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Diuretics acting on the distal renal tubule for preterm infants with (or developing) chronic lung disease.

OBJECTIVES: The aim of this review is to assess the risks and benefits of diuretics acting on distal segments of the renal tubule (distal diuretics) in preterm infants with or developing chronic lung disease (CLD). Primary objectives are to assess changes in need for oxygen or ventilatory support and effects on long-term outcome, and secondary objectives are to assess changes in pulmonary mechanics and potential complications of therapy. SEARCH STRATEGY: We used the standard method of the Cochrane Neonatal Review Group. We used the following keywords: ¿ or ¿ and , limited to and limited to or . We searched Medline (1966-1998), Embase (1974-1998) and the Cochrane Controlled Trials Register (CCTR) from the Cochrane Library (1999, issue 2). In addition, we hand searched several abstract books of national and international American and European Societies. SELECTION CRITERIA: We included in this analysis trials in which preterm infants with or developing CLD and at least five days of age were all randomly allocated to receive a distal diuretic (i.e., a diuretic acting on the distal renal tubule). Eligible studies needed to assess at least one of the outcome variables defined a priori for this systematic review. Primary outcome variables included changes in need for respiratory support and oxygen supplementation, mortality, bronchopulmonary dysplasia (BPD), death or BPD, chronic lung disease at 36 weeks of postconceptional age (gestational age + postnatal age), length of stay, and number of rehospitalizations during the first year of life. Secondary outcome variables included pulmonary mechanics and potential complications of therapy. DATA COLLECTION AND ANALYSIS: We used the standard method for the Cochrane Collaboration which is described in the Cochrane Collaboration Handbook. Two investigators extracted, assessed and coded separately all data for each study, using a form that was designed specifically for this review. Any disagreement was resolved by discussion. We combined parallel and cross-over trials and, whenever possible, transformed baseline and final outcome data measured on a continuous scale into change scores using Follmann's formula. MAIN RESULTS: Of six studies fulfilling entry criteria, most focused on pathophysiological parameters and did not assess effects on important clinical outcomes defined in this review, or the potential complications of diuretic therapy. In preterm infants > 3 weeks of age with CLD, a four-week treatment with thiazide and spironolactone improved lung compliance and reduced the need for furosemide. Thiazide and spironolactone decreased the risk of death and tended to decrease the risk for lack of extubation after 8 weeks in intubated infants. There is no evidence to support the hypothesis that adding spironolactone to thiazide or that adding metolazone to furosemide improves the outcome of preterm infants with CLD. REVIEWER'S CONCLUSIONS: In preterm infants > 3 weeks of age with CLD, acute and chronic administration of distal diuretics improve pulmonary mechanics. Chronic administration of diuretics (thiazide with spironolactone) reduces mortality in intubated patients. Large studies are needed to assess (1) whether chronic diuretic administration improves mortality, duration of oxygen dependency, ventilator dependency, length of hospital stay and long-term outcome in patients without long-term toxicity and (2) whether adding spironolactone to thiazides or adding metolazone to furosemide has any beneficial effect.

Chronic Disease↗

Intravenous or enteral loop diuretics for preterm infants with (or developing) chronic lung disease.

BACKGROUND: Lung disease in preterm infants is often complicated with lung edema. OBJECTIVES: The aim of this review was to assess the risks and benefits of administration of a diuretic acting on the loop of Henle (loop diuretic) in preterm infants with or developing chronic lung disease (CLD). Primary objectives were to assess changes in need for oxygen or ventilatory support and effects on long-term outcome, and secondary objectives were to assess changes in pulmonary mechanics and potential complications of therapy. SEARCH STRATEGY: We used the standard search method of the Cochrane Neonatal Review Group. We used the following keywords: ¿ or ¿ and , limited to and limited to or . We searched Medline (1966-1998), Embase (1974-1998) and the Cochrane Controlled Trials Register (CCTR) from the Cochrane Library (1998, issue 4). In addition, we hand searched several abstract books of national and international American and European Societies. SELECTION CRITERIA: We included in this analysis trials in which preterm infants with or developing chronic lung disease and at least 5 days of age were all randomly allocated to receive a loop diuretic either enterally or intravenously. Eligible studies needed to assess at least one of the outcome variables defined a priori for this systematic review. Primary outcome variables included important clinical outcomes, and secondary outcome variables included toxicity and pulmonary mechanics (e.g., lung compliance and airway resistance). DATA COLLECTION AND ANALYSIS: We used the standard method for the Cochrane Collaboration which is described in the Cochrane Collaboration Handbook. Two investigators extracted, assessed and coded separately all data for each study, using a form that was designed specifically for this review. Any disagreement was resolved by discussion. We combined parallel and cross-over trials and, whenever possible, transformed baseline and final outcome data measured on a continuous scale into change scores using Follmann's formula. MAIN RESULTS: The only loop diuretic used in the studies which met the selection criteria was furosemide. Most studies focused on pathophysiological parameters and did not assess effects on important clinical outcomes defined in this review, or the potential complications of diuretic therapy. In preterm infants < 3 weeks of age developing CLD, furosemide administration has either inconsistent effects or no detectable effect. In infants > 3 weeks of age with CLD, a single intravenous dose of 1 mg/kg of furosemide improves lung compliance and airway resistance for 1 hour. Chronic administration of furosemide improves both oxygenation and lung compliance. REVIEWER'S CONCLUSIONS: In preterm infants > 3 weeks of age with CLD, acute and chronic administration of furosemide improve lung compliance. Chronic administration of intravenous or enteral furosemide improves oxygenation. In view of the lack of data from randomized trials concerning effects on important clinical outcomes, routine or sustained use of systemic loop diuretics in infants with (or developing) CLD cannot be recommended based on current evidence. Randomized trials are needed to assess the effects of furosemide administration on survival, duration of ventilatory support and oxygen administration, length of hospital stay, potential complications and long-term outcome.

Chronic Disease↗

[Pharmacological studies on diuretic action of azosemide [5-(4'-chloro-5'-sulfamoyl-2'-thenylamino)-phenyltetrazole], a new diuretic (2). Diuretic action of azosemide in HgCl2-induced acute renal failure in rats].

The diuretic effect of azosemide in HgCl2-induced acute renal failure of rats was investigated in comparison with that of furosemide. Acute renal failure was induced by the single s.c. injection of 1, 2, or 4 mg/kg HgCl2; and the test drug was administered 48 hr after treatment with HgCl2. Treatment with HgCl2 resulted in a dose related elevation of plasma urea nitrogen and creatinine levels (mg/dl). In rats with 1 mg/kg HgCl2-induced acute renal failure, azosemide at doses ranging from 10 to 40 mg/kg p.o. dose-dependently increased urinary volume (ml/5 hr) and urinary Na+, K+, and Cl- excretions (mEq/5 hr). In this case, azosemide at 40 mg/kg caused a 3.5-fold increase in urinary volume and 4.5-, 2.1, and 4.1-fold increases in urinary Na+, K+, and Cl- excretions, respectively. Although plasma electrolyte levels were little affected by azosemide, plasma urea nitrogen and creatinine levels were significantly elevated by doses of more than 20 mg/kg of this drug. The diuretic effect of azosemide was more markedly reduced in rats with 2 mg/kg HgCl2-induced acute renal failure than in rats with 1 mg/kg HgCl2-induced acute renal failure. In the case of treatment with HgCl2 of 2 mg/kg, the diuretic effect of azosemide at doses ranging from 40-320 mg/kg p.o. was dose-dependent. However, azosemide had no effect on plasma electrolyte, urea nitrogen, and creatinine levels. The diuretic effect of azosemide in rats given 4 mg/kg HgCl2 was more pronouncedly reduced as compared with that in the case of 2 mg/kg HgCl2. In this case, azosemide at 320 mg/kg brought about a 2.6-fold increase in urinary volume and 4.8-, 4.6-, and 3.9-fold increases in urinary Na+, K+, and Cl- excretions, respectively. This drug had no effect on any plasma parameters. The diuretic effect of azosemide was slightly more potent than those of furosemide in the case of acute renal failure induced by 2 and 4 mg/kg HgCl2.

Acute Kidney Injury↗

[Pharmacological studies on diuretics (8). Diuretic activity and mechanism of action of a new hypotensive diuretic, SE-1520 (author's transl)].

Effects of SE-1520 were compared with those of thiazide diuretics, hydrochlorothiazide (HCT) and trichlormethiazide (TCM) in rats and dogs. SE-1520 in an oral dose of 0.1 approximately 10.0 mg/kg resulted in a strong and dose-dependent increase in urine volume as well as in the urinary excretion of Na+ and Cl-, while that of K+ significantly increased with an oral dose over 3.0 mg/kg. In experimental acidotic, alkalotic, nephritic and spontaneously hypertensive rats, almost the same strong natriuretic activity seen in normal rats was observed with SE-1520. The diuretic potency of these three diuretics in rats was MCT greater than or equal to SE-1520 greater than HCT. SE-1520 also exhibited a strong diuretic activity in dogs. In the renal clearance test of dogs, SE-1520 0.1 approximately 1.0 mg/kg i.v. did not influence the renal plasma flow (RPF) or glomerular filtration rate (GFR). The renal tubular Na+ reabsorption rate decreased by a maximum of 2.11% and the urinary Na+ excretion increased by 15.3 times the normal level 20 min after the injection of SE-1520 in a dose of 1.0 mg/kg i.v. From the results of clearance test and stop flow test in dogs, the site of action of SE-1520 was observed to be mainly in the distal tubules.

Acidosis↗

The physiologic basis of diuretic synergism: its role in treating diuretic resistance.

Diuretic drugs usually improve edema when used judiciously. Some patients, however, become resistant to their effects. Diuretic resistance may result from dietary indiscretion, poor compliance, impaired bioavailability, imparied diuretic secretion into the lumen of the renal tubule, or because other drugs interfere with diuretic activity. When easily treatable causes of diuretic resistance have been excluded, resistance often reflects the intensity of the stimuli to sodium retention. Recent experimental work has indicated ways in which the kidney adapts to chronic diuretic treatment and has indicated how these adaptations may limit diuretic effectiveness. First, nephron segments downstream from the site of diuretic action increase sodium-chloride (NaCl) reabsorption because the delivered NaCl load increases. Second, diuretic-induced contraction of the extracellular fluid volume stimulates kidney tubules to retain NaCl until the next dose of diuretic is administered. Third, kidney tubules themselves may become hypertrophic because they are chronically stimulated by diuretic-induced increases in NaCl delivery. These adaptations all increase the rate of NaCl reabsorption and blunt the effectiveness of diuretic therapy. When diuretic resistance is present, using a second diuretic drug that acts in a different nephron segment is often effective. Recent experimental results suggest that a second class of drug may act synergistically with the first by blocking the adaptive processes that limit diuretic effectiveness. On the basis of an understanding of the mechanisms of diuretic adaptation and resistance, treatment regimens can be designed to block specific adaptive mechanisms and to improve diuretic therapy.

Adaptation, Physiological↗

Equivalent antihypertensive effects of combination therapy using diuretic + calcium antagonist compared with diuretic + ACE inhibitor.

To test the hypothesis that the combination of a calcium antagonist and diuretic is less effective in lowering BP than the combination of ACE inhibitor plus diuretic, we compared two groups of patients. The first was a group of 157 consecutive patients (32% male, 90% black, aged 57 +/- 1 years) in whom the only change in therapy was the addition or deletion of either a calcium antagonist or diuretic. Each patient served as his/her own control, with a follow-up time of 41 +/- 4 days. The BP responses of this group were compared with those of another group of 170 consecutive patients (33% male, 85% black, aged 55 +/- 1 years), who had had the addition or deletion of an ACE inhibitor or diuretic some 32 +/- 2 days previously. As there were no statistically significant differences either between drugs within the classes or between the addition or deletion of a drug, the BP results were pooled. Combination therapy with calcium antagonist + diuretic was associated with a 13.4 +/- 1.7/5.4 +/- 0.9 mmHg drop in supine BP; the ACE inhibitor + diuretic combination lowered supine BP by 12.3 +/- 1.6/8.0 +/- 0.9 mmHg compared with monotherapy (all P less than 0.001 by paired t-test). The effects on standing BP were similar: calcium antagonist + diuretic, 13.2 +/- 1.9/5.6 +/- 0.9 mmHg; and ACE inhibitor + diuretic, 12.3 +/- 1.5/7.0 +/- 0.9 mmHg (all P less than 0.001). There were no significant differences in BP responses between the calcium antagonist + diuretic and ACE inhibitor + diuretic combinations. These data indicate that, regardless of the order of addition or subtraction, the combination of calcium antagonist + diuretic was more effective in lowering BP than either agent used alone, and that the combination of calcium antagonist + diuretic was as effective as the ACE inhibitor + diuretic combination.

Angiotensin-Converting Enzyme Inhibitors↗

Aerosolized diuretics for preterm infants with (or developing) chronic lung disease.

BACKGROUND: Lung disease in preterm infants is often complicated with lung edema. OBJECTIVES: The aim of this review is to assess the risks and benefits of aerosolized diuretic administration in preterm infants with or developing chronic lung disease (CLD). Primary objectives are to assess effects on short term outcome (changes in need for oxygen or ventilatory support) and effects on long-term outcome. Secondary objectives are to assess changes in pulmonary mechanics and potential complications of therapy. SEARCH STRATEGY: We used the standard search method of the Cochrane Neonatal Review Group. We used the following keywords: ¿ or ¿ and , limited to and limited to or . We searched Medline (1966-1998), Embase (1974-1998) and the Cochrane Controlled Trials Register (CCTR) from the Cochrane Library (1998, Issue 4). In addition, we hand searched several abstract books of national and international American and European Societies. SELECTION CRITERIA: We included in this analysis trials in which preterm infants with or developing chronic lung disease and at least five days of age were all randomly allocated to receive an aerosolized loop diuretic. Eligible studies needed to assess at least one of the outcome variables defined a priori for this systematic review. Primary outcome variables included important clinical outcomes, and secondary outcome variables included pulmonary mechanics and potential complications of therapy. DATA COLLECTION AND ANALYSIS: We used the standard method for the Cochrane Collaboration which is described in the Cochrane Collaboration Handbook. Two investigators extracted, assessed and coded separately all data for each study, using a form that was designed specifically for this review. Any disagreement was resolved by discussion. We combined parallel and cross-over trials and, whenever possible, transformed baseline and final outcome data measured on a continuous scale into change scores using Follmann's formula. MAIN RESULTS: We identified eight studies which met selection criteria. Most studies focused on pathophysiological parameters and did not assess effects on important clinical outcomes defined in this review or the potential complications of diuretic therapy. No study assessed the amount of diuretic effectively delivered to the patient. Furosemide was the only diuretic used in the eight studies included in this review. Among preterm infants < 3 weeks of age developing CLD, not enough information is available to assess the effect of aerosolized furosemide on outcome or lung function. Among infants > 3 weeks with CLD, a single aerosolized dose of 1 mg/kg of furosemide may transiently improve pulmonary mechanics. Not enough information is available to assess the effect of chronic administration of aerosolized furosemide on oxygenation and pulmonary mechanics. REVIEWER'S CONCLUSIONS: In preterm infants > 3 weeks with CLD administration of a single dose of aerosolized furosemide improves pulmonary mechanics. In view of the lack of data from randomized trials concerning effects on important clinical outcomes, routine or sustained use of aerosolized loop diuretics in infants with (or developing) CLD cannot be recommended based on current evidence. More double-blinded randomized trials are needed (1) to analyze factors likely to affect the response to aerosolized furosemide, e.g. , washout period and delivery of furosemide to distal airways, and (2) to assess the effects of chronic administration of aerosolized furosemide on mortality, O2 dependency, ventilator dependency, length of hospital stay and long-term outcome.

Aerosols↗

Diuretic-related hypokalaemia: the role of diuretics, potassium supplements, glucocorticoids and beta 2-adrenoceptor agonists. Results from the comprehensive hospital drug monitoring programme, berne (CHDM).

All 5,047 consecutive inpatients admitted to the Internal Medicine Division of a teaching hospital (Zieglerspital, Berne) between 1982 and 1985 were registered in accordance with the CHDM (Comprehensive Hospital Drug Monitoring) questionnaire of adverse drug reactions (ADRs). Of them, 2,439 were treated with at least one potassium losing diuretic. The hospital records of the patients were reviewed with particular regard to serum potassium levels, and on the basis of this evaluation, the patients were assigned to four different diuretic treatment groups, and the incidence of hypokalaemia related to diuretic treatment was estimated. The overall rate of occurrence of hypokalaemia was 21.1% at a serum potassium level < 3.5 mmol.l-1, and 3.8% < 3.0 mmol.l-1. Hypokalaemia of less than 3.5 mml.l-1 developed 24.9% (217/870) of patients treated with potassium losing diuretics alone; in 19.7% (101/513) treated with potassium losing diuretics in conjunction with potassium substitution, in 15.1% (66/438) treated with a combination of diuretics (potassium losing with potassium sparing), and in 20.0% (12/60) treated with combined diuretics and potassium substitution. Only the differences between the first and the two subsequent groups were statistically significant. The overall incidence of hypokalaemia below 3.0 + mmol.l-1 was significantly lower in the patients on combined diuretics without potassium substitution than in the patients on potassium losing diuretics with potassium substitution. Oral or parenteral administration of glucocorticoids (prednisone 5 to 2,000 mg/d) was a significant risk factor for hypokalaemic events. beta 2-Adrenoceptor agonists had not effect. The patient's age, sex, renal function and numbers of drugs received were evaluated in a multivariate analysis, in order to take into account their influence on the risk of developing hypokalaemia. The number of drugs above 12 (and, less importantly, female sex) was the main risk factor for this ADR. The comparison between hypokalaemia and hyperkalaemia in this group of inpatients showed the significance of reduced renal function in the occurrence of hyperkalaemia.

Adolescent↗

Diuretic treatment and diuretic resistance in heart failure.

Diuretic therapy decreases capillary wedge pressure and improves New York Heart Association (NYHA) functional class both in acute and chronic heart failure. In advanced symptomatic heart failure, loop diuretics are generally necessary to improve symptoms of congestion. Diuretic resistance in the edematous patient has been defined as a clinical state in which diuretic response is diminished or lost before the therapeutic goal of relief from edema has been reached. The major causes of diuretic resistance are functional renal failure (prerenal azotemia), hyponatremia, altered diuretic pharmacokinetics, and sodium retention caused by counterregulatory mechanisms intended to reestablish the effective arterial blood volume. Therapeutic approaches to combat diuretic resistance include restriction of fluid and sodium intake, use of angiotensin-converting-enzyme (ACE) inhibitors, changes in route (oral, intravenous) and timing (single dose, multiple doses, continuous infusion) of diuretic therapy, and use of diuretic combinations.

Diuretics↗

Diuretics vs. paracentesis followed by diuretics in cirrhosis: effect on ascites opsonic activity and immunoglobulin and complement concentrations.

Ascitic fluid opsonic activity and ascitic fluid C3 concentrations are important protective factors against spontaneous bacterial peritonitis. This randomized controlled study was performed to compare the effect of diuretic administration alone vs. single large-volume therapeutic paracentesis followed by administration of diuretics on ascitic fluid opsonic activity and on ascites and serum immunoglobulin and complement concentrations in patients with alcoholic cirrhosis and tense ascites. Twenty-one patients were randomly allocated to two groups: group 1 included 11 patients who were treated with diuretics alone, and group 2 included 10 patients who were treated with single large-volume therapeutic paracentesis (5 to 6 L of ascites removed) followed by diuretics. Ascitic fluid opsonic activity and serum and ascites immunoglobulin and complement concentrations were measured at the beginning and at the end of treatment. The ascitic fluid opsonic activity increased significantly in patients treated with diuretics alone (p < 0.05), whereas in the group of patients treated with therapeutic paracentesis followed by diuretics, the ascites opsonic activity remained stable. Although ascitic fluid IgG, IgA and C3 concentrations increased significantly in patients treated with diuretics alone (p < 0.05), ascitic fluid C3 concentration significantly decreased in patients from group 2 (p < 0.05), whereas IgG and IgA concentrations remained unchanged. However, in both groups of patients serum immunoglobulin and complement concentrations remained unchanged. This study suggests that in cirrhotic patients with tense ascites, treatment with diuretics alone may have the potential advantage over single large-volume therapeutic paracentesis followed by the administration of diuretics of providing better protection from spontaneous bacterial peritonitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Diuretics for respiratory distress syndrome in preterm infants.

BACKGROUND: Lung edema may complicate respiratory distress syndrome (RDS) in preterm infants. OBJECTIVES: The aim of this review was to assess the risks and benefits of diuretic administration in preterm infants with RDS. SEARCH STRATEGY: We used the standard search method of the Cochrane Neonatal Review Group. We searched Medline, Embase and the Cochrane Controlled Trials Register from the Cochrane Library, using the following keywords: and . In addition, we searched the abstract books of the American Thoracic Society and Pediatric Research Societies. SELECTION CRITERIA: We only included trials in which preterm infants with RDS and less than 5 days of age were randomly allocated to diuretic administration. Of those trials, we only included studies in which at least one of the following outcomes measures was evaluated: mortality, patent ductus arteriosus, hypovolemic shock, intraventricular hemorrhage, renal failure, duration of oxygen supplementation, duration of mechanical ventilation, need for oxygen supplementation at 28 days of life, oxygen supplementation at 36 weeks of postconceptional age (gestational age + postnatal age), length of stay, number of rehospitalizations during the first year of life, and neurodevelopmental outcome. DATA COLLECTION AND ANALYSIS: We used the standard method for the Cochrane Collaboration which is described in the Cochrane Collaboration Handbook. Two investigators extracted, assessed and coded separately all data for each study. Any disagreement was resolved by discussion. MAIN RESULTS: Six studies met inclusion criteria. Studies available for this systematic review were all done before the current era of prenatal steroids, surfactant, indomethacin and fluid restriction. Furosemide administration had no long-term benefits. Furosemide-induced transient improvement in pulmonary function did not outweigh an increased risk for patent ductus arteriosus and for hemodynamic instability. REVIEWER'S CONCLUSIONS: There are no current data to support routine diuretic administration in preterm infants with RDS. Elective administration of furosemide or any diuretic to any patient with RDS should be carefully weighed against the risk of precipitating hypovolemia. In addition, elective administration of furosemide should be weighed against the risk of developing a symptomatic patent ductus arteriosus.

Diuretics↗

Diuretic use in the elderly: potential for diuretic-induced hypokalemia.

The more potent "loop" diuretics are being used with increasing frequency. The elderly constitute a growing portion of the population undergoing treatment with diuretics. The alterations in renal function and pharmacokinetics in the elderly (over 60 years of age) may result in the development of certain adverse effects. In patients over 70 years old, there is a progressive decline in overall renal function, resulting in a more than 50% decrease in glomerular filtration rate. Most of the pharmacokinetic changes in the elderly consist of alterations resulting in enhanced plasma levels of any given drug; diminished hepatic drug extraction, detoxification/metabolism or prodrug conversion; decreased renal excretion of drug; and diminished volume of distribution of drug. Adverse reactions to diuretics may be grouped into metabolic changes (e.g., hypokalemia), physiologic alteration (e.g., volume contraction), toxic manifestation (e.g., interstitial nephritis) and allergic or idiosyncratic phenomena (e.g., rash or thrombocytopenia). There is general agreement that significant hypokalemia, particularly among elderly patients receiving digitalis glycosides, is significant and requires therapy. Diuretic-associated hypokalemia reflects the potency and duration of action of a diuretic, factors modulating potassium balance including dietary intake and concurrent medical processes. The short duration of action and greater natriuresis relative to kaliuresis characteristic of loop diuretics may result in a lesser degree of hypokalemia than that seen with traditional thiazide diuretics.

Aged↗

[Correlations between blood pressure, blood volume and plasma renin during therapy with diuretics in essential hypertension. Comparison between the mineralocorticoid antagonist spironolactone and the "loop" diuretic mefruside].

35 patients with benign essential hypertension were treated for 6 weeks with high doses of the mineralocorticoid-antagonist spironolactone (400 mg/day), or with the "loop-diuretic" mefruside (mean maximal dose 110 mg/day). Spironolactone caused greater reductions in blood pressure and blood volume and a more marked increase in plasma renin activity (PRA) than mefruside (p less than 0.05). It appears possible that he weaker antihypertensive effect of mefruside may relate partly to its lesser influence on circulatory volume. With both diuretics, mean decreases in blood pressure were greater in patients with low pre-therapeutic PRA than in patients with normal or high PRA. However, the diuretic-induced changes in blood pressure did not correlate with the associated variations in blood volume or PRA. Thus, the increased blood pressure sensitivity to diuretics in patients with low-renin essential hypertension did not appear to be volume or renin-dependent. Under normal conditions, the maintenance of a constant blood pressure during volume depletion may partly depend on compensatory activation of the sympathetic nervous system. Moreover, patients with low-renin essential hypertension have been found to have decreased adrenergic activity. It seems possible, therefore, that the marked blood pressure sensitivity to diuretic treatment in such patients may be the result of an impaired compensatory sympathetic response to sodium and volume depletion. Analysis of the literature suggests that the diuretic furosemide, a structural relative of mefruside, may also have less blood pressure lowering efficacy in patients with essential hypertension than the distally-acting thiazides, chlorthalidone or spironolactone. Consideration of possible differences in the blood pressure reducing potential of certain diuretics thus appears to be necessary in planning the pharmacotherapy of essential hypertension.

Blood Pressure↗

Acute administration of captopril lowers the natriuretic and diuretic response to a loop diuretic in patients with chronic cardiac failure.

Angiotensin-converting enzyme inhibitors suppress plasma concentrations of the sodium retaining hormones angiotensin II and aldosterone. This action should potentiate the natriuretic and diuretic effects of loop diuretics. Some studies indicate, however, that the introduction of angiotensin-converting enzyme inhibitors for the treatment of cardiac failure is associated with transient weight gain and the development of oedema. We have compared the natriuretic and diuretic response to intravenous frusemide 40 mg alone with the natriuretic and diuretic response to intravenous frusemide 40 mg following the administration of a single dose of captopril in 12 supine male patients with stable chronic cardiac failure. Captopril lowered the 4 h diuretic response to frusemide from 1160 (60) to 685 (77) ml (P less than 0.05) and the natriuretic response from 120 (9.6) to 68 (11.7) mmol (P less than 0.05). Creatinine clearance fell after captopril from 91 (7.2) to 57 (7.7) ml min-1 (P less than 0.05). Systolic and diastolic blood pressures were lower after the administration of captopril but these changes were not significant. Plasma renin activity rose from 3.8 (1.04) to 12.34 (2.94) ng ml h-1 (P less than 0.05) and plasma angiotensin II was reduced from 24.9 (5.05) to 8.14 (1.8) pg ml-1 (P less than 0.05). Plasma aldosterone concentrations were not significantly lower following captopril. Angiotensin-converting enzyme inhibitors cause an acute fall in creatinine clearance which may reduce the effects of loop diuretics and attention must be paid to diuretic dosage when initiating angiotensin-converting enzyme inhibitors for the treatment of cardiac failure.

Aged↗