Pharmacokinetics of loop diuretics in congestive heart failure

Dc, Brater

doi:10.1136/hrt.72.2_suppl.s40

Cited by 49 publications

(44 citation statements)

References 20 publications

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“…It is also important to note that patients with certain disease states (e.g., nephrotic syndrome, hepatic cirrhosis, and congestive heart failure) may fail to achieve a normal response to loop diuretics, regardless of the urinary diuretic excretion rate achieved [14,[103][104][105]. The mechanism of this diuretic resistance is not well defined, but may involve enhanced proximal and distal sodium reabsorption.…”

Section: Pharmacodynamicsmentioning

confidence: 97%

The clinical pharmacology of loop diuretics in the pediatric patient

Eades

Christensen

1998

Pediatric Nephrology

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The loop diuretics furosemide and bumetanide are frequently employed in the pediatric population for the management of fluid overload in both acute and chronic disease states. They act mainly by inhibiting sodium reabsorption in the nephron at the thick ascending limb of Henle's loop. Important pharmacokinetic differences between adults and infants include a reduced clearance and prolonged half-life, that may cause accumulation of these agents to potentially toxic levels if dosing intervals are not adjusted. Unfortunately, little is known about the time required for maturation of loop diuretic elimination in older infants, children, and adolescents. Similar to adults, limited pharmacodynamic evidence in neonates suggests that a maximally efficient diuretic dose exists. Increasing the diuretic dose beyond this maximum does not offer further benefit, but may increase the risk of toxicity. Common problems encountered in the pediatric patient as well as in adults are loop diuretic tolerance and resistance. Loop diuretic dosing strategies aimed at overcoming these phenomena include administration by continuous infusion, coadministration with albumin, and coadministration with metolazone or thiazides. This article reviews the pharmacology, pharmacokinetics, and pharmacodynamics of furosemide and bumetanide in pediatric patients. A better understanding of the clinical pharmacology of the loop diuretics should aid clinicians in the development of dosing regimens aimed at producing adequate diuresis without promoting excessive diuretic tolerance.

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Section: Pharmacodynamicsmentioning

confidence: 97%

The clinical pharmacology of loop diuretics in the pediatric patient

Eades

Christensen

1998

Pediatric Nephrology

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“…[IO,ll,22,23] This finding is in distinct contrast to the delays in absorption that have been observed with furosemide and bumetanide in patients with both compensated and decompensated CHF.l24, 25] It should be noted on the one hand that the preserved rapidity of absorption of torasemide could have important clinical ramifications. [IO,ll,22,23] This finding is in distinct contrast to the delays in absorption that have been observed with furosemide and bumetanide in patients with both compensated and decompensated CHF.l24, 25] It should be noted on the one hand that the preserved rapidity of absorption of torasemide could have important clinical ramifications.…”

Section: Effects Of Chf On Diuretic Efficacymentioning

confidence: 99%

Benefits and Risks of Torasemide in Congestive Heart Failure and Essential Hypertension

1996

Drug Safety

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Torasemide is a lipophilic anilinopyridine sulphonylurea derivative that acts as a high ceiling loop diuretic and has been used for the treatment of both acute and chronic congestive heart failure (CHF) and hypertension. Torasemide is similar to other loop diuretics in terms of its mechanism of diuretic action; namely, blockade of Na+/K+/2Cl- cotransport in the thick ascending limb of the loop of Henle. It has high bioavailability (> 80%), as does bumetanide, but a longer elimination half-life (3 to 4 hours) than either bumetanide or furosemide (frusemide). In the treatment of chronic CHF, oral torasemide (5 to 20 mg/day) has been shown to be an effective diuretic. Patients treated with torasemide for up to 1 year have reduced bodyweight, improved pulmonary haemodynamics, and decreased CHF severity. Intravenous torasemide (20 to 60mg as a single dose) has been shown to be as effective as furosemide in the treatment of acute CHF, and resulted in significant diuresis, bodyweight loss, and improved pulmonary haemodynamics and exercise performance. 'Non-diuretic' dosages (2.5 to 5 mg/day) of oral torasemide have been used to treat essential hypertension, both as monotherapy and in combination with other antihypertensive agents. When used in these dosages, torasemide lowered diastolic blood pressure (DBP) to below 90mm Hg in 8 to 12 weeks in 70 to 80% of patients. With dose doubling, this level of efficacy occurred in more than 90% of hypertensive patients. Clinical trials have established that blood pressure can be maintained at this level for at least 1 year with low dose torasemide. Torasemide is well tolerated in dosages up to 20 mg/day for at least 1 year. The most commonly reported adverse effects are those associated with loop diuretics in general. These include transient hypokalaemia, hyperuricaemia, dizziness, headache, gastrointestinal disturbances, orthostatic hypotension and fatigue. Adverse effects are comparable with those of other diuretics and rarely necessitate drug withdrawal.

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“…The delayed rate of absorption may be due to delayed gastric emptying and impaired gastrointestinal mobility or to edema of the gastrointestinal wall. 12 …”

Section: Pharmacokinetic and Pharmacodynamic Considerations In Heart mentioning

confidence: 99%

Loop Diuretic Therapy in Heart Failure: The Need for Solid Evidence on a Fluid Issue

Chiong

Cheung

2010

Clinical Cardiology

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BackgroundHeart failure (HF) is a common condition associated with substantial cost, morbidity, and mortality. Because results of clinical trials in the acute decompensated heart failure (ADHF) setting have been mostly neutral, loop diuretics remain the mainstay of treatment.HypothesisLoop diuretic use may be associated with unfavorable outcomes.MethodsA MEDLINE literature search was performed to identify articles relating to heart failure and loop diuretics. The current evidence on the risks and benefits of loop diuretics for the treatment of ADHF is reviewed.ResultsLoop diuretics are associated with symptomatic improvements in congestion, urine output, and body weight, but have shown no long‐term mortality benefit. Loop diuretics, especially at high doses, are associated with worsened renal function and other poor outcomes.ConclusionsLoop diuretics still prove useful in HF treatment, but risk‐benefit analysis of these agents in the treatment of ADHF requires a well‐designed prospective study. Copyright © 2010 Wiley Periodicals, Inc.

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Pharmacokinetics of loop diuretics in congestive heart failure

Cited by 49 publications

References 20 publications

The clinical pharmacology of loop diuretics in the pediatric patient

The clinical pharmacology of loop diuretics in the pediatric patient

Benefits and Risks of Torasemide in Congestive Heart Failure and Essential Hypertension

Loop Diuretic Therapy in Heart Failure: The Need for Solid Evidence on a Fluid Issue

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