Diuretic effect of metoprolol

Metoprolol caused a significant (P less than 0.001) increase in urine output in rabbits. There was no change in serum sodium concentration but serum potassium levels increased significantly. The most probable mechanism of action was increase in renal blood flow and glomerular filtration rate.     

Diuretic resistance in heart failure

The use of diuretics for the treatment of heart failure (HF) is ubiquitous in any basic HF medical regimen. Although initially these drugs clearly show benefit by relieving symptomatic episodes of decompensated HF, long-term use of these drugs can lead to a ‘diuretic-resistant’ state and is associated with an increased risk of morbidity and mortality. A number of factors may be responsible for this, including dietary noncompliance, inadequate diuretic dosing or methods of administration, and concomitant use of certain medications. Diuretics themselves may set in motion an iatrogenic cardiorenal syndrome leading to worsening renal function and diuretic resistance. The methods for overcoming this resistance are varied and require a focused approach with emphasis on relieving the congestive symptoms related to HF while attempting to preserve renal function and minimize any untoward systemic effects.     

Diuretic use in renal disease

Diuretics are agents commonly used in diseases characterized by excess extracellular fluid, including chronic kidney disease, the nephrotic syndrome, cirrhosis and heart failure. Multiple diuretic classes, including thiazide-type diuretics, loop diuretics and K(+)-sparing diuretics, are used to treat patients with these diseases, either individually or as combination therapies. An understanding of what determines a patient's response to a diuretic is a prerequisite to the correct use of these drugs. The response of patients with these diseases to diuretics, which is related to the dose, is best described by a sigmoid curve whose contour can become distorted by any of the several sodium-retaining states that are directly or indirectly associated with renal disease. Diuretic actions are of considerable importance to patients who have renal disease, as their effective use assists in extracellular fluid volume control, reducing excretion of protein in urine and lessening the risk of developing hyperkalemia. Diuretic-related adverse events that involve the uric acid, Na(+) and K(+) axes are not uncommon; therefore the clinician must be vigilant in looking for biochemical disturbances. As a result of diuretic-related adverse events, clinicians must be resourceful in the dose amount and frequency of dosing.     

Hemodynamic Actions of Diuretic Agents

The blood pressure lowering effect of diuretics in hypertensive disease is well documented. The hemodynamic actions underlying this antihypertsive effect differ in the early phase from the effects observed during long-term treatment. This article first describes new experiments on the hemodynamic effects of three diuretics, viz. hydrochlorothiazide, chlorthalidon and furosemide in conscious, chronically instrumented spontaneously hypertensive rats. This animal model was chosen in view of its good applicability for the study of the hemodynamics of antihypertensive drug action. Results show a marked early fall in stroke volume and cardiac index with all three diuretics. Mean arterial blood pressure was decreased only after a delay of several hours, because of an early large increase in total peripheral resistance. This article furthermore discusses possible mechanisms involved in the long-term return of peripheral resistance close to or below pre-treatment values. On the basis of data in the literature it is concluded that adaptation of baroreceptor reflexes, auto-regulatory responses of the peripheral vascular resistance and enhanced production of endogeneous vasodilator substances play an increasingly important role during the long-term hemodynamic actions of diuretic agents.     

Diuretic use in critical care

Diuretics have found wide application in critical care medicine. The use of mannitol and loop diuretics in a variety of life-threatening disorders is reviewed. The combined venodilatory and natriuretic effects of bumetanide, furosemide and ethacrynic acid relieve congestive symptoms in pulmonary edema. Although commonly administered to prevent development of acute tubular necrosis or in varying stages of evolving disease, few data are available to demonstrate the efficacy of mannitol or loop diuretics. An approach to the oliguric patient with acute tubular necrosis is described. The dangers of hyponatremia are reviewed, and the rational use of loop diuretics and hypertonic saline is outlined. The 3 loop-active agents inhibit calcium reabsorption in the thick ascending limb of Henle's loop and therefore have proved useful in treating hypercalcemia. A practical approach to the diuretic-saline treatment of severe hypercalcemia is outlined. The kaliuretic effect of loop diuretics can be used to advantage in patients with acute or chronic hyperkalemia. A guide to such therapy is described.     

Diuretic action of estradiol.

Several clinical situations are strongly suggestive that estrogens are diuretic substances that secondarily promote sodium and water retention in the body by stimulation of adreno-cortical hormone secretion. To investigate the direct action of estradiol on diuresis, the hormone was administered to the isolated, perfused rabbit kidney. Results demonstrated that estradiol increases urine volume, tubular sodium excretion and potassium reabsorption, and diminishes arterial pressure and renovascular resistance. The possible relationships between these effects and with pre-menstrual syndrome, pre-eclampsia, and menopausal hypertension are discussed.     

Diuretic therapeutics in the pediatric patient

Careful management of fluid and electrolytes has long been an intrinsic part of pediatric practice. However, the augmentation of these manipulations through the rational use of diuretic agents requires considerable skill. In pediatric medicine, the regulation of pharmacokinetic processes and their interface with pharmacodynamic processes show dramatic age-related changes. These ontogenetic processes and their modification by various disease states must be considered carefully before selection and application of diuretic agents. The available data concerning the ontogeny of renal function and the attempts to apply diuretic therapy to pediatric disease are reviewed. It is concluded that results obtained to date suffer from the absence of a rigorous attempt to answer the fundamental therapeutic questions: What drug? What dose? What duration of therapy? A rational "target-effect" strategy is proposed for the application of diuretic agents to pediatric medicine.     

Diuretic therapy in congestive heart failure

Diuretics are a mainstay of therapy in patients with congestive heart failure. A small number of patients can achieve adequate diuresis with a thiazide diuretic alone, but most require a loop diuretic. Some patients with severe disease require combinations of diuretics. Most patients with congestive heart failure manifest resistance to diuretics by having a diminished natriuresis compared with healthy counterparts. This diminished response even to potent diuretics means that dietary sodium may exceed sodium excretion, resulting in patient decompensation. The pharmacokinetics and pharmacodynamics of loop diuretics have been characterized in patients with congestive heart failure, thereby allowing rational therapeutic strategies in terms of what type of doses should be administered, how often, and when to use diuretic combinations. The purpose of this review is to show how understanding pharmacokinetics and pharmacodynamics results in logical diuretic use. (c)2000 by CHF, Inc.     

Multinephron Segment Diuretic Therapy to Overcome Diuretic Resistance in Acute Heart Failure: A Single-Center Experience

BackgroundThe concept of multinephron segment diuretic therapy (MSDT) has been recommended in severe diuretic resistance with only expert opinion and case-level evidence. The purpose of this study was to investigate the safety and efficacy of MSDT, combining 4 diuretic classes, in acute heart failure (AHF) complicated by diuretic resistance.Methods and ResultsA retrospective analysis was conducted in patients hospitalized with AHF at a single medical center who received MSDT, including concomitant carbonic anhydrase inhibitor, loop, thiazide, and mineralocorticoid receptor antagonist diuretics. Subjects served as their own controls with efficacy evaluated as urine output and weight change before and after MSDT. Serum chemistries, renal replacement therapies, and in-hospital mortality were evaluated for safety. Patients with severe diuretic resistance before MSDT were analyzed as a subcohort. A total of 167 patients with AHF and diuretic resistance received MSDT. MSDT was associated with increased median 24-hour urine output in the first day of therapy compared with the previous day (2.16 L [0.95–4.14 L] to 3.08 L [1.74–4.86 L], P = .003) in the total cohort and in the Severe diuretic resistance cohort (0.91 L [0.43–1.43 L] to 2.08 L [1.13–3.96 L], P < .001). The median cumulative weight loss at day 7 or discharge was –7.4 kg (–15.3 to –3.4 kg) (P = .02). Neither serum sodium, chloride, potassium, bicarbonate, or creatinine changed significantly relative to baseline (P > .05 for all).ConclusionsIn an AHF cohort with diuretic resistance, MSDT was associated with increased diuresis without changes in serum chemistries or kidney function. Prospective studies of MSDT in AHF and diuretic resistance are warranted.     

Diuretic therapy in congestive heart failure

The principal goals of treatment of the patient in heart failure are the relief of their symptoms and improvement in their prognosis. Of all antiheart failure drugs currently available, the diuretics are therapeutically superior in their efficacy in relieving clinical symptoms and signs. Whether administered intravenously or orally, all diuretics result in a substantial reduction in the raised pulmonary vascular pressures in combination with a small reduction in cardiac output. Diuretics stimulate release of renin with subsequent activation of the renin-angiotensin-aldosterone system, particularly if used in large doses, although their quantitative impact on the neuroendocrine profile at different stages of heart failure remains to be defined. In patients with mild heart failure, diuretics reduce plasma catecholamine concentrations, but their sympatholytic effects in more severe cases are unknown, as are their effects on the metabolically active tissues in these patients. Diuretic resistance can be circumvented by segmental nephron blockade with a combination of low-dose diuretics that simultaneously block sodium reabsorption in the proximal tubule, the loop of Henle, the distal tubule, and the collecting duct. Diuretics improve symptoms of breathlessness and signs of peripheral edema in patients with congestive heart failure in direct relationship to the induced diuresis. These benefits are frequently associated with a substantial improvement in patients' appreciation of quality of life and economic capacity. There are few adverse reactions to chronic diuretic therapy, but the serum electrolytes should be monitored for hypokalemia and hypomagnesemia. The impact of diuretics on prognosis of patients with congestive heart failure is unknown; however, diuretics have been a major ingredient of the therapies used in all the survival trials with vasodilators, angiotensin-converting enzyme inhibitors, and beta-blocking drugs. In addition to their clinical benefits, diuretics are the most cost-effective treatment of any single drug group currently available for the treatment of patients with congestive heart failure.