Search PubMed⌕ Search

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.

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

At least 775 records · Page 43Linked to original sources
PubMed1991

Reduced nephrotoxicity and hepatoxicity in cyclosporin A therapy by enalapril and spironolactone in rats.

The aim of the study was to define a therapy to be combined with an immunosuppressive drug such as cyclosporin A, in order to partially reduce the nephrotoxic and hepatotoxic effects in the treated rats. Two drugs were considered: enalapril, which is an inhibitor of the angiotensin-converting enzyme, and spironolactone, which is an antagonist of aldosterone. These two drugs interrupt the renin-angiotensinogen-angiotensin chain after this has been activated by cyclosporin A, preventing peripheral vasoconstriction and more specifically the constriction of both glomerular arterioles and hepatic vessels from occurring, thus diminishing the cyclosporin A toxicity in both liver and kidney.

Animals↗
PubMed1991

Role of the steroid 17 alpha-hydroxylase in spironolactone-mediated destruction of adrenal cytochrome P-450.

Previous investigations have established that spironolactone (SL) is converted to a reactive metabolite by adrenal microsomal enzymes, resulting in the degradation of cytochrome P-450 (P-450). Deacetylation of SL to 7 alpha-thiospironolactone (7 alpha-thio-SL) is the first step in the activation pathway, but further NADPH-dependent metabolism of 7 alpha-thio-SL is required for P-450 destruction. Studies were done to evaluate the role of the steroid 17 alpha-hydroxylase in the activation of 7 alpha-thio-SL by adrenal microsomes. Incubation of guinea pig adrenal microsomes with 7 alpha-thio-SL in the presence of NADPH effected greater than 50% declines in P-450 content and in 17 alpha-hydroxylase activity but no change in the rate of 21-hydroxylation. Preincubation of the microsomes with antisera to the 17 alpha-hydroxylase P-450 isozyme (P-450(17 alpha,lyase)) decreased 17 alpha-hydroxylase but not 21-hydroxylase activity and prevented the degradation of P-450 by 7 alpha-thio-SL. Control IgG had no effect on 17 alpha-hydroxylase activity or on the 7 alpha-thio-SL-mediated destruction of P-450. When added to a purified P-450(17 alpha,lyase) preparation, 7 alpha-thio-SL and the endogenous substrate progesterone caused typical type I spectral changes, but SL did not. Incubation of a purified and reconstituted 17 alpha-hydroxylase system, consisting of P-450(17 alpha,lyase), NADPH-P-450 reductase, cytochrome b5, and dilauroylphosphatidylcholine, with 7 alpha-thio-SL plus NADPH effected the complete degradation of the P-450(17 alpha,lyase). Neither progesterone nor SL caused P-450 destruction with the reconstituted enzyme preparation. The results provide direct evidence for the activation of 7 alpha-thio-SL by the 17 alpha-hydroxylase and support the hypothesis that a mechanism-based inhibition of the enzyme occurs. The data also provide additional evidence that 7 alpha-thio-SL is an obligatory intermediate in the degradation of P-450 by SL.

Adrenal Glands↗
PubMedDate not supplied

Oral and topical spironolactone therapies in skin androgenization.

The most important clinical studies using spironolactone as an antiandrogen drug either per os or topically are referred. Menstrual disturbances very often occur during SP treatments thus limiting its systemic use. As far as the topical use is concerned SP seems to be highly effective with absence of systemic effects. Local mild side effects were present in a small number of patients.

Acne Vulgaris↗
PubMed1990

[Experience in the therapy of acne with topical administration of spironolactone as an antiandrogen].

The authors report their clinical experience with topical treatment of seborrheic acne with a 5% spironolactone cream in 20 patients, 11 males and 9 females aged 12 to 28 years (average 20.5). Treatment duration, about one month. Treatment proved remarkably effective in that it brought about complete regression of acne in 30%, improvement in 65% of the patients. The drug was always well tolerated, side effects were never observed.

Acne Vulgaris↗
PubMedDate not supplied

Spironolactone metabolism in target tissues. Characteristics of deacetylation in kidney, liver, adrenal cortex, and testes.

Prior investigations demonstrated that many of the actions of spironolactone (SL) required deacetylation of the parent compound as the first step in the formation of biologically active metabolites. Studies were done to characterize the process of deacetylation in several target tissues. The reaction was catalyzed by microsomal and cytosolic fractions of livers, kidneys, adrenal glands, and testes. Microsomal activity was greatest in liver and kidney and far exceeded cytosolic metabolism in those tissues. In adrenal glands and testes, by contrast, deacetylation was greater in cytosolic than microsomal fractions. The metabolism-mediated destruction of adrenal microsomal cytochromes P-450 by SL was enhanced by coincubation of microsomes with cytosol, illustrating the potential importance of combined microsomal and cytosolic metabolism in the actions of SL. The deacetylation of SL was decreased by various esterase inhibitors; the organophosphate compounds were the most potent inhibitors. The effectiveness of the esterase inhibitors varied from tissue to tissue, as well as from microsomes to cytosol within each tissue. The results indicate that SL deacetylation is catalyzed by microsomal and cytosolic esterases in various target tissues; several isozymes appear to be involved. These and prior observations suggest that tissue metabolism of SL is of major importance in the actions of the drug.

Adrenal Cortex↗
PubMedDate not supplied

In vitro digitoxin metabolism. Rate-limiting step and alteration following spironolactone pretreatment.

The biotransformation of digitoxin was considered as a linear transformation comprised of dual deoxy sugar cleavages culminating with product conjugation to glucuronic acid. Digitoxin and two metabolites, digitoxigenin bisdigitoxoside and digitoxigenin monodigitoxoside, were each incubated for 1 hr with rat liver slices. Measurements of amounts of various metabolites allowed determination of rate constants, showing the cleavage of the terminal sugar from digitoxigenin bisdigitoxoside to be the rate-limiting step. The inductive action of spironolactone predominately affected the rate-limiting step.

Animals↗
PubMed1988

Effect of spironolactone on the renin-aldosterone system in rats.

PRA, PRC and the plasma concentration of aldosterone (Aldo) were measured in rats (Sp-rats) receiving a daily sc injection of Spironolactone, (Sp, 20 mg in olive oil) and in control rats (C-rats) receiving olive oil only. Animals were studied one day after starting treatment, 5 days on treatment or after 5 weeks on the study. PRA, PRC and Aldo were significantly increased in Sp-rats as compared to C-rats throughout all the study. In additional Sp-rats and C-rats, the urine volume, serum Na+ and K+ concentration, Na+ and K+ intake and the urinary excretion of Na+, K+ and aldosterone-18-glucuronide (UAldV) were serially measured during 5 weeks. The total radioactivity plasma clearance after an i.v. bolus injection of 3H-aldosterone was subsequently measured in (5 Sp-rats and 5 C-rats). No significant differences in serum Na+ and K+ concentration and in Na+ and K+ balance were observed between Sp-rats and C-rats. UAldV was significantly higher in Sp-rats than in C-rats during all the study. After 5 weeks on treatment the total radioactivity plasma clearance was significantly higher in Sp-rats than in C-rats. These results indicate that Sp, at high dosage, stimulates renin release and aldosterone secretion by a mechanism unrelated to alterations in Na+ and K+ balance.

Aldosterone↗
PubMed1987

Influence of uridine diphosphoglucuronic acid on bilirubin glucuronidation in liver microsomes from normal and spironolactone-treated rats.

The formation of bilirubin glucuronides was studied using liver microsomes from normal and spironolactone (SP)-treated rats. Increasing amounts of uridine diphosphoglucuronic acid (UDPGA) were added to the incubation mixture to investigate the influence of this nucleotide on bilirubin glucuronidation. The results demonstrated that microsomal preparations from SP-treated rats had a greater capability for bilirubin glucuronidation than normal microsomes which was mostly produced at the expense of bilirubin diglucuronide (BDG) formation. On the other hand, the increase in UDPGA concentration in the incubation mixture also produced an increase of BDG formation which was more important than that of monoglucuronide. These results support the hypothesis of different subunits in the glucuronyl-transferase moiety with different substrate specificities. In addition, the inducer effect of SP on bilirubin glucuronidation is in agreement to the results obtained in living rats which were described previously.

Animals↗
PubMed1985

Spironolactone in combination drug therapy for unresponsive hirsutism.

Clinical and laboratory evaluations of nine hirsute women were performed for determination the efficacy of combination drug therapy. Each patient had previously failed to respond to single drug therapy with oral contraceptives (OC), dexamethasone (DEX), or spironolactone (S) and received S (100 to 150 mg) and either an OC (mestranol, 0.05 to 0.08 mg, and norethindrone, 1 mg) or DEX (0.5 mg) daily. Total testosterone, dehydroepiandrosterone sulfate, free testosterone, and sex-hormone-binding globulin were measured before therapy and 4 to 6 weeks after initiation of therapy and were compared with the responses to OC (n = 7), DEX (n = 8), and S (n = 6). A satisfactory clinical response in the rate of hair growth was defined as at least a doubling of the time interval between adjunctive therapies (electrolysis, shaving, or bleaching) and patient satisfaction with treatment. The responses of the androgenic parameters were not statistically different between combination and single drug therapy. Although all patients noted a subjective improvement in hair growth, eight of nine fulfilled the criteria for a clinical response (P less than 0.001). Transient diuresis was the only side effect noted. The study suggests that combination drug therapy is an efficacious and well-tolerated approach to the management of unresponsive hirsutism.

Contraceptives, Oral↗
PubMed1987

Effect of spironolactone on premenstrual syndrome symptoms.

The premenstrual syndrome (PMS) has long been considered one in which fluid retention plays an important role. Detailed studies, however, have failed to reveal good evidence for this assumption, and investigations of weight change and of sodium and water balance have yielded contradictory results. Even so, a number of the etiologic theories and treatment regimens are based on this premise. Many of the endocrine theories depend on the endocrine effect on water balance to explain the mechanism, and the treatment often proposed involves salt and water restriction and the liberal use of diuretics. There is no justification for this advice except for a few well-conducted studies that showed the benefits of diuretic therapy. The evidence from these studies suggests that diuretics, especially spironolactone, have a particular role in the management of the PMS symptoms of bloatedness and abdominal distension despite the fact that the underlying water retention theory remains in doubt. An improvement in the various psychologic symptoms of PMS has also been reported.

Adult↗
PubMed1987

Spironolactone in the treatment of hirsutism.

Clinical and laboratory studies were performed in 18 hirsute women for evaluation of the efficacy of spironolactone (S) therapy. Each patient received S 100 mg daily. The grade of hirsutism was assessed using a semiquantitative scale of Ferriman and Gallwey. Total testosterone, androstendione, dehydroepiandrosterone sulphate and sexhormone binding globulin were measured before initiation and after six months of therapy. A clinical response was seen in 12 women. The total score of hirsutism in the whole patient group was decreased from 14.1 +/- 6.3 (mean +/- S.D.) to 11.8 +/- 6.4 (p less than 0.01). No changes were found in the hormonal values. The findings of the present study confirm the efficacy of S in decreasing the hair growth by mainly a peripheral mode of action.

Adult↗
PubMed1977

Antihypertensive effect and serum potassium homeostasis: comparison of hydrochlorothiazide and spironolactone alone and in combination.

Hydrochlorothiazide (HCT) and spironolactone (SP), alone and in combination, were utilized in the treatment of 79 adult men with mild to moderate essential hypertension. Comparative effects were determined with regard to anti-hypertensive action, serum potassium homeostasis and BUN. Both HCT and SP, alone and in combination, produced significant anti-hypertensive effects. Anti-hypertensive response to SP was clearly dose-related. All medications produced a moderate and transient elevation of BUN. The most marked differences were observed with regard to serum potassium levels (K). HCT produced a marked decrease in K which persisted through 12 weeks of therapy. SP produced moderate dose-related elevations of K which reverted toward baseline levels between the 4th and 12th weeks of treatment. The "safety advantage" of SP is discussed relative to its role in producing K homeostasis due to its unique mechanism of action.

Adult↗
PubMed1987

Biochemical and morphometric analysis of the effect of spironolactone on the livers from immature and adult rats.

Biochemical and morphometric studies were carried out to characterize the effect of spironolactone (SP) on liver tissue from immature and adult young rats: 1. The SP produced an increase in total protein in all the groups. 2. Hypertrophy in 24 days-old rats. 3. Hypertrophy and hyperplasia in 48 days-old rats. 4. The morphometric studies were correlated to the biochemical parameters.

Aging↗
PubMed1987

In vivo interaction of spironolactone and phenobarbital with cholesterol; effect on cholesterol organ concentration.

In this work, the effect of pretreatment with spironolactone or phenobarbital on female Wistar rats after a chronic administration of cholesterol, upon the cholesterol concentration in blood, brain and liver was examined. It was found that the pretreatment reduced cholesterol in all tissues in the order, brain - plasma - liver. The findings were attributed to an increased biodegradation and disposition of cholesterol. It could also be concluded that after the pretreatment we may have a predominance of the catabolic and/or the disposition rather than of the synthetic and/or absorption processes for the steroid.

Animals↗
PubMed1986

The effect of spironolactone on the cardiocirculatory responses to upright tilt at sea level and at simulated high altitude.

The objective of this study was to determine if spironolactone (S) alters the cardiocirculatory responses to upright tilt at sea level (SL;50 m) and during 44 h of simulated altitude (HA;4,600 m). In a double-blind, crossover-designed study, 9 male subjects (age range: 18-25 years) received 25 mg orally, four times per day of either S or an identically-appearing placebo (P) 2 d prior to and during HA. The crossover was separated by 2 weeks. Heart rate, stroke volume, cardiac output, calf blood flow, total peripheral resistance and systemic blood pressure were obtained during supine rest and after 10 min of 60 degrees head-up tilt using an impedance monitor and an electro-sphygmomanometer. The 24-h determinations of urinary volume, sodium and potassium as well as venous plasma values for sodium, potassium and chloride were obtained daily. There were no statistically significant differences between P and S treatment periods for: caloric, electrolytes or fluid ingestion; urinary volume or electrolytes; plasma electrolytes; or any of the cardiocirculatory parameters measured in the supine or upright position at SL or during HA. It was concluded that S did not induce a significant diuresis or significantly alter vascular responsiveness to negatively effect the normal cardiocirculatory responses to upright tilt at sea level or simulated high altitude.

Adult↗
PubMed1986

Metabolism of spironolactone by adrenocortical and hepatic microsomes: relationship to cytochrome P-450 destruction.

Previous investigations have established that spironolactone (SL) is converted to a reactive metabolite by adrenocortical NADPH-dependent enzymes, resulting in the destruction of microsomal cytochrome(s) P-450 and decreases in steroid hydroxylase activities. Hepatic microsomes, by contrast, do not activate SL. Studies were done to characterize the activation pathway by comparing adrenal with hepatic metabolism of SL in guinea pigs. In the absence of NADPH, both adrenal and hepatic microsomal preparations converted SL to its deacetylated metabolite, 7 alpha-thio-SL. NADPH had no effect on hepatic SL metabolism but stimulated adrenal metabolism of SL. In the presence of NADPH, very little 7 alpha-thio-SL was recovered from the adrenal incubations, suggesting that the 7 alpha-thio-SL was further metabolized by NADPH-dependent enzymes. The latter hypothesis was confirmed by incubating microsomal preparations with 7 alpha-thio-SL as the substrate. In the presence of NADPH, 7 alpha-thio-SL was rapidly metabolized by adrenal microsomes but was not metabolized by hepatic preparations. Under the same incubation conditions, 7 alpha-thio-SL promoted the destruction of adrenal cytochrome(s) P-450 but had no effect on hepatic monooxygenases. 7 alpha-Thio-SL was far more potent than SL in promoting the destruction of cytochrome(s) P-450, suggesting that the metabolite might be an intermediate in the actions of the parent compound. Indeed, inhibition of SL conversion to 7 alpha-thio-SL by the esterase inhibitor, diethyl p-nitrophenyl phosphate blocked the effects of SL on adrenal cytochrome(s) P-450. Diethyl p-nitrophenyl phosphate did not affect the actions of 7 alpha-thio-SL on cytochrome(s) P-450.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗
PubMed1979

Long-term use of propranolol, ibuprofen, and spironolactone in the management of Bartter's syndrome.

This report concerns two patients with Bartter's syndrome who were treated with propranolol, spironolactone, and potassium supplements. When ibuprofen was added to this regimen, potassium supplements were no longer required. In both patients, plasma renin activity decreased, plasma volumes increased, and a "catch-up" in linear growth ensued. This report confirms others that indicate prostaglandin synthetase inhibitors are a useful adjunct in the therapy of Bartter's syndrome.

Adolescent↗
PubMed1979

Canrenoate--a spironolactone metabolite. Acute cardiac effects in digitalized patients.

Canrenoate (Soldactone)--a spironolactone metabolite for intravenous use--has recently been suggested as a specific antidote in patients suffering from digitalis intoxication. Theoretically, this would imply that canrenoate could counteract the effect of digoxin. The influence of canrenoate on inotropy in 12 digitalized patients was investigated by measurement of sytolic time intervals. Canrenoate improved the left ventricular contractility, since both preejection period (PEP) and the ratio between PEP and left ventricular ejection time (PEP/LVET) decreased significantly. The maximal changes in controlled atrial fibrillation, canrenoate had no effect on ventricular rate, whereas atropine increased the ventricular rate significantly.

Aged↗