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PubMed1976

Diuretic drugs and pregnancy.

Perinatal mortality and delivery patterns are compared for 4035 gravidas who were prescribed diuretic drugs during pregnancy and 13,103 gravidas who were not. Diuretic drugs were prescribed primarily for edema; gravidas with hypertensive disorders were excluded. The 2 groups, differing in both condition and drug excluded. The 2 groups, differing in both condition and drug usage, had significantly different gestational age distributions. The gravidas prescribed diuretic drugs delivered infants of higher mean birthweight and had significantly higher incidences of induction of labor, stimulation of labor, uterine inertia, and meconium staining. Their perinatal mortality rates also tended to be higher. The findings support the contention that higher risk is associated with one or more factors differentiating the 2 groups, namely, edema, undefined factors associated with edema, or the consumption of a diuretic drug.

Adult↗
PubMed1999

Expression of aldose reductase, sorbitol dehydrogenase and Na+/myo-inositol and Na+/Cl-/betaine transporter mRNAs in individual cells of the kidney during changes in the diuretic state.

The effect of changes in medullary extracellular tonicity on mRNA expression for aldose reductase (AR), sorbitol dehydrogenase (SDH), Na+/Cl-/betaine (BGT) and Na+/myo-inositol (SMIT) cotransporter in different kidney zones was studied using Northern blot analysis and non-radioactive in situ hybridization in four groups of rats: controls, acute diuresis (the loop diuretic furosemide was administered), chronic diuresis (5 days of diuresis), and antidiuresis [5 days of diuresis followed by 24 h deamino-Cys1, d-Arg8 vasopressin (dDAVP)]. Acute administration of the loop diuretic furosemide significantly reduced AR, SMIT and BGT gene expression in the inner and outer medulla compared with controls. Administration of dDAVP to chronically diuretic rats raised the expression of these three mRNAs in the inner but not the outer medulla compared with the chronically diuretic rats. None of these alterations in medullary tonicity significantly changed SDH expression. The in situ hybridization studies showed AR, BGT and SMIT mRNAs to be expressed in both epithelial and non-epithelial cells of the outer and inner medulla. The various cell types (epithelial, endothelial and interstitial cells) differed in their expression pattern and intensity of AR, SDH, BGT and SMIT mRNA, but the inner medullary cells responded uniformly to a decrease in extracellular tonicity with a reduction, and to an increase with enhancement of their AR, BGT and SMIT expression.

Aldehyde Reductase↗
PubMed2006

Diuretic potential of energy drinks.

Recent literature suggests that both caffeine and taurine can induce diuresis and natriuresis in rat and man. Although they act via different cellular mechanisms, their diuretic actions might be additive. This is of considerable interest, as several commercially available energy drinks contain both substances. In this study we examined the possible diuretic effects of caffeine and taurine in a cross-over-design in which 12 healthy male volunteers received each of 4 different test drinks (750 ml of energy drink containing 240 mg caffeine and 3 g taurine, the three other test drinks either lacked caffeine, taurine or both) after restraining from fluids for 12 h. Mixed model analyses demonstrated that urinary output and natriuresis were significantly increased by caffeine (mean differences 243 ml and 27 mmol; both p < 0.001) and that there were no such effects of taurine (mean differences 59 ml and -4 mmol). Additionally, urinary osmolarity at baseline was significantly related to the urinary output (p < 0.001). Urine osmolarity values at baseline and in the 6 h urine collection did not differ significantly between treatments. Taken together, our study demonstrates that diuretic and natriuretic effects of the tested energy drink were largely mediated by caffeine. Taurine played no significant role in the fluid balance in moderately dehydrated healthy young consumers. Consequently, the diuretic potential of energy drinks will not differ significantly from other caffeine containing beverages.

Adolescent↗
PubMed1995

Prevention of nitroglycerin tolerance with diuretics.

Tolerance to prolonged nitroglycerin (NTG) may be due to drug-induced intravascular expansion. To test the hypothesis that concomitant diuretics may reduce volume expansions and thus prevent NTG tolerance, we studied 23 healthy volunteers randomized to hydrochlorthiazide or placebo before and during 74-hour continuous NTG exposure. Venodilator response to NTG was tested serially with venous forearm plethysmography. In the preNTG patch phase venodilator response was similar in both the placebo and diuretic groups. Venodilator capacity was compared after "acute" (2-hour) and "chronic" (74-hour) NTG exposure with NTG patches. Attenuation to NTG was seen in the placebo group, but NTG venodilator activity was fully maintained in the diuretic group. These data suggest that diuretics may be helpful in the prevention of NTG tolerance.

Administration, Oral↗
PubMed1993

Spironolactone in congestive heart failure refractory to high-dose loop diuretic and low-dose angiotensin-converting enzyme inhibitor.

Patients with severe congestive heart failure (New York Heart Association [NYHA] functional classes III-IV) often can tolerate only low doses of angiotensin-converting enzyme (ACE) inhibitors because pronounced hypotension caused by additional ACE inhibitor increments may decrease renal perfusion. The use of high-dose loop diuretics is currently advised to overcome diuretic resistance in refractory congestive heart failure (CHF). In a baseline controlled study, we evaluated 21 patients with diuretic resistance and evident fluid retention for the responses to 5 days of double drug therapy consisting of high-dose loop diuretic (10 mg oral bumetanide) in combination with the maximum tolerable dose of an ACE inhibitor (individualized to blood pressure and kidney function). Five patients (24%) showed a gross natriuresis and reduction in excess weight > 25% in response to this therapy. The remaining 16 patients (76%) with insufficient responses (i.e., < 25% reduction in excess weight) subsequently received 100 mg spironolactone once a day for 7 days in addition to the double therapy. Spironolactone coadministration was highly effective in 13 of 16 patients (81%). Marked natriuresis and diuresis were achieved within the next week of treatment, and CHF symptoms regressed or disappeared. The clinical course was similar in the bumetanide-ACE inhibitor and the bumetanide-ACE inhibitor-spironolactone treatment (triple therapy) groups. Plasma aldosterone was significantly higher (p < 0.05) in the patients who needed spironolactone. The 3 patients who were considered refractory to triple therapy exhibited the highest baseline plasma aldosterone concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Pharmacokinetics and pharmacodynamics of the diuretic bumetanide in the elderly.

In a cross-sectional study of the pharmacokinetics and pharmacodynamics of peroral and intravenous bumetanide (0.5 mg, single dose), total and renal clearance of the diuretic was significantly lower in elderly persons than in young adults, resulting in higher bumetanide plasma levels in the aged. Nonrenal clearance, bioavailability, and the volume of distribution were not significantly changed. Together with the decreased delivery into the urine the diuretic and natriuretic effect of bumetanide was reduced in the elderly. Renal clearance of bumetanide was linearly related with creatinine clearance, hence the decreases in bumetanide clearance and diuretic efficacy in the elderly are attributed to the age-dependent decline in renal function. The bumetanide concentration in urine and the fractional sodium excretion were not different in the two age groups, suggesting that the decrease in diuretic response in the elderly is a result of a reduction in the number of functioning nephrons, whereas the response of the remaining nephrons to bumetanide is unaltered.

Administration, Oral↗
PubMed1987

Diuretic renography in evaluating dilated upper urinary tract in children.

The diuretic renogram provides a previously unavailable noninvasive method for assessing and following urinary tract dilation of diverse cause, and defining true obstruction in children. Technetium-99m-DTPA (diethylenetriaminepentaacetic acid) is injected intravenously and a posteriorly placed gamma scintillation camera used to image the kidneys, ureters, and bladder. Furosemide is subsequently injected to stimulate a diuresis, and the washout pattern of isotope is monitored (time-activity histogram). Nonobstructive, obstructive, and poor renal function patterns were seen. Forty patients with varying degrees of hydroureteronephrosis were evaluated. Tracings were performed serially and compared with the clinical course in time, as well as with pressure flow studies and operative findings. All patients with a nonobstructed diuretic renogram did well, except for 1 boy in whom ureteropelvic obstruction developed later. Difficulty in evaluating the obstructive renogram pattern occurred only in some children with severe (grade V) hydronephrosis. Further standardization of the diuretic renogram with regard to time of diuretic injection, state of patient hydration, and regions of imaging may improve diagnostic accuracy.

Child↗
PubMed2006

Management of cirrhotic ascites: physiological basis of diuretic action.

Ascites is a significant complication of cirrhosis that occurs in approximately 50% of patients. The mortality rate is high in patients with cirrhosis and ascites. Conventional interventions rest with dietary sodium restriction, diuretic use, large-volume paracentesis, peritoneovenous shunts and transjugular intrahepatic portosystemic shunts. The mainstay of therapy, however, is the judicious use of diuretics. This article reviews the physiological basis of diuretic use in patients with cirrhosis and ascites, as well as recent concepts on the pathogenesis of ascites formation. Through a better understanding of the pathophysiology of ascites formation and the mechanism of action of diuretics, improved extracellular fluid balance can be achieved in these patients.

Journal Article↗
PubMed1979

Salt intake and diuretic treatment of hypertension.

24 h urinary sodium excretion was used to monitor salt intake in 36 patients with essential hypertension to determine whether limitation of the antihypertensive action of thiazide diuretics could be explained by increased salt appetitie stimulated by salt depletion. Sodium excretion in these patients was similar before treatment to that observed in normotensive controls, and no change was observed during 2 years' treatment with bendrofluazide. However, plasma-renin rose progressively over the 2 years even in 5 of 8 patients whose renin was not stimulated initially by diuretics. Thus, there is no evidence that a voluntary increase in salt intake limits the efficacy of diuretic treatment; on the other hand, progressive stimulation of the renin-angiotensin system may be an important limiting factor to the antihypertensive action of diuretics. If so, the antihypertensive effect of dietary salt restriction may be similarly limited.

Adult↗
PubMed1976

Aminobenzioc acid diuretics. 8.(2) 3, 4-Disubstituted 5-methylsulfonylbenzioc acids and related compounds.

Various 2, 4- and 3, 4-disubstituted 5-methylsulfonylbenzoic acids were synthesized as methylsulfonyl analogues of previously described 5-sulfamoylbenzoic acid diuretics. The results of the diuretic screening in dogs reveal that substitution of the sulfamoyl group by the spatially and sterically similar methylsulfonyl group does not affect the diuretic pattern but leads generally to somewhat decreased potency. For the highly potent 3-benzylamino-4-phenoxy-5-methylsulfonylbenzoic acid the corresponding 5-methylthio and 5-methylsulfinyl analogs were prepared and found still to exhibit diuretic activity. Internal aldol condensation and subsequent dehydration of 3-benzylamino-and 3-n-butylamino-4-benzoyl-5-methylsulfonylbenzoic acid provided the corresponding inactive 4-alkylamino-6-carboxy-2, 3-dihydro-3-hydroxy-3-phenylbenzo[b]thiophene 1, 1-dioxides and 4-alkylamino-6-carboxy-3-phenyl-benzo[b]thiophene 1,1-dioxides.

Aminobenzoates↗
PubMed1982

Effectiveness of centrally acting drugs and diuretics in adolescent hypertension.

The effectiveness and tolerance of a centrally acting antihypertensive agent (clonidine) was compared to that of a diuretic (hydrochlorothiazide) in treatment of adolescents with essential hypertension. After a phase on placebo 29 adolescents with fixed primary hypertension were randomly assigned, double blind, to one of two treatment groups. Active therapy was initiated at a low dose (0.1 mg clonidine b.i.d. or 24 mg hydrochlorothiazide b.i.d.) for 12 wk. In those in whom treatment goals for blood pressure control had not been reached, the dose was increased (clonidine to 0.2 mg and hydrochlorothiazide to 50 mg) for 12 wk. In the clonidine-treated group there was a reduction during low-dose therapy in systolic (P less than 0.05) and diastolic pressure (P less than 0.01) and heart rate (P less than 0.01). With low-dose diuretic therapy there was a reduction in systolic pressure only (P less than 0.05). Linear growth patterns were normal for both groups, but there was a reduction in serum potassium in the diuretic group (P less than 0.001). Of the two drugs investigated the centrally acting clonidine was more effective in blood pressure control (85%) than the diuretic (40%).

Adolescent↗
PubMed1989

[Basic therapy of chronic heart failure with digitalis or diuretics?].

Sixteen patients in heart failure and sinus rhythm were, after a four-week treatment-free period, randomly assigned to receive, for four to six weeks, either a diuretic combination (hydrochlorothiazide + triamterene) or a digitalis glycoside. Subsequently the treatment was exchanged between the two groups. Without treatment nine patients were in stage II (New York Heart Association classification), seven in stage III. Pulmonary wedge pressure at rest was 27 +/- 14, on exercise 32 +/- 8 mm Hg, cardiac output 5.3 +/- 1.0 at rest and 7.8 +/- 2.3 l/min on exercise. Digitalis glycosides improved symptoms by one stage in three of 16 patients. All objective measures showed slight but not significant improvement. Diuretic treatment improved symptoms in five patients, while heart size and echocardiographically measured ventricular volume decreased slightly. Cardiac output decreased at rest, but not significantly, and on exercise not at all. Pulmonary arterial pressure (21 +/- 9 mm Hg), pulmonary wedge pressure (13 +/- 7 mm Hg) and pulmonary artery pressure on exercise (39 +/- 11 mm Hg) were significantly lower on diuretics than without treatment. The results support the primary use of diuretics in the treatment of chronic heart failure.

Aged↗
PubMed1988

Ventricular ectopic activity with diuretic therapy.

The arrhythmogenic potential of diuretic-induced hypokalemia in patients with uncomplicated hypertension has been controversial. Thirty-two hypertensive patients with previous diuretic-induced hypokalemia, normal 24-hour ambulatory ECG monitoring, and normal exercise testing were treated with 100 mg hydrochlorothiazide (HCTZ) daily (Group 1) to induce hypokalemia or with a combination of HCTZ with amiloride (Group 2) to attempt to maintain plasma potassium levels in the normal range during diuretic therapy. Those Group 1 patients (Group 1A) with increased ventricular ectopic activity (VEA) during HCTZ therapy were subsequently potassium-repleted with amiloride and with supplemental potassium chloride to evaluate the effect of these treatments on VEA. One Group 1 patient died suddenly after 12 days of HCTZ therapy. Autopsy findings suggested an arrhythmic death. Six Group 1 patients who had increased VEA with HCTZ treatment had reductions in VEA with amiloride or supplemental potassium chloride. Group 2 patients did not have a significant increase in VEA. Thus, diuretic therapy appears to cause VEA primarily by electrolyte changes that are induced.

Adult↗
PubMed1994

Antihypertensive treatment with felodipine but not with a diuretic reduces episodes of myocardial ischaemia in elderly patients with hypertension.

Episodes of transient myocardial ischaemia can frequently be observed in hypertensive patients. To assess the effects of antihypertensive treatment with the calcium antagonist felodipine or the diuretic combination hydrochlorothiazidel triamterene on episodes of ischaemic-type ST-segment depression (ST-D), simultaneous ambulatory electrocardiographic and blood pressure (BP) monitoring was performed in 42 elderly hypertensives without manifest coronary artery disease. All patients (mean age 79 +/- 6 years, office BP > or = 160/95 mmHg) were evaluated off any antihypertensive or anti-ischaemic therapy and after 3 months treatment with either felodipine or the diuretic (randomized, double-blind study) for episodes of significant ST-D (> or = 0.1 mV, duration > or = 1 min, interval > or = 1 min). The reduction in office BP and daytime ambulatory BP was similar for both agents, as was a significant reduction in the heart rate x systolic BP product (DP) over 24 h (felodipine: 12,441 +/- 2076 vs 11,643 +/- 1953 mmHg.min-1; P = 0.048; diuretic: 12,366 +/- 2782 vs 11,062 +/- 2012 mmHg.min-1; P = 0.003). While felodipine significantly decreased the total number of ST-D (from 40 to six episodes; P = 0.03), the total number of ST-D remained unchanged with the diuretic (non-significant increase from 31 to 45 episodes; P = 0.24). The same trend was observed for the number of patients with ST-D.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1986

Beta-blocker versus diuretic for control of the blood pressure response to stress in hypertensive patients.

To compare the antihypertensive effects of beta-blockers and diuretics on the blood pressure increase to stress, a randomized single-blind crossover study was performed in 27 patients with mild or moderate hypertension. At the initial examination and after two subsequent periods of therapy with 100 mg atenolol or with a combination of 50 mg hydrochlorothiazide and 5 mg amiloride hydrochloride, once a day, blood pressure and heart rate were measured at rest, during mental arithmetic, sustained handgrip and cycloergometric test. Both treatment significantly decreased supine and standing systolic and diastolic pressure at rest, during and immediately after mental stress and isometric exercise, with the reduction of diastolic pressure significantly greater after atenolol. During dynamic exercise, systolic and diastolic pressures were significantly decreased by diuretics at the lowest work-load only, whereas beta-blocker caused significant and greater blood pressure reductions throughout the exercise. The combination of two classes of drug normalized resting blood pressure in 8 of 9 subjects in which the monotherapy had failed to obtain values less than 140/90 mmHg and gave a better control of systolic and diastolic pressures throughout all the stress tests. It is concluded that atenolol is more effective than diuretics during stress, suggesting that beta-blocking drugs are the first choice treatment for mild to moderate hypertension and that when the antihypertensive effect of a single agent is insufficient, a combination of beta-blockers and diuretics is also effective during stress.

Adult↗
PubMed1987

A double-blind study of the blood pressure lowering effect of a thiazide diuretic in hypertensive patients already on nifedipine and a beta-blocker.

Twelve hypertensive patients who were already on treatment with atenolol (100 mg once daily) and nifedipine as tablets (20 mg twice daily) were entered into a double-blind, randomized crossover study of the addition of 1 month's treatment with either bendrofluazide (5 mg once daily) or a matching placebo. The addition of bendrofluazide to the combination of atenolol and nifedipine did not cause any statistically significant fall in the blood pressure 2 h after the last dose of nifedipine compared to treatment with placebo [bendrofluazide: 135.2 +/- 5.1/89.8 +/- 2.5 (mean +/- s.e.), versus placebo: 132.1 +/- 4.6/89.9 +/- 3.1 mmHg; P = NS]. However, 12 hours after the last dose of nifedipine blood pressure tended to be lower whilst on bendrofluazide compared with placebo. Plasma urate levels were significantly higher on the diuretic compared to placebo (461 +/- 27 versus 396 +/- 21 mumol P less than 0.001). Plasma potassium was lower on the diuretic compared to placebo (3.59 +/- 0.12 vs 3.76 +/- 0.10) but this difference just failed to reach statistical significance. The results of this study suggest that a thiazide diuretic has little additive effect on blood pressure in patients already on treatment with atenolol and nifedipine, particularly when nifedipine is maximally effective. However, the addition of a diuretic does have potentially deleterious metabolic effects.

Adult↗
PubMed1992

Antihypertensive efficacy and side effects of three beta-blockers and a diuretic in elderly hypertensives: a report from the STOP-Hypertension study.

OBJECTIVE: To compare the blood pressure-lowering efficacy, the frequency of side effects and changes in laboratory values of three beta-blockers and a potassium-sparing diuretic combination in elderly hypertensive patients. DESIGN: The Swedish Trial in Old Patients with Hypertension (STOP-Hypertension) was a prospective, randomized, double-blind, multicentre trial comparing active antihypertensive treatment with placebo in patients aged 70-84 years. METHODS: The study group consisted of 1627 elderly hypertensive patients (mean +/- SD age 75.7 +/- 3.7 years; 37% males, 63% females). Supine and standing blood pressure, heart rate and side effects were recorded at each visit. Blood was drawn for routine analysis. The mean length of follow-up was 25 months (range 6-65). No patient was lost to follow-up. RESULTS: After 2-months' single-drug therapy, all four active drugs were found to be equally effective in reducing diastolic blood pressure (DBP). However, there were differences in their efficacy in reducing systolic blood pressure (SBP); the diuretic was significantly more effective than the beta-receptor blockers. The results of a series of multiple linear regression analyses showed that the observed differences in effect on SBP could not be explained by the different effects of the drugs on heart rate. More than two-thirds of the patients were given supplementary treatment, most of them already by the 2-month visit, after which there was no significant difference in blood pressure among the treatment regimens. The changes in laboratory values and in the prevalence of symptoms were minor for all four regimens. CONCLUSION: Metoprolol (controlled release), atenolol, pindolol and the combination hydrochlorothiazide + amiloride were equally effective as single drugs in reducing DBP. There were differences in their efficacy in reducing SBP, the diuretic being more effective than the beta-blockers. After addition of supplementary treatment (beta-blocker to diuretic, or vice versa) there were no significant differences in blood pressure reduction among the groups. The changes in laboratory values and in the prevalence of symptoms were minor for all active treatment regimens. Thus, the satisfactory effect on cardiovascular morbidity and mortality was not impaired by low tolerability of the drugs.

Aged↗
PubMed1985

Effect of chronic nifedipine in patients inadequately controlled by a converting enzyme inhibitor and a diuretic.

Nifedipine, in a slow release preparation, was given at a mean daily dosage of 47 +/- 4 mg to 12 patients with severe hypertension in whom arterial pressure was not satisfactorily controlled (mean arterial pressure 132 +/- 4 4 mm Hg) by the combination of a converting enzyme inhibitor and a diuretic. The addition of nifedipine induced an appreciable decrease in mean arterial pressure of 31 +/- 5 mm Hg and of serum potassium and plasma aldosterone. After adequate control of hypertension and because of severe hypokalemia in some patients, discontinuation of the diuretic was attempted in 10 subjects. After 1.7 +/- 0.5 months of treatment by the converting enzyme inhibitor and nifedipine no change in arterial pressure occurred while serum potassium had returned to normal in most patients. These results show that nifedipine may be useful in patients with a residual rise of arterial pressure when treated by converting enzyme inhibitor plus diuretics; in such patients, however, the serum potassium concentration should be carefully monitored. In addition, our observations suggest that calcium blockers may be an effective alternative to diuretics in patients receiving a converting enzyme inhibitor.

Adult↗