Spironolactone is least commonly used in which of the following: September 2011
Correct Answer: Hypeension
Description: Ans. C: Hypeension As an add-on drug, spironolcatone may be useful in hypeensive patients with significant hyperuricemia, hypokalemia, or glucose intolerance Spironolactone It is a synthetic 17-lactone drug that is a renal competitive aldosterone antagonist in a class of potassium-sparing diuretics It used primarily to treat hea failure, ascites in patients with liver disease, low-renin hypeension, hypokalemia, secondary hyperaldosteronism (such as occurs with hepatic cirrhosis), and Conn's syndrome (primary hyperaldosteronism). On its own, spironolactone is only a weak diuretic because its effects target the distal nephron (collecting tubule), where urine volume can only be slightly modified; but it can be combined with other diuretics to increase efficacy. Due to its antiandrogen effect, it can also be used to treat hirsutism. It is also used for treating hair loss and acne in women, and can be used as a topical medication for treatment of male baldness. It is commonly used to treat symptoms of polycystic ovary syndrome (PCOS) such as excess facial hair and acne. Spironolactone can cause gynecomastia in males and, unless regularly monitored, should not be given with potassium supplementation for fear of development of hyperkalemia. Spironolactone inhibits the effect of aldosterone by competing for intracellular aldosterone receptors in the coical collecting duct. This decreases the reabsorption of sodium and water, while decreasing the secretion of potassium. Spironolactone has a fairly slow onset of action, taking several days to develop, and, so, the effect diminishes slowly. Spironolactone has anti-androgen activity by directly binding to and blocking androgens from interacting with the androgen receptor, by blocking androgen production, and by increasing estrogen levels. Production of androgens is decreased by inhibiting 17alpha-hydroxylase and 17, 20-desmolase, which are enzymes in the testosterone biosynthesis pathway. Estrogen levels are increased by enhancing the peripheral conversion of testosterone to estradiol and by displacing estradiol from sex hormone-binding globulin (SHBG) Spironolactone is a synthetic steroid that acts as a competitive antagonist to aldosterone. Its onset and duration of action are determined by the kinetics of the aldosterone response in the target tissue. Substantial inactivation of spironolactone occurs in the liver and hepatitis or cirrhosis can lead to secondary aldosteronism, which is one indication for treatment. Spironolactone is associated with an increased risk of bleeding from the stomach and duodenum Because it also affects androgen receptors and other steroid receptors, it can cause gynecomastia, menstrual irregularities and testicular atrophy. Spironolactone often increases serum potassium levels and can cause hyperkalemia, therefore, it is recommended that people using this drug avoid potassium supplements and salt substitutes containing potassium. Long-term administration of spironolactone gives the histologic characteristic of spironolactone bodies in the adrenal coex. Spironolactone bodies are eosinophilic, round, concentrically laminated cytoplasmic inclusions surrounded by clear halos in preparations stained with hematoxylin and eosin.
Category:
Pharmacology
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