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PubMed1976

Failure of aspirin to antagonize the antihypertensive effect of spironolactone in low-renin hypertension.

Aspirin has been shown to acutely block the natriuretic effect of spironolactone in the mineralocorticoid-treated normal rat, dog, and man. It has been suggested that aspirin is contraindicated in hypertensive patients receiving spironolactone. Five patients with low-renin essential hypertension and two with hypertension due to primary aldosteronism, all of whom have normalized their blood pressure on chronic spironolactone therapy, were cotreated in a double-blind fashion with either aspirin or aspirin-placebo during alternate six-week periods. Aspirin did not appear to alter the effect of spironolactone on blood pressure, serum electrolytes, urea nitrogen, or plasma renin activity.

Adult↗

PubMed1987

Spironolactone as a source of interference in commercial digoxin immunoassays.

Eight commercial digoxin immunoassay methods were tested in 17 subjects taking spironolactone (but not digoxin) to evaluate cross-reactivity from parent drug and/or metabolites. Four of these methods showed significant (up to 1.9 nmol/L) and variable "apparent digoxin" concentrations, despite the absence of digoxin in the drug regimen. The results suggest that clinical laboratories require a knowledge of their method with respect to spironolactone-related cross-reactivity and should exercise caution when interpreting digoxin results where spironolactone is coadministered. Further, the presence of concurrent renal and/or hepatic impairment could delay clearance of spironolactone metabolites (as well as digoxin metabolites and endogenous substances) and further distort a genuine digoxin result.

Adult↗

PubMed1990

Influence of spironolactone and its metabolite canrenone on serum digoxin assays.

Although current immunoassay kits for digoxin supposedly have antibodies of high specificity, serum digoxin levels in patients taking spironolactone suggest that spironolactone interferes with the determination. In vitro determinations of digoxin performed on blank serum spiked with spironolactone and its metabolite canrenone showed that contrary to the belief gained from reading the manuals of some diagnostic immunoassay kits, spironolactone significantly influences digoxin determinations.

Canrenone↗

PubMed2003

A new turbidometric digoxin immunoassay on the ADVIA 1650 analyzer is free from interference by spironolactone, potassium canrenoate, and their common metabolite canrenone.

Spironolactone and potassium canrenoate (aldosterone antagonist diuretics) are often used with digoxin in clinical practice. It has been well documented in the literature that spironolactone, potassium canrenoate, and their common metabolite canrenone cross-react with the fluorescence polarization immunoassay (FPIA) for digoxin and falsely elevate measured serum digoxin concentrations. Recently a new turbidometric assay for digoxin became commercially available from Bayer Diagnostic for application on the ADVIA 1650 Chemistry analyzer. We studied the potential interference of these compounds in this new digoxin assay. Aliquots of drug-free serum were supplemented with therapeutic and above-therapeutic concentrations of spironolactone, canrenone, and potassium canrenoate, and apparent digoxin concentrations were measured. We observed apparent digoxin concentrations with the FPIA digoxin assay as expected but observed no apparent digoxin levels with the new turbidometric immunoassay. When serum pools prepared from patients receiving digoxin were supplemented with these compounds in concentrations expected in serum in patients receiving these medications, we observed falsely elevated digoxin levels with the FPIA digoxin assay, but no statistically significant change was observed with the new turbidometric assay. We conclude that the new turbidometric assay for digoxin is free from interference by spironolactone, potassium canrenoate, and their common metabolite canrenone.

Canrenoic Acid↗

PubMed1982

Inhibition of sebaceous gland activity by spironolactone in Syrian hamster.

In the animal model of the Syrian hamster the antiandrogenic action of spironolactone on the sebaceous glands of the ventral side of the pinna was examined. Spironolactone reduces both labeling index and cross-sectional surface area of sebaceous glands significantly in a dose-dependent manner. Equally there was a significant decrease in serum testosterone levels in spironolactone treated animals. Our results seem to justify clinical studies with spironolactone in patients with hirsutism, seborrhea, and possibly acne vulgaris.

Animals↗

PubMed1979

A comparison of some extra-renal effects of spironolactone and canrenone.

1 Measurement of changes in trans-mural rectal potential difference (t.m.r.p.d.) and plasma aldosterone levels have been used in a comparison of the extra-renal activities of spironolactone and its major metabolite canrenone. 2 A characteristic pressure artifact was observed during measurement of t.m.r.p.d. When pressure artifacts were eliminated, there was a log-linear relationship between increasing doses of intravenous aldosterone and maximum increase in t.m.r.p.d. 3 Pre-treatment for 5 days with spironolactone or canrenone produced a similar attenuation of the increase in t.m.r.p.d. produced by infused aldosterone, suggesting that canrenone is the active metabolite of spironolactone in the rectum. This is in contrast to the significantly greater renal activity of spironolactone that has been demonstrated after a similar treatment period. Neither antagonist treatment produced significant changes in pre-infusion plasma aldosterone concentrations. 4 The need for assay of the extra-renal activities of aldosterone antagonists in the assessment of their therapeutic potential is discussed.

Aldosterone↗

PubMed1982

Spironolactone dose-response relationships in healthy subjects.

1 The effect of single oral doses of spironolactone 25 mg, 50 mg, 100 mg, 200 mg, 400 mg, and placebo in reversing the urinary electrolyte changes induced by fludrocortisone between 2-10 h and 12-16 h after treatment was examined in healthy subjects. 2 In the two collection periods, there were statistically significant log linear dose-response relationships for sodium excretion (P less than 0.001), potassium excretion (P less than 0.001 and P less than 0.025 respectively) and log10 10 Na/K (P less than 0.001). 3 However, there was evidence that the log spironolactone dose-urinary sodium responses did not increase monotonically, while the relationship for urinary potassium appeared to enter the lower 'plateau' at doses between 100 mg and 200 mg, and when compared to placebo values, potassium excretion was not significantly depressed 12-16 h after treatment (P greater than 0.1). Thus, sodium and potassium responses were dissociated in dose producing maximal effect and in duration of activity, reinforcing the view that functions or the urinary sodium/potassium ratio alone cannot be considered an adequate description of renal antimineralocorticoid activity. 4 Dose-response relationships for all urinary electrolyte variables seem consistently steep and linear between 25 mg and 100 mg of spironolactone, suggesting that, in studies employing this model, the doses of spironolactone should be restricted to this range.

Adult↗

PubMed1982

Relative potency of spironolactone, triamterene and potassium chloride in thiazide-induced hypokalaemia.

1 The influence of spironolactone 50 mg and 100 mg daily, triamterene 100 mg and 200 mg daily, potassium chloride 32 mmol and 64 mmol daily and placebo on plasma potassium and other variables was examined in a random crossover study of nine hypertensive patients taking bendrofluazide 10 mg daily. 2 Spironolactone and triamterene had significant and parallel dose-response curves for plasma potassium, with a relative potency for triamterene:spironolactone of 0.25:1, significantly lower than the accepted 0.5:1 ratio. These drugs also lowered serum sodium, bicarbonate and body weight, and increased serum urea and creatinine. 3 Potassium chloride increased plasma potassium above placebo values, but the dose-response was not significant and was not parallel with those of the potassium-sparing drugs. Seven of nine patients remained hypokalaemic despite treatment with 64 mmol potassium chloride daily. 4 The relative expense, convenience and toxicity of the potassium-sparing drugs should be assessed at equivalent doses, namely spironolactone 50 mg:triamterene 200 mg:amiloride 20 mg. Potassium chloride does not correct moderate diuretic-induced hypokalaemia even at doses of 64 mmol daily.

Adult↗

PubMed2005

Spironolactone reduces brachial pulse wave velocity and PIIINP levels in hypertensive diabetic patients.

AIMS: To assess whether spironolactone has beneficial effects on blood pressure (BP), N-terminal propeptide of type III procollagen (PIIINP) and pulse wave velocity (PWV) in hypertensive, type II diabetics. METHODS: Ten patients with type II diabetes and hypertension were enrolled in a randomized, double-blind crossover study comparing 4 months' treatment with spironolactone and placebo with a 4-week washout phase. BP, PIIINP and carotid-radial PWV were measured at the end of each treatment phase. RESULTS: Compared with placebo, spironolactone reduced systolic BP by 15.6 +/- 46.1 mmHg (P = 0.005, 95% CI 2.7-28.5 mmHg), PIIINP by 0.6 +/- 0.3 microg l(-1) (P = 0.04, 95% CI 0.02-1.1 microg l(-1)) and PWV by 0.6 +/- 0.2 m s(-1) (P = 0.008, 95% CI 0.18-1.02 m s(-1)). CONCLUSIONS: Spironolactone is effective at reducing systolic BP and brachial artery stiffness as indicated by PWV. It also reduces PIIINP in type II diabetic patients with hypertension.

Aged↗

PubMed1978

Endocrine effects of spironolactone in man.

A double blind, controlled study was carried out in order to investigate the effects of administering spironolactone, 200 mg daily, to five healthy male volunteers. The patterns of change in plasma testosterone (T) and luteinizing hormone (LH) after spironolactone were significantly different from placebo and there were significant increases in the urinary excretion of androsterone (A), aetiocholanolone (EC) and total oestrogen. Urinary dehydroepiandrosterone (DHA) excretion, after an initial rise, declined progressively during the treatment period relative to controls. The results are discussed in the light of previous observations. It is concluded that treatment with spironolactone for 2--4 days will lead to a transient rise in plasma T and urinary DHA. Continued treatment (4--10 days) is thought to cause increased LH secretion, with normalization of plasma T and DHA excretion. These changes are accompanied by increased androgen catabolism and a slightly increased conversion of androgens to oestrogens. Healthy men may therefore show alterations in sex steroid metabolism if treated for several days with high doses of spironolactone.

17-Ketosteroids↗

PubMed2004

Differences in the determinants of eplerenone, spironolactone and aldosterone binding to the mineralocorticoid receptor.

The importance of mineralocorticoid receptor (MR) antagonists in the treatment of cardiovascular disease has been emphasised by two recent clinical trials, one using spironolactone and the other using a new selective MR antagonist, namely eplerenone. Eplerenone has a very low affinity for the glucocorticoid receptor (GR). Determinants of binding specificity of eplerenone to the MR were investigated using chimeras created between the ligand-binding domains (LBD) of the MR and the GR. These chimeras had been used previously to investigate aldosterone and spironolactone binding specificity to the MR. Eplerenone competed strongly for [(3)H]-dexamethasone binding to a MR/GR chimera containing amino acids 804-874 of the MR and weakly to a chimera containing amino acids 672-803 of the MR. Within the 804-874 region, eplerenone competed for [(3)H]-dexamethasone binding to a chimera containing amino acids 820-844 of the MR, although the calculated affinity was approximately 10-fold lower than for binding to the full-length MR LBD. Similar results were obtained using another MR antagonist, namely spironolactone. Modelling of eplerenone binding to the MR LBD, based on the GR LBD crystal structure, suggests that amino acids 820-844 affect the overall shape of the ligand-binding pocket and that eplerenone acts as an MR antagonist because it fails to stabilize the active conformation of the receptor. In contrast with results with the MR antagonists eplerenone and spironolactone, amino acids 820-844 are sufficient in themselves to confer high-affinity aldosterone binding to the MR, suggesting that the binding determinants of the two antagonists are similar to each other but differ from those of aldosterone.

Aldosterone↗

PubMed2005

Effects and side-effects of spironolactone therapy in women with acne.

BACKGROUND AND AIMS: Androgen hormones play an important role in the pathogenesis of acne. Despite the demonstrated effects, spironolactone, an androgen receptor blocker, is not commonly used to treat acne. We planned an open-labelled, prospective study to evaluate the effects and side-effects of spironolactone therapy in women with acne. MATERIALS AND METHODS: Thirty-five consecutive patients with acne were treated with spironolactone 100 mg/day, 16 days each month for 3 months. The patients were divided according to the clinical severity of the lesions as having mild, moderate and severe acne. Serum total testosterone and dehydroepiandrosterone sulfate (DHEAS) levels were measured before and after treatment. Lesion numbers and hormone levels before and after treatment were compared with one-sampled t-test. RESULTS: The mean age of the patients was 21.4 +/- 3.5 years. Two patients discontinued the study due to side-effects. Five patients were lost in the follow-up. Clinically significant improvement was noted in 24 patients (85.71%). No response was seen in four patients. All of the nonresponding patients had received previous unsuccessful therapies. Mean number of lesions and mean DHEAS levels of the 24 patients with clinical improvement decreased significantly after treatment (P < 0.01 and P < 0.05, respectively). There was no change in the mean total testosterone levels before and after treatment (P > 0.05). CONCLUSION: Spironolactone is a safe and effective medication for women with acne vulgaris. Although its side-effects seem to be high, they are in the majority of cases not a reason to stop treatment.

Acne Vulgaris↗

PubMed1969

Effect of spironolactone and norbolethone on the toxicity of digitalis compounds in the rat.

1. In the rat, both spironolactone (an antimineralocorticoid) and norbolethone (an anabolic steroid) inhibit the characteristic neuromuscular disturbances and the mortality produced by digitoxin, gitalin, proscillaridin, digoxin and digitalin. The corresponding effects of strophanthin K, ouabain and digitoxigenin could not be prevented.2. It may be concluded that, in our experimental conditions, both spironolactone and norbolethone counteract the toxicity of some, but not all, digitalis compounds tested and that both the protective steroids affect the toxicity of the same digitalis derivatives.3. This antidigitalis effect is not merely a secondary consequence of either antimineralocorticoid or anabolic potency because spironolactone lacks anabolic and norbolethone lacks antimineralocorticoid properties. Indeed, it appears that the ability to antagonize the toxicity of digitalis compounds represents a pharmacological property independent of all known steroid hormone actions, since spironolactone is virtually devoid of these.

Anabolic Agents↗

PubMed1991

Premenstrual syndrome and spironolactone.

A double blind placebo controlled randomized cross over study was conducted to assess the response to spironolactone by patients suffering from 'Premenstrual Syndrome'. Somatic and neuropsychiatric symptoms were self-assessed daily and a total score was calculated for each symptom for the 14 days prior to menstruation. No significant difference was noted for the symptoms assessed on or off spironolactone. The levels of oestradiol, progesterone and prolactin showed no changes from the first to the second half of the cycle. In those patients who did respond to spironolactone, a significant difference in androgen levels from the follicular to the luteal phase of the cycle prior to treatment was demonstrated. Significant differences in androgen levels from the follicular to the luteal phase of the menstrual cycle may therefore be an important determinant in predicting those patients with premenstrual syndrome likely to respond to spironolactone therapy.

Androgens↗

PubMed1976

Spironolactone in essential hypertension: evidence against its effect through mineralocorticoid antagonism.

The effect of a six-week course of spironolactone 300 mg/day was examined in 25 unselected patients with essential hypertension. In the blood spironolactone produced a significant rise in urea and potassium concentrations and a fall in sodium and bicarbonate concentrations. In six patients blood pressure was normal at the end of the course, while in five patients there was almost no change. Studies of the effects of spironolactone on various indices usually affected by mineralocorticoids-namely, blood electrolytes, total body potassium, and rectal electrical properties-showed no differences between responding and non-responding patients. Mineralocorticoid excess therefore seems to be rarely responsible for essential hypertension and the influence of spironolactone cannot at present be fully explained.

Adult↗

PubMed2001

Serious adverse events experienced by patients with chronic heart failure taking spironolactone.

In patients with chronic heart failure, spironolactone added to conventional treatment may lead to serious and, occasionally, fatal hyperkalaemia. In some cases this seems to happen because spironolactone causes diarrhoea. Four cases involving men with New York Heart Association functional class III heart failure are presented. As these cases revealed, close monitoring of blood chemistry is mandatory after starting spironolactone, and patients should be advised to stop spironolactone immediately if diarrhoea develops.

Aged↗

PubMed1973

Fine structure and morphogenesis of spironolactone bodies in the zona glomerulosa of the human adrenal cortex.

Numerous spironolactone bodies have been detected in the zona glomerulosa cells of the adrenal cortex of a 36-year-old spironolactone-treated woman whose non-tumorous right adrenal gland was removed surgically because of primary hyperaldosteronism. Electron microscopy revealed spherical laminated whorls which consisted of a central core composed of an amorphous electron-dense material surrounded by numerous smooth-walled concentric membranes. Continuous with and deriving from the endoplasmic reticulum, they were present in viable cells and were not associated with ultrastructural features indicating cellular injury. Cytoplasmic inclusions similar to spironolactone bodies can be detected in other organs after the administration of various compounds. Thus, they can be regarded as neither specific to spironolactone treatment nor exclusively inducible in the zona glomerulosa of the adrenal cortex.

Adrenal Glands↗

PubMed1989

Lack of effect of spironolactone on hair shaft diameter in hirsute females.

Because of its anti-androgenic activity spironolactone 50-200 mg daily is advocated widely for the management of female hirsutism but this practice lacks adequately controlled experimental support. In a double-blind placebo controlled study of the efficacy of spironolactone 100 mg daily in idiopathic hirsutism we were unable to demonstrate objective benefit from spironolactone treatment. The mean effect of spironolactone given over a 9 month period was to increase hair shaft diameter by +15% with 95% CI (-0.4% to +29%). In addition there were no changes in circulating serum androgen concentrations.

Androgens↗