-
Cardiology 1994The mechanism(s) responsible for diuretic resistance differ in different clinical conditions. Renal insufficiency is a prototype of a pharmacokinetic mechanism wherein... (Review)
Review
The mechanism(s) responsible for diuretic resistance differ in different clinical conditions. Renal insufficiency is a prototype of a pharmacokinetic mechanism wherein the disease causes decreased delivery of diuretic to its urinary site of action. Hepatic cirrhosis, on the other hand, is a prototype of a pharmacodynamic mechanism wherein normal amounts of diuretic reach the site of action but nephron response is subnormal. The mechanism of this effect is unknown. In congestive heart failure and in nephrotic syndrome, both pharmacokinetic and pharmacodynamic mechanisms occur. The different mechanisms of diuretic resistance in these various diseases dictate specific therapeutic strategies for each clinical condition.
Topics: Diuretics; Drug Resistance; Heart Failure; Humans; Liver Cirrhosis; Nephrotic Syndrome; Renal Insufficiency
PubMed: 7954547
DOI: 10.1159/000176458 -
JACC. Heart Failure Mar 2024
Topics: Humans; Heart Failure; Furosemide; Diuretics; Sodium Potassium Chloride Symporter Inhibitors; Acute Disease
PubMed: 38206231
DOI: 10.1016/j.jchf.2023.11.010 -
Journal of the American Society of... Mar 2002Patients with chronic renal insufficiency (CRI) or the nephrotic syndrome frequently manifest diuretic resistance. Factors limiting diuretic responsiveness in patients... (Review)
Review
Patients with chronic renal insufficiency (CRI) or the nephrotic syndrome frequently manifest diuretic resistance. Factors limiting diuretic responsiveness in patients with CRI may include a reduced basal level of fractional Na(+) reabsorption that places an upper limit on diuretic response, and enhanced NaCl reabsorption in downstream segments, combined with a reduced delivery of diuretic to the kidney. Diuretics are secreted by the recently characterized organic anion transporters (OATs), which are expressed in proximal tubule cells. Secretion may be inhibited by retained organic anions, urate, or acidosis. These limitations necessitate an increased diuretic dosage, up to a defined ceiling level, and consideration of the use of a nonrenally metabolized loop diuretic rather than furosemide. Diuretic responsiveness in patients with the nephrotic syndrome is limited by avid Na(+) reabsorption by the terminal nephron. Experimental studies have shown that a reduced serum albumin concentration can increase the volume of distribution of loop diuretics, reduce their tubular secretion, and enhance the inactivation of furosemide within the kidney by glucuronidization. Binding of loop diuretics can curtail their action in the loop of Henle. Recent clinical investigations have challenged the importance of some of these mechanisms that were identified in animal models. Strategies to improve loop diuretic responsiveness include increasing diuretic dosage, concurrent use of a thiazide diuretic to inhibit downstream NaCl reabsorption and attempts to maximally reduce albumin excretion. Strategies to limit albumin excretion include the use of an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker and appropriate limitation of protein intake. These measures are more logical, effective, and less expensive than infusion of albumin solutions.
Topics: Animals; Chronic Disease; Diuretics; Drug Resistance; Humans; Kidney Diseases; Kidney Failure, Chronic; Nephrotic Syndrome
PubMed: 11856788
DOI: 10.1681/ASN.V133798 -
Drugs & Aging Apr 2000Long term prescription of diuretics for heart failure is very prevalent among elderly patients, although the rationale for such a treatment strategy is often unclear, as... (Review)
Review
Long term prescription of diuretics for heart failure is very prevalent among elderly patients, although the rationale for such a treatment strategy is often unclear, as diuretics are not indicated if volume overload is absent. The concept of diastolic heart failure in the elderly might particularly change the role of diuretic therapy, since diuretics may have additional adverse effects in these patients. This paper reviews the effects of diuretic therapy in elderly patients with heart failure, emphasising the differences between patients with normal and decreased left ventricular systolic function. Studies on diuretic withdrawal in elderly patients with heart failure are discussed, with emphasis on issues involved in decision making such as diuretic dose reduction and withdrawal in elderly patients and factors that have been established to predict successful withdrawal. Existing guidelines on the prescription of diuretics in elderly patients with heart failure with normal and decreased left ventricular systolic function and in those with diastolic heart failure are also discussed. By reducing intravascular volume, diuretics may further impair ventricular diastolic filling in patients with diastolic heart failure and thus reduce stroke volume. Indeed, preliminary studies demonstrate that diuretics may provoke or aggravate hypotension on standing and after meals in these patients. Therefore, it is suggested that elderly patients with heart failure with intact left ventricular systolic function should not receive long term diuretic therapy, unless proven necessary to treat or prevent congestive heart failure. This implies that physicians should carefully evaluate the opportunities for diuretic dose tapering or withdrawal in all of these patients, and that a cautiously guided intermittent diuretic treatment modality may be critical in the care for older patients with heart failure with intact left ventricular systolic function.
Topics: Aged; Diastole; Diuretics; Heart Failure; Humans; Systole; Ventricular Dysfunction, Left
PubMed: 10874524
DOI: 10.2165/00002512-200016040-00005 -
American Journal of Health-system... Sep 2009The management of loop diuretic resistance in the intensive care unit (ICU) is reviewed. (Review)
Review
PURPOSE
The management of loop diuretic resistance in the intensive care unit (ICU) is reviewed.
SUMMARY
Volume overload, a common complication of fluid resuscitation, is frequently encountered in the ICU and is associated with numerous adverse effects, including pulmonary and peripheral edema, acute lung injury, and pleural effusions. Loop diuretics are used to treat volume overload and acute renal failure and to ameliorate their associated complications. When administered intravenously, these drugs induce vigorous and prompt diuresis, which may result in negative fluid balance. This may also result in significant adverse effects, including electrolyte imbalance, ototoxicity, and volume contraction. Prolonged use of loop diuretics may lead to loop diuretic resistance, a frequent observation in the ICU. Three general mechanisms are used to explain loop diuretic resistance: rebound sodium retention, postdiuretic effect, and diuretic braking. While very few agents have joined the armamentarium and no new strategies have been developed to deal with this phenomenon, several options are available to clinicians for managing loop diuretic resistance, including salt restriction, administration of i.v. loop diuretics, continuous infusion of loop diuretics, and combination therapy using loop diuretics and thiazides.
CONCLUSION
Loop diuretic resistance presents a challenge for clinicians in the ICU setting. Strategies to improve patients' responsiveness to these agents include fluid and salt restriction, switching from oral to i.v. loop diuretics, increasing diuretic dose, continuous infusion, and combination therapy with thiazides. Several of these strategies may be used concurrently to combat diuretic resistance and promote symptomatic relief of edema in the critically ill patient.
Topics: Diuretics; Drug Resistance; Drug Therapy, Combination; Edema, Cardiac; Humans; Intensive Care Units; Sodium Potassium Chloride Symporter Inhibitors; Water Intoxication
PubMed: 19729568
DOI: 10.2146/ajhp090068 -
Drugs & Aging Aug 1995Hypertension is the most important risk factor for cardiovascular events in the elderly and it is present in more than 50% of acculturated populations over 60 years of... (Review)
Review
Hypertension is the most important risk factor for cardiovascular events in the elderly and it is present in more than 50% of acculturated populations over 60 years of age. Morbidity trials have clearly demonstrated the benefits of treating hypertension in the elderly in all subgroups examined, including diabetics, those over 80 years of age, those with or without electrocardiographic abnormalities, and in both men and women. These reductions in strokes, coronary events, and other hypertensive complications have been seen primarily with diuretic-based regimens, with or without potassium-sparing therapy. However, in the 1990s physicians are initiating diuretics less often for older patients with hypertension in spite of this scientific evidence. Low doses of diuretics have been well tolerated, successful in recent morbidity trials, and avoid much of the concerns about theoretical toxicities from diuretics, although higher doses have also been shown to reduce cardiovascular events. Until calcium channel blockers, angiotensin converting enzyme inhibitors, alpha-blockers, or some other class of antihypertensive agent has been demonstrated to be at least as effective as diuretics in reducing cardiovascular events or mortality, diuretics should be the first drug class to consider for the treatment of hypertension in the elderly.
Topics: Aged; Diuretics; Female; Humans; Hypertension; Male; Risk Factors
PubMed: 7579787
DOI: 10.2165/00002512-199507020-00003 -
Journal of Nephrology 2010Diuretics are a heterogeneous class of drugs of tremendous importance in both the prevention and treatment of cardiovascular and renal disease. Used as... (Review)
Review
Diuretics are a heterogeneous class of drugs of tremendous importance in both the prevention and treatment of cardiovascular and renal disease. Used as antihypertensives, diuretic-based therapy to lower blood pressure reduces cardiovascular events. In addition to their role as preventive agents, diuretics are critical to the management of several commonly encountered edematous conditions, including chronic kidney disease and the nephrotic syndrome. Because a threshold amount of diuretic is necessary to elicit the intended natriuretic effect, alterations in the pharmacokinetic and pharmacodynamic parameters occurring in the presence of a variety of renal conditions necessitate careful dose titrations and adjustment. Higher doses or more frequent administration may be necessary to maintain the drug level above the diuretic threshold. In refractory cases, diuretics with differing sites of action in the nephron can be combined to potentiate therapeutic effects. Selection of the proper diuretic agent and its dosing strategy are dependent on knowledge of within-class characteristics, as well as a commensurate understanding of the physiology of the disease being treated.
Topics: Diuretics; Humans; Hypertension; Kidney Diseases
PubMed: 20677164
DOI: No ID Found -
Hellenic Journal of Cardiology : HJC =... 2023The treatment of congestion in heart failure (HF) is a challenge despite the therapeutic arsenal available. The aim of this study was to analyze different combinations...
BACKGROUND
The treatment of congestion in heart failure (HF) is a challenge despite the therapeutic arsenal available. The aim of this study was to analyze different combinations of diuretics used to resolve congestion in patients admitted for decompensated HF and to define clinical profiles according to these treatments.
METHODS
Single-center study of 1,559 patients admitted for decompensated HF was done between 2016 and 2020. Patients were grouped according to the diuretic combination that led to clinical stabilization and discharge from the hospital: (1) Loop diuretic. (2) Loop diuretic + distal tubule (antialdosterone ± thiazides). (3) Loop diuretic + distal + proximal tubule (acetazolamide ± SGLT2 inhibitor). (4) Loop diuretic + distal tubule + collecting duct (tolvaptan). (5) Loop diuretic + distal + proximal + collecting duct. Based on these diuretic combinations, profiles with clinical, analytical, and echocardiographic differences were established.
RESULTS
There were more previous hospitalizations in groups 4 and 5 (p = 0.001) with a predominance of pulmonary congestion in profiles 1 and 2 and systemic congestion in 3, 4, and 5. Creatinine and CA125 were higher in profiles 4 and 5 (p = 0.01 and p = 0.0001), with no differences in NT-proBNP. Profiles 4 and 5 had a higher proportion of dilatation and depression of right ventricular (p = 0.0001) and left ventricular (p = 0.003) function. Diuretic therapy-defined groups showed difference in clinical characteristics.
CONCLUSIONS
The diuretic treatment used identifies five clinical profiles according to the degree of congestion, renal function, CA125, and right ventricular functionality. These profiles would guide the best diuretic treatment on admission.
Topics: Humans; Diuretics; Sodium Potassium Chloride Symporter Inhibitors; Treatment Outcome; Heart Failure; Phenotype
PubMed: 37068639
DOI: 10.1016/j.hjc.2023.03.009 -
The Medical Clinics of North America May 1997Diuretics have changed the approach to many disease and have turned once fatal conditions into tolerable ones. Treatment of salt and water overload and edema can be... (Review)
Review
Diuretics have changed the approach to many disease and have turned once fatal conditions into tolerable ones. Treatment of salt and water overload and edema can be quite satisfying for the clinician as long as the patient is closely watched for side effects. Thiazide diuretics have their greatest use in hypertension, loop diuretics in edema and congestive heart failure, CA inhibitors in glaucoma and altitude sickness, potassium-sparing diuretics in hypokalemia induced by other diuretics and ascites, and osmotic diuretics in acute renal failure and dialysis. They are among the most widely prescribed medications in the world today and rightly have a prominent place in the armamentarium against disease.
Topics: Diuretics; Edema; Heart Failure; Humans; Hypertension; Kidney
PubMed: 9167652
DOI: 10.1016/s0025-7125(05)70540-x -
Current Heart Failure Reports Feb 2023Heart failure is characterized by episodes of congestion with need for hospitalization. The current metrics lack the accuracy to predict and prevent episodes of... (Review)
Review
PURPOSE OF REVIEW
Heart failure is characterized by episodes of congestion with need for hospitalization. The current metrics lack the accuracy to predict and prevent episodes of congestion and to guide diuretic titration to reach euvolemia in case of decompensation. This article aims to provide answers to the role of urinary sodium measurements in acute and chronic heart failure.
RECENT FINDINGS
In acute heart failure, urinary sodium concentrations at the moment of admission and after diuretic administration are correlated with short- and long-term outcome. As this is a reflection of the degree of sodium retention, it can be used as a guide in the diuretic titration. In chronic heart failure, it might be used to predict and consequently prevent episodes of decompensation. Urinary sodium measurements hold great promises to be a novel diagnostic and therapeutic parameter in patients with acute and chronic heart failure. However, more research is needed.
Topics: Humans; Heart Failure; Follow-Up Studies; Sodium Potassium Chloride Symporter Inhibitors; Diuretics; Sodium; Chronic Disease
PubMed: 36807114
DOI: 10.1007/s11897-023-00591-4