Normally, sodium is reabsorbed in the collecting tubules of a renal nephron. This occurs via epithelial sodium channels or ENaCs, located on the luminal surface of principal cells that line the collecting tubules. Positively-charged Na+ entering the cells during reabsorption leads to an electronegative luminal environment causing the secretion of potassium (K+) into the lumen/ urine in exchange.[2] Sodium reabsorption also causes water retention.[8][9]
When the kidneys detect low blood pressure, the renin–angiotensin–aldosterone system (RAAS) is activated and eventually, aldosterone is secreted. Aldosterone binds to aldosterone receptors (mineralocorticoid receptors) increasing sodium reabsorption in an effort to increase blood pressure and improve fluid status in the body. When excessive sodium reabsorption occurs, there is an increasing loss of K+ in the urine and can lead to clinically significant decreases, termed hypokalemia. Increased sodium reabsorption also increases water retention.[8][9]
Potassium-sparing diuretics act to prevent sodium reabsorption in the collecting tubule by either binding ENaCs (amiloride, triamterene) or by inhibiting aldosterone receptors (spironolactone, eplerenone). This prevents excessive excretion of K+ in urine and decreased retention of water, preventing hypokalemia.[10]
Because these diuretics are weakly natriuretic, they do not cause clinically significant blood pressure changes and thus, are not used as primary therapy for hypertension.[11] They can be used in combination with other anti-hypertensives or drugs that cause hypokalemia to help maintain a normal range for potassium. For example, they are often used as an adjunct to loop diuretics (usually furosemide) to treat fluid retention in congestive heart failure and ascites in cirrhosis.[11]
Adverse effects
On their own this group of drugs may raise potassium levels beyond the normal range, termed hyperkalemia, which risks potentially fatal arrhythmias. Triamterene, specifically, is a potential nephrotoxin and up to half of the patients on it can have crystalluria or urinary casts.[12][13] Due to its activity as an androgen receptor antagonist and progesterone receptor agonist, spironolactone causes adverse effects, including gynecomastia or decreased libido in males and menstrual abnormalities in females.[14] Spironolactone also causes hyperkalemia[15] and renal insufficiency.[16]
Drug Interactions
Spironolactone interacts with the following medications:[17]
^Weber KT, Villarreal D (January 1993). "Aldosterone and antialdosterone therapy in congestive heart failure". The American Journal of Cardiology. 71 (3): A3–A11. doi:10.1016/0002-9149(93)90238-8. PMID 8422002.
^Martin KA, Anderson RB, et al. (1 April 2018). "Evaluation and Treatment of Hirsutism in Premenopausal Women: An Endocrine Society* Clinical Practice Guideline". The Journal of Clinical Endocrinology & Metabolism. 103 (4): 1233–1257. doi:10.1210/jc.2018-00241. PMID 29522147.
^Grandhi R, Alikhan A (2017). "Spironolactone for the Treatment of Acne: A 4-Year Retrospective Study". Dermatology. 233 (2–3): 141–144. doi:10.1159/000471799. PMID 28472793.
^Sica DA, Gehr TW (1989). "Triamterene and the Kidney". Nephron. 51 (4): 454–461. doi:10.1159/000185375. PMID 2662034.
^Lainscak M, Pelliccia F, et al. (December 2015). "Safety profile of mineralocorticoid receptor antagonists: Spironolactone and eplerenone". International Journal of Cardiology. 200: 25–29. doi:10.1016/j.ijcard.2015.05.127. PMID 26404748.
^ a bStruthers, Allan; Krum, Henry; Williams, Gordon H. (April 2008). "A Comparison of the Aldosterone-blocking Agents Eplerenone and Spironolactone". Clinical Cardiology. 31 (4): 153–158. doi:10.1002/clc.20324. ISSN 0160-9289. PMC 6652937. PMID 18404673.
^ a bBatterink, Josh; Stabler, Sarah N; Tejani, Aaron M; Fowkes, Curt T (2010-08-04). Cochrane Hypertension Group (ed.). "Spironolactone for hypertension". Cochrane Database of Systematic Reviews. doi:10.1002/14651858.CD008169.pub2.
^Horisberger J, Giebisch G (1987). "Potassium-Sparing Diuretics". Kidney and Blood Pressure Research. 10 (3–4): 198–220. doi:10.1159/000173130. PMID 2455308.
^ a bHropot M, Fowler N, Karlmark B, Giebisch G (September 1985). "Tubular action of diuretics: Distal effects on electrolyte transport and acidification". Kidney International. 28 (3): 477–489. doi:10.1038/ki.1985.154. PMID 4068482.
^Modell JH, Graves SA, Ketover A (August 1976). "Clinical course of 91 consecutive near-drowning victims". Chest. 70 (2): 231–8. doi:10.1378/chest.70.2.231. PMID 780069.
^Fairley KF, Woo KT, Birch DF, Leaker BR, Ratnaike S (October 1986). "Triamterene-induced crystalluria and cylinduria: clinical and experimental studies". Clinical Nephrology. 26 (4): 169–73. PMID 3780069.
^Batterink, Josh; Stabler, Sarah N; Tejani, Aaron M; Fowkes, Curt T (2010-08-04). Cochrane Hypertension Group (ed.). "Spironolactone for hypertension". Cochrane Database of Systematic Reviews. doi:10.1002/14651858.CD008169.pub2.
^Struthers, Allan; Krum, Henry; Williams, Gordon H. (April 2008). "A Comparison of the Aldosterone-blocking Agents Eplerenone and Spironolactone". Clinical Cardiology. 31 (4): 153–158. doi:10.1002/clc.20324. ISSN 0160-9289. PMC 6652937. PMID 18404673.
^Marrs, Joel C (November 2010). "Spironolactone Management of Resistant Hypertension". Annals of Pharmacotherapy. 44 (11): 1762–1769. doi:10.1345/aph.1P338. ISSN 1060-0280. PMID 20978214 – via National Library of Medicine.
^Marrs, Joel C (November 2010). "Spironolactone Management of Resistant Hypertension". Annals of Pharmacotherapy. 44 (11): 1762–1769. doi:10.1345/aph.1P338. ISSN 1060-0280. PMID 20978214 – via National Library of Medicine.
External links
Potassium+Sparing+Diuretics at the U.S. National Library of Medicine Medical Subject Headings (MeSH)