Influence of hepatic cirrhosis and end-stage renal disease on pharmacokinetics and pharmacodynamics of furosemide

Keller, E.; Hoppe-Seyler, G.; Mumm, Rebekka; Schollmeyer, P.

doi:10.1007/bf00554663

Cited by 82 publications

(22 citation statements)

References 22 publications

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“…5 The mechanisms of resistance to furosemide have been evaluated in cirrhotic patients with ascites in several studies reported over the last 20 years. [6][7][8][9] It is now well recognized that furosemide pharmacokinetics are not altered by cirrhosis. The reduction in pharmacodynamic response, i.e.…”

Section: Discussionmentioning

confidence: 99%

Furosemide-induced natriuresis as a test to identify cirrhotic patients with refractory ascites

et al. 2001

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The diagnosis of refractory ascites in cirrhotic patients carries a poor prognosis and liver transplantation should always be considered in this situation. Identification of patients who will not respond to diuretic therapy usually requires several weeks of observation during which a trial of diuretics is instituted using stepwise increases in dosage in order to classify ascites as refractory. In the present study we evaluated the effect of a single dose of 80 mg intravenous furosemide on urinary sodium excretion over 8 hours in cirrhotic patients with ascites responsive to diuretic treatment (group 1; n ‫؍‬ 14) and patients with refractory ascites (group 2; n ‫؍‬ 15). The test was performed after 3 days without diuretics and patients were on a 80 mEq sodium/ day diet.

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Section: Discussionmentioning

confidence: 99%

Furosemide-induced natriuresis as a test to identify cirrhotic patients with refractory ascites

et al. 2001

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“…Proximal Na ÷ hyperreabsorption in diseases with reduced effective arterial blood volume, EABV Diseases presenting a "depressed" dose-response curve or resistance to diuretics include congestive heart failure (CHF) [2], decompensated cirrhosis of the liver [9], and nephrotic syndrome [10]. The common denominator of these disease entities is the reduced "effective arterial blood volume" (EABV), in which the relationship between cardiac output (CO) and peripheral vascular resistance dictates the filling of the arterial vascular tree [26,27].…”

Section: Dose-response Relationships For Diureticsmentioning

confidence: 99%

Low-dose segmental blockade of the nephron rather than high-dose diuretic monotherapy

Knauf

Mutschler

1993

Eur J Clin Pharmacol

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The specific renal effect of diuretics is due to the fact that their concentrations is almost 100-fold greater in the renal tubule than in the plasma. The function of the different segments of the nephron may be altered following changes in the effective arterial blood volume (EABV) and the extracellular fluid volume (ECFV). In diseases with reduced EABV, e.g., congestive heart failure, decompensated cirrhosis of the liver, and the nephrotic syndrome, proximal tubular hyperreabsorption of sodium occurs, leaving only a low Na+ load in the distal segments of the nephron, the site of diuretic action. Clinically, the response to diuretics is reduced or resistance to diuretics may even ensue, which can be predicted by a FENa < 0.2%. Resistance to diuretics can be overcome by short-term comedication with acetazolamide, which increases Na+ delivery to the site of action of the other diuretics used concomitantly. In states with increased ECFV, e.g. in chronic renal failure, there is distal tubular Na+ rejection, leading to a greater increase in FENa the more GFR is reduced. The remaining intact nephrons present a relatively increased response to diuretics. The efficacy of diuretic treatment in renal failure can be optimised by combining loop diuretics with thiazides. In conclusion, low-dose combination therapy, inducing "segmental blockade of the nephron", meets the functional changes along the nephron. It is therefore more effective and safer than high-dose monotherapy.

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“…For example, studies on frusemide disposition are contradictory. Some indicate impairment of frusemide elimination (Fuller et al, 1981;Sawhney et al, 1981) whereas others have found no change (Allgulander et al, 1980;Keller et al, 1981;Verbeeck et al, 1982). More importantly, none of these studies have shown a clinically important reduction in frusemide clearance.…”

Section: Discussionmentioning

confidence: 98%

An intensive drug monitoring study suggesting possible clinical irrelevance of impaired drug disposition in liver disease.

Naranjo¹,

Busto²,

Janecek³

et al. 1983

Brit J Clinical Pharma

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1 Liver disease can alter the disposition and clinical effects of drugs. However, even though altered drug disposition occurs, there is no clinical evidence relating it to an increased susceptibility to adverse drug reactions (ADRs). 2 An intensive prospective drug monitoring study of 2,582 hospitalized patients was conducted. The adverse drug reactions probability scale (APS) was used to assess ADRs. Only non‐mild, definite or probable ADRs (APS greater than or equal to 5) were included. Severity of liver dysfunction was assessed by a composite clinical and laboratory index (CCLI). 3 The frequency of ADRs was higher in 402 patients with cirrhosis (27.4%) than in 661 with renal dysfunction (22.8%) and in 249 with other parenchymatous liver diseases (13.7%) or in 1,270 patients with neither liver diseases nor renal dysfunction (10.9%) (chi 2 3 = 85.53, P less than 0.001). The frequency of ADRs in cirrhotics was highly correlated with the severity of the liver dysfunction measured by CCLI (r = 0.82, P less than 0.001). 4 Drugs predominantly eliminated by liver metabolism were not among those most commonly inducing ADRs or those causing severe reactions in cirrhotics. Thus, frusemide caused the most common and the most severe ADRs, whereas reactions induced by sedatives were uncommon. Drug‐induced hepatic encephalopathy was more common in cirrhotics receiving diuretics (13.3%) than in those receiving sedatives (1.8%) (chi 2 y.c. = 5.29, P less than 0.025). Patients with alcoholic liver disease had more drug‐induced hepatic encephalopathy (7.7%) than those with non‐alcoholic liver disease (1.2%) (chi 2 y.c. = 11.86, P less than 0.001). 5 These results indicate that susceptibility to ADRs is increased only in severe cirrhosis and that the most common and severe ADRs seem more likely related to enhanced pharmacodynamic action than to impaired drug disposition.

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Influence of hepatic cirrhosis and end-stage renal disease on pharmacokinetics and pharmacodynamics of furosemide

Cited by 82 publications

References 22 publications

Furosemide-induced natriuresis as a test to identify cirrhotic patients with refractory ascites

Furosemide-induced natriuresis as a test to identify cirrhotic patients with refractory ascites

Low-dose segmental blockade of the nephron rather than high-dose diuretic monotherapy

An intensive drug monitoring study suggesting possible clinical irrelevance of impaired drug disposition in liver disease.

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