Spironolactone: Difference between revisions

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{{Image|Spironolactone DEVolk.jpg|right|150px|Spironolactone, an aldosterone antagonist.}}
'''Spironolactone''' is an [[aldosterone]] antagonist used to treat [[edema]] associated with congestive [[heart failure]], [[nephrotic syndrome]] or [[ascites]] from hepatic [[cirrhosis]].  Although it can also be used treat [[hirsutism]] and [[acne]] by effecting the [[endocrine system]], such use can lead to adverse side effects. It is also used to treat [[hypertension]].
Its IUPAC name is S-[(7R,8R,9S,10R,13S,14S,17R)-10,13-dimethyl-3,5'-dioxospiro[2,6,7,8,9,11,12,14,15,
16-decahydro-1H-cyclopenta[a]phenanthrene-17,2'-oxolane]-7-yl] ethanethioate.
== Trade names ==
<div class= style="-moz-column-count:3; column-count:3;">
*Abbolactone
*Acelat
*Aldace
*Aldactazide
*Aldactide
*Aldactone
*Aldactone A
*Alderon
*Aldopur
*Almatol
*Altex
*Aquareduct
*Deverol
*Diatensec
*Dira
*Duraspiron
*Espironolactona [INN-Spanish]
*Euteberol
*Lacalmin
*Lacdene
*Laractone
*Melarcon
*Nefurofan
*Osyrol
*SNL
*Sagisal
*Sincomen
*Spiresis
*Spiretic
*Spiridon
*Spiro-Tablinen
*Spiroctan
*Spiroctanie
*Spiroderm
*Spirolactone
*Spirolakton
*Spirolang
*Spirolone
*Spirone
*Spironocompren
*Spironolactone A
*Spironolactone [BAN:INN:JAN]
*Spironolactonum [INN-Latin]
*Spironolattone [DCIT]
*Sprioderm
*Supra-puren
*Suracton
*Uractone
*Urusonin
*Verospiron
*Verospirone
*Verospirone Opianin
*Xenalon
</div>
==Clinical use==
===Ascites===
===Ascites===
Since salt restriction is important in treatment, and [[aldosterone]] is one of the hormones that acts to increase salt retention, a medication that counteracts aldosterone should be beneficial. [[Spironolactone]] (or other distal-tubule diuretics such as [[triamterene]] or [[amiloride]])  block the aldosterone receptor in the collecting tubule. Theri benefit was shown in a [[randomized controlled trial]].<ref name="pmid7035545">{{cite journal |author=Fogel MR, Sawhney VK, Neal EA, Miller RG, Knauer CM, Gregory PB |title=Diuresis in the ascitic patient: a randomized controlled trial of three regimens |journal=J. Clin. Gastroenterol. |volume=3 Suppl 1 |issue= |pages=73-80 |year=1981 |pmid=7035545 |doi=}}</ref>
Since salt restriction is important in treatment, and [[aldosterone]] is one of the hormones that acts to increase salt retention, a medication that counteracts aldosterone should be beneficial. [[Spironolactone]] (or other distal-tubule diuretics such as [[triamterene]] or [[amiloride]])  block the aldosterone receptor in the collecting tubule. Theri benefit was shown in a [[randomized controlled trial]].<ref name="pmid7035545">{{cite journal |author=Fogel MR, Sawhney VK, Neal EA, Miller RG, Knauer CM, Gregory PB |title=Diuresis in the ascitic patient: a randomized controlled trial of three regimens |journal=J. Clin. Gastroenterol. |volume=3 Suppl 1 |issue= |pages=73-80 |year=1981 |pmid=7035545 |doi=}}</ref>
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Generally, the starting dose is oral spironolactone 100 mg/day (max 400 mg/day). 40% of patients will respond to spironolactone.1860680 For nonresponders, a [[loop diuretic]] may also be added and generally, [[furosemide]] is added at a dose of 40 mg/day (max 160 mg/day), or alternatively ([[bumetanide]] or [[torasemide]]). The ratio of 100:40 reduces risks of potassium imbalance.<ref name="pmid8277955">{{cite journal| author=Runyon BA| title=Care of patients with ascites. | journal=N Engl J Med | year= 1994 | volume= 330 | issue= 5 | pages= 337-42 | pmid=8277955  
Generally, the starting dose is oral spironolactone 100 mg/day (max 400 mg/day). 40% of patients will respond to spironolactone.1860680 For nonresponders, a [[loop diuretic]] may also be added and generally, [[furosemide]] is added at a dose of 40 mg/day (max 160 mg/day), or alternatively ([[bumetanide]] or [[torasemide]]). The ratio of 100:40 reduces risks of potassium imbalance.<ref name="pmid8277955">{{cite journal| author=Runyon BA| title=Care of patients with ascites. | journal=N Engl J Med | year= 1994 | volume= 330 | issue= 5 | pages= 337-42 | pmid=8277955  
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=8277955 }} <!--Formatted by http://sumsearch.uthscsa.edu/cite/--></ref> Serum [[potassium]] level and renal function should be monitored closely while on these medications.<ref name="pmid15084697">{{cite journal |author=Ginès P, Cárdenas A, Arroyo V, Rodés J |title=Management of cirrhosis and ascites |journal=N. Engl. J. Med. |volume=350 |issue=16 |pages=1646-54 |year=2004 |pmid=15084697 |doi=10.1056/NEJMra035021}}</ref>
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=8277955 }} <!--Formatted by http://sumsearch.uthscsa.edu/cite/--></ref> Serum [[potassium]] level and renal function should be monitored closely while on these medications.<ref name="pmid15084697">{{cite journal |author=Ginès P, Cárdenas A, Arroyo V, Rodés J |title=Management of cirrhosis and ascites |journal=N. Engl. J. Med. |volume=350 |issue=16 |pages=1646-54 |year=2004 |pmid=15084697 |doi=10.1056/NEJMra035021}}</ref>
===Heart failure===
Spironolactone can help patients who have New York Heart Association (NYHA) class IV [[heart failure]] and had a left ventricular ejection fraction of no more than 35%.<ref name="pmid10471456">{{cite journal| author=Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A et al.| 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 | year= 1999 | volume= 341 | issue= 10 | pages= 709-17 | pmid=10471456
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=10471456 }} <!--Formatted by http://sumsearch.uthscsa.edu/cite/--></ref>, although it is both used incorrectly<ref name="pmid15295047">{{cite journal| author=Juurlink DN, Mamdani MM, Lee DS, Kopp A, Austin PC, Laupacis A et al.| title=Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study. | journal=N Engl J Med | year= 2004 | volume= 351 | issue= 6 | pages= 543-51 | pmid=15295047
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15295047 | doi=10.1056/NEJMoa040135 }} <!--Formatted by http://sumsearch.uthscsa.edu/cite/--></ref> and at the same time is underutilized<ref name="pmid19843900">{{cite journal| author=Albert NM, Yancy CW, Liang L, Zhao X, Hernandez AF, Peterson ED et al.| title=Use of aldosterone antagonists in heart failure. | journal=JAMA | year= 2009 | volume= 302 | issue= 15 | pages= 1658-65 | pmid=19843900
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19843900 | doi=10.1001/jama.2009.1493 }} <!--Formatted by http://sumsearch.uthscsa.edu/cite/--></ref>.
===Hypertension===
Resistant [[hypertension]] is characterized by volume expansion and abnormalities of the [[renin-angiotensin system]] with high [[aldosterone]] and [[cortisol]] with low [[renin]] levels in the plasma<ref name="pmid19487712">{{cite journal |author=Sowers JR, Whaley-Connell A, Epstein M |title=Narrative review: the emerging clinical implications of the role of aldosterone in the metabolic syndrome and resistant hypertension |journal=Ann. Intern. Med. |volume=150 |issue=11 |pages=776–83 |year=2009 |month=June |pmid=19487712 |doi= |url=http://www.annals.org/cgi/pmidlookup?view=long&pmid=19487712 |issn=}}</ref><ref name="pmid18541823">{{cite journal |author=Gaddam KK, Nishizaka MK, Pratt-Ubunama MN, ''et al'' |title=Characterization of resistant hypertension: association between resistant hypertension, aldosterone, and persistent intravascular volume expansion |journal=Arch. Intern. Med. |volume=168 |issue=11 |pages=1159–64 |year=2008 |month=June |pmid=18541823 |doi=10.1001/archinte.168.11.1159 |url=http://archinte.ama-assn.org/cgi/pmidlookup?view=long&pmid=18541823 |issn=}}</ref> in spite of many patients taking thiazide [[diuretic]]s.<ref name="pmid18541823"/>{ This suggests that high [[corticotropin]] may contribute<ref name="pmid18541823"/>, in some cases due to an abnormal [[cytochrome P-450]] 3A5 allele that may reduce metabolism of [[cortisol]] and [[corticosterone]] (a precursor of [[aldosterone]]).<ref name="pmid12754175">{{cite journal |author=Givens RC, Lin YS, Dowling AL, ''et al'' |title=CYP3A5 genotype predicts renal CYP3A activity and blood pressure in healthy adults |journal=J. Appl. Physiol. |volume=95 |issue=3 |pages=1297–300 |year=2003 |month=September |pmid=12754175 |doi=10.1152/japplphysiol.00322.2003 |url=http://jap.physiology.org/cgi/pmidlookup?view=long&pmid=12754175 |issn=}}</ref> Resistent hypertension is also associated with insulin resistance.<ref name="pmid3299096">{{cite journal |author=Ferrannini E, Buzzigoli G, Bonadonna R, ''et al'' |title=Insulin resistance in essential hypertension |journal=N. Engl. J. Med. |volume=317 |issue=6 |pages=350–7 |year=1987 |month=August |pmid=3299096 |doi= |url= |issn=}}</ref>
In an unblinded, uncontrolled extension of the ASCOT [[randomized controlled trial]], spironolactone 25-50 mg per day as a fourth medication for [[hypertension]] reduced the blood pressure by  21.9/9.5. This result was not affected by whether one of the first three medications included a [[diuretic]].<ref name="pmid17309946">{{cite journal |author=Chapman N, Dobson J, Wilson S, ''et al'' |title=Effect of spironolactone on blood pressure in subjects with resistant hypertension |journal=Hypertension |volume=49 |issue=4 |pages=839–45 |year=2007 |month=April |pmid=17309946 |doi=10.1161/01.HYP.0000259805.18468.8c |url=http://hyper.ahajournals.org/cgi/pmidlookup?view=long&pmid=17309946 |issn=}}</ref> A second study study, also uncontrolled, corroborated the role of spironolactone.<ref name="pmid14573330">{{cite journal |author=Nishizaka MK, Zaman MA, Calhoun DA |title=Efficacy of low-dose spironolactone in subjects with resistant hypertension |journal=Am. J. Hypertens. |volume=16 |issue=11 Pt 1 |pages=925–30 |year=2003 |month=November |pmid=14573330 |doi=10.1016/S0895-7061(03)01032-X  |url= |issn=}}</ref> In this study, 54% of patients were African-American, 45% had primary hyperaldosteronism.
== External links ==
{{CZMed}}
==References==
<references/>

Revision as of 18:48, 22 October 2009

Ascites

Since salt restriction is important in treatment, and aldosterone is one of the hormones that acts to increase salt retention, a medication that counteracts aldosterone should be beneficial. Spironolactone (or other distal-tubule diuretics such as triamterene or amiloride) block the aldosterone receptor in the collecting tubule. Theri benefit was shown in a randomized controlled trial.[1]

Generally, the starting dose is oral spironolactone 100 mg/day (max 400 mg/day). 40% of patients will respond to spironolactone.1860680 For nonresponders, a loop diuretic may also be added and generally, furosemide is added at a dose of 40 mg/day (max 160 mg/day), or alternatively (bumetanide or torasemide). The ratio of 100:40 reduces risks of potassium imbalance.[2] Serum potassium level and renal function should be monitored closely while on these medications.[3]

  1. ↑ Fogel MR, Sawhney VK, Neal EA, Miller RG, Knauer CM, Gregory PB (1981). "Diuresis in the ascitic patient: a randomized controlled trial of three regimens". J. Clin. Gastroenterol. 3 Suppl 1: 73-80. PMID 7035545. [e]
  2. ↑ Runyon BA (1994). "Care of patients with ascites.". N Engl J Med 330 (5): 337-42. PMID 8277955.
  3. ↑ Ginès P, Cárdenas A, Arroyo V, Rodés J (2004). "Management of cirrhosis and ascites". N. Engl. J. Med. 350 (16): 1646-54. DOI:10.1056/NEJMra035021. PMID 15084697. Research Blogging.
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