Spironolactone: Difference between revisions

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'''Spironolactone''' is an [[aldosterone]] antagonist used to treat [[edema]] associated with [[congestive heart failure]], [[nephrotic syndrome]] or [[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.
{{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,
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.
16-decahydro-1H-cyclopenta[a]phenanthrene-17,2'-oxolane]-7-yl] ethanethioate.


== trade names ==
== Trade names ==
Abbolactone  
<div class= style="-moz-column-count:3; column-count:3;">
*Abbolactone  
*Acelat  
*Acelat  
*Aldace  
*Aldace  
Line 57: Line 60:
*Verospirone  
*Verospirone  
*Verospirone Opianin  
*Verospirone Opianin  
*Xenalon  
*Xenalon
</div>
 
==History==
Aldactone brand (GD Searle) of spironolactone was approved by the [[Food and Drug Administration]] in the [[United States of America]] with a [http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/NewDrugApplicationNDA/ New Drug Application] (NDA) on January 21, 1960.<ref>{{FDA-Drug_Details|020579}}</ref> A generic version with a AB [[Food and Drug  Administration/Catalogs/Therapeutic Equivalence Code|Therapeutic Equivalence Code]] was approved with a [http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/AbbreviatedNewDrugApplicationANDAGenerics/ Abbreviated New Drug Application] (ANDA) on July 29, 1999.<ref>{{FDA-Drug_Details|040353}}</ref>
 
==Clinical use==
===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. Their 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>
 
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 }}</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 }}</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 }}</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 }}</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==
Material adapted from Drug Bank at (http://redpoll.pharmacy.ualberta.ca/drugbank/cgi-bin/getCard.cgi?CARD=APRD01234)
<references/>

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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

  • 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

History

Aldactone brand (GD Searle) of spironolactone was approved by the Food and Drug Administration in the United States of America with a New Drug Application (NDA) on January 21, 1960.[1] A generic version with a AB Therapeutic Equivalence Code was approved with a Abbreviated New Drug Application (ANDA) on July 29, 1999.[2]

Clinical use

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. Their benefit was shown in a randomized controlled trial.[3]

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.[4] Serum potassium level and renal function should be monitored closely while on these medications.[5]

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%.[6], although it is both used incorrectly[7] and at the same time is underutilized[8].

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[9][10] in spite of many patients taking thiazide diuretics.[10]{ This suggests that high corticotropin may contribute[10], in some cases due to an abnormal cytochrome P-450 3A5 allele that may reduce metabolism of cortisol and corticosterone (a precursor of aldosterone).[11] Resistent hypertension is also associated with insulin resistance.[12]

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.[13] A second study study, also uncontrolled, corroborated the role of spironolactone.[14] In this study, 54% of patients were African-American, 45% had primary hyperaldosteronism.

External links

The most up-to-date information about Spironolactone and other drugs can be found at the following sites.


References

  1. ↑ Anonymous. Drugs@FDA for FDA Application No. 020579. U S Food and Drug Administration
  2. ↑ Anonymous. Drugs@FDA for FDA Application No. 040353. U S Food and Drug Administration
  3. ↑ 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]
  4. ↑ Runyon BA (1994). "Care of patients with ascites.". N Engl J Med 330 (5): 337-42. PMID 8277955.
  5. ↑ 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.
  6. ↑ Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A et al. (1999). "The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators.". N Engl J Med 341 (10): 709-17. PMID 10471456.
  7. ↑ Juurlink DN, Mamdani MM, Lee DS, Kopp A, Austin PC, Laupacis A et al. (2004). "Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study.". N Engl J Med 351 (6): 543-51. DOI:10.1056/NEJMoa040135. PMID 15295047. Research Blogging.
  8. ↑ Albert NM, Yancy CW, Liang L, Zhao X, Hernandez AF, Peterson ED et al. (2009). "Use of aldosterone antagonists in heart failure.". JAMA 302 (15): 1658-65. DOI:10.1001/jama.2009.1493. PMID 19843900. Research Blogging.
  9. ↑ Sowers JR, Whaley-Connell A, Epstein M (June 2009). "Narrative review: the emerging clinical implications of the role of aldosterone in the metabolic syndrome and resistant hypertension". Ann. Intern. Med. 150 (11): 776–83. PMID 19487712. [e]
  10. ↑ 10.0 10.1 10.2 Gaddam KK, Nishizaka MK, Pratt-Ubunama MN, et al (June 2008). "Characterization of resistant hypertension: association between resistant hypertension, aldosterone, and persistent intravascular volume expansion". Arch. Intern. Med. 168 (11): 1159–64. DOI:10.1001/archinte.168.11.1159. PMID 18541823. Research Blogging.
  11. ↑ Givens RC, Lin YS, Dowling AL, et al (September 2003). "CYP3A5 genotype predicts renal CYP3A activity and blood pressure in healthy adults". J. Appl. Physiol. 95 (3): 1297–300. DOI:10.1152/japplphysiol.00322.2003. PMID 12754175. Research Blogging.
  12. ↑ Ferrannini E, Buzzigoli G, Bonadonna R, et al (August 1987). "Insulin resistance in essential hypertension". N. Engl. J. Med. 317 (6): 350–7. PMID 3299096. [e]
  13. ↑ Chapman N, Dobson J, Wilson S, et al (April 2007). "Effect of spironolactone on blood pressure in subjects with resistant hypertension". Hypertension 49 (4): 839–45. DOI:10.1161/01.HYP.0000259805.18468.8c. PMID 17309946. Research Blogging.
  14. ↑ Nishizaka MK, Zaman MA, Calhoun DA (November 2003). "Efficacy of low-dose spironolactone in subjects with resistant hypertension". Am. J. Hypertens. 16 (11 Pt 1): 925–30. DOI:10.1016/S0895-7061(03)01032-X. PMID 14573330. Research Blogging.
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