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| __NOTOC__
| | #REDIRECT [[Spironolactone#Pharmacology]] |
| {{drugbox
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| | IUPAC_name = 7α-Acetylthio-3-oxo-17α-pregn-4-ene-21,17-carbolactone
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| | image = Spironolactone structure.png
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| | CAS_number = 52-01-7
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| | ATC_prefix = C03
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| | ATC_suffix = DA01
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| | ATC_supplemental =
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| | PubChem = 5833
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| | DrugBank = APRD01234
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| | synonyms = Aldactone<br>Spirotone<br>Spirolactone
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| | smiles = CC(=O)SC1CC2=CC(=O)CCC2(C3C1C4CCC5(C4(CC3)C)CCC(=O)O5)C
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| | C=24 | H=32 | O=4 | S=1
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| | molecular_weight = 416.574 g/mol
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| | bioavailability =
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| | protein_bound =
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| | metabolism = [[Liver|Hepatic]]
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| | elimination_half-life = 10 minutes
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| | excretion = [[Urine]], [[bile]]
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| | pregnancy_AU = B3
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| | pregnancy_US = C
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| | legal_UK = POM
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| | routes_of_administration = Oral
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| }}
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| {{SI}}
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| {{CMG}}
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| {{Editor Join}}
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| '''''For patient information, click [[Spironolactone (patient information)|here]]
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| '''''
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| <br>
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| '''Spironolactone''' (marketed under the trade names '''Aldactone''', '''Novo-Spiroton''', '''Spiractin''', '''Spirotone''', '''Verospiron''' or '''Berlactone''') is a [[diuretic]] and is used as an [[antiandrogen]].
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| It is a synthetic 17-[[lactone]] drug which is a renal competitive [[aldosterone]] antagonist in a class of [[pharmaceutical]]s called [[potassium-sparing diuretic]]s, used primarily to treat [[ascites]] in patients with liver disease, low-[[renin]] [[hypertension]], [[hypokalemia]], and [[Conn's syndrome]] as well as high blood pressure. On its own, spironolactone is only a weak diuretic, but it can be combined with other diuretics. About one person in one hundred with hypertension has elevated levels of aldosterone; in these persons the antihypertensive effect of spironolactone may exceed that of complex combined regimens of other antihypertensives. Due to its anti-[[androgen]] effect, it can also be used to treat [[hirsutism]], and is a common component in [[Hormone replacement therapy (trans)|hormone therapy]] for male-to-female [[Transwoman|transsexual]] and [[transgender]]ed people. It is also used for treating [[Alopecia|hair loss]] and [[acne]] in women and can be used as a [[topical]] medication for treatment of male hairloss.
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| ==Mechanism of action==
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| Spironolactone inhibits the effect of aldosterone by competing for intracellular [[Mineralocorticoid receptor|aldosterone receptor]] in the [[distal convoluted tubule|distal tubule]] cells. This increases the secretion of water and [[sodium]], while decreasing the excretion of potassium. Spironolactone has a fairly slow onset of action, taking several days to develop and similarly the effect diminishes slowly. Spironolactone has anti-androgen activity by binding to the [[androgen receptor]] and thus preventing it to interact with [[dihydrotestosterone]].<ref>{{cite journal | last = Berardesca | first = E | authorlink = | coauthors = Gabba P, Ucci G, Borroni G, Rabbiosi G. | title = Topical spironolactone inhibits dihydrotestosterone receptors in human sebaceous glands: an autoradiographic study in subjects with acne vulgaris. | journal = Int J Tissue React. | volume = 10 | issue = 2 | pages = 115-119 | publisher | date = 1988 | url = http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2972662&dopt=Abstract | id = PMID 2972662 }}</ref>
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| ==Pharmacokinetics==
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| Spironolactone is fairly rapidly absorbed from the gastrointestinal tract. It is also rapidly metabolised and bound in plasma proteins. Many of its metabolites are also active and one of them, canrenone as potassium canrenoate, is used parenterally when rapid effect is needed. Spironolactone's half-life is 85 minutes, but canrenone's half-life is 10 to 35 hours, depending on the dose. The main elimination route is in the urine and some also in the bile.
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| ==Mortality and morbidity benefit in severe heart failure==
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| Spironolactone was shown to have a significant [[death|mortality]] and [[morbidity]] benefit in the Randomized Aldactone Evaluation Study (RALES), which studied people with severe [[Heart failure|congestive heart failure]] ([[New York Heart Association Functional Classification|New York Heart Association functional class]] III or IV).<ref>{{cite journal | author = Pitt B, Zannad F, Remme W, Cody R, Castaigne A, Perez A, Palensky J, Wittes J | title = The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. | journal = N Engl J Med | volume = 341 | issue = 10 | pages = 709-17 | year = 1999 | url= http://content.nejm.org/cgi/content/full/341/10/709 | id = PMID 10471456}}</ref> Patients in the study arm of the trial (those receiving spironolactone) had a [[relative risk]] of death (when compared to the placebo group) equal to 0.70 or a 30% [[relative risk reduction]]. Patients in the study arm also had significantly less symptoms of [[Heart failure|CHF]] and were hospitalized less frequently.
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| ==Adverse effects and interactions==
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| Following the publication of the RALES study, there was an increase in the incidence of hyperkalemia, particularly among those patients treated concomitantly with [[ACE inhibitors]]<ref name="pmid15295047">{{cite journal | author = Juurlink DN, Mamdani MM, Lee DS, ''et al.'' | title = Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study | journal = [[The New England Journal of Medicine]] | volume = 351 | issue = 6 | pages = 543–51 | year = 2004 | month = August | pmid = 15295047 | doi = 10.1056/NEJMoa040135 | url = | issn = | accessdate = 2011-02-22}}</ref>.
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| Spironolactone is associated with an increased risk of bleeding from the [[stomach]] and [[duodenum]], but a causal relationship between the two has not been established.<ref>{{cite journal | title=Spironolactone and risk of upper gastrointestinal events: population based case-control study | journal=Brit Med J | year=2006 | author=Verhamme KMC, Mosis G, Dieleman JP, ''et al.'' | volume=333 | issue=7563 | pages=330–3 | doi=10.1136/bmj.38883.479549.2F }}</ref> Since it also affects steroid receptors elsewhere in the body, it can cause [[gynecomastia]], menstrual irregularities and testicular atrophy. Other side effects include [[ataxia]], [[erectile dysfunction]], drowsiness and rashes. A [[carcinogen]]ic effect has been demonstrated in rats. Spironolactone has been shown to be immunosuppressive in the treatment of [[sarcoidosis]].<ref>{{cite journal | title = Aldactone in the treatment of sarcoidosis of the lungs | journal=JZ Erkr Atmungsorgane. | year=1977 | author=Wandelt-Freerksen E. | volume=149(1) | pages=156-9 | url = http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=607621&query_hl=22&itool=pubmed_DocSum | id = PMID 607621 }}</ref>
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| People using this drug should avoid salt substitutes containing potassium.<ref>{{cite web | title = Advisory Statement | publisher = Klinge Chemicals / LoSalt | url = http://www.losalt.com/docs/lo_salt_web_advice.pdf | format = pdf}}</ref>
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| ==Carcinogenicity==
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| Studies of spironolactone and the related compound [[potassium canrenoate]] (which, like spironolactone, metabolizes to [[canrenone]]) in rats for one to two year periods show an increase in carcinogenesis in the thyroid gland, testes, liver, breasts, and myelocytic leukocytes. Mammalian cells, depending on the presence of metabolic activation, show mixed results for mutagenicity ''in vitro''.<ref>{{cite web | title = Spironolactone RX Monograph | publisher = Sandoz Inc. | url = http://dailymed.nlm.nih.gov/dailymed/fdaDrugXsl.cfm?id=2479&type=display | format = html}}</ref> In light of this research, Sandoz has recommended that unnecessary use of spironolactone be avoided.
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| ==See also==
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| *[[Baldness treatments]]
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| ==References==
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| {{Reflist|2}}
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| ==External links==
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| *[http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682627.html nih.gov information site]
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| *[http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/ald1010.shtml Aldactone patient info leaflet]
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| {{Antihypertensives and diuretics}}
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| {{Sex hormones}}
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| {{SIB}}
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| [[Category:Aldosterone antagonists]]
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| [[Category:Antiandrogens]]
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| [[Category:Lactones]]
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| [[Category:Hair loss]]
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| [[Category:Drugs]]
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| [[Category:Endocrinology]]
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| [[ja:スピロノラクトン]]
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