SEARCH · Search PubMed

Results for “SPIRONOLACTONE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 433 records · Page 24Linked to original sources

PubMed2003

Spectophotometric quantitative resolution of hydrochlorothiazide and spironolactone in tablets by chemometric analysis methods.

Spectrophotometric simultaneous determination of hydrochlorothiazide and spironolactone in tablets was performed by classical least-squares (CLS), inverse least-squares (ILS), principal component regression (PCR) and partial least-squares (PLS). The methods of the chemometric analysis do not require sample pretreatment procedure. A training set of 25 standard mixture containing both drugs was prepared in the concentration range of 2-20 mug/ml according to mixture design. The multivarate calibrations were obtained by measuring the zero-order and first-derivative absorbances at 15 points from 220 to 290 nm using the training set. The validation of the multivariate methods was realised by analysing the synthetic mixtures of hydrochlorothiazide and spironolactone. The result obtained on the synthetic mixture and tablets were statistically compared by the one-way ANOVA test. The chemometrics analysis methods were satisfactorily applied to the simultaneous determination of hydrochlorothiazide and spironolactone in the pharmaceutical tablet formulation.

Hydrochlorothiazide↗

PubMed2005

Ratio spectra derivative spectrophotometry for the determination of furosemide and spironolactone in a capsule formulation.

The determination of furosemide and spironolactone in a capsule formulation has been investigated using techniques such as Vierordt's method and derivative spectroscopy dA/d lambda and d2A/d lambda2 applying the zero-crossing technique following reported methods. In our hands, using standard mixtures, these methods gave unreliable results. We have therefore investigated the use of ratio spectra derivative spectrophotometry for this determination. The technique of ratio spectra derivative spectrophotometry was developed in 1990, and has recently been used for a number of analyses of co-formulated products. The method was applied to the analysis of standard mixtures of the two drugs and the combined contents of 20 capsules resulting in values (mean +/- standard deviation) of 102.1 +/- 1.9% and 101.4 +/- 4.0% of the stated content for furosemide and spironolactone, respectively. Similarly, the analysis of individual capsules resulted in values of 101.5 +/- 1.6% and 102.2 +/- 1.4% of the stated content for furosemide and spironolactone, respectively.

Calibration↗

PubMed1988

Spironolactone does not affect in vitro androgen secretion by human granulosa-luteal cells.

Although spironolactone has been documented to decrease peripheral serum androgen levels in women treated for androgen excess of ovarian origin, the site of action does not appear to be the granulosa cell. In vitro cell culture studies using human granulosa-luteal cells isolated from women undergoing ovarian stimulation for IVF have shown no affect on T, delta 4A, or DHT secretion in the presence of clinically therapeutic levels of spironolactone (0-10(-6) M). In addition, neither P nor E2 production was affected by increasing concentrations of spironolactone.

Androgens↗

PubMed1989

Effect of spironolactone-hydrochlorothiazide on lung function in infants with chronic bronchopulmonary dysplasia.

To test the hypothesis that spironolactone-hydrochlorothiazide (Aldactazide) will improve urine output and lung function in infants with bronchopulmonary dysplasia, we studied 21 hospitalized, spontaneously breathing, oxygen-dependent infants with chronic bronchopulmonary dysplasia. Infants were randomly assigned to receive either a 1:1 mixture of spironolactone and hydrochlorothiazide orally (n = 12) (3 mg/kg/day of both compounds) or no treatment (n = 9) for 6 to 8 days each. Dynamic lung compliance, total pulmonary resistance, and hemoglobin oxygen saturation were measured on the first and last days of each study period. Fluid intake and urine output were measured each day. Although the treatment significantly increased urine output, neither lung mechanics nor oxygenation were improved by the drug. The magnitude of the diuresis achieved with spironolactone-hydrochlorothiazide treatment was comparable to the diuresis achieved in a previous study of furosemide treatment (J Pediatr 1986:109;1034-9). Statistical analysis indicated that a type II error was an unlikely explanation for our failure to detect a beneficial effect. In three patients, doubling the oral dose did not improve lung mechanics or oxygenation. We speculate that diuresis per se is not responsible for lung function improvement during treatment with other drugs with diuretic properties.

Bronchopulmonary Dysplasia↗

PubMed1996

Effect of spironolactone on antipyrine metabolism in calves.

Ten female calves of the Black and White breed aged seven to eight days were studied before and after seven days of treatment with spironolactone at a dose rate of 1 mg kg bodyweight-1 twice a day. The treatment was associated with a statistically significant decrease in the half-life of antipyrine in plasma and an increase in its rate of metabolic clearance. The excretion of 4-hydroxyantipyrine in urine was significantly increased after the treatment with spironolactone, but there were no changes in the rates of excretion of 3-hydroxymethylantipyrine or norantipyrine. These results indicate that spironolactone enhanced the activity of the microsomal drug-metabolising enzyme system and induced cytochrome P-450 in the calves.

Animals↗

PubMed2000

Increased activity of the hypothalamus-pituitary-adrenal system after treatment with the mineralocorticoid receptor antagonist spironolactone.

The hippocampal mineralocorticoid receptor (MR) is critical for the regulation of the basal activity of the hypothalamus-pituitary-adrenocortical (HPA) system. It has been hypothesized that reduced capacity of the hippocampal MR is involved in the HPA-system dysregulation found in depression and aging. We applied the combined dexamethasone suppression/corticotropin releasing hormone stimulation (DEX/CRH) test to six healthy young females both before and after 12 days of treatment with the MR antagonist spironolactone to assess HPA regulation. Treatment with spironolactone caused a significant increase in post-dexamethasone cortisol concentrations (75.1+/-56.7 vs. 36.6+/-24.6 nmol/l, p<0.05). Furthermore, we observed a significant rise in peak cortisol concentration after additional human CRH (hCRH) application (223. 6+/-139.1 vs. 126.7+/-73.3 nmol/l, p<0.02). There was no change in ACTH plasma concentrations. We thus conclude that (1) the MR antagonist spironolactone affects HPA system regulation as reflected in the DEX/CRH test and (2) these findings are in accordance with the assumption that MR dysfunction may underlie HPA-system dysfunction in depression and/or aging.

Adrenal Glands↗

PubMed2005

Comparative pilot study of repeated large volume paracentesis vs the combination on clonidine-spironolactone in the treatment of cirrhosis-associated refractory ascites.

OBJECTIVES: To study the usefulness of the combination of clonidine--spironolactone in refractory ascites. METHODS: Twenty cirrhotic patients with refractory ascites were randomly assigned to receive repeated large volume paracentesis plus intravenous albumin (group 1), or a combination of clonidine (0.075 mg twice daily) and spironolactone (200 to 400 mg daily) (group 2). RESULTS: During the first hospitalisation,, the mean weight loss in group 1 was higher than in group 2 (12.4 +/- 3.2 versus 4.3 +/- 1.1 kg, P < or = 0.01). Mean stay in hospital was shorter in group 2 (20 +/- 1.5 versus 10 +/- 2.8 days; P < or = 0.01). Paracentesis did not induce changes in neuro-hormonal measurements. Oppositely, clonidine induced a decreased sympathetic activity, an increased glomerular filtration rate and a delayed reduction of the renin-aldosterone levels. During the follow-up in group 1, the number of rehospitalisations for ascites was higher than in group 2 (37 versus 3; P < or = 0.01), and the mean time to the first readmission was shorter (10 +/- 2.7 versus 23.7 +/- 5.6 days; P < or = 0.01). The total duration spent in hospital were similar in both groups. CONCLUSION: Paracentesis is more effective for short-term treatment of ascites but clonidine-spironolactone association might provide better long-term control.

Adrenergic alpha-Agonists↗

PubMed2001

Prevention of aortic and cardiac fibrosis by spironolactone in old normotensive rats.

OBJECTIVES: Because the synthesis of aldosterone is mainly modulated by angiotensin II through type I receptor stimulation and because converting enzyme inhibition (CEI) does not modify aortic extracellular matrix in old normotensive rats, the aim of the present study was to determine whether inhibition of aldosterone formation was able to prevent aortic fibrosis in old Sprague-Dawley normotensive rats. BACKGROUND: We have previously shown that long-term aldosterone antagonism prevents the age-related increase in aortic collagen accumulation in young spontaneously hypertensive rats, independent of blood pressure changes. In contrast, we reported that the positive effects of CEI in the prevention of aortic collagen accumulation were related to the inhibition of angiotensin II actions on angiotensin II type I receptors. METHODS: For this purpose, we studied the histomorphometric and stiffness (echo-tracking technique) changes of an eight-week treatment with the aldosterone antagonist spironolactone by comparison with placebo. RESULTS: At the end of treatment, spironolactone in conscious animals did not change intra-arterial blood pressure, aortic and carotid wall thickness, and cardiac weight. Cardiac collagen density and, to a lesser extent, carotid collagen and elastin densities and contents were significantly decreased in association with an increase of carotid distensibility. CONCLUSIONS: These results show that in old normotensive rats, spironolactone can markedly prevent cardiac and, to a lesser extent, arterial fibrosis and improve arterial stiffness, despite a lack of hypotensive effect.

Age Factors↗

PubMed2002

Addition of spironolactone to angiotensin-converting enzyme inhibition in heart failure improves endothelial vasomotor dysfunction: role of vascular superoxide anion formation and endothelial nitric oxide synthase expression.

OBJECTIVES: We sought to investigate the effects of adding spironolactone (SP) to angiotensin-converting enzyme (ACE) inhibition on endothelium-dependent vasodilation in rats with chronic heart failure (CHF). BACKGROUND: Adding SP to ACE inhibitors reduces mortality and morbidity in CHF. Endothelial vasomotor dysfunction contributes to increased peripheral vascular resistance and reduced myocardial perfusion in CHF. METHODS: Seven days after extensive myocardial infarction (CHF) or sham operation, Wistar rats were treated with placebo, the ACE inhibitor trandolapril (TR, 0.3 mg/kg body weight per day), SP (10 mg/kg per day) or a combination of both for 11 weeks. RESULTS: Maximal acetylcholine-induced, nitric oxide (NO)-dependent relaxation was significantly attenuated in aortic rings from rats with CHF as compared with sham-operated animals (R(max) 44 +/- 3% vs. 63 +/- 3%). Spironolactone alone had no influence (46 +/- 5%) and TR improved NO-mediated relaxation (55 +/- 4%), whereas treatment with both completely restored endothelium-dependent vasorelaxation (64 +/- 4%). Aortic superoxide formation was significantly increased in rats with CHF as compared with sham-operated animals, but was normalized by treatment with SP or SP plus TR. In addition, aortic messenger ribonucleic acid expression of the oxidase subunit p22(phox) in rats with CHF was significantly reduced by SP or TR plus SP. Endothelial NO synthase expression was increased in TR-treated animals. Incubation of isolated porcine coronary arteries with SP dose-dependently attenuated superoxide formation. CONCLUSIONS: Spironolactone added to an ACE inhibitor normalizes NO-mediated relaxation in experimental CHF by beneficially modulating the balance of NO and superoxide anion formation.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2003

Spironolactone-induced agranulocytosis: a case report.

A 43-year-old woman with liver cirrhosis and hepatocellular carcinoma was admitted for the chief problem of ascites. Laboratory data revealed a leukocyte count of 3.8 x 10(9)/L on the second day of admission. Spironolactone was prescribed for diuresis beginning on the third day. Routine blood tests on the tenth day disclosed marked leukopenia (1.8 x 10(9)/L). Four days later, the leukocyte count was still 1.8 x 10(9)/L and a differential count revealed agranulocytosis (neutrophils, 0.25 x 10(9)/L). Eight days after withdrawal of spironolactone, the leukocyte count returned to normal (leukocytes, 4.9 x 109/L; neutrophils, 1.76 x 10(9)/L). On review of the patient's clinical condition, concurrent medication, and previous reports, we highly suspected that this episode of agranulocytosis was caused by spironolactone. Unlike four previously reported cases, this one did not involve furosemide, which is reported to be associated with leukopenia and agranulocytosis.

Adult↗

PubMed2000

Treatment of hypertension with valsartan combined with spironolactone.

Preliminary observations were made to assess the antihypertensive efficacy and safety of treatment with valsartan plus spironolactone. Thirteen hypertensive patients were studied, 7 were males (54%), and 6 females (46%) with an age range from 61 years to 83 years (mean: 74+/-7.1 years). Patients had a mean daytime SBP/DBP of 164+/-9.2/99+/-9.5 mmHg. Echocardiography showed cardiac hypertrophy and mild cavity enlargement in all patients. After baseline measurements of HR, serum creatinine and electrolytes (potassium and sodium), patients received valsartan 80 mg/day plus spironolactone 100 mg/day for concomitant chronic heart failure due to hypertension. Study parameters were measured at the 30, 60, and 90 day of therapy. Mean ambulatory SBP/DBP monitoring, mean Holter heart rate, mean serum creatinine, and mean serum electrolytes (sodium and potassium) were recorded. These parameters did not show statistically significant changes after 90 days of follow up, except in one patient who had an increase in serum potassium concentration from 4.3 mmol/l to 5.8 mmol/l after 30 days of therapy. Mean BP was reduced up a maximum of 7%. No side effect was seen in the study patients. Combination therapy valsartan and spironolactone seemed to be an effective and safe approach for older hypertensive patients with mild concomitant chronic heart failure.

Aged↗

PubMed1997

Chronic splanchnic hemodynamic effects of low-dose transdermal nitroglycerin versus low-dose transdermal nitroglycerin plus spironolactone in patients with cirrhosis.

We studied the hemodynamic changes following a four-week administration of either low-dose transdermal nitroglycerin (a constant release of 5 mg of nitroglycerin/day) (N = 10) or low-dose transdermal nitroglycerin plus spironolactone (100 mg/day) (N = 9) in patients with cirrhosis and portal hypertension. Two patients in the latter group did not undergo repeat measurements after dropping out because of severe headaches or developing ascites during the study. Transdermal nitroglycerin induced a significant reduction in the hepatic venous pressure gradient (HVPG) (-11.7 +/- 14.9%, P < 0.05), which was associated with a significant reduction of cardiac output (-10.5 +/- 7.3%). Nitroglycerin plus spironolactone induced a significant reduction in the HVPG (-18.3 +/- 16.0%, P < 0.05) associated with a significant reduction of cardiac output (-13.8 +/- 5.6%), right atrial pressure (-35.0 +/- 30.0%), mean arterial pressure (-7.5 +/- 6.8%), and plasma volume (-10.2 +/- 7.0%). The difference of the mean HVPG reduction between the groups was insignificant. A decrease in the HVPG greater than 10% was observed in six of 10 patients (60%) and in five of seven patients (71.4%), defined as "responders," at four weeks. The difference in percentage of responders between the groups was insignificant. We found that in some cirrhotic patients, low-dose transdermal nitroglycerin is potentially useful in the treatment of portal hypertension. Spironolactone as an adjunct to low dose transdermal nitroglycerin did not demonstrate therapeutic advantages in the treatment of portal hypertension in cirrhotics. That there were nonresponders indicates that there are variable responses in splanchnic hemodynamics to these drugs.

Administration, Cutaneous↗

PubMed1980

Spironolactone and warfarin interaction.

Spironolactone has been reported to diminish the hypoprothrombinemic effect of oral anticoagulants in animals and digitoxin blood levels in man by induction of hepatic enzymes. To evaluate this in man, single oral doses of racemic warfarin, 1.5 mg/kg body weight, with and without 200 mg oral spironolactine daily, were administered to 9 normal subjects. Daily venous blood samples were analyzed for 1-stage prothrombin activity, hematocrit, and warfarin content. There was a decrease in hypoprothrombinemic effect (p less than 0.01), an increase in venous hematocrit (p less than 0.001), and no change in warfarin level (p greater than 0.5) during warfarin with spironolactone-induced diuresis over that with warfarin alone. It is concluded that the interaction of warfarin and spironolactone results primarily from the diuresis with consequent concentration of clotting factors and decreased anticoagulant effect.

Adult↗

PubMed1981

Steady-state relative potency of aldosterone antagonists: spironolactone and prorenoate.

The dose ratio approach was used to define the steady-state relative potency of the competitive mineralocorticoid antagonists prorenoate potassium and spironolactone in six healthy male subjects using fludrocortisone as mineralocorticoid agonist. Log fludrocortisone dose-response relationships in the presence or absence of antagonists did not differ from linearity and parallelism, supporting the theoretical basis of the method. Urinary sodium and plasma potassium responses appeared to behave according to the law of mass action, which made possible estimation of the potency of prorenoate relative to spironolactone on a weight basis-4.2:1 (95% C.L. 2.7-6.9:1) and 2.68:1 (95% C.L. 0.71-6.57:1, respectively. The steady-state relative potency for sodium excretion was greater than previously estimated after single doses. Mass action theory could not explain the urinary potassium and log 10 Na/K responses to repeated doses of spironolactone, precluding valid estimation of relative potency for these variables and suggesting that the latter response alone is an unreliable index of overall renal antimineralocorticoid activity.

Adult↗

PubMed1982

Relative potency of amiloride and spironolactone in healthy man.

The renal antimineralocorticoid activity of single oral doses of amiloride, a physiologic aldosterone antagonist, was compared to that of spironolactone, a competitive aldosterone antagonist, in 12 healthy men pretreated with fludrocortisone. For up to 20 hr amiloride induced linear log dose-urinary electrolyte response relationships but spironolactone dose-response trends were demonstrated only in the period from 10 to 20 hr after treatment. In this period, the best estimate of the potency of amiloride relative to spironolactone for urine log10 10 Na/K was 36 (95% confidence limits 23 to 69). The fludrocortisone model seems appropriate for quantitative comparisons of physiologic and competitive aldosterone antagonists, but does not indicate therapeutic relative potency.

Adult↗

PubMed2005

Effect of losartan and spironolactone on left ventricular mass and heart sympathetic activity in prehypertensive obese subjects: a 16-week randomized trial.

Obesity has been shown to be associated with increased left ventricular mass (LVM) and heart sympathetic activity even in nonhypertensive subjects. These factors are predictors of cardiovascular morbidity and mortality independent of other traditional risk factors. We evaluated the effect of losartan and spironolactone on LVM and heart sympathetic activity in prehypertensive obese subjects. A 16-week blinded randomized trial was performed in middle-aged men selected from a Health Public program. Anthropometric and clinical variables were measured at baseline and after losartan (50 mg/day; n=25) or spironolactone (25 mg/day; n=25) treatment. Heart sympathetic activity was evaluated with 60-min electrocardiograph monitoring, and spectral analysis was carried out. LVM was measured by echocardiography according to Devereux and Reicheck's formula indexed for body height (m2.7) to account for obesity. Anthropometric variables, systolic, and diastolic blood pressure levels decreased in both groups of treatment without statisticall difference between them. Losartan increased heart rate variability (from 70.0 to 82.3 ms; P=0.01), and decreased low frequency-high frequency index (from 6.6 to 4.9; P=0.001), and LVM (from 49.2 to 45.2 g; P=0.004). In the multiple regression analysis for factors associated with reduction in LVM; treatment with losartan, and decrease in SBP were the only factors included in the model (R2=0.60; P=0.003). To conclude losartan, but not spironolactone, decreased LVM and heart sympathetic overactivity in prehypertensive obese subjects after 16 weeks of treatment. Regression on LVM was associated with reduction on SBP levels.

Adult↗

PubMed1998

Comparison between theophylline and spironolactone in the management of cirrhotic ascites: a randomized controlled study.

BACKGROUND: It has been suggested that adenosine is involved in the renal haemodynamic and tubular abnormalities observed in cirrhosis. Low-dose theophylline is an adenosine antagonist and recent studies have shown that this drug can improve renal blood flow and sodium excretion in cirrhotic patients. METHODS: Fifteen patients with newly diagnosed cirrhotic ascites were randomized to receive either 100 mg spironolactone daily for 7 days or 250 mg theophylline on days 1, 2, 4 and 6. Baseline clinical and urinary and serum biochemical data were collected and compared following therapy. RESULTS: After 7 days of spironolactone there were increases in urinary sodium excretion (43.5 +/- 15.6 vs. 106.8 +/- 34.7 mmol/day; P < 0.05) and urine volume (769.1 +/- 206.5 vs. 1541.6 +/- 342.6 mL/day; P < 0.05). No changes in the patients' weight, creatinine clearance or serum electrolytes were observed. No change was detected in any of these parameters following theophylline therapy. CONCLUSION: Adenosine antagonism in the form of low-dose theophylline is less efficacious than spironolactone in the management of cirrhotic ascites.

Adenosine↗

PubMed2002

Muscle strength, Na,K-pumps, magnesium and potassium in patients with alcoholic liver cirrhosis -- relation to spironolactone.

OBJECTIVES: To evaluate the muscle strength in relation to muscle contents of magnesium (Mg), potassium (K) and sodium, potassium (Na,K)-pumps in patients with alcoholic cirrhosis. DESIGN: An open cross-sectional study. SETTING AND SUBJECTS: Fifty-one consecutive patients with liver cirrhosis admitted to the Department of Hepatology, Aarhus University Hospital, Denmark, and 28 age- and sex-matched healthy control subjects. MAIN OUTCOME MEASURES: Biopsies of skeletal muscle were performed in patients and controls for measurements of Mg, K, and Na,K-pumps. Furthermore, maximum isokinetic knee extension and skeletal muscle mass were evaluated. RESULTS: Muscle mass, muscle strength, muscle Mg and muscle K were substantially reduced in the patients (P < 0.01, all), and fell with increasing severity of the liver disease reflected in the Child-Pugh (C-P) class. Patients treated with spironolactone for 2 weeks or more, had increased muscle strength, muscle Mg and content of Na,K-pumps, compared with the rest of the patients (P < 0.05, all). In a multivariate analysis of the patients, skeletal muscle mass, muscle Mg and daily alcohol consumption (g) were independent predictors of isokinetic muscle strength (P < 0.05, all). CONCLUSIONS: Patients with alcoholic liver cirrhosis showed considerably reduced muscle strength and muscle Mg was an independent predictor of muscle strength. Surprisingly, in the spironolactone treated patients, muscle weakness was less pronounced, possibly because of the action of spironolactone on muscle Mg, K and Na,K-pump content.

Adult↗