Spironolactone

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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[edit]

History[edit]

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[edit]

Ascites[edit]

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[edit]

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[edit]

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[edit]

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[edit]