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At least 667 records · Page 37Linked to original sources
PubMed1994

Safety of concomitant potassium-sparing diuretics in angiotensin-converting enzyme inhibitor therapy in severe congestive heart failure. Xamoterol in Severe Heart Failure Study Group.

The safety of concomitant use of angiotensin-converting enzyme (ACE) inhibitors and potassium-sparing diuretics (PSD) in severe heart failure remains a controversial issue. The database of the recently reported double-blind international trial, "Xamoterol in Severe Heart Failure," was investigated to elucidate this question. Of 516 patients with New York Heart Association (NYHA) class III-IV, despite diuretics and ACE inhibitor therapy, 352 were randomized to xamoterol, a beta 1 partial agonist, and 164 were randomized to placebo. During the 13-week study, 28% of all patients (xamoterol, 104; placebo, 42) received potassium-sparing diuretics. All groups were comparable in hemodynamics and dose of other diuretics. At study end, patients with or without PSD showed no significant differences in serum K+ or creatinine, independent of xamoterol or placebo therapy. Mortality rate was consistently lower: 4.6% in patients with PSD and 8.5% in patients without PSD, although statistical significance was not reached. As compared with baseline, K+ values of 6 patients with and 17 patients without PSD had increased by > 5.0 mM at study end (p = NS); 1 patient with and 11 patients without PSD had a creatinine level > 180 microM (p = NS). For 3 patients receiving PSD, and 2 patients not receiving PSD because of renal impairment, study was discontinued because of hyperpotassemia. No significant differences were noted in long and short action or different dosages of ACE inhibitors. PSD may be administered concomitantly with ACE inhibitors, but serum K+ should be monitored as with other diuretics.

Adult↗
PubMed1995

Risk of renal cell cancer in relation to diuretics, antihypertensive drugs, and hypertension.

Although recent data have suggested an association between renal cell cancer and the use of diuretics, it remains unclear whether these medications or hypertension is the important risk factor. In a population-based case-control study including 440 renal cell cancer cases, spouses of an additional 151 cases, and 691 controls, we assessed renal cell cancer risk associated with hypertension and use of diuretics and other antihypertensive medications. Risks increased with the use of diuretics or other drugs that lower blood pressure, especially among persons who reported no history of hypertension. After adjustment for hypertension, the use of diuretics alone was associated with a 40% excess risk (OR = 1.4; 95% CI = 0.8-2.2), while use of other antihypertensive drugs was linked to a 2-fold risk (OR = 2.0; 95% CI = 1.2-3.3). The excess risk was not restricted to any specific products, and no trend was observed with estimated lifetime consumption of any product. Furthermore, risk was not potentiated by the presence of both hypertension and the use of antihypertensive drugs. Among persons who did not use antihypertensive drugs, a history of hypertension was associated with a significant 40-50% excess risk of renal cell cancer. Excluding subjects with hypertension diagnosed within 5 years of cancer diagnosis or interview had only a small effect on risk. These findings suggest small effects on renal cell cancer risk associated with hypertensive disease and with the use of diuretics and other antihypertensive drugs, but it is difficult to disentangle the separate effects due to potential misclassification of highly correlated events.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

The use of diuretics in congestive heart failure.

Diuretic resistance in patients with congesting heart failure is for the most part due to pharmacodynamic factors related to increased reabsorption of solute at other parts of the nephron. This mechanism explains the rationale for using combinations of diuretic agents affecting solute reabsorption at different nephron sites in such patients in contrast to a strategy of escalation of loop diuretic doses. Understanding the mechanisms by which diuretic resistance occurs in patients with CHF has allowed design of appropriate dosing regimens of these drugs and rational use of combinations of diuretics.

Biological Availability↗
PubMed1994

Magnesium and potassium deficiency. Its diagnosis, occurrence and treatment in diuretic therapy and its consequences for growth, protein synthesis and growth factors.

Thiazides and loop diuretics facilitate the loss of K and Mg through the kidneys leading to deficiencies that may require treatment with supplements. These losses may be overlooked, however, because serum concentrations may remain normal even when the muscle concentrations are appreciably reduced. In 76 patients who had received diuretics for 1-17 years, the mean concentrations of K, Mg and Na,K-pumps in skeletal muscle biopsies were significantly lower than in those from an age- and sexmatched control group, and muscle Mg and K concentrations were significantly correlated. The serum concentrations, however, were only below the control range in a few patients. The fact that Mg,K deficiencies may often be overlooked emphasises the need for data on the contents of skeletal muscle. A recently developed simple biopsy needle procedure permitted the detection of disorders of electrolytes during long-term diuretic treatment despite normal serum concentrations. With the same technique it was possible to detect repletion of the muscle electrolytes after a Mg supplementation period. Oral Mg supplementation could reestablish normal Mg as well as K status in patients in long-term diuretic therapy, provided that the supplementation was maintained for 6 months. Moreover, the normalization of muscle Mg and K was accompanied by a restoration of the concentration of Na,K-pumps measured as the [3H]ouabain binding site capacity in skeletal muscle. Mg and K contents were closely correlated in human muscle biopsies from patients on diuretic treatment, but also in rat muscle which had been moderately Mg depleted in vivo or in vitro. In isolated soleus muscle, which had been moderately Mg-depleted in vitro, reduction in cellular K could not be ascribed to reduced Na,K-pump mediated K-influx. The reduced K content might rather be related to increased K efflux from the muscles. In rats, insufficient dietary supplies of K, Mg and Zn were characterized by inhibition of growth and protein synthesis. These effects could not readily be related to the loss of these elements from muscle tissue, but rather should be seen as a response to a general deficiency. The most marked evidence of deficiency was seen in the serum levels, which pointed to the serum concentration as a possible mediator for the regulation of tissue growth. IGF-I is a low molecular weight peptide possessing growth promoting properties in many tissues probably as an interplay of both autocrine/paracrine and endocrine actions. In both animals and man insufficient supplies of energy and protein are accompanied by growth retardation and a decrease in serum IGF-I.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Sodium, large arteries, and diuretic compounds in hypertension.

Clinical and experimental data have shown that antihypertensive drugs do not cause the same change in arterial compliance for an equipotent blood pressure reduction. However, there is not clear data on the effect of sodium and diuretics on the visco-elastic properties of the hypertensive arterial wall. Cross-sectional epidemiologic studies suggest that, at any given value of age and blood pressure, pulse wave velocity is lower in the presence of decreased sodium intake. Longitudinal studies indicate that, in hypertensive subjects, low sodium intake is associated with a larger brachial artery diameter than is high sodium intake. In hypertension in the elderly and in severe hypertension with end-stage renal disease, sodium overload causes a reduction in arterial compliance and distensibility unrelated to blood pressure changes. In animal studies, the diuretic compounds cycletanine and indapamide were shown to increase systemic and carotid compliance independently of blood pressure changes. In contrast, a crossover study of hypertensive subjects showed that the diuretic agent hydrochlorothiazide did not change arterial compliance and pulse wave velocity, whereas the calcium entry blocker, felodipine, improved these parameters. Nevertheless, indapamide decreased the pulse pressure on stroke volume ratio, a parameter used as a marker of aortic distensibility. Taken together, such studies indicate that sodium may act on the arterial wall independently of blood pressure changes. The contribution of counter regulatory mechanisms, possibly related to the renin-angiotensin and sympathetic nervous systems, might explain the differences between the clinical and experimental changes observed with diuretic compounds. Of the various antihypertensive agents, diuretics seem to have the least effect on the arterial system.

Animals↗
PubMed1993

[Loop diuretics. Rational pharmacotherapy].

UNLABELLED: The pharmacodynamics and -kinetics as well as rational pharmacotherapy of furosemide and bumetanide is reviewed. In renal insufficiency, a reduced response to diuretics is due to altered pharmacokinetics. The optimum dose can be determined within three to four hours by titration and the effect is measured by the amount of excreted sodium. In nephrotic syndrome, both pharmaco-kinetics and--dynamics are altered. The optimum dose is established as above. Starting and ceiling doses are given in tables for both drugs in renal insufficiency and nephrotic syndrome. In congestive heart failure, the difference is greater between oral and intravenous doses than apparent from the bioavailability of the drugs. If potent diuretics are without effect, the heart failure must be treated more vigorously or a combination with thiazides tried out. Potent diuretics are seldom used in the treatment of liver cirrhosis, but, if used, large doses are necessary. Non-steroidal antiinflammatory drugs are usually considered contra-indicated in patients with severe renal insufficiency, since the pharmacodynamics of the diuretics are altered. CONCLUSION: The general strategy when using potent diuretics is titration to an effective dose and then using this dose as frequently as needed in order to obtain the desired response.

Acute Kidney Injury↗
PubMed1993

Infraadditive diuretic efficacy of concurrent aminophylline and frusemide.

Male albino rats weighing between 150-225 gm fasted over night but freed having water ad libitum were used to assess the diuretic efficacy of intramuscular aminophylline and frusemide separately and concurrently after intraperitoneal 10 ml of distilled water loading. The normal rate of diuretic weight loss was less augmented by aminophylline and more augmented by frusemide. The diuretic response was more by the concurrent intramuscular administration of aminophylline and frusemide in comparison with that due to either drug alone. However, the observed diuretic response of the two drugs administered concurrently was lesser (infraadditive) than the sum of the individual diuretic response (additive).

Aminophylline↗
PubMed1993

[Ventricular arrhythmia in patients treated with diuretics].

A quantitative and qualitative analysis of ventricular arrhythmia was performed in 120 patients (64 men and 56 women, mean age 54 +/- 16) who suffered from arterial hypertension or congestive heart failure in the course of organic heart disease or ischaemic heart disease. 60 of them were treated with diuretics and the other 60 were control group. Neither antiarrhythmic drugs nor digitalis were used. There were no signs of left ventricular hypertrophy. Most patients treated with diuretics received potassium supplementation. Besides clinical examination all patients underwent 24 hours monitoring of Holter ECG. 38 patients treated with diuretics were evaluated before and after 6 months of therapy. In the diuretic group significantly higher percentage of patients with greater density of premature ventricular beats (count of premature ventricular beats [PVB]/100,000 heart evolutions) was observed. Number of patients with complex ventricular arrhythmia (Lown IVa and IVb) was also greater in this group. Serum levels of potassium and magnesium fell within the normal range, but the latter was significantly lower (p < 0.05) in those treated with diuretics.

Adult↗
PubMed1977

Clearance and micropuncture studies of the effects of a new indanyloxyacetic acid diuretic on segmental nephron function in rats.

The renal effects of a new, substituted indanyloxyacetic acid diuretic agent were evaluated in 16 anesthetized rats using micropuncture and clearance techniques. Glomerular filtration rate, mean arterial pressure and hematocrit remained unchanged. Urine flow increased 13 times after i.v. administration of 50 mg/kg b.wt. of the diuretic. Sodium excretion increased from 0.4 +/- 0.05% of the amount filtered to 6.62+/-0.87%. Potassium urine/plasma concentration ratio declined 6-fold while potassium excretion nearly doubled. Proximal tubular reabsorption was not altered significantly by this indanone diuretic. Reabsorption was markedly inhibited between late proximal and early distal micropuncture sites, that is, in the loop of Henle. The diuretic did not appear to interfere with normal distal tubular function. In the collecting tubules, reabsorption was markedly reduced from 41+/-0.2 mul/min/100 g b.wt. to 26+/-5 (with P less than .005). This new indanone compound appears to be a potent, specific natriuretic diuretic agent which inhibits tubular reabsorption primarily in the loop of Henle and collecting tubules, that is, in distal nephron segments located deep within the kidney. It produces a somewhat delayed but prolonged diuresis in the rat.

Animals↗
PubMed1995

[Hemodynamic and renal effects of strong diuretic atrial natriuretic peptide in patients with acute myocardial infarction].

The hemodynamic and renal effects of strong diuretic atrial natriuretic peptide (ANP) were investigated in 12 patients with acute myocardial infarction. Strong diuretic ANP was administered as a bolus injection of 100 micrograms and followed by a continuous infusion of 2 micrograms/kg within 10 minutes into the right atrium via a catheter. We found that strong diuretic ANP induced an increase in cardiac index and stroke volume index. Right atrial pressure, pulmonary arterial pressure, pulmonary capillary wedge pressure, systemic vascular resistance and pulmonary vascular resistance were decreased after ANP infusion. The maximal responses were observed immediately after the infusion was completed. No significant change of arterial blood pressure and heart rate was observed. Furthermore, strong diuretic ANP also increased the urine volume, urinary sodium, urinary chloride and urinary potassium. These results suggest that strong diuretic ANP infusion may induce significant changes of hemodynamics and may be used to prevent the development of severe circulatory volume overload in patients with AMI.

Adult↗
PubMed1996

[Potassium-sparing diuretics (spironolactone, triamterene, amylorid)].

The group of drugs, so-called "potassium sparing diuretics" represent an important part of our modern therapeutic arsenal. Their "weak diuretic" properties are especially beneficial in cirrhotic patients with ascites, when highly effective loop diuretics may be hazardous. Potassium sparing diuretics have not only the advantage of avoiding potassium loss, but can potentiate the effects of diuretics acting in distal tubules and Henle's loop also. They may be combined by each other or ACE inhibitors too, taking the necessary precautions and laboratory monitoring. Their indications include the hypertension and special diseases as Conn's, Bartter's, Liddle syndromes and hirsutism. The broad clinical usefulness justifies the drug inventory ambition to develop new, more effective potassium sparing compounds without side effects. Authors overview their main clinicofarmacological properties, therapeutical indications alone or in combinations and their potential side effects.

Amiloride↗
PubMed1996

Evaluation of ureteropelvic junction obstruction (UPJO) by diuretic renography.

Of 52 cases with 56 affected renal units having symptoms and signs suggestive of Ureteropelvic Junction Obstruction (UPJO) evaluated by conventional (F + 15) diuretic renography where frusemide is given 15 minutes post-injection of radiopharmaceutical m99TC.DTPA.F + 15, twelve (21%) showed a good clearance (group A), 16 (28%) showed partial (group B) and 28 (50%) a poor clearance pattern (group C) indicating a definite obstruction. A high flow (F-15) diuretic renography where frusemide is given 15 minutes prior to the radiopharmaceutical m99TC.DTPA, was done in 23 cases with 27 affected renal units. Eleven renal units showed a good clearance (group A). Of these, 7 (64%) showed a persistent good clearance, 3 (27%) converted to poor clearance and 1 (9%) to partial clearance pattern. Of 8 renal units in group B, 5 (63%) converted to poor clearance and two (25%) to good clearance on F-15 and one remained unchanged. All renal units which presented as poor clearance (group C) on conventional (F + 15) diuretic renography remained unchanged on high flow (F-15) diuretic renography. In majority of cases conventional (F + 15) renography gave a reliable assessment of the upper tract drainage, however, since equivocal group was resolved by the F-15 and the intermittent obstruction group was definitely diagnosed, high flow (F-15) diuretic renography was more conclusive in assessment as compared to F + 15.

Adult↗
PubMed1997

[The clinical spectrum of potassium-sparing diuretics].

The role of potassium-sparing diuretics in the treatment of hypertension is discussed. The results of two newer case-control studies showing both an increased risk for sudden cardiac death in patients receiving non-potassium-sparing diuretics compared to those receiving potassium-sparing diuretics are presented. As a consequence of these studies thiazides should be given only at a low dose or in combination with a potassium-sparing agent. Data from several large intervention trials in elderly patients with hypertension show that treatment of high blood pressure with potassium-sparing diuretics is clearly beneficial since cerebral and cardiac events are both significantly reduced. Finally, potassium-sparing diuretics, especially spironolactone, play an important role in controlling high blood pressure in patients with primary aldosteronism. The presentation of a case report demonstrates, that development of resistance toward medical treatment may be due to elevated aldosterone levels and suppressed plasma renin activity and that the addition of spironolactone efficiently reduces elevated blood pressure values in this condition.

Aged↗
PubMed2005

Continuous infusion versus bolus injection of loop diuretics in congestive heart failure.

BACKGROUND: Loop diuretics, when given as intermittent bolus injections in acutely decompensated heart failure, may cause fluctuations in intravascular volume, increased toxicity and development of tolerance. Continuous infusion has been proposed to avoid these complications and result in greater diuresis, hopefully leading to faster symptom resolution, decrease in morbidity and possibly, mortality. OBJECTIVES: To compare the effects and adverse effects of continuous intravenous infusion of loop diuretics with those of bolus intravenous administration among patients with congestive heart failure Class III-IV. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 2, 2003), MEDLINE (1966 to 2003), EMBASE (1980 to 2003) and the HERDIN database. We also contacted pharmaceutical companies . SELECTION CRITERIA: Randomized controlled trials comparing the efficacy of continuous intravenous infusion versus bolus intravenous administration of loop diuretics in congestive heart failure were included DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed study eligibility, methodological quality and did data extraction. Included studies were assessed for validity. Authors were contacted when feasible. Adverse effects information was collected from the trials. MAIN RESULTS: Eight trials involving 254 patients were included. In seven studies which reported on urine output, the output (as measured in cc/24 hours) was noted to be greater in patients given continuous infusion with a weighted mean difference (WMD) of 271 cc/24 hour (95%CI 93.1 to 449; p<0.01). Electrolyte disturbances (hypokalemia, hypomagnesemia) were not significantly different in the two treatment groups with a relative risk (RR) of 1.47 (95%CI 0.52 to 4.15; p=0.5). Less adverse effects (tinnitus and hearing loss) were noted when continuous infusion was given, RR 0.06 (95%CI 0.01 to 0.44; p=0.005). Based on a single study, the duration of hospital stay was significantly shortened by 3.1days with continuous infusion WMD -3.1 (95%CI -4.06 to -2.20; p<0.0001) while cardiac mortality was significantly different in the two treatment groups, RR 0.47 (95% CI 0.33 to 0.69; p<0.0001). Based on two studies, all cause mortality was significantly different in the two treatment groups, RR 0.52 (95%CI 0.38 to 0.71; p<0.0001). AUTHORS' CONCLUSIONS: Currently available data are insufficient to confidently assess the merits of the two methods of giving intravenous diuretics. Based on small and relatively heterogenous studies, this review showed greater diuresis and a better safety profile when loop diuretics were given as continuous infusion. The existing data still does not allow definitive recommendations for clinical practice and larger studies should be done to more adequately settle this issue.

Heart Failure↗
PubMed1981

A study of erythrocyte membrane cation transport adenosine triphosphatases in pregnancy-induced hypertension and of in vivo effects of diuretic treatment.

Plasma and erythrocyte Na+ and K+ and erythrocyte membrane (EM) Na+, K+ ATPase, Mg2+ ATPase and Ca2+, Mg2+ Atpase activities were studied in four groups of women -- non-pregnant, normal pregnant, with pregnancy edema (PE) and with pregnancy induced hypertension (PIH). The effect of diuretic therapy in PE and PIH was also evaluated. Plasma Na+ concentration was higher in PE and PIH. There was a significant reduction in (Na+ + K+) ratio between cell and plasma in these two groups. EM Na+, K+ ATPase was unaltered in PE and PIH. The Mg2+ ATPase was elevated by 44% in PE and by 100% in PIH subjects. There was a 50% reduction in Ca2+, Mg2+ ATPase activity in PE. Diuretic therapy had no effect either on electrolyte levels or on any of the EM ATPases. From these results it may be concluded that Na, K, ATPase -- which in kidney is a site of action for furosemide, a potent diuretic -- is unaffected in PE and PIH and, hence, treatment with diuretics -- is unaffected in PE and PIH and, hence, treatment with diuretics in such patients may be ineffective.

Adenosine Triphosphatases↗
PubMed1983

Cardionatrin I - a novel heart peptide with potent diuretic and natriuretic properties.

Rat atrial muscle extracts are able to induce a powerful diuretic and natriuretic response. In the present work it was found that when rat atrial extracts are subjected to reverse phase-high pressure liquid chromatography, diuretic and natriuretic activities are recovered in four distinct chromatographic regions. From one of these chromatographic regions we purified to chemical homogeneity a peptide referred to as "Cardionatrin I" which has potent diuretic and natriuretic properties. Amino acid analysis showed that cardionatrin I has 49 residues, including one cystine, and a molecular weight of 5,499. Yield of cardionatrin I was 12-20 nmole per 1,000 atria. Injection of 0.5 nmole induced a characteristic diuretic and natriuretic response in the non-diuretic assay rat.

Amino Acids↗
PubMed1982

Reversal of diuretic-induced increases in serum low-density-lipoprotein cholesterol by the betablocker pindolol.

Seventeen patients with mild to moderate essential hypertension received during three consecutive 4 wk periods a matched placebo, the thiazide-like diuretic, clopamide in a low dosage of 5 mg/day, or this diuretic combined with the betablocker, pindolol in a low dosage of 10 mg/day. Compared to placebo conditions, clopamide monotherapy significantly increased serum low-density lipoprotein cholesterol (LDL-C) by 13% (p less than 0.025). Following addition of pindolol, serum LDL-C was restored to control values. These variations in serum LDL-C were unrelated to concomitant changes in blood pressure, plasma potassium, renin activity or aldosterone levels. Blood pressure in the supine position was reduced from 152/99 +/- 13/9 mm Hg (+ SD) to 141/93 +/- 15/7 mm Hg following diuretic-monotherapy and to 139/90 +/- 12/9 mm Hg following diuretic-betablocker combination treatment. These findings suggest that antihypertensive combination treatment with low doses of clopamide and pindolol is not only effective and well tolerated, but may also avoid the increase in serum LDL-C levels occurring when the thiazide-like diuretic is given alone.

Adult↗
PubMed2005

The aldosterone antagonist and facultative diuretic eplerenone: a critical review.

Eplerenone is a new aldosterone-receptor blocker that differs from spironolactone by virtue of higher selectivity for the aldosterone receptor. Therefore, eplerenone treatment is associated with comparative and absolute low incidences of gynecomastia, mastodynia, and abnormal vaginal bleeding. Similarly, a lower incidence of sexual impotence than that associated with spironolactone administration may be anticipated. Eplerenone and spironolactone increase natriuresis and cause renal retention of potassium when plasma aldosterone is high, i.e., both agents are facultative diuretics. Eplerenone reduces high blood pressure effectively. The results of a recent large study and an ensuing meta-analysis on antihypertensive treatment suggest that a diuretic should be the first-choice agent in most circumstances. Low-dose eplerenone combinations with a low-dose thiazide-type diuretic appear to be options worth investigating, since the overall cardiovascular benefit brought about by reducing blood pressure with the thiazide would be increased, inter alia, by the antikaliuretic action and by the blockade of extrarenal aldosterone receptors provoked by eplerenone. Eplerenone should replace spironolactone as a natriuretic and antikaliuretic in heart failure and as add-on treatment in severe systolic cardiac insufficiency, and it is indicated after an acute myocardial infarction complicated by left ventricular dysfunction and heart failure. The finding that hypertension control with diuretic-based pharmacotherapy results in better prevention of heart failure than pressure reduction with other drugs makes it pertinent to investigate whether diuretics in general, and eplerenone in particular, should constitute part of the initial pharmacotherapy for heart failure when there is no overt fluid retention and independent of the etiology. Eplerenone may cause hyperkalemia, and it might favor the development of metabolic acidosis or hyponatraemia in some circumstances.

Journal Article↗