Spironolactone: Difference between revisions
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==Clinical use== | ==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. | 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 | 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 | ||
Revision as of 17:49, 22 October 2009
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
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.[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]
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%.[4], although it is both used incorrectly[5] and at the same time is underutilized[6].
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[7][8] in spite of many patients taking thiazide diuretics.[8]{ This suggests that high corticotropin may contribute[8], in some cases due to an abnormal cytochrome P-450 3A5 allele that may reduce metabolism of cortisol and corticosterone (a precursor of aldosterone).[9] Resistent hypertension is also associated with insulin resistance.[10]
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.[11] A second study study, also uncontrolled, corroborated the role of spironolactone.[12] 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.
- Spironolactone - FDA approved drug information (drug label) from DailyMed (U.S. National Library of Medicine).
- Spironolactone - Drug information for consumers from MedlinePlus (U.S. National Library of Medicine).
- Spironolactone - Detailed information from DrugBank.
References
- ↑ 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]
- ↑ Runyon BA (1994). "Care of patients with ascites.". N Engl J Med 330 (5): 337-42. PMID 8277955.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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]
- ↑ 8.0 8.1 8.2 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.
- ↑ 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.
- ↑ 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]
- ↑ 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.
- ↑ 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.