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PubMed2006

Sodium and water retention in heart failure and diuretic therapy: basic mechanisms.

The pathophysiology of sodium and water retention in heart failure is characterized by a complex interplay of hemodynamic and neurohumoral factors. Relative arterial underfilling is an important signal that triggers heart failure-related sodium and water retention. The response to perceived arterial underfilling is modulated by the level of neurohormonal activation, the degree of renal vasoconstriction, and the extent to which renal perfusion pressure is reduced. Sodium retention can also be exceeded by water retention, with the result being dilutional hyponatremia. Sodium and water retention in heart failure also function to dampen the natriuretic response to diuretic therapy. The attenuated response to diuretics in heart failure is both disease-specific and separately influenced by the rate and extent of diuretic absorption, the rapidity of diuretic tubular delivery, and diuretic-related hypertrophic structural changes that surface in the distal tubule.

Body Water↗
PubMed1999

Antihypertensive drugs: diuretics and betablockers are the best assessed.

(1) In trials involving hypertensive non diabetic patients under 65, some diuretics and betablockers have prevented strokes, without conferring protection from coronary events or death. In one trial captopril had an effect comparable to that of diuretics or betablockers in terms of overall cardiovascular prevention, but was a little less effective in preventing strokes. (2) In trials involving hypertensive subjects over 65, some diuretics and betablockers have reduced the risk of stroke, coronary events, heart failure, and death. In one trial a diuretic was superior to a betablocker in terms of preventive efficacy and adverse effects. Nitrendipine, in combination with other antihypertensive drugs, prevented strokes in one trial. (3) In a trial involving hypertensive diabetic patients, captopril and atenolol reduced the risk of stroke, heart failure and worsening of retinal disease, without preventing coronary events or death. In two trials coronary events were more frequent on dihydropyridine than on an angiotensin-coverting-enzyme (ACE) inhibitor. (4) In one trial a diuretic reduced the risk of relapse after stroke, even in patients without severe hypertension.

Adrenergic beta-Antagonists↗
PubMed1999

Randomized double-blind comparison of a calcium antagonist and a diuretic in elderly hypertensives. National Intervention Cooperative Study in Elderly Hypertensives Study Group.

Although diuretics are recommended for the treatment of hypertension, decreased diuretic use and increased calcium antagonist use necessitate a comparison of the efficacy of these drugs in preventing cardiovascular events. Patients >/=60 years of age with systolic blood pressure of 160 to 220 mm Hg and diastolic blood pressure <115 mm Hg were enrolled. Patients were randomly assigned to 20 mg of sustained-release nicardipine hydrochloride twice daily or 2 mg of trichlormethiazide once daily by the double-dummy method and followed up for 5 years. A total of 414 patients were analyzed: 204 in the nicardipine group and 210 in the diuretic group. Blood pressure at entry was 172/94 mm Hg and 173/93 mm Hg, respectively, and decreased to 147/81 mm Hg and 147/79 mm Hg, respectively. Cardiovascular morbidity rates per 1000 persons per year were similar in the nicardipine and diuretic groups (27.8 and 26.8, respectively; P=0.923). The sex- and age-adjusted risk ratio for the nicardipine group was 0.973 (95% confidence interval, 0.514 to 1.839, P=0.932). The calcium antagonist and diuretic groups had a similarly decreased rate of cardiovascular events.

Aged↗
PubMed2000

Localization of diuretic effects along the loop of Henle: an in vivo microperfusion study in rats.

In order to clarify the effects on sodium reabsorption in the loop of Henle of methazolamide (a carbonic anhydrase inhibitor), chlorothiazide and the loop diuretics frusemide and bumetanide, superficial loops were perfused in vivo in anaesthetized rats and the individual diuretics were included in the perfusate. Differentiation between effects in the pars recta and in the thick ascending limb of Henle (TALH) was achieved by comparing responses to the diuretics when using a standard perfusate, designed to mimic native late proximal tubular fluid, and a low-sodium perfusate, designed to block net sodium reabsorption in the pars recta. With the standard perfusate, methazolamide caused decreases in sodium reabsorption (J(Na)) and water reabsorption (J(V)); with the low-sodium perfusate, a modest effect on J(Na) persisted, suggesting that carbonic anhydrase inhibition reduces sodium reabsorption in both the pars recta and the TALH. The effects of chlorothiazide were very similar to those of methazolamide with both the standard and low-sodium perfusates, suggesting that chlorothiazide also inhibits sodium reabsorption in the pars recta and TALH, perhaps through inhibition of carbonic anhydrase. With the standard perfusate, both frusemide and bumetanide produced the expected large decreases in J(Na), but J(V) was also lowered. With the low-sodium perfusate, the inhibitory effects of the loop diuretics, particularly those of frusemide, were substantially reduced, while net potassium secretion was found. These observations indicate that a significant component of the effect of frusemide (and possibly of bumetanide) on overall sodium reabsorption is located in the pars recta, and that loop diuretics induce potassium secretion in the TALH.

Absorption↗
PubMed2000

Diuretic use: a risk for subclinical thiamine deficiency in elderly patients.

Long term diuretic therapy represents one central pharmacologic therapy of heart insufficiency and hypertension. Diuretics lead not only to an increased urinary excretion of electrolytes but also of water soluble vitamins. In this prospective study we evaluated the effect of hospitalization on the overall biochemical vitamin status in subjects older than 50 years (n=149, mean +/- SD age 70 +/- 10 years). Vitamin nutriture and other parameters were assessed at admission and discharge (duration of the hospitalization 19 +/- 1 day). Only vitamin B1 nutriture worsened during the hospitalization and in a multivariate procedure the only significant predictor of the change in the vitamin B1 nutriture was the use of diuretics during the hospitalization (F=4.06, p < 0.001). The changes in the ETK (erythrocyte transketolase activity in whole blood) and a-ETK (ETK activity coefficient) during the hospital stay correlated with the cumulative dosage of furosemide adjusted for the duration of the therapy (r = 0.36, p < 0.001 and r = - 0.28, p > 0.03). Our data suggest that hospitalized elderly are at increased risk for vitamin B1 deficiency especially when on a diuretic treatment. It is possible that a low dose thiamine supplementation my help to prevent the development of a subclinical wet-beriberi in older subjects on diuretics.

Aged↗
PubMedDate not supplied

Diuretic therapy and the risk for renal cell carcinoma.

Diuretics are important drugs in the treatment of arterial hypertension, congestive heart failure, the nephrotic syndrome, and other clinical conditions. With diuretic treatment, reduction of both morbidity and mortality has been clearly shown in those conditions. However, a recent meta-analysis showed an increased risk for renal cell carcinoma in patients treated with diuretics. We summarize and critically review data from studies examining the association between diuretic use and renal cell carcinoma. In general, in many clinical conditions, the reduction of mortality with diuretic therapy outweighs a potential risk of renal cell carcinoma. However, in certain conditions, alternative medical treatment should be considered.

Carcinoma, Renal Cell↗
PubMed2002

A comparison of unenhanced helical computerized tomography findings and renal obstruction determined by furosemide 99m technetium mercaptoacetyltriglycine diuretic scintirenography for patients with acute renal colic.

PURPOSE: We assessed unenhanced helical computerized tomography (CT) secondary findings as predictors of renal obstruction as determined by diuretic scintirenography, and determined their reproducibility. MATERIALS AND METHODS: We performed a retrospective review of the records of 77 consecutive patients with unenhanced helical CT findings (stones and secondary findings, including renal parenchymal edema, hydronephrosis, hydroureter, perinephric fat stranding, periureteral fat stranding and extravasation) of urinary lithiasis who had also undergone concomitant diuretic scintirenography during the initial emergency room evaluation during a 1-year period. Unenhanced helical CT films were independently reviewed by 2 attending radiologists (blinded to clinical outcome) to determine interobserver variability. The results were compared to those of diuretic scintirenography. RESULTS: Considerable interobserver variability, as evidenced by kappa values ranging from 0.26 to 0.60, existed for the diagnosis of secondary findings associated with urinary lithiasis on unenhanced helical CT. There was no significant difference in terms of CT findings between patients diagnosed by diuretic scintirenography as having high grade/complete obstruction and those with partial obstruction (p values 0.24 to 0.85 for the 6 unenhanced helical CT findings analyzed). Analyses of variance followed by Tukey's pairwise comparisons showed no significant difference in average number of unenhanced helical CT findings between patients with high grade/complete obstruction (mean plus or minus standard deviation 4.4 +/- 1.31), partial obstruction (4.4 +/- 1.30), and decompression/no obstruction (4.2 +/- 1.16). However, the mean number of unenhanced helical CT findings for patients with normal scintirenography/no obstruction (1.9 +/- 1.41) was significantly different from each of the other 3 diuretic scintirenography groups. Separate logistic regression analyses showed that each unenhanced helical CT finding, except for renal parenchymal edema and urinary extravasation, was a significant predictor of "any degree of obstruction" (high grade and partial obstruction groups) compared to "no obstruction" (decompressed and no obstruction groups). Odds ratios (95% confidence interval) ranged from 6.15 (2.25, 16.82) for perinephric fat stranding to 3.41 (1.30, 8.97) for hydroureter. When these analyses were repeated after exclusion of 8 patients with bladder/passed stones, only perinephric fat stranding and periureteral fat stranding remained significant predictors of "any degree of obstruction," with respective odds ratios of 4.21 (1.49, 11.91) and 4.08 (1.31, 12.65). CONCLUSIONS: Measures of agreement between trained, independent radiologists with respect to unenhanced helical CT secondary findings show considerable variability. The average number of CT consensus findings is not helpful in differentiating patients with variable degrees of obstruction, except for those with normal scintirenography/no obstruction. Unenhanced helical CT findings, except for renal parenchymal edema and urinary extravasation, are significant predictors of "any degree of obstruction" (high grade or partial obstruction) compared to "no obstruction" (decompressed or no obstruction). Therefore, unenhanced helical CT findings may be useful for identifying patients with any degree of obstruction but do not differentiate between those with high grade and partial obstruction.

Acute Disease↗
PubMedDate not supplied

[Diuretic activity of the infusion of flowers from Lavandula officinalis].

The diuretic activity of an infusion of Lavandula officinalis was studied in the Wistar rat. Thus, the kinetics of hydroelectrolytic elimination in response to the oral administration of an infusion of pharmaceutical lavender flowers were measured in the rats. Experiments were completed under similar conditions using a synthetic pharmacological diuretic, Diamox. The aqueous extract of this aromatic plant accelerated the elimination of the water overload. At the peak of the diuretic response, urinary osmolarity was significantly less than that of controls (111+/-14 vs. 195+/-11 mosmol x kg(-1)). Sodium excretion was moderate following administration of the infusion when compared to the synthetic diuretic. The stability of the aldosterone concentrations in the plasma and the absence of correlation with plasma sodium concentrations, coupled with the observed clearance of the free water (0.055+/-0.007 vs. 0.045+/-0.012 mL x min(-1)) show that the increase in diuresis and the moderate increase in sodium excretion are of tubular origin. The result of the phytochemical analysis of hexane extracts in the infusion and in urine indicated that four or five chemical factors may be involved in the diuretic effect of lavender.

Acetazolamide↗
PubMed2003

Are diuretics helpful in acute renal failure?

Although widely used to treat acute renal failure, diuretics may actually be harmful. The results of this observational study demonstrated a higher risk of death and non-recovery of renal function when diuretics were initiated during the first week of hospitalization. It didn't matter whether a single or combination diuretic was used. A randomized controlled trial would better answer this question by minimizing the inherent flaws in an observational study. Although this study doesn't conclusively prove that diuretics cause poorer outcomes, it certainly raises the possibility and should prompt us to think twice before initiating diuretic therapy for acute renal failure.

Acute Kidney Injury↗
PubMed1992

[The use of diuretics in heart insufficiency in the elderly].

The kidney function alterations with age and on congestive heart failure, are reviewed as the pharmacocynetic and pharmacodynamic of the diuretics on old patients with this syndrome. The therapeutic importance of hiposodic diet was considered. The reasons for the susceptibility of old people to diuretics and the criteria for the choice of the diuretic on this age, are reviewed. So are the most important adverse effect of diuretics on old people and the contra-indication for the use of these drugs on elderly. The importance of hypocalaemia on old people and how to prevent or correct it are considered. The haemodynamic risks of an excessive diureses are reviewed. Finally, we propose some recommendations about the use of diuretics on the elderly.

Aged↗
PubMed1992

[Diuretics and their current role in the treatment of essential arterial hypertension].

Diuretics have been most commonly used to treat hypertension in the last 25 years. Their tolerance is good, they have been effective specially in negroes, older and obese patients and they are relatively inexpensive. The emergence of new and more potent drugs: beta blockers, calcium antagonists, and ACE inhibitors, has led to a decrease in diuretic use. Hyperglycemia and lipid disorders induced by diuretics have been invoked to explain the lack of effect on coronary mortality among treated hypertensive patients. Hypokalemia induced by diuretics has been suspected as the cause for sudden deaths. However, these effects are not sufficiently proven and do not warrant, at present, the elimination of diuretics in the treatment of hypertension.

Diuretics↗
PubMed1992

Treatment of ascites in cirrhosis. Diuretics, peritoneovenous shunt, and large-volume paracentesis.

The medical treatment of ascites in cirrhosis is based on sodium restriction and the administration of diuretics. Because the natriuretic potency of spironolactone is greater than that of loop diuretics (i.e., furosemide) in patients with marked sodium retention, spironolactone is the basic drug for the treatment of ascites. The simultaneous administration of spironolactone and furosemide increases the natriuretic effect of each drug and diminishes their effects on potassium metabolism. Recent studies indicate that large-volume paracentesis associated with intravenous albumin infusion is more effective than diuretic therapy in eliminating the ascitic fluid; is associated with a lower incidence of complications (hepatic encephalopathy, renal impairment, and hyponatremia); and considerably reduces the duration of hospital stay. Therapeutic paracentesis associated with intravenous albumin infusion is therefore the treatment of choice for cirrhotic patients with tense ascites. The mobilization of the ascitic fluid by paracentesis without plasma volume expansion is constantly associated with a deterioration of effective circulating blood volume and may induce renal impairment and severe hyponatremia. Dextran 70 and polygeline appear as effective as albumin in preventing these abnormalities. Cirrhotic patients treated with paracentesis require the administration of diuretics to avoid reaccumulation of ascites. Peritoneovenous shunt, a prosthesis capable to correct most abnormalities involved in the accumulation of fluid in the abdominal cavity, is an effective treatment of ascites in cirrhosis. It is especially indicated in patients who do not respond to diuretics and develop repeated episodes of ascites despite adequate treatment. The use of peritoneovenous shunting is limited by the high incidence of complications induced by the procedure, however. In addition, approximately 40% of patients develop an obstruction of the prosthesis within the first postoperative year.

Albumins↗
PubMed2005

[The place of diuretics in the treatment of chronic heart failure. Part I].

In series of papers the authors analyze the literature data concerned with clinical pharmacology of four main classes of diuretics and their use in long-term treatment of congestive chronic heart failure (CHF). Part I is devoted to basic clinical pharmacology of three main classes of diuretics -- loop, thiazide and potassium-sparing. The site of action in nephron, mechanisms and duration of action different loop and thiazide diuretics with emphasis to furosenide, torasemide, hydrochlorothiazide, metolazone and indapamide as well as contraindications and limitations for their use in the complex treatment of CHF are considered in detail. In long-term comparative studies showed long acting loop diuretic torasemide improved symptomatology and functional class of NYHA in patients with CHF in compared with furosenide. Thiazide-like diuretic indapamide does also act as vasodilator and decreases afterload of left ventricle of heart. But indapanide should be used with special caution because of their capacity to prolong the Q-T interval, which associates with polymorphic ventricular tachycardia, or torsades de poites.

Diuretics↗
PubMed2006

[Diuretics].

Diuretics interfere with the sodium retention of heart failure by inhibiting the reabsorption of sodium in the renal tubes, increase urine output and decrease physical signs of fluid retention in patients with heart failure (HF). Diuretics are the only drugs used for the treatment of HF that can adequately control the fluid retention of HF. Loop diuretics, potassium-sparing agents and thiazides are used for treatment. Tolvaptan, vasopressin receptor antagonists, is a new drug and long-term clinical trials are under way to determine the role. The use of inappropriate doses of diuretics will lead to result in fluid retention, renal insufficiency with ACE inhibitors and ARBs, increase the risk of treatment with beta blockers or volume contraction, increase the risk of hypotention and diminish the response to ACE inhibitors and ARBs. Appropriate use of diuretics is important in the success of the treatment of HF.

Diuretics↗
PubMed2006

Current thinking regarding the use of diuretics in heart failure.

The majority of therapies used in the contemporary management of chronic heart failure (CHF) have been rigorously evaluated by means of large-scale clinical trials to assess their beneficial effects on quality of life and prognosis. Such therapies include angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and cardiac resynchronization therapy (CRT). Diuretics are the most commonly prescribed class of drugs in CHF patients and in the short term they remain the most efficacious treatment for relief from fluid congestion. There is, however, scant evidence to suggest that they confer any long term benefit in terms of disease progression or prognosis to the CHF sufferer. Injudicious use of diuretics has been demonstrated to be potentially harmful and consideration should be paid to avoiding dietary salt indiscretion as well as the pharmacokinetic properties of individual diuretics to achieve optimal diuretic response. In this article, we explore the current insight into the use of diuretics in CHF.

Absorption↗
PubMed1991

Excess mortality associated with diuretic therapy in diabetes mellitus.

OBJECTIVE: To determine whether the high mortality among diabetic patients receiving treatment for hypertension can be explained by associated risk factors or must be attributed to a deleterious effect of antihypertensive treatment. DESIGN: Cohort analytic study with a median follow-up of 4.5 years. SETTING: Outpatients with diabetes and severe retinopathy who were enrolled in a multicenter, randomized clinical trial of laser treatment to prevent blindness had ophthalmologic examinations every 4 months and annual medical examinations that included measurement of blood pressure and recording of anti-hypertensive treatment. Only 5.5% of the patients were unavailable for follow-up. When a patient died, the circumstances surrounding the death were reviewed and classified by a mortality review committee. PARTICIPANTS: --There were 759 participants in the study; they were white, were aged 35 to 69 years, and had normal serum creatinine levels at the baseline examination. MEASUREMENTS AND MAIN RESULTS: --Patients were classified into five groups according to information recorded at the baseline and first annual follow-up examinations: normotensive (diastolic blood pressure less than 90 mm Hg), untreated hypertensive, hypertensive treated by diuretics alone, hypertensive treated by other agents alone, and hypertensive treated by both agents. Cardiovascular mortality was higher in patients treated for hypertension than in patients with untreated hypertension. The excess was primarily found in patients treated with diuretics alone, although that group had the lowest blood pressure with treatment. After adjusting for differences in risk factors, cardiovascular mortality was 3.8 times higher in patients treated with diuretics alone than in patients with untreated hypertension (P less than .001). CONCLUSIONS: --In individuals with diabetes, intervention with diuretics to reduce hypertension is associated with excess mortality. Until there is a clinical trial showing a beneficial effect of diuretic treatment in diabetic patients, there is urgent need to reconsider its continued usage in this population.

Adult↗
PubMed1990

Combination of converting enzyme inhibitor with diuretic for the treatment of hypertension.

In recent years there has been increased discussion about goals of antihypertensive therapy other than blood pressure reduction. The development of angiotensin-converting enzyme inhibitors has provided a class of drugs with a very low side-effect profile. However, single-drug therapy is effective in only about half of hypertensive patients. In the past, diuretics have traditionally been used as the initial or second antihypertensive. Increasingly, diuretic therapy is being avoided, and other antihypertensive combinations are being used. In controlled trials, combination converting enzyme inhibitor-diuretic therapy is effective in about 85% of patients. This synergistic combination allows the diuretic dose to be reduced so that the adverse effects and metabolic complications are minimized. At this time, the combination of converting enzyme inhibitor and diuretic provides an ideal choice in terms of efficacy, compliance, side effects, and cost.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Interaction between nonsteroidal anti-inflammatory drugs and loop diuretics: modulation by sodium balance.

Nonsteroidal anti-inflammatory drugs have been shown to decrease the natriuretic response to loop diuretics in many but not all studies. Recently, indomethacin was shown not to affect the natriuretic response to the new loop diuretic torasemide in healthy volunteers. Inasmuch as sodium balance has been reported to modify the effect of indomethacin on furosemide-induced natriuresis in dogs, we investigated the effect of indomethacin, under two sodium balances (50 and 150 mEq/day), on the natriuretic response to two doses of torasemide in six healthy volunteers. Under the low sodium diet, indomethacin reduced the natriuretic response to torasemide like that to furosemide. In contrast, on the normal sodium diet, indomethacin failed to affect the natriuretic response to torasemide. Indomethacin reduced base-line and diuretic-induced increase in plasma renin activity, plasma angiotensin II levels and urinary excretion of prostaglandin 6-keto F1 alpha to a similar extent under the two sodium diets. Our data show that indomethacin reduces the natriuretic response to torasemide in humans. Dietary sodium restriction is a significant determinant of the interaction between nonsteroidal anti-inflammatory drugs and loop diuretics in healthy volunteers, presumably because it allows loop diuretics to provoke an increase in renal blood flow which participates in their natriuretic action and is blocked by nonsteroidal anti-inflammatory drugs.

Adult↗