Furosemide Disposition in Cirrhotic Patients

Sawhney, Vinod K.; Gregory, Peter B.; Swezey, Sarah E.; Blaschke, Terrence F.

doi:10.1016/s0016-5085(81)80006-6

Cited by 48 publications

(10 citation statements)

References 14 publications

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“…More importantly, none of these studies have shown a clinically important reduction in frusemide clearance. In spite of the discrepancy in findings, there is agreement that differences in disposition play little role, if any, in the clinical effect of frusemide in cirrhotics (Sawhney et al, 1981;Verbeeck et al, 1982). Our findings are consistent with this view.…”

Section: Discussionsupporting

confidence: 85%

“…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: 97%

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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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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 97%

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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“…32 The good oral bioavailability of furosemide in the patient with cirrhosis, together with the acute reductions in glomerular filtration rate associated with intravenous furosemide, favor the use of the oral administration. 33,34 The dose of both oral diuretics can be increased simultaneously, maintaining the 100 mg:40 mg ratio, if weight loss and natriuresis are inadequate on the lower doses. In general, this ratio maintains normokalemia.…”

Section: Treatmentmentioning

confidence: 99%

Management of adult patients with ascites caused by cirrhosis†

Runyon¹

1998

Hepatology

302

131

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Ascites is the most common of the major complications of cirrhosis. The development of ascites is an important landmark in the natural history of cirrhosis and has been proposed as an indication for liver transplantation. The initial evaluation of a patient with ascites should include a history, physical evaluation, and abdominal paracentesis with ascitic fluid analysis. Treatment should consist of abstinence from alcohol, sodium restricted diet, and diuretics. This regimen is effective in Ϸ90% of patients. The treatment options for the diuretic-resistant patients include serial therapeutic paracenteses, liver transplantation, and peritoneovenous shunting. (HEPATOLOGY 1998;27;264-272.) PREAMBLE These guidelines provide a data-supported approach to the care of patients with ascites. They are based on the following: 1) a formal review and analysis of the published world literature (1,045 papers) on ascites (Medline Search from 1966-1996, search terms included ascites, diet therapy, drug therapy, radiotherapy, surgery, and therapy); 2) the American College of Physician' s Manual for Assessing Health Practices and Designing Practice Guidelines 1 ; and 3) several published and draft guidelines, including the American Association for the Study of Liver Diseases' Policy Statement on Development and Use of Practice Guidelines and American Gastroenterological Association' s Policy Statement on Guidelines 2 ; and 4) 15 years of experience on the part of the author in the clinical and laboratory investigations of and care for patients with this problem.These guidelines, intended for use by physicians, suggest preferable approaches to the diagnostic, therapeutic, and preventative aspects of care. These guidelines are intended to be flexible, in contrast with ''standards of care,'' which are inflexible policies to be followed in almost every case. 1 Furthermore, these guidelines were developed for the care of adult patients with clinically detectable ascites. Although the general approach may be applicable to children, the pediatric data base is much smaller and there may be unanticipated differences between adults and children. Patients with ascites that is detected by imaging modalities alone, but not yet clinically evident, are not included because of the lack of published information regarding the natural history of this entity.Specific recommendations are based on relevant published information. In an attempt to standardize recommendations, the Practice Guidelines Committee of the American Association for the Study of Liver Diseases modified the categories of the Infectious Diseases Society of America' s Quality Standards. 3 These categories are reported with each recommendation, using the letters A through E to determine the strength of recommendation and roman numerals I through III to determine quality of evidence upon which recommendations are based, as follows: A, survival benefit; B, improved diagnosis; C, improvement in quality of life; D, relevant pathophysiologic parameters improved; E, impacts cost of heal...

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“…[4][5][6] Several mechanisms for this loop diuretic resistance have been investigated and they include hypoalbuminaemia, diminished glomerular filtration rate (GFR), altered pharmacokinetics and pharmacodynamics of loop diuretics, and simultaneous usage of NSAIDs. [7][8][9][10][11] Of these, diminished GFR is perhaps one of the important mechanisms for loop diuretic resistance in patients with cirrhotic ascites. In a previous study, Villeneuve et al 8 investigated the furosemide pharmacokinetics and pharmacodynamics in eight normal volunteers and 14 patients with cirrhosis, eight of whom were resistant to diuretic therapy.…”

Section: Discussionmentioning

confidence: 99%

The effects of midodrine on the natriuretic response to furosemide in cirrhotics with ascites

Misra

Vuppalanchi

Jones

et al. 2010

Aliment Pharmacol Ther

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SUMMARY Background Resistance to loop diuretics is common in patients with ascites. Diminished glomerular filtration rate (GFR) is thought to mediate resistance to loop diuretics. Midodrine, a commonly used alpha-1 agonist, has been shown to improve GFR in non-azotemic patients with cirrhosis. Aim To conduct a randomized, double-blind, placebo-controlled, cross-over study to test the hypothesis that midodrine significantly increases natriuretic response of IV furosemide in non-azotemic cirrhotics with ascites. Methods All subjects participated in both phases, which were (i) furosemide IV infusion + oral midodrine 15 mg administered 30 min before furosemide (ii) furosemide IV infusion + oral placebo administered 30 min before furosemide. Primary outcomes were 6-h urine sodium excretion and 6-h total urine volume. Results A total of 15 patients (men: 8; age: 52.7 ± 7.6 years; serum creatinine: 1.06 ± 0.2 mg/dL) were studied. Total 6-h urine sodium excretion was 109 ± 42 mmol in the furosemide + midodrine treatment phase and was not significantly different from that in the furosemide + placebo treatment phase (126 ± 69 mmol, P = 0.6). Similarly, mean 6-h total urine volume was not significantly different between two groups (1770 ± 262 mL vs. 1962 ± 170 mL, P = 0.25). Conclusions Oral midodrine does not increase the natriuretic response to furosemide in non-azotemic cirrhotic patients with ascites. Orally administered midodrine does not increase natriuretic response to furosemide in non-azotemic cirrhotic patients with ascites.

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Furosemide Disposition in Cirrhotic Patients

Cited by 48 publications

References 14 publications

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

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

Management of adult patients with ascites caused by cirrhosis†

The effects of midodrine on the natriuretic response to furosemide in cirrhotics with ascites

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