharmacodynamics of torasemide and furosemide in healthy volunteers.
  • M. Lesne
  • Medicine, Biology
  • 1988
The pharmacodynamic effects and the pharmacokinetic parameters of torasemide (1-isopropyl-3- ([4-(3-methyl-phenylamino)pyridine]-3-sulfonyl)urea) 20 mg and furosemide 40 mg were compared after oral
Pharmacokinetics and metabolism of torasemide in man.
The renal clearances of the metabolites exceeded that of the parent drug, renal impairment may change their elimination kinetics, and M1 and M3 probably contribute to the diuretic action of torasemide.
Acute tolerance to furosemide diuresis in humans. Pharmacokinetic-pharmacodynamic modeling.
The time course of furosemide excretion, as well as the degree of renal compensation, determine the renal sensitivity to furoSemide, which has important implications for the proper design and interpretation of studies of the excretion-response relationship of diuretics.
Pharmacodynamics and kinetics of torasemide and its metabolites in chronic renal failure after i.v. administration of 20 mg torasemide
Torasemide is a new loop diuretic with a similar pharmacodynamic action as furosemide and undergoes extensive oxidative biotransformation, which produces metabolites Ml and M3 which are biologically active.
Effect of probenecid on the dose-response relationship of bumetanide at steady state.
The results from this study demonstrate that adequate luminal levels of bumetanide are required for the pharmacodynamics of the drug.
Diuretics: sites and mechanisms of action.
This review examines the renal pharmacology of diuretic drugs with respect to their sites and mechanisms of action as determined largely by micropuncture and in vitro microperfusion.