Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “DIURETICS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 451 records · Page 25Linked to original sources
PubMed1996

Demonstration of an in vitro direct vascular relaxant effect of diuretics in the presence of plasma.

OBJECTIVE: To determine whether diuretics have direct vascular actions and to compare the in vitro effects of a loop diuretic with thiazide and thiazide-like diuretics. DESIGN: A randomized, double-blind, vehicle-controlled design was used to avoid experimenter bias. METHODS: Concentration-response curves to hydrochlorothiazide, chlorthalidone, indapamide, and furosemide were tested on the following male Wistar rat vascular smooth muscle preparations: rat aortic rings, rat pulmonary artery rings, and rat mesenteric portal vein. RESULTS: All four diuretics demonstrated no vasorelaxant action in Krebs solution. They all exhibited vasorelaxant actions in aortic and pulmonary artery rings when plasma was mixed with Krebs solution in a 50:50 ratio. The magnitude of the relaxation was greater in the aortic ring preparation. This direct vascular action was found to be concentration dependent and endothelium independent. The order of potency of the vasorelaxant action of the diuretics was (from most to least) indapamide, hydrochlorothiazide, chlorthalidone, and furosemide on both aortic and pulmonary artery rings. CONCLUSION: Diuretics possess direct vasorelaxant effects that are dependent upon the presence of plasma; this action may contribute to their antihypertensive properties.

Animals↗
PubMed1998

What is the plasma cofactor required by diuretics for direct vascular relaxant effect in vitro?

OBJECTIVE: To determine the plasma cofactor which is required by diuretics (hydrochlorothiazide, chlorthalidone, indapamide, and furosemide) for direct vasorelaxant effects in vitro. DESIGN: A randomized, double-blind, vehicle-control design was used to avoid experimenter bias. METHODS: We plotted concentration-response curves for responses to hydrochlorothiazide, chlorthalidone, indapamide, and furosemide of male Wistar rat aortic rings in the presence of different bath solutions containing various plasma factors. RESULTS: Plasma was found both to make possible and facilitate the vasodilator action of the diuretics tested by an action on the membrane and to decrease the action by binding the diuretics. The diuretics retained their vasorelaxant properties in Krebs solution alone, 30 min after having been incubated in a 50:50 solution of Krebs solution and plasma for 1 h. All four diuretics exerted significant vasorelaxant actions in Krebs solution-plasma, Krebs solution-serum, and Krebs solution plus human or bovine albumin (40 g/l) media. No vasorelaxant action was found in Krebs solution alone, Krebs solution plus denatured plasma, Krebs solution plus egg albumin, and Krebs solution plus insulin. CONCLUSION: Albumin is the main cofactor required by the diuretics tested for direct relaxant action in vitro, and these findings may explain some of the contradictory evidence concerning this action in the literature.

Animals↗
PubMed1984

Adverse reactions to long-term diuretic therapy for hypertension.

Diuretics are important drugs used in therapy for hypertension. Diuretics have a number of side effects, some of which have long-term consequences. In this study diuretics were used to treat individuals with mild hypertension. Patients receiving diuretics as sole therapy had an increased mortality due to an excess number of deaths from myocardial infarction or sudden death. In patients given alpha-methyldopa or propranolol as well as a diuretic drug, this effect was not observed. The increased mortality may be due to an increased susceptibility to arrhythmias in individuals receiving diuretics, and this was prevented by drugs that interfere with the effects of the sympathetic nervous system.

Adrenergic beta-Antagonists↗
PubMed1997

Sequential nephron blockade breaks resistance to diuretics in edematous states.

Diuretic therapy in edematous diseases often yields an inadequate natriuretic response ("diuretic resistance"). To study the functional changes in patients with congestive heart failure, liver cirrhosis with ascites, and nephrotic syndrome, characterized by a reduced effective arterial blood volume (EABV), different diuretic strategies were studied. It was shown that monotherapy with hydrochlorothiazide or furosemide was followed by an inadequate natriuretic response. Correlation of diuretic response with pretreatment fractional sodium excretion of the patient revealed a clear-cut interdependency: Those patients were resistant whose FENa+ was greatly below normal (<0.2%). In addition, it was found that the coadministration of the carboanhydrase inhibitor acetazolamide to diuretic therapy was very effective. We therefore conclude that an increase in proximal-tubular Na+ reabsorption is the major ("pharmacodynamic") determinant for diuretic resistance in edematous diseases with functional "underfilling" of the vascular tree. This alteration of the kidney can easily be overcome by coadministration of a carboanhydrase inhibitor (e.g., acetazolamide).

Acetazolamide↗
PubMed2003

Impaired drainage on diuretic renography using half-time or pelvic excretion efficiency is not a sign of obstruction in children with a prenatal diagnosis of unilateral renal pelvic dilatation.

PURPOSE: Delayed drainage on diuretic renography is an accepted sign of obstruction in adults and symptomatic children. We investigated how to analyze the diuretic challenge as well as assess the significance of impaired drainage. MATERIALS AND METHODS: We followed 24 children with a unilateral prenatal diagnosis of pelvic dilatation up to a minimum of 2 years. A total of 91 diuretic renograms were performed. All children had stable differential renal function and renal pelvic diameter did not change by greater than 9 mm. on sequential ultrasound. Kidneys with stable differential function and no increase in dilatation were considered not obstructed. Analysis of the diuretic challenge included half-time, a post-void image with a change in posture, that is the child erect for 5 to 7 minutes, and drainage considering renal function using the pelvic excretion efficiency. Prolonged drainage was defined as a half-time of greater than 20 minutes or a post-void pelvic excretion efficiency of less than 71%. RESULTS: Median patient age at presentation was 0.32 years and median followup was 3.07 years. The affected nonobstructed hydronephrotic kidney showed impaired drainage in 68% of the children using the half-time parameter, and in 80% and 44% using pelvic excretion efficiency before and after voiding, respectively. Variability in drainage was documented on sequential diuretic renography. CONCLUSIONS: Using the guidelines for data acquisition and processing of diuretic renograms we nevertheless noted impaired drainage in 44% of this young group with nonobstructed kidneys. The half-time parameter was an inappropriate parameter. The diagnosis of obstruction cannot be simply based on delayed drainage in this group of asymptomatic children with a prenatal diagnosis of unilateral renal pelvic dilatation.

Age Factors↗
PubMed1987

Evolution of diuretics and ACE inhibitors, their renal and antihypertensive actions--parallels and contrasts.

The emergence of diuretic drugs and angiotensin converting enzyme (ACE) inhibitors ranks amongst the major therapeutic advances of modern medicine. The discovery of these drug groups arose largely by chance, yet each has dramatically influenced the treatment of congestive cardiac failure and arterial hypertension. The central role which diuretics have had in the management of both oedema and hypertension hinges on their ability to induce a net renal excretion of solute and water by selective interference with either active or passive ion transport processes in different segments of the nephron. Irrespective of sites of action, the continued antihypertensive action of diuretics is characterized by a reduction in plasma volume and extracellular fluid (ECF) volume that lasts for as long as the diuretic is given. The mechanism of this effect remains unclear but may involve autoregulatory reactions that leave cardiac output unaltered but maintain a sustained reduction in total peripheral resistance. ACE inhibitors also lower blood pressure by decreasing total peripheral resistance, leaving cardiac output, plasma volume and ECF volume unchanged. The detailed way these haemodynamic changes are achieved remains unknown but inhibition of converting enzyme present not only in the kidney but also in many extrarenal tissue sites, appears important. In both hypertension and cardiac failure, however, the kidney acts as a key target organ for ACE inhibitors. The increased renal vascular resistance and inappropriate renal salt excretion are reversed with enhanced renal blood flow and saluresis. Both angiotensin II (AII) and vasopressin-mediated contraction of glomerular mesangial cells is inhibited, making glomerular filtration more efficient. Reduced aldosterone secondary to blockade of AII formation contributes to saluresis whilst encouraging positive potassium balance. ACE inhibition also impairs breakdown of kinins which may contribute to intrarenal and peripheral vasodilation either on their own or via release of prostaglandins and other vasoactive substances. The hypotensive actions of diuretics are potentiated by ACE inhibition primarily through blockade of AII formation and prevention of secondary aldosteronism. In combination, these drugs permit low doses to be used because of their synergistic effects. Caution has to be exercised whenever ACE inhibition is used, without and especially with diuretics, in the management of renovascular hypertension and other low-perfusion states. In these circumstances, AII plays an important autoregulatory role in preserving glomerular filtration through an increase in post-glomerular resistance.(ABSTRACT TRUNCATED AT 400 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Refractory oedema in congestive heart failure: a contributory role of loop diuretics?

We report a patient with congestive heart failure (CHF) who presented with massive oedema resistant to therapy with maximal doses of loop diuretics, despite an adequate renal function. After a diuretic pause and dietary salt restriction, a conventional dose of furosemide in combination with distally active diuretics induced a prompt weight loss exceeding 30 kg with stable renal function. We suggest that the 'refractory' oedema in this patient was due to a combination of CHF and inappropriate (loop) diuretic therapy in conjunction with a high dietary sodium intake. We conclude that in the absence of hyponatremia and renal failure, even severe oedema may not represent a negative prognostic indicator. The recognition of diuretic-associated mechanisms complicating cardiac oedema is essential to avoid the vicious circle of worsening oedema whilst escalating therapy with loop diuretics.

Adult↗
PubMed1988

Diuretics and hyperkalaemia in diabetic ketoacidosis.

Diabetic ketoacidosis (DKA) often presents with hyperkalaemia. We investigated whether it was more likely in patients taking potassium-retaining diuretics. A retrospective survey of all patients (552 cases) presenting in DKA between 1974 and 1984 was undertaken. Initial biochemical data were compared for patients recorded as taking potassium-retaining diuretics (7 cases) at the time of presentation with those taking potassium-losing diuretics (13 cases), and age matched control groups were selected from those who presented in DKA but were not taking diuretics. There was no significant difference in initial serum potassium levels between the diuretic treated groups. The serum sodium was higher in the control group than in the potassium losing group (p = 0.045) and the serum urea significantly lower (p = 0.045). We conclude that potassium-retaining diuretics do not predispose to hyperkalaemia in diabetic ketoacidosis.

Adult↗
PubMed1959

The effects of loading rats with intravenous isotonic sodium chloride on the renal response to diuretics.

The effect of a number of diuretic agents was investigated on rats with different degrees of expansion of extracellular fluid volume. With moderate saline loading aminoisometradine and chlorthiazide were the most efficient diuretics. However, with a more severe saline load aminoisometradine and mersalyl had the greatest effect while chlorthiazide had no significant diuretic activity. The action of acetazolamide seemed independent of the saline load. Potassium chloride showed no diuretic activity. Injecting the drugs in pairs resulted in probable potentiation only with acetazolamide plus chlorthiazide. Since all the diuretics were used in doses which gave maximal effects, the summation of the effects of the other pairs of diuretics suggested different sites of action.

Acetazolamide↗
PubMed2003

Misperceptions about beta-blockers and diuretics: a national survey of primary care physicians.

BACKGROUND: Based on a series of clinical trials showing no difference in the effectiveness or tolerability of most major classes of antihypertensive medications, the Joint National Commission on High Blood Pressure Treatment recommends that physicians prescribe beta-blockers or diuretics as initial hypertensive therapy unless there are compelling indications for another type of medication. Nevertheless, many physicians continue to favor more expensive medications like angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers as first line agents. The persistent use of these agents raises questions as to whether physicians perceive ACE inhibitors and calcium channel blockers to be better than beta-blockers and diuretics. METHODS: We surveyed 1,200 primary care physicians in 1997, and another 500 primary care physicians in 2000, and asked them to estimate the relative effectiveness and side effects of 4 classes of medication in treating a hypothetical patient with uncomplicated hypertension: ACE inhibitors, beta-blockers, calcium channel blockers, and diuretics. In addition, we asked them to indicate whether they ever provided free samples of hypertension medications to their patients. RESULTS: Perceptions of the relative effectiveness and side effects of the 4 classes of hypertension medications did not significantly change over the 3 years, nor did prescription recommendations. Physicians perceive that diuretics are less effective at lowering blood pressure than the other 3 classes (P <.001). They also perceive that beta-blockers are less tolerated than the other 3 classes (P <.001). In a multivariate model, perceptions of effectiveness and tolerability displayed significant associations with prescription preference independent of background variables. The only other variable to contribute significantly to the model was provision of free medication samples to patients. CONCLUSIONS: Despite numerous clinical trials showing no difference in the effectiveness or side-effect profiles of these 4 classes of drugs, most physicians believed that diuretics were less effective and beta-blockers were less tolerated than other medications. Moreover, their prescription practices were associated with their provision of free samples provided by pharmaceutical representatives, even after adjusting for other demographic characteristics. Efforts to increase physicians' prescribing of beta-blockers and diuretics may need to be directed at overcoming misunderstandings about the effectiveness and tolerability of these medicines.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Pharmacotherapy in congestive heart failure: diuretic resistance and strategies to overcome resistance in patients with congestive heart failure.

Congestive heart failure is a complex clinical hemodynamic disorder characterized by chronic and progressive pump failure and fluid accumulation. Although the overall impact of diuretic therapy on congestive heart failure mortality remains unknown, diuretics remain a vital component of symptomatic congestive heart failure management. Over time, sodium and water excretion are equalized before adequate fluid elimination occurs. This phenomenon is thought to occur in one out of three patients with congestive heart failure on diuretic therapy and is termed diuretic resistance. In congestive heart failure, both pharmacokinetic and pharmacodynamic alterations are thought to be responsible for diuretic resistance. Due to disease chronicity, symptomatic management is vital to improved quality of life and enhancing diuretic response is therefore pivotal.

Diuretics↗
PubMed1996

Urinary excretion profile of torasemide and its diuretic action in dogs.

The plasma concentration profile, urinary excretion rate and diuretic response were studied in anaesthetized dogs after an intravenous administration of torasemide or furosemide. The urinary excretion rate of furosemide decreased rapidly after administration. The plasma concentration, which is related to the urinary excretion profile, also decreased rapidly. The diuretic response, which reflected the excretion rate, occurred rapidly after administration but lasted for a short time. The urinary excretion rate of torasemide was much lower than that of furosemide and decreased slowly after administration. The plasma concentration also decreased slowly. The diuretic response to torasemide occurred more slowly but lasted longer than the response to furosemide. These results suggest that the diuretic response profile of either diuretic depends on their urinary excretion rate, and that the difference in the diuretic response between torasemide and furosemide may be explained by the different transfer rate of the drugs from the plasma to the nephron.

Animals↗
PubMed1994

Combination diuretic treatment in severe heart failure: a randomised controlled trial.

OBJECTIVES: (a) To test the hypothesis that a fixed 3 day course of the combination of a thiazide and loop diuretic is as effective as more prolonged treatment in the management of severe resistant cardiac failure. (b) To compare two thiazide diuretics (bendrofluazide and metolazone) in combination with loop diuretics in the treatment of severe resistant cardiac failure. DESIGN: Randomised study with a 2 x 2 factorial design. SETTING: Provincial teaching hospital. PATIENTS: 33 consecutive patients (40 episodes) admitted with severe congestive cardiac failure (New York Heart Association class III or IV) unresponsive to intravenous loop diuretics for 48 hours. MAIN OUTCOME MEASURES: Change in daily weight and serum electrolytes and clinical improvement in heart failure. RESULTS: Diuresis was established during 37 of 40 episodes; of the rest two patients died in hospital. On 36 occasions improvement was sufficient to allow discharge from hospital. Median (range) maximal weight loss was -5.05 (-11.3 to 1.6) kg after the addition of bendrofluazide and -5.6 (-12.2 to 4.8) kg after the addition of metolazone (NS). Area under the body weight loss against time curves showed no significant difference between the two thiazide diuretics. Median (range) maximal weight loss after three days of treatment was -5.4 (-12.2 to 4.8) kg and -5.5 (-10.3 to 1) kg after a more prolonged course of median (range) 5.6 (1 to 13) days (NS). Area under the body weight loss time curves showed no significant difference between the two durations of treatment. Bendrofluazide was associated with fewer electrolyte disturbances. CONCLUSIONS: Bendrofluazide and metolazone were equally effective in establishing a diuresis in patients with severe congestive cardiac failure resistant to loop diuretics. A fixed three day course of the combination was as effective as a longer course.

Adolescent↗
PubMed1986

Renal calcium metabolism and diuretics.

Diuretic agents have variable effects on calcium excretion as studied in vivo and in isolated kidneys and nephron segments. Generally, by increasing sodium and water excretion, diuretics will cause a concomitant increase in calcium excretion. As they diminish blood volume and alter renal hemodynamics, diuretics enhance calcium reabsorption in the proximal tubule, modulating their usual effects on calcium excretion. These general effects can be further modulated by additional metabolic actions. For instance, chronic administration of thiazide diuretics may diminish calcium excretion on the basis of altered levels of or responsiveness to PTH. Agents such as acetazolamide, which diminish bicarbonate reabsorption in the proximal tubule, will cause a modest calciuria, if any, because of reabsorption of the increased delivery of calcium, but not sodium, at the distal nephron. Agents acting in the loop of Henle that increase chloride excretion relative to sodium tend to cause greater calcium excretion. Finally, agents that act beyond the loop of Henle, which have their primary effects on cation excretion, tend to cause lesser degrees of calcium excretion, especially relative to sodium. These principles indicate that it may be appropriate to select a specific diuretic agent for different patients, depending upon the state of their calcium balance. It also may be possible to predict alterations in calcium balance, so that these may be anticipated and compensated for with patients on long-term therapy with various diuretic agents.

Animals↗
PubMed2003

Loop diuretics: from the Na-K-2Cl transporter to clinical use.

The diuretic response to loop diuretics in various disease states has consistently been found to be subnormal. One of the key determinants of the degree of diuretic response is the functional integrity of the sodium-potassium-chloride transporter in the loop of Henle. Studies in animal models suggest that expression/activity of the transporter may be affected by factors such as altered natural splicing events of NKCC2 (the gene encoding for the renal transporter), renal prostanoids, vasopressin, and other autacoids. We have reviewed the pharmacokinetics and pharmacodynamics of loop diuretics in health and in edematous disorders for which they are used. On the basis of evidence reviewed in this paper, we propose that altered expression or activity of the sodium-potassium-chloride transporter in the loop of Henle, in conjunction with events occurring in other segments of the nephron, possibly accounts for the altered diuretic response to these agents. Thus the modulators of this altered expression/activity could serve as important therapeutic targets for alternative diuretic regimens in these conditions.

Animals↗
PubMedDate not supplied

Diuretic resistance.

Resistance to diuretic action is frequently encountered in the clinical setting. This is best managed by systematically optimizing the pharmacodynamic-pharmacokinetic factors that may be involved. Important pharmacodynamic measures include improving the underlying disease state, restriction of salt intake, limiting the use of vasodilators which may cause hypotension, lowering protein excretion, and eliminating drugs which may modify the response to the diuretic. Pharmacokinetic measures include using doses which result in diuretic excretion rates which fall on the steep part of the dose-response curve, sustaining diuretic excretion in this range by frequent drug administration, or constant infusion, using more bioavailable drugs and drugs which have less hepatic elimination, and by increasing the diuretic concentration in blood by coadministration with albumin. Using diuretic combinations to systematically inhibit absorption in the proximal tubule, Henle's loop, distal convoluted tubule, and connecting/collecting tubule will usually effect diuresis in all but the most refractory of cases.

Diet, Sodium-Restricted↗
PubMed1994

Functional state of the nephron and diuretic dose-response--rationale for low-dose combination therapy.

The functions of the different nephron segments follow changes in the effective arterial blood volume and the extracellular fluid volume. In syndromes with reduced effective arterial blood volume, for example congestive heart failure, decompensated hepatic cirrhosis and nephrotic syndrome, hyperreabsorption of sodium in the proximal tubule reduces the sodium load in the more distal segments of the nephron. As this is a major site of sodium excretion, reduction in the response to a diuretic may be predicted by a reduced fractional excretion of sodium (< 0.2%). Such diuretic resistance may be overcome with acetazolamide, which increases delivery of sodium to the distal tubule. In syndromes with increased extracellular fluid volume, such as chronic renal failure, distal tubular rejection of sodium leads to a progressive increase in its fractional excretion as the glomerular filtration rate is reduced. The remaining intact nephrons exhibit a relatively increased response to diuretics. The efficacy of loop diuretics in renal failure can be optimized by combination with thiazides. The latter prevent early distal tubular hyperreabsorption following diuretic-induced blockade of sodium transport in the loop of Henle. For these reasons, low-dose combinations of different diuretics induce 'segmental nephron blockade' and are, therefore, potentially more clinically effective and safer than high doses of single compounds.

Diuretics↗
PubMed1999

Diuretics shift circadian rhythm of blood pressure from nondipper to dipper in essential hypertension.

BACKGROUND: Recently, we found that sodium restriction shifted the circadian rhythm of blood pressure from nondipper to dipper in patients with the sodium-sensitive essential hypertension. This study examined whether diuretics can transform the circadian rhythm of blood pressure from nondipper to dipper. METHODS AND RESULTS: We studied 21 patients with essential hypertension during both a baseline period and a period of treatment with hydrochlorothiazide (25 mg daily). The periods lasted 4 weeks each. Twenty-four hour ambulatory blood pressures were measured on the same day of the week at the end of the each period. In nondippers (n=11), but not in dippers (n=10), a significant interaction existed between diuretic therapy and nocturnal fall in systolic and diastolic blood pressure, which indicated that the degree of nocturnal blood pressure fall was affected by diuretic therapy. Nocturnal fall, which was diminished in nondippers, was restored by diuretic therapy with hydrochlorothiazide, indicating that the circadian rhythm of blood pressure shifted from nondipper to dipper patterns. CONCLUSIONS: The present study demonstrated that diuretics can restore nocturnal blood pressure decline in a manner similar to sodium restriction, which suggests that the kidneys and sodium metabolism may play important roles in the genesis of the circadian rhythm of blood pressure. Diuretic-based treatment may have an additional therapeutic advantage of reducing the risk for cardiovascular complications by transforming the circadian rhythm of blood pressure.

Aged↗