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PubMed2005

The increase in serum uric acid concentration caused by diuretics might be beneficial in heart failure.

Patients with mild-moderate chronic heart failure (CHF) often have raised levels of serum uric acid (UA). This is due, amongst other factors, to reduced UA excretion by the kidneys, which is partly explained by restriction of sodium intake and treatment with diuretics. The decline in renal function that parallels worsening cardiac function also contributes to elevated serum UA in patients with advanced CHF. However, UA production also appears to be augmented in CHF. Because UA scavenges various reactive oxygen species, diuretic-induced elevations in serum UA could be beneficial in patients with CHF. This concept is supported by the superior performance of antihypertensive therapy with diuretics in preventing heart failure. The present hypothesis may be tested by examining the effects of add-on treatment with a thiazide-type diuretic on morbidity and mortality, or surrogate variables, in asymptomatic patients with left ventricular dysfunction but without fluid retention.

Allopurinol↗
PubMed2004

Bone mineral density changes in hypercalciuretic osteoporotic men treated with thiazide diuretics.

UNLABELLED: A few studies suggest that thiazide diuretic agents may have modest beneficial effects on bone. Few data are available on the effects of these medications in patients with osteoporosis and hypercalciuria. OBJECTIVE: To evaluate the effects of thiazide diuretic therapy on bone mass and urinary calcium excretion in hypercalciuretic osteoporotic male patients. PATIENTS AND METHODS: Osteoporosis was defined as a greater than 2.5 standard deviation (S.D.) decrease in bone mineral density (BMD) at the lumbar spine or hip (T-score). We used an open-label prospective design to compare 14 patients with hypercalciuretic osteoporosis treated with a thiazide diuretic for 18 months and 13 patients with primary osteoporosis treated with calcium and vitamin D supplementation. Mean age was 53.5 +/- 9.6 years in the thiazide group and 48.7 +/- 8.4 years in the calcium-vitamin D supplementation group. The following serum parameters were assayed at baseline: 25OH-D3, 1,25OH-D3, parathyroid hormone (PTH), and bone turnover markers. Urinary calcium excretion and BMD by dual-energy X-ray absorptiometry at the spine and hip were determined at baseline and after 18 months of treatment. RESULTS: Annual BMD increases were similar in the two groups during the 18-month treatment period: lumbar spine, 0.6 +/- 2.5% (P = 0.47) in the thiazide group and 0.004 +/- 3% (P = 0.78) in the supplementation group; femoral neck, 0.47 +/- 2.6% (P = 0.89) and 1.1 +/- 3.2% (P = 0.22); total hip, 0.65 +/- 2.5% (P = 0.37) and 0.12 +/- 2.1% (P = 0.51). Urinary calcium excretion fell by 45.9% in the thiazide group from baseline to study completion (P = 0.0015). CONCLUSION: We found no evidence that thiazide therapy increased bone mass in patients with hypercalciuria and osteoporosis as compared to calcium-vitamin D supplementation in patients with osteoporosis but no hypercalciuria. In contrast, our results establish the efficacy of thiazide diuretics in reducing urinary calcium excretion, an effect that may decrease the risk of urinary lithiasis. Studies in larger patient cohorts treated for longer periods are needed to confirm or refute our findings.

Benzothiadiazines↗
PubMed2004

Diuretic effect of the crude extracts of Carissa edulis in rats.

Carissa edulis (forssk) vahl (Apocynaceae) is used traditionally for the treatment of headache, chest complaints, rheumatism, gonorrhoea, syphilis, rabies and as a diuretic. In the present study, the diuretic activity of different extracts of Carissa edulis was investigated. The diuretic activity of the different extracts of Carissa edulis in a dose range of 50-1000 mg/kg was assessed orally in rats using hydrochlorothiazide as a standard drug. The root bark maceration extract showed no effect on the urine output up to a dose of 1000 mg/kg, while the root bark soxhlet extract produced a significant increase (P < 0.05) in urine output at a dose of 1000 mg/kg. The root wood maceration and root wood soxhlet extracts produced a significant increase in urine output at a dose of 50 mg/kg, with a P-value of <0.05. Urinary electrolyte excretion was also affected by the extracts: the root bark soxhlet extract increased urinary excretion of sodium, potassium and chloride ions; root wood maceration extract increased excretion of sodium and potassium, while root wood soxhlet extract increased excretion of potassium ion. These findings support the traditional use of Carissa edulis as a diuretic agent.

Animals↗
PubMed2004

Diuretic activity of the stem-bark extracts of Steganotaenia araliacea hochst [Apiaceae].

The diuretic activity of the stem-bark extracts of Steganotaenia araliacea (SbESa) and effects on urine electrolytes in rats was studied. Furthermore, a toxicological effect of the SbESa on several tissues was investigated. Groups of male Wister albino rats (170 +/- 0.77 g) were employed. Four doses of 20mg/kg body weight (b.w.), of SbESa (water, methanol, ethanol) and furosemide were administered intraperitoneally (IP). The control group received normal saline alone by oral administration. The 24-h urine outputs per day (in ml) were: normal saline (1.57 +/- 0.11); water extract (3.18 +/- 0.24); methanol extract (3.22 +/- 0.29); ethanol extract (3.62 +/- 0.27) and furosemide (4.22 +/- 0.23). The urine output among the extracts (water, methanol, ethanol) and the furosemide against the control was statistically significant, (P < 0.05), (P < 0.05), (P < 0.02), and (P < 0.01), respectively. The ethanol preparation gave the highest diuretic activity among the extracts. There was marked increase in K(+) ion excretion (122 +/- 7.3 mMol/l) in the ethanol extract as compared to control (95.8 +/- 1.2 mMol/l) and furosemide (standard) (90.05 +/- 0.1 mMol/l). The LD(50) of 1.75 g/kg body weight was observed and the histopathological examination reveals damage to vital organs. The authors conclude that though there are compelling evidence of diuretic potentials in the use of the stem-bark of Steganotaenia araliacea, the toxic effects on vital organs is a drawback to its recommendation for use as a diuretic agent.

Animals↗
PubMed2005

Diuretic activity of Artemisia thuscula, an endemic Canary species.

A pharmacological evaluation for diuretic activity of infusions at 5, 10 and 15% of Artemisia thuscula Cav. was carried out. Urinary excretion of water, pH, density, conductivity and Na(+), K(+) and Cl(-) content were investigated in saline-loaded rats. The infusions showed a dose-dependent decrease diuretic effect, but augmented significantly with respect to the control group for the urinary excretion of water and sodium. Furthermore, a potassium-sparing effect at 5 and 10% was showed. The diuretic effect does not seem to be related to the potassium content of the starting material. The results justify the use of Artemisia thuscula as diuretic agent by the canary traditional medicine.

Animals↗
PubMed2006

Diuretic activity of the aqueous extracts of Carum carvi and Tanacetum vulgare in normal rats.

In the Moroccan traditional medicine, the ripe fruits of Carum carvi L. (Apiaceae) and the leaves of Tanacetum vulgare L. (Asteraceae/Compositae), two widely available plant materials, are used as diuretics. Since, the diuretic activity of these substances has not been investigated in scientifically controlled studies, the aim of the present study was to evaluate the diuretic potential of aqueous extracts of Carum carvi fruit (caraway) and the leaves of Tanacetum vulgare (tansy) in normal rats after acute and sub-chronic oral administration. Water extracts of Carum carvi and Tanacetum vulgare (100 mg/kg) or the reference drug, furosemide (10 mg/kg) were administrated orally to male Wistar rats and their urine output was quantitated at several intervals of time after the dose. After single doses of the extracts of both caraway seeds and tansy leaves, urine output was significantly increased at all time points, and at 24 h after the dose, the total volume of urine excreted was similar for the plant extracts and furosemide. Both extracts increased urinary levels of Na(+) and K(+), to about the same extent, while furosemide increased urinary levels of only Na(+) and decreased urinary K(+). Despite changes in urinary excretion of the electrolytes, plasma Na(+) and K(+) levels were not affected by any of the three substances. In the 8-day sub-chronic study, all three substances induced significant diuresis and natriuresis; only tansy increased urinary potassium excretion. The plant extracts did not appear to have renal toxicity or any other adverse effects during the study period. In conclusion, water extracts of both Carum carvi and Tanacetum vulgare have strong diuretic action confirming their ethnopharmacological use. From the pattern of excretion of water, sodium and potassium, it may be deduced that there are atleast two types of active principals present in these extracts, one having a furosemide-like activity and the other a thiazide-like activity.

Animals↗
PubMed1999

Effects of short-acting and long-acting loop diuretics on heart rate variability in patients with chronic compensated congestive heart failure.

BACKGROUND: We investigated the effects of a short-acting loop diuretic (furosemide) and a long-acting loop diuretic (azosemide) on heart rate variability, fluid balance, and neurohormonal responses in patients with mild to moderate chronic congestive heart failure. METHODS: Nineteen patients with mild to moderate chronic congestive heart failure received furosemide (40 to 60 mg/day) or azosemide (60 to 90 mg/day) for 5 days in a crossover manner. We performed time-domain and frequency-domain analyses of 24-hour Holter electrocardiographic recordings to assess heart rate variability. RESULTS: The 24-hour urinary sodium excretion was similar during the furosemide and azosemide treatment periods but was significantly greater in the first 2 hours after drug administration during furosemide treatment. Plasma renin activity and the hematocrit level increased and high-frequency power significantly decreased 2 hours after the administration of furosemide only. The standard deviation of all normal R-R intervals and the root mean square of successive differences in the R-R interval were lower with furosemide than with azosemide (P <.05). CONCLUSIONS: Furosemide, a short-acting loop diuretic, has a greater influence on heart rate variability and fluid balance than azosemide, a long-acting loop diuretic, in patients with mild to moderate chronic congestive heart failure.

Blood Pressure↗
PubMed1983

Negative effects of diuretic drugs on metabolic risk factors for coronary heart disease: possible alternative drug therapies.

The results of 8 major hypertension treatment trials, all using diuretics as first-line therapy, show a clear-cut reduction in stroke and congestive heart failure, but coronary heart disease (CHD) is not consistently benefited. It is unclear why CHD is not controlled, but diuretics can subtly upset metabolic risk factors for CHD, among which are lipid and glucose concentrations. Although these metabolic disturbances appear clinically unimpressive, risk table analysis reveals that they can offset or even reverse the benefits of reducing blood pressure. A link between glucose intolerance and increased serum lipid concentrations during diuretic-based therapy is suggested by multiple correlations between them. Replacement of diuretics as first-line therapy for mild and moderate hypertension should therefore be considered. Spironolactone seems to counter the adverse metabolic effects, but its effect on lipoproteins needs more study. A drug that does not disturb glucose and lipid metabolism would seem preferable. Thus prazosin is a promising candidate.

Antihypertensive Agents↗
PubMed1996

Diuretics: cornerstone of antihypertensive therapy.

Diuretics have been used less often for the treatment of hypertension over the past few years for a variety of reasons. However, their use will almost certainly go back up for many reasons, including the recent publication of trials with appropriately low doses of diuretics that have shown excellent protection against the major cardiovascular causes of death. Moreover, resistance to antihypertensive therapy is most commonly caused by inadequate diuretic therapy. Therefore, I believe diuretics will continue to be a cornerstone of antihypertensive therapy in the future.

Aged↗
PubMed1996

The evolution of low-dose diuretic therapy: the lessons from clinical trials.

Safe and effective antihypertensive therapy became available in the 1950s with the introduction of thiazide diuretics. Prior to that time, we did have agents that lowered blood pressure but they often needed to be given parenterally and were too poorly tolerated to be used for the treatment of any but those with life-threatening elevations of blood pressure. When thiazide diuretics-first chlorothiazide and then hydrochlorothiazide-became available, it was possible to lower blood pressure in most hypertensives and assess whether that reduction would lead to a reduction in cardiovascular morbidity and mortality. The results of 17 large trials have now made it clear that antihypertensive therapy with regimens based on diuretics and beta blockers reduces cardiovascular events and saves lives. When first introduced, thiazide diuretics were prescribed at doses we now know are excessively high (100-200 mg of hydrochlorothiazide/day), and we have learned that much lower doses, even as little as 12.5 mg of hydrochlorothiazide, are effective. These lower doses will reduce blood pressure and do so with considerably less in the way of metabolic effects. This article will trace the development of antihypertensive therapy and review how data from clinical trials have influenced the recommendations of the Joint National Committees on the Detection, Evaluation and Treatment of Hypertension.

Benzothiadiazines↗
PubMed1985

High-performance liquid chromatographic behaviour of some pharmaceutically important thiazide, loop and potassium-sparing diuretics.

This paper deals with the specific identification of several thiazide, potassium-sparing and loop diuretics. The liquid chromatographic behaviour of these compounds is studied. Different organic modifiers (methanol, acetonitrile and tetrahydrofuran) are compared in terms of selectivity for the thiazide diuretics. An acetonitrile-water (40:60) eluent can be used to identify the thiazide diuretics. The loop and potassium-sparing diuretics are well chromatographed at an acidic pH in the presence of propylamine hydrochloride. This study enables us to select the right mobile phase composition for any given selectivity or resolution. The determination of the dead volume in different chromatographic systems is also discussed. A mixture of organic solvent and deuterium oxide in the same volume ratio as the eluent is used as dead volume marker. The signal is monitored with a UV detector at low wavelength.

Benzothiadiazines↗
PubMed1976

Effect of long-term diuretic treatment on body-potassium in heart-disease.

Plasma and total body potassium have been measured in 151 patients with chronic heart-disease, 83 of whom were taking diuretics and potassium supplements. After allowance for age and body-size, the deficit in total body-potassium was only 3-5% (100-150 mmol) in the diuretic group. 13 of the 83 patients taking diuretic had hypokalaemia (less than 3-5 mmol/1) but the potassium deficit was no greater than in the patients with normal plasma-potassium. There was no relation between the dose of potassium supplements and either the plasma-potassium or the total body-potasium. It is suggested that potassium depletion is not a major problem in patients with heart-failure treated with diuretics. The dose of potassium supplements should therefore be determined entirely by the plasma-potassium.

Adult↗
PubMed1999

The prognostic implications of outpatient diuretic dose in heart failure.

In 111 patients with left ventricular ejection fraction < or =30% who required hospitalization for heart failure, we examined the association between outpatient dose of diuretic agents and all-cause mortality. In comparison to patients who were not on treatment with diuretics prior to hospitalization, patients being treated with 'low' doses of diuretics (<80 mg/day of furosemide) and those being treated with 'high' doses of diuretics (> or =80 mg/day of furosemide) were more likely to die during follow-up after adjustment for other clinical parameters (adjusted relative risks, RR, 3.1 and 4.6).

Aged↗
PubMed1997

Diuretic requirements after therapeutic paracentesis in non-azotemic patients with cirrhosis. A randomized double-blind trial of spironolactone versus placebo.

BACKGROUND/AIMS: Diuretic requirements after mobilization of ascites by paracentesis have never been assessed in cirrhosis. It is also unknown whether diuretics increase the incidence of postparacentesis circulatory dysfunction. The aim of this study was to investigate these features and to assess whether measurement of plasma renin activity and aldosterone prior to paracentesis predicts diuretic response after this procedure. METHODS: Thirty-six patients with non-azotemic cirrhosis and ascites treated by total paracentesis plus i.v. albumin were randomly assigned to receive placebo (n=17) or spironolactone 225 mg/day (n=19) immediately after paracentesis and followed-up for 4 weeks. RESULTS: Five patients (three in the placebo and two in the spironolactone group) abandoned the treatment prior to ascites recurrence or the end of the study due to complications or lack of compliance. The analysis was performed in the remaining 31 patients. Ascites recurrence was more common in the placebo group (13 cases, 93%) than in the spironolactone group (3 cases, 18%) (p<0.0001) and occurred within the first 2 weeks of follow-up in more than 50% of patients. Patients developing ascites in the spironolactone group had higher levels of renin (14.1, 20.6, 32.4 ng/ml per h) and aldosterone (120, 149, 288 ng/dl) than those who did not develop ascites (renin: 2.0+/-2.1 ng/ml per h; range 0.1-6.8; aldosterone: 43+/-38 ng/dl; range 4-116). Three patients in the placebo group and two in the spironolactone group developed postparacentesis circulatory dysfunction (defined as an increase in renin at the third day after paracentesis greater than 50% over baseline levels up to a value higher than 4 ng/ml per h). CONCLUSIONS: Patients with cirrhosis treated by paracentesis should receive diuretics immediately after this procedure to prevent early recurrence of ascites. The administration of 225 mg/day of spironolactone is a good empiric treatment for non-azotemic patients with cirrhosis, because it is effective in most cases and does not increase the incidence of postparacentesis circulatory dysfunction. The determination of plasma levels of renin or aldosterone prior to paracentesis predicts the efficacy of spironolactone in the prevention of ascites recurrence.

Aldosterone↗
PubMed1987

Liquid chromatographic screening of diuretics in urine.

We describe a liquid chromatographic screening procedure for the detection, in urine, of twelve of the fifteen potassium-depleting diuretics available in Australia. A 2-ml urine sample was acidified with NaH2PO4 (pH 4.1) and extracted with 4 ml ethyl acetate. The sample was cleaned up further by washing with 5 ml Na2HPO4 (pH 7.5). The ethyl acetate was then evaporated to dryness, the residue reconstituted in 100 microliters mobile phase and 5 microliter were injected onto a Merck LiChrosorb RP-18 (5 microns) column. The ultraviolet absorbance of the eluent was monitored at 271 nm for 10 min. The screen was evaluated by giving each of thirty volunteers the lowest recommended dose of one of the diuretics in the study and obtaining urine samples 4, 8 and 24 h after having taken the dose. Twelve diuretics, chlorothiazide, hydrochlorothiazide, quinethazone, chlorthalidone, methyclothiazide, clopamide, frusemide, metolazone, mefruside, bendrofluazide, cyclopenthiazide and bumetanide, were all detectable up to 24 h after a dose. We therefore conclude that the screen would be reliable for the detection of these diuretics in urine.

Chromatography, High Pressure Liquid↗
PubMed1997

Plants from Réunion Island with alleged antihypertensive and diuretic effects--an experimental and ethnobotanical evaluation.

Eighty species of vascular plants were collected on Reunion Island and tested for their ability to inhibit the angiotensin converting enzyme (ACE), which plays an important role in the regulation of blood pressure and diuresis. Of these species, 26 serve as antihypertensive remedies in traditional medicine, and 38 as diuretics-10 of the 64 species have both alleged antihypertensive and diuretic effects. Of the species examined, 26 have not been reported to have any of these effects. Plant material was extracted with both acetone, ethanol and water, and samples were considered active if ACE inhibition was 50% or more in one of the extracts. Of the species with alleged antihypertensive or diuretic effect, 44% proved active. Of the species with no report of such effects, 31% proved active. There were no overall differences in the range of inhibition of the three extracts, but amongst the species considered active there was a strong negative correlation between inhibition of acetone and water extracts. A statistical analysis of the results demonstrated clear differences between plants with alleged antihypertensive effects, diuretic effects, and no alleged use with respect to inhibition of the three extracts.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Differential effects of angiotensin converting enzyme inhibition and diuretic therapy on reductions in ambulatory blood pressure, left ventricular mass, and vascular hypertrophy.

Diuretic-based therapy is less effective in reducing the cardiac complications of hypertension than the risk of stroke and may be less effective in reducing left ventricular (LV) mass than is therapy with angiotensin converting enzyme (ACE) inhibition. In view of the strong association of LV hypertrophy with cardiovascular risk, this study was designed to compare the impact of therapy with a diuretic and ACE inhibition on cardiac and vascular structure. Fifty essential hypertensives (74% male, 88% nonwhite) participated in a double-blind study for 6 months and were randomized to either ramipril or hydrochlorothiazide (HCTZ). Echocardiography, carotid ultrasonography, and ambulatory blood pressure (BP) monitoring were performed at baseline and 3 and 6 months after initiation of therapy. The 22 ramipril patients were comparable to the 28 HCTZ patients at baseline in age, race, and 24-h BP. Although HCTZ resulted in a greater reduction in 24-h BP, only treatment with ramipril resulted in a decrease in LV mass (193 to 179 g, P < .005, v 184 to 182 g, P = NS), attributable to a reduction in wall thicknesses but not in chamber diameter. In multivariate analysis, both change in BP and treatment group were independent predictors of change in LV mass. Importantly, although neither drug reduced carotid artery cross-sectional area, relative wall thickness increased due to a tendency for vessel diameter to decrease and wall thickness to increase, particularly in the diuretic group. Ramipril caused a sustained fall in plasma angiotensin II, whereas HCTZ increased angiotensin II levels. Although diuretic therapy was more effective in lowering ambulatory BP in this predominantly nonwhite population, only therapy with ACE inhibition was associated with regression of LV mass. Vascular geometry was altered consistent with the reduction in distending pressure resulting in vascular remodelling.

Adult↗
PubMed2003

Rational diuretic management in congestive heart failure: a case-based review.

The pharmacology and pharmacokinetics of diuretics are unique among therapeutic drugs. Knowledge of these principles can be used to great advantage in the management of heart failure, whereas ignoring them can lead to either minor or life-threatening adverse consequences. Two major categories of potential therapeutic problems are diuretic resistance and the development of disturbances in serum potassium and other electrolytes. Inhibition of sodium reabsorption in the loop of Henle or distal convoluted tubule leads to renal potassium wasting, whereas inhibition of sodium reabsorption in the collecting duct (either directly, as with triamterene or amiloride, or through aldosterone antagonism) causes potassium retention. Combining diuretics of different classes, a rational and frequently used strategy to counter diuretic resistance, can be anticipated to balance or magnify these effects, depending on the site of action of the individual drugs.

Aged↗