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.
PMID8422002.
^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.
PMID26404748.