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PubMed2004

Thiazide diuretics in the management of hypertension.

Hypertension is highly prevalent in Canada, affecting more than 20% of all adults. Thiazide diuretics have been shown in numerous studies to be effective agents for controlling blood pressure and reducing cardiovascular disease and death in hypertensive patients. Thiazide diuretics are recommended as initial first line therapy for uncomplicated hypertension in the 2003 Canadian Hypertension recommendations. However, these agents are underutilized and in Canada, the proportion of persons with hypertension treated with diuretics is declining. To improve understanding of thiazide diuretic use, this document outlines the clinical pharmacology of thiazide diuretics, evidence for effectiveness in treating hypertension, as well as the side effects and controversies surrounding their use.

Canada↗
PubMed2006

[Torasemide--new generation loop diuretic: clinical pharmacology and therapeutic application].

Peculiarities of clinical pharmacology of new generation loop diuretic torasemide and its possible place in the treatment of arterial hypertension, chronic heart failure (CHF) and liver cirrhosis are considered. Main advantage of torasemide over loop diuretics of furosemide and bumetamide type is that in addiction to powerful diuretic and natriuretic actions it produces potassium sparing effect that is explainded by ability its of to tosasimide to block aldosterone receptors in renal tubules. Moreover torasemide exerts longer action than furosemide and bumetamide what allows to take it once a day. In low doses torasemide produces pronounced antihypertensive effect without augmentation of excretion of potassium and water with urine. Because of this it can be used as antihypertensive drug for monotherapy or in combination with other drugs. Contrary to thiazide and loop diuretics prescription of subdiuretic doses of torasemide usually does not require control of potassium content in the blood or addition of potassium preparations. In higher doses (10 mg/day or more) torasemide acts as typical loop diuretic and can be used in the treatment of CHF and liver cirrhosis with ascites. Due to potassium sparing action it more rarely than furosemide and bumetamide causes hypokalemia. Comparative studies have shown than in CHF torasemide exerts more favorable effect on clinical signs of disease and functional status of patients than furosemide. Total mortality, cardiovascular mortality and requirements in hospitalization of patients receiving torasemide is substantially less than of patients receiving furosemide.

Heart Failure↗
PubMed1989

[Dynamic scintigraphy of the kidneys using a diuretic].

The authors describe the application of the method of dynamic scintigraphy of the kidneys, using a diuretic, in patients with signs of stasis in the upper urinary pathways, based on findings of excretory urography and standard radioisotope examination of the kidneys. They obtained three groups of results: 1. Obstruction during the standard radioisotope examination of the kidneys became normal after administration of the diuretic. 2. The obstruction receded during the standard radioisotope examination of the kidneys as a result of the diuretic, but only insignificantly. 3. There were signs of obstruction on standard radioisotope examination of the kidneys and they persisted also after administration of the diuretic. These results of dynamic scintigraphy of the kidneys using a diuretic make it possible to differentiate more readily dilatation of the upper urinary pathways in the absence of an obstruction from dilatation due to a significant obstruction, which is important when deciding on further diagnostic and therapeutic procedures in clinical urological practice.

Adolescent↗
PubMed1988

Diuretics and hypertension in black adults.

A randomized controlled, single-blind trial was conducted to compare the effectiveness of a high-dose diuretic with a combination of a diuretic and metoprolol in black adults with hypertension. All subjects were first treated with 50 mg/d of hydrochlorothiazide for four weeks. Only subjects with a diastolic blood pressure of 95 mm Hg or higher at the end of this four-week period entered the randomized trial. We hypothesized that black patients with uncontrolled hypertension and low plasma renin activity on usual-dose hydrochlorothiazide therapy (ie, 50 mg/d) would respond better to higher doses of hydrochlorothiazide (ie, 100 to 150 mg/d) than to a usual-dose diuretic and metoprolol. Diuretic-metoprolol combination therapy was significantly more effective than high-dose diuretic therapy regardless of plasma renin status.

Adult↗
PubMedDate not supplied

The relationship between diuretics and serum cholesterol in Hypertension Detection and Follow-up Program participants.

The effect of diuretics, mainly chlorthalidone, on serum cholesterol was studied in 7,006 of the Hypertension Detection and Follow-up Program (HDFP) hypertensive patients not on antihypertensive medication at baseline. Several investigators have reported that diuretic therapy increases serum cholesterol in treated subjects. However, data from two long-term studies indicated that no increase in cholesterol occurred after two years of diuretic treatment. In the present study, yearly changes in serum cholesterol in hypertensives treated with diuretics were observed. The results were in agreement with those reported from both short-term and long-term studies, in that a significant increase in cholesterol was observed in six months to one year into the study but not from the second to the fifth year of therapy. In fact, the serum cholesterol levels were the same as baseline values after two years of drug treatment and decreased slightly thereafter. In the untreated group, no change or a decrease in serum cholesterol was observed during the course of the study. The possible causes for changes in serum cholesterol concentration such as regression to the mean, change in body weight, baseline cholesterol concentration, and the action mechanism of diuretic drugs are discussed.

Adult↗
PubMed1982

Increased transvascular escape rate and lymph drainage of albumin in pigs during intravenous diuretic medication. Relations to treatment in man and transport mechanisms.

Transvascular escape rate of albumin (TERalb, i.e. the fraction of intravascular mass of albumin (IVMalb) passing to (or during steady state returning from) the extravascular space per unit time) was determined from the initial disappearance rate of i.v. injected radioiodinated serum albumin in anaesthetized pigs during control conditions and during diuretic medication (furosemide i.v. 20 mg/15 min, total 160-200 mg). During diuretic medication TERalb (mean 17.1% IVMalb X h-1, range 11.5-21, n = 6) increased significantly above the control period (mean 12.3% IVMalb X h-1, range 9.5-16.5, P less than 0.05). Pressures in artery, right atrium, hepatic and portal veins did not change significantly from control to diuretic period. TERalb equals the lymphatic return rate of albumin provided the transport mechanisms are filtrative-convective (i.e. no local back transport). Additional measurements in five pigs with proteins of different molecular size confirmed a dominating filtrative-convective transport. The increased TERalb during diuretic medication is best explained by an increased lymph drainage, which may decrease interstitial fluid pressure and thereby increase the transmural capillary pressure difference being essential for a filtrative-convective transvascular albumin transport. Increased lymph drainage may contribute to the therapeutic effect of diuretic treatment in oedema and ascites.

Albumins↗
PubMed1994

The effects of diuretics on posttraumatic joint stiffness and limb swelling in a rabbit periarticular fracture model.

Periarticular long bone fractures usually result in soft-tissue swelling because of edema and hemorrhage, as well as progressive, often permanent joint stiffness. The authors evaluated the effects of chlorothiazide, a commonly used diuretic, and acetazolamide, a weaker diuretic with a different mechanism of action, on joint stiffness and swelling using an established rabbit hindlimb model. Bilateral distal tibial fractures were produced in 30 adolescent New Zealand white rabbits. Twelve rabbits served as age-matched controls and received no treatment, 11 were treated with chlorothiazide, and seven were treated with acetazolamide, each for five days at doses adjusted for body weight but equivalent to human dosing. Eleven limbs were excluded from study because of fracture angulation in excess of 10 degrees. The mean stiffness ratios, comparing preoperative stiffness with stiffness at the end of the three-week study period, for diuretic-treated rabbits were significantly less than those in the control rabbits; there was no difference between the two treated groups. The total swelling and time to peak swelling did not differ among the three groups; however, peak swelling was least in the chlorothiazide group, the strong diuretic, when compared with the control and acetazolamide groups. The marked effect of diuretics on joint stiffness and their minimal effect on limb swelling were unexpected results and, taken in conjunction with previous treatment modalities tested in this model, indicate a complex, still poorly understood sequence of events leading to joint stiffness after periarticular injury.

Acetazolamide↗
PubMed2004

Should we use diuretics in acute renal failure?

Because oliguria is a bad prognostic sign in patients with acute renal failure (ARF), diuretics are often used to increase urine output in patients with or at risk of ARF. From a pathophysiological point of view there are several reasons to expect that loop diuretics also could have a beneficial effect on renal function. However, clinical trials on the prophylactic use of loop diuretics rather point to a deleterious effect on parameters of kidney function. In patients with established ARF loop diuretics have been shown to increase urine output, which may facilitate patient management. A beneficial effect on renal function has, however, not been demonstrated. On the other hand, such an effect cannot be excluded because the available trials lack statistical power. Possible explanations for the absence of a renoprotective effect are discussed. The evidence for a renoprotective effect of mannitol is restricted to the setting of renal transplantation.

Acute Kidney Injury↗
PubMed1971

Diuretic synergy in the treatment of acute experimental cerebral edema.

Acute cerebral edema was created in dogs by the intracarotid injection of sodium lauryl sulfate, a method that produces no structural or vascular disruption in the brain. Cerebrospinal fluid (CSF) pressure elevations were measured through subdural balloons, and ranged from 300 to 1500 mm H2O. The nature of the cerebral edema produced was studied with intravital Trypan blue, electrocorticography, and visual observation of cerebral circulation, and by postmortem histological sections and determinations of brain water content. Two dissimilar diuretic agents were studied: the osmotic diuretic, mannitol; and the renal diuretic, ethacrynic acid. As expected, mannitol reduced CSF pressure effectively, with no significant rebound overshoot. Ethacrynic acid, despite favorable reports, proved to have only a slight effect on CSF pressure but did prove to be a potent diuretic. Unexpectedly, the two agents were found to act synergistically. When both agents were administered, significantly greater reductions in pressure were obtained and pressure reductions were maintained for longer periods.

Animals↗
PubMed1992

Diuretics.

Diuretics are the mainstay of therapies for many diseases, including hypertension congestive heart failure. While their use can be beneficial, many side effects and interactions are attributed to diuretic therapy. This chapter reviews the mechanism of action for the various diuretics and elucidates differences between classes. Major drug-drug and drug-nutrient interactions are examined with information on intervention and patient teaching. Several therapeutic dilemmas in the treatment of hypertension, renal failure, congestive heart failure, and pulmonary edemas are reviewed. With proper nursing assessment and intervention, the diuretics can have beneficial effects in hypertension therapies and the treatment of edema and cause a minimum of adverse drug experiences.

Benzothiadiazines↗
PubMed1983

Diuretic regimens in essential hypertension. A comparison of hypokalemic effects, BP control, and cost.

Intolerable side effects and hypokalemia during thiazide treatment of hypertension frequently necessitate a change in diuretic regimen. The hypokalemic effects, effectiveness in controlling BP, and cost of several alternate diuretic regimens were evaluated. Prevalences of serum K+ values less than 3.5 mEq/L were as follows for the various regimens: hydrochlorothiazide, 50 mg daily, 11.0% (n = 500); chlorthalidone, 25 mg daily, 8.1% (n = 37); triamterene, 100 mg, plus hydrochlorothiazide, 50 mg daily, 5.3% (n = 357); hydrochlorothiazide, 25 mg daily, 2.2% (n = 183); and furosemide, 40 mg daily, 3.5% (n = 284). In paired studies comparing hydrochlorothiazide with alternate diuretic regimens, potassium conservation was comparable with furosemide, the triamterene/hydrochlorothiazide combination, the spironolactone/hydrochlorothiazide combination, and adding potassium, 37 mEq daily. All alternate diuretic regimens were as effective as hydrochlorothiazide in controlling BP. Furosemide reduced serum glucose and calcium levels compared with hydrochlorothiazide. When these factors and costs are considered, furosemide appears to be the most cost-effective alternative in patients with hypertension in whom intolerable side effects or hypokalemia develops while taking hydrochlorothiazide.

Blood Pressure↗
PubMed2005

Obesity, weight change, hypertension, diuretic use, and risk of gout in men: the health professionals follow-up study.

BACKGROUND: Limited prospective information exists on the relation between obesity and weight change and the risk of gout. Similarly, both hypertension and diuretic use have been considered risk factors for gout; however, their independent contributions have not been established prospectively. METHODS: We prospectively examined over a 12-year period (1986-1998) the relation between adiposity, weight change, hypertension, and diuretic use and incident gout in 47,150 male participants with no history of gout at baseline. We used a supplementary questionnaire to ascertain the American College of Rheumatology criteria for gout. RESULTS: During 12 years we documented 730 confirmed incident cases of gout. Compared with men with a body mass index (BMI) of 21 to 22.9, the multivariate relative risks (RRs) of gout were 1.95 (95% confidence interval [CI], 1.44-2.65) for men with a BMI of 25 to 29.9, 2.33 (95% CI, 1.62-3.36) for men with a BMI of 30 to 34.9, and 2.97 (95% CI, 1.73-5.10) for men with a BMI of 35 or greater (P for trend <.001). Compared with men who had maintained their weight (+/-4 lb) since age 21 years, the multivariate RR of gout for men who had gained 30 lb or more since age 21 years was 1.99 (95% CI, 1.49-2.66). In contrast, the multivariate RR for men who had lost 10 lb or more since the study baseline was 0.61 (95% CI, 0.40-0.92). The multivariate RRs of gout were 2.31 (95% CI, 1.96-2.72) for the presence of hypertension and 1.77 (95% CI, 1.42-2.20) for diuretic use. CONCLUSIONS: Higher adiposity and weight gain are strong risk factors for gout in men, while weight loss is protective. Hypertension and diuretic use are also important independent risk factors for gout.

Adult↗
PubMed1987

A comparison of combinations of diuretics in nephrotic edema.

The metolazone-furosemide combination of diuretics was compared with the thiazide-furosemide combination in nephrotic patients with edema. Nine patients underwent a crossover, randomized study receiving furosemide (2 mg/kg per dose) and either metolazone (dose varied according to weight) or chlorothiazide (10 mg/kg per dose). An additive natriuretic and diuretic effect was observed after both metolazone and thiazide were combined with furosemide. The use of both types of diuretic combination was associated with marked kaliuresis. These combinations of diuretics seem equally effective in inducing natriuresis and diuresis in edematous nephrotic patients.

Administration, Oral↗
PubMed2006

Diuretics for Ménière's disease or syndrome.

BACKGROUND: Ménière's disease is a disorder characterised by hearing loss, tinnitus and disabling vertigo. Diuretics are used to try and reduce the severity and frequency of episodes but there is little evidence behind this treatment. OBJECTIVES: To assess the effect of diuretic treatment in patients with Ménière's disease. SEARCH STRATEGY: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1 2005), MEDLINE (1966 to 2005), EMBASE (1974 to 2005), CINAHL and the metaRegister of Controlled Trials (mRCT) (up to 2005). SELECTION CRITERIA: Randomised controlled trials of diuretic versus placebo in Ménière's patients. DATA COLLECTION AND ANALYSIS: One author identified studies which loosely met the inclusion criteria and full texts were retrieved. Two authors independently applied the inclusion criteria. Seven studies were excluded from the review due to inappropriate study design or absence of randomisation. MAIN RESULTS: There were no trials of high enough quality to meet the standard set for this review. AUTHORS' CONCLUSIONS: There is insufficient good evidence of the effect of diuretics on vertigo, hearing loss, tinnitus or aural fullness in clearly defined Ménière's disease.

Diuretics↗
PubMed2005

Fluids and diuretics for acute ureteric colic.

BACKGROUND: Acute ureteric colic is a common cause of severe and debilitating pain. Theoretically, increasing fluid flow through the affected kidney might expedite stone passage, thereby improving symptoms more quickly. Unfortunately, for interventions such as high volume intravenous or oral fluids and diuretics that are aimed at doing this, the efficacy and safety is uncertain. OBJECTIVES: To look at the benefits and harms of diuretics and high volume (above maintenance) intravenous or oral fluid therapy for treating adult patients presenting with uncomplicated acute ureteric colic. SEARCH STRATEGY: We searched the Cochrane Renal Group's specialised register (July 2004), the Cochrane Central Register of Controlled Trials (CENTRAL - The Cochrane Library, issue 3, 2004), MEDLINE (1966 - July 2004), EMBASE (1980 - July 2004) and handsearched reference lists of nephrology and urology textbooks, review articles, relevant trials, and abstracts from nephrology scientific meetings. We sent letters seeking information about unpublished or incomplete trials to investigators known to be involved in previous trials. SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi-RCTS (including the first period of randomised cross-over studies) looking at diuretics or high volume intravenous or oral fluids for treating uncomplicated acute ureteric colic in adult patients presenting to the emergency department for the first time during that episode were to be included. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) for dichotomous outcomes or weight mean difference (WMD) for continuous data with 95% confidence intervals (CI). MAIN RESULTS: One trial (60 participants) was identified. This study compared no fluids for six hours versus three litres of IV fluids received over a six hour period. There was no significant difference in pain at six hours (RR 1.06, 95% CI 0.71 to 1.57), surgical stone removal (RR 1.20, 95% CI 0.41 to 3.51) or manipulation by cystoscopy (RR 0.67, 95% CI 0.21 to 2.13). AUTHORS' CONCLUSIONS: Unfortunately, we could find no credible evidence in the literature regarding either of these two treatment modalities. Given their potential positive impact, the role of diuretics and high volume fluid therapy in acute ureteric colic should be examined to determine their safety and efficacy in facilitating stone passage.

Acute Disease↗
PubMed2001

Are certain diuretics also anticonvulsants?

A history of diuretic use has been shown to be protective for first unprovoked seizure in adult patients. Recent animal studies suggest that certain diuretics have anticonvulsant activity. We evaluated the potential for the anticonvulsant activity of current diuretic use in a population-based, case-control study in older adults. We also tested chlorthiazide and furosemide for seizure protection in animal models of epilepsy. Concurrent medical prescription of any diuretic was protective for the development of epilepsy [odds ratio (OR) = 0.62, 95% confidence interval (CI) = 0.39-0.99]. A protective effect for current thiazide use was observed (OR = 0.53, CI = 0.31-0.90), and a protective effect for furosemide was suggested (OR = 0.44, CI = 0.1-1.9). In mice, both chlorthiazide and furosemide suppressed the occurrence of maximal electroshock-induced seizures in a dose-dependent manner. Chlorthiazide's toxic dose for 50% of animals tested (TD50) could not be achieved even with dosing as high as 1,500 mg/kg for furosemide; TD50 was 549 mg/kg. Results were similar in rats. Furosemide and chlorthiazide are protective for unprovoked seizures in an epidemiological study and in animal models. Given the potential therapeutic value for seizure control, low toxicity, and low cost, therapeutic efficacy should be explored in clinical studies.

Aged↗
PubMed2002

Screening for 18 diuretics and probenecid in doping analysis by liquid chromatography-tandem mass spectrometry.

A fast and selective liquid chromatography-tandem mass spectrometric (LC/MS/MS) method for the screening of 18 diuretics and probenecid in human urine is presented. Analyses were performed on a LCQ-Deca instrument equipped with ESI-interface using scan by scan polarity changing. All diuretics and probenecid were separated in less than 20 min after liquid-liquid extraction with ethyl acetate. The LOD for all substances was 100 ng/mL or better. The method was applied to detect diuretics after the oral administration of several drugs including hydrochlorothiazide, bumetanide, spironolactone, furosemide, amiloride, triamterene, chlortalidone and epithizide. All diuretics could be detected for periods up to 96 h after the intake of therapeutic amounts.

Chromatography, Liquid↗
PubMedDate not supplied

Effects of a new loop diuretic (muzolimine) in cirrhosis with ascites: comparison with furosemide.

Muzolimine is a loop diuretic with both the dose-dependent increasing effectiveness of loop diuretics and the long-lasting effect of thiazides. This is a potential advantage in the treatment of ascites in advanced cirrhosis since these patients have a low tolerance to sudden reductions of blood volume. Equivalent single, oral doses of furosemide (40 mg) and muzolimine (30 mg) were given to 10 cirrhotic patients with ascites and reduced renal perfusion (glomerular filtration rate = 30 to 75 ml per min). The study was preceded by 4 days of equilibration (dietary sodium 40 mmoles per day), and the drugs were alternated via a single-blind, cross-over protocol after a wash-out period of 3 days. Renal function was monitored under basal conditions and after diuretic administration through 4-hr clearance periods for 24 hr. The renin-aldosterone axis was evaluated before diuretic administration and after 8 and 24 hr. Muzolimine led to a 12-hr cumulative diuresis [AUC0-12 = 2.52 +/- 0.42 (S.E.) ml per min] and natriuresis (5.14 +/- 1.05 mmoles per hr), which were comparable to those of furosemide (2.85 +/- 0.29 ml per min and 6.75 +/- 1.63 mmoles per hr). Its effect, however, was distributed over a longer period (8 hr) than furosemide (4 hr). Muzolimine activity mainly differed from furosemide because of: significantly lower 12-hr potassium excretion (AUC0-12 = 0.28 +/- 0.82 vs. 2.69 +/- 0.46 mmoles per hr; p less than 0.005); greater sodium/chloride excretion ratio (0.45 +/- 0.08 vs. 0.26 +/- 0.06; p less than 0.025), and absence of rebound phenomena.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗