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PubMed1975

Renal distension in response to water-soluble contrast medium and various diuretics.

Measurement of the increase in area of the renal silhouette, as it appears on radiographs following the administration of water-soluble contrast medium and certain diuretics, seems to be useful in the diagnosis of renovascular hypertension. In order to assess the optimal technique for such measurements, washout urography was performed in 32 hypertensive patients in two consecutive examinations so that the distensive effect of etacrynic acid, furosemide and hypertonic mannitol, respectively, were compared with that of urea in the same patients. In spite of their stronger diuretic effect, none of the above-mentioned diuretics caused a greater renal distension than urea, the maximum increase in area of the renal silhouette being about 7 to 20%, average about 11%. Since urea is probably the best siuted diuretic for the washout test, it seems to be the drug of choice for these diagnostic procedures.

Adult↗
PubMed1988

Diuretics and hyperuricemia in the elderly.

Serum uric acid (SUA) was studied in a rural population of 420 males and 592 females aged 65 years or more. The mean SUA concentration was 0.313 mmol/l in males and 0.316 mmol/l in females. In males, 47 (11.2%) and in females 60 (10.1%) had a SUA level of 0.42 mmol/l or more. Both the mean serum values and the frequency of hyperuricemia were higher than 11 years earlier in another, similar study. The SUA concentration was 0.361 mmol/l in the 435 individuals using diuretics and 0.281 mmol/l in the remaining 578. Of the 107 hyperuricemic individuals, 82% used diuretics, and only 2 out of those 20 where the SUA level was 0.50 mmol/l or more did not use diuretics. Apart from diuretics, only the serum creatinine concentration, the Body Mass Index, body weight and the hematocrit level were significantly associated with hyperuricemia in both sexes.

Aged↗
PubMed1983

Hemodynamic actions of diuretic agents.

The blood pressure lowering effect of diuretics in hypertensive disease is well documented. The hemodynamic actions underlying this antihypertensive effect differ in the early phase from the effects observed during long-term treatment. This article first describes new experiments on the hemodynamic effects of three diuretics, viz. hydrochlorothiazide, chlorthalidon and furosemide in conscious, chronically instrumented spontaneously hypertensive rats. This animal model was chosen in view of its good applicability for the study of the hemodynamics of antihypertensive drug action. Results show a marked early fall in stroke volume and cardiac index with all three diuretics. Mean arterial blood pressure was decreased only after a delay of several hours, because of an early large increase in total peripheral resistance. This article furthermore discusses possible mechanisms involved in the long-term return of peripheral resistance close to or below pre-treatment values. On the basis of data in the literature it is concluded that adaptation of baroreceptor reflexes, auto-regulatory responses of the peripheral vascular resistance and enhanced production of endogeneous vasodilator substances play an increasingly important role during the long-term hemodynamic actions of diuretic agents.

Animals↗
PubMed1983

The use of diuretics in varying degrees of renal impairment: an overview.

Administration of diuretics during acute renal failure in animals has been demonstrated to be of value with mannitol and/or loop-blocking diuretics, furosemide or ethacrynic acid. There is evidence that if these drugs are given very early in the controlled experimental environment that there will be some beneficial effect in maintaining renal function. However, in man the temporal relationship between the acute onset and the successful response to the administration of the drugs is, at best, coincidental and the use of diuretics in acute renal failure may not produce the same results as seen in the laboratory. One of the best guides to the underlying disease when there is acute decompensation in renal function is the utility of the renal failure index which utilizes urine and plasma sodium and urine and plasma creatinine ratios. Large doses of loop-blocking diuretics can be of benefit in patients with mild to moderate chronic renal insufficiency and fluid retention and/or hypertension. When renal insufficiency is severe in the pre-dialysis setting, furosemide, bumetanide or muzolimine may be of some benefit; however, as renal failure worsens the response of the kidney is sluggish and it is wise to begin to dialyze when glomerular filtration deteriorates below 5 ml per minute.

Acute Kidney Injury↗
PubMed1989

Diuretics and other antihypertensive drugs and glycemic control in non-insulin-dependent diabetics with hypertension. A survey by the Fukuoka Diabetes Clinic Group.

We compared the levels of fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1) in non-insulin-dependent diabetics with hypertension who were treated with monotherapy of diuretics or other antihypertensive drugs (AHD) and in those who were not given any AHD. Total 162 patients were divided into the four groups; the control group without AHD (n = 45), the diuretics group (n = 42), the beta-blocker group (n = 30) and the Ca-antagonist group (n = 45). FPG and HbA1 levels were 153 +/- 44 mg/dl and 10.0 +/- 2.3% for the control group, 145 +/- 55 mg/dl and 9.8 +/- 2.2% for the diuretics, 165 +/- 63 mg/dl and 10.2 +/- 2.1% for the beta-blocker and 158 +/- 42 mg/dl and 10.4 +/- 2.0% for the Ca-antagonist, respectively. There were no significant differences in the levels of FPG and HbA1 among the four groups. Multivariate analysis also revealed no difference in glycemic control even when anti-diabetic treatment (diet alone, oral hypoglycemic agents or insulin), body mass index, serum potassium, systolic and diastolic blood pressures and age were taken into account. Blood pressure levels did not differ among the groups except control and they were well controlled at the low doses of AHD. Our results suggest that the choice of low dose diuretics for the treatment of hypertension in non-insulin-dependent diabetics might not be necessarily excluded by the only reason of the possible deleterious influence on glycemic control.

Adrenergic beta-Antagonists↗
PubMed1992

Fluid and electrolyte disorders caused by diuretic therapy.

A wide spectrum and class of diuretics have been used to treat an assortment of cardiovascular disorders and various hypertensive states. Fluid and electrolyte imbalances are a major side effect of diuretic use. They predispose the patient to potential fluid disequilibrium and problems associated with electrolyte regulation. Such problems can prove to be lethal if not corrected. Very often, the ability to tolerate diuretic therapy is influenced by adequate renal function and hydration status of the patient. It becomes an important nursing responsibility to detect the development of dysfunction as a result of diuretic use or misuse. The responsive nurse, through meticulous assessment, can detect problems related to fluid and electrolyte disorder that can threaten patient well-being.

Diuretics↗
PubMed1989

Cardiovascular-risk reduction: initial diuretic therapy compared with calcium-antagonist (felodipine) therapy for primary hypertension.

Drug therapy for hypertension has failed to demonstrate a significant reduction in coronary mortality. We compared a calcium-antagonist agent, felodipine, with diuretic therapy as a first-line antihypertensive treatment in a randomized study, to assess the effects of six months of each regimen on over-all cardiovascular risk. Both regimens lowered blood pressure to less than 85 mmHg by one month. Felodipine alone was sufficient to control blood pressure in 90% of patients, while 50% of patients who were receiving diuretic therapy required a second agent for control. Diuretic therapy produced a 10% fall in serum potassium levels (P less than 0.001) and a three-fold increase in plasma renin activity (P less than 0.005) by one month; and a 6% rise in serum cholesterol levels (P less than 0.05) and a 38% rise in serum triglyceride levels (P less than 0.05) by three months. Felodipine did not influence these measurements, but caused a 43% increase in plasma noradrenaline levels by one month of therapy (P less than 0.025). In both groups, a significant fall occurred in the risk percentile score at six months, as calculated from the Multiple Risk Factor Intervention Trial data. However, the decrease was significantly greater in the felodipine group at six months (45% compared with 29%; P less than 0.05). Thus, when doses were titrated to achieve equivalent effects on blood pressure, felodipine had the advantages over diuretic treatment of being effective as monotherapy, of having fewer metabolic effects, and of reducing cardiovascular risk to a greater degree.

Adult↗
PubMed1999

Changes of renal resistive index in response to hydration and diuretic administration in normal subjects and in patients with small ureteral stone.

The renal resistive index has been measured before and after hydration and administration of diuretics in persons with normal kidneys and in kidneys with small ureteral stone, either obstructing or nonobstructing, to assess induced flow changes and to identify features differentiating obstructing from nonobstructing stones. In normal kidneys the resistive index was normal (mean, 0.62+/-0.03); no changes in the resistive index occurred within 15 to 60 min after hydration alone, whereas the resistive index rose within 15 min after hydration plus administration of diuretics and then returned to initial values within 30 min. In both cases the resistive index decreased below basal values after 75 to 90 min. Similar changes were observed in kidneys with a nonobstructing ureteral stone. In kidneys with an obstructing ureteral stone the resistive index was higher than in normal subjects (mean, 0.73+/-0.02, P<0.01), increased further within 15 min after hydration and administration of diuretics (P<0.01), and remained higher than basal values during the following 90 min. In conclusion, different resistive index changes have been observed in response to hydration and diuretics in normal and obstructed kidneys. Duplex Doppler sonography and diuresis duplex Doppler sonography seem promising diagnostic tools to identify obstructing stones.

Diuretics↗
PubMed1999

Diuretic effects on calcium metabolism.

Diuretics have numerous effects on calcium metabolism. The loop diuretics promote, and the thiazide diuretics inhibit, renal calcium excretion. In this review we detail the basic mechanisms of renal calcium excretion and then explain how diuretics influence this excretion. Finally we review how these agents can be used to alter calcium homeostasis in a clinically efficacious manner.

Animals↗
PubMed1999

Use of diuretics in cirrhosis and nephrotic syndrome.

Patients with cirrhosis and with nephrotic syndrome have subnormal responses to diuretics. The mechanism of this effect in cirrhosis is decreased pharmacodynamics of response. Large doses of diuretic are not useful in this setting. Instead, more frequent administration of modest doses is required. In nephrotic syndrome, substantial amounts of diuretic are rendered inactive by binding to urinary albumin, thereby mandating larger doses. In addition, the pharmacodynamics of response are altered so that doses must be administered more frequently. Rarely, patients may benefit from combinations of albumin and a loop diuretic.

Diuretics↗
PubMed1999

[Renaissance of diuretics in the treatment of hypertension].

Diuretics and beta-blockers are the only antihypertensives known for their significant reduction of cardiovascular morbidity and mortality, particularly in the elderly. The use of low-dose diuretics can improve the efficacy-safety ratio. Hypokalemia, hypomagnesemia as well as disturbances of carbohydrate and lipid metabolism are dose-dependent side effects of diuretics but only minimal during the low-dose therapy. A novel low-dose formulation of indapamide was developed as a sustained-release (SR) coated tablet (1.5 mg/day) and compared to the immediate release (IR) formulation of indapamide (2.5 mg/day). A > 50% reduction in the number of patients with serum potassium levels < 3.4 mmol/l among hypertensive patients treated with indapamide SR as compared to IR was observed. Indapamide SR has also been shown to be effective (more than 20 mg enalapril) in the reduction of left ventricular mass index (LVMI) in hypertensive patients treated for one year (LIVE study). Therefore, low-dose diuretics are, in accordance with international recommendations for the low-dose antihypertensive drugs, a first line therapy of hypertension.

Antihypertensive Agents↗
PubMed1999

Vasodilatory effect of diuretics is dependent on inhibition of vascular smooth muscle carbonic anhydrase by a direct mechanism of action.

Five years ago, our in vitro and in vivo studies demonstrated for the first time that diuretic agents such as furosemide, hydrochlorothiazide, amiloride, triamterene and spironolactone inhibit carbonic anhydrase (CA) I, II and renal CA IV by a direct mechanism of action. In this paper we investigate the relationship between diuretics and CA I in the vasodilatory mechanism. Both in vitro (on purified CA I, erythrocyte CA I and smooth muscle CA I) and in vivo (in human and rabbits) we studied the effect of acetazolamide, hydrochlorothiazide, indapamide, furosemide, amiloride and triamterene on purified CA I, on human erythrocyte CA I, as well as on CA I isolated from vascular smooth muscle. Our results demonstrate that in vitro all diuretics inhibit CA I by a direct mechanism of action. Inhibition reached 100% with acetazolamide, 45% with hydrochlorothiazide, 82% with indapamide, 85% with furosemide, 68% with amiloride and 58% with triamterene. In vivo, similar inhibition of erythrocyte and smooth muscle CA I was obtained, being parallel with a reduction in arterial blood pressure values. Our data show that in addition to their already known mechanisms, diuretics also inhibit CA in vascular smooth muscle. Our results suggest that this mechanism is achieved by means of pH changes induced by CA I inhibition.

Acetazolamide↗
PubMed2000

Efficacy of diuretics and beta-blockers in diabetic hypertensive patients. Results from a meta-analysis. The INDANA Steering Committee.

OBJECTIVE: To review the effectiveness of diuretic or beta-blocker-based treatment of hypertension in diabetic patients. RESEARCH DESIGN AND METHODS: A meta-analysis on individual patient data was performed on four trials of the treatment of hypertension in which diabetic patients were included and treated with first-line diuretics or beta-blockers. The main outcomes were the relative risk of death, fatal or nonfatal stroke, fatal or nonfatal coronary events, and major cardiovascular events. RESULTS: There were 92 diabetic patients who received first-line beta-blockers and 1,008 who received diuretics. In the control groups, diabetic patients had nearly twice the risk of any outcome when compared with nondiabetic patients. The same blood pressure reduction was achieved under treatment in the diabetic and nondiabetic patients, except for systolic pressure, which decreased more in the nondiabetic patients at 1 year. In the 15,843 nondiabetic patients, the risk of all four outcomes was reduced significantly in the treated group. In the 2,254 diabetic patients, the risk reduction was significant only for fatal and nonfatal stroke (36%, P = 0.011) and major cardiovascular events (20%, P = 0.032), but not for death (5%, P = 0.65) and fatal or nonfatal coronary events (15%, P = 0.23). However, no heterogeneity was detected between diabetic patients and nondiabetic patients for any outcome. The numbers of outcomes avoided for 1,000 patients treated for 5 years were higher in diabetic patients (e.g., 38 major cardiovascular events) than with nondiabetic patients (e.g., 28 major cardiovascular events). CONCLUSIONS: These results show that hypertensive diabetic patients benefit from first-line treatment with diuretics. No conclusion can be drawn for beta-blockers, owing to the small sample size.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

[Diuretic and hypotensive effects of Nigella sativa in the spontaneously hypertensive rat].

Nigella sativa (ranunculaceae) is used in Arab folk medicine as a diuretic and hypotensive plant. We report here the diuretic and hypotensive effects of dichloromethane extract of Nigella sativa seeds in the spontaneously hypertensive rat (SHR). An oral dose of Nigella sativa extract (0.6 ml/kg/day) and furosemide (5 mg/kg/day) increased significantly the diuresis by 16 and 30 per cent respectively after 15 days of treatment; urinary excretion of Cl-, Na+, K+ and urea is also increased. Simultaneously, the mean arterial pressure decreased respectively by 22 and 18 per cent in the Nigella sativa treated rat and nifédipine treated rat (0.5 mg/kg/day). In conclusion, the diuretic activity observed in the SHR rat treated with Nigella sativa seeds may be partially responsible for its diuretic action; it seems that other pathways may also be involved in their cardiovascular effects.

Animals↗
PubMed1975

Effect of diuretics on oxidative phosphorylation of dog kidney mitochondria.

An effect of diuretics on cellular metabolism has been shown. In order to examine further the direct effect of diuretics on renal mitochondria, their effect on isolated cortical (C) and outer medullary (OM) mitochondrial respiration was examined. Oxygen consumption rate (QO2) was measured in a Gilson oxygraph utilizing either glutamate-malate or succinate as substrate. QO2, expressed in nanoatoms of O2 per milligram of protein per minute, was always higher in C than OM: 140.7 +/- 2.8 VS. 121.2 +/- 2.4 (P less than 0.001) with glutamate-malate and 181.1 +/- 6.3 vs. 129.7 +/- 5.2 (P less than 0.001) with succinate. A dose-response curve was constructed for each of the following: sodium ethacrynate, furosemide, chlorothiazide, acetazolamide and chlormerodrin. All diuretics inhibited C and OM equally. The 50% inhibitory molar concentration for EA was 6.2 times 10(-4); for furosemide 1.5 times 10(-3); for chlorothiazide 8.1 times 10(-3); for acetazolamide 10.8 times 10(-3); and for chlomerodrin 3.1 times 10(-5). Neither cysteine nor dithiothreitol inhibited the effect of EA. The effect of chlormerodrin was abolished by cysteine. These results demonstrate that while a difference exists between C and OM mitochondria during control studies, each of the diuretics examined exerted an equal inhibitory effect on mitochondrial respiration from both C and OM. Mercurials are the most potent inhibitors and presumably exert their effect by reacting with sulfhydryl groups. They are followed in potency by ethacrynic acid, furosemide, chlorothiazide and acetazolamide.

Animals↗
PubMed1992

Pharmacological properties of the novel highly potent diuretic 7-chloro-2,3-dihydro-1-(2-methylbenzoyl)-4(1H)-quinolinone 4-oxime-O-sulfonic acid potassium salt.

7-Chloro-2,3-dihydro-1-(2-methylbenzoyl)-4(1H)-quinolinone 4-oxime-O-sulfonic acid potassium salt (M17055, CAS 114417-20-8) showed potent diuretic and saluretic effects dose-dependently, in rats (p.o.), mice (p.o.) and dogs (i.v.), at doses of 0.1-100 mg/kg, 0.3-100 mg/kg and 0.01-30 mg/kg, respectively. The efficacy of M17055 for diuresis, natriuresis and chloruresis was much higher than that of hydrochlorothiazide and almost the same as that of furosemide. These results indicate that this compound may be classified as a "high ceiling diuretic". The potencies of M17055 for natriuresis in rats (p.o.), mice (p.o.) and dogs (i.v.) calculated with ED50 values were 38, 34 and 24 times, respectively, more potent than those of furosemide. Urinary excretions of sodium, chloride and potassium increased in parallel with urinary volume with the administration of M17055 or furosemide, whereas an apparent dissociation with urinary calcium and sodium excretion was observed with M17055 alone. In rats, the increase of urinary calcium excretion with M17055 was significantly lower than that with furosemide under comparable conditions of natriuresis. Moreover, in mice, M17055 decreased urinary calcium excretion at doses with low effectiveness. In clearance studies using anesthetized dogs, M17055 suppressed negative free water clearance (CH2O) under saline loaded conditions, and it decreased positive CH2O under water diuretic conditions. These changes in the effects on CH2O induced by M17055 resemble those of loop diuretics. However, M17055 could not shift negative CH2O to positive, while furosemide was able to do so. Moreover, positive CH2O decreased to nearly zero with M17055, while urine remained dilute with furosemide even at 30 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1992

Action of diuretics at the cellular level.

Classification of diuretics is based on their site and mechanism of action in the nephron. The most frequently used substances comprise 1. the mostly proximally acting carbonic anhydrase inhibitors (CAI); 2. the loop diuretics (LD); 3. the early distally acting thiazides (TZ); and 4. the K+ sparing diuretics (KS) acting in the distal tubule. CAI such as acetazolamide inhibit the dehydration of H2CO3 at the luminal membrane, the hydration of CO2 within the proximal tubule cell and the exit of HCO-3 out of the cell. As a result of this proximal reabsorption of HCO-3 is reduced, a slight diuresis and saluresis is induced. The enhanced urinary excretion of HCO-3 will cause a metabolic acidosis. LD inhibit the Na+2Cl-K+ carrier in the thick ascending limb of the loop of Henle (TAL). This produces a marked diuresis and saluresis which is accompanied by enhanced Ca2+, Mg2+, K+ and acid excretion. TZ inhibit the Na+Cl- cotransporter in the early distal tubule. The diuresis is less marked than that induced by LD but the renal losses of K+ are comparable. KS inhibit Na+ channels present in the luminal membrane of the cortical collecting tubule. This leads to a very limited diuresis, but a marked attentuation of renal K+ losses. All diuretics act by inhibiting the admission of Na+ (LD, TZ, KS) or HCO-3 (CAI) into the cell. Their organotropy is merely due to the fact that they are concentrated in tubule fluid by volume reabsorption and by proximal tubule secretion.

Animals↗
PubMed1992

[Captopril in mild and moderate hypertension resistant to diuretics: predictive value of the efficacy by captopril acute test].

PURPOSE: To evaluate if acute blood pressure response with captopril can be applied as a predictive test of treatment efficacy in hypertensive patients uncontrolled with large dose of diuretics. METHODS: Mild and moderate 120 uncontrolled hypertensive patients treated with hydrochlorothiazide 100 mg, were submitted to captopril (25 mg) test. The systolic (SBP) and diastolic (DBP) blood pressure acute and chronic responses were correlated and the linear discriminate function (LDF) and qui-square were applied to test the treatment efficacy. Previously two groups (G) patients were obtained as bad responders (G1) and good responders (G2) respectively, if the mean arterial pressure fall less or equal/more than 15% at the end of the associated treatment with diuretic and captopril. RESULTS: Mean arterial pressure values during placebo were 168 +/- 2/109 +/- 1 mmHg. This values after diuretic and associated captopril treatment were, respectively, 151 +/- 1/101 +/- 1 and 137 +/- 1/90 +/- 1 mmHg, all significant different (p < 0.05). Blood pressure normalization was obtained in 58% of patients. The calculated LDF formula were: LDF = 7.92 - % SBP +/- 1.21 delta % DBP. The G1 LDF mean value was 192 and 361 to G2. The value 276 represents the separation medium point between both groups. As far the distance from the separation medium point for a calculated LDF for a calculated LDF for a problematic patient, as more will be the probability for this patient to belong to this group. LDF and qui-square classified correctly, respectively, 80% and 47% of patients in G1. To G2 good responders patients, LDF and qui-square agreed, respectively, in 72 and 77%. CONCLUSION: The results obtained suggest that captopril test, could be useful as an auxiliary methodology to select hypertensive patients, uncontrolled with diuretic treatment, which might benefit with the association of converting enzyme inhibitors drugs.

Adolescent↗