Potassium-sparing diuretic

• Epithelial sodium channel blockers:{{cite journal |vauthors=Sica DA, Gehr TW |title=Triamterene and the Kidney |journal=Nephron |date=1989 |volume=51 |issue=4 |pages=454–461 |doi=10.1159/000185375|pmid=2662034 }}
• Amiloride{{snd}} better tolerated than triamterene
• Triamterene{{snd}} increased renal side-effects
• Aldosterone antagonists, also known as mineralocorticoid receptor antagonists:{{cite journal |vauthors=Lainscak M, Pelliccia F, Rosano G, Vitale C, Schiariti M, Greco C, Speziale G, Gaudio C |title=Safety profile of mineralocorticoid receptor antagonists: Spironolactone and eplerenone |journal=International Journal of Cardiology |date=December 2015 |volume=200 |pages=25–29 |doi=10.1016/j.ijcard.2015.05.127 |pmid=26404748 |display-authors = 2}}
• Spironolactone{{snd}} most widespread use, inexpensive
• Eplerenone{{snd}} more selective so reduced side-effects but more expensive and less potent
• Finerenone{{snd}} non-steroidal, more selective and potent than spironolactone and eplerenone
• Canrenone{{snd}} very limited use

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. Sodium reabsorption also causes water retention.{{Cite journal |last1=Struthers |first1=Allan |last2=Krum |first2=Henry |last3=Williams |first3=Gordon H. |date=April 2008 |title=A Comparison of the Aldosterone-blocking Agents Eplerenone and Spironolactone |journal=Clinical Cardiology |language=en |volume=31 |issue=4 |pages=153–158 |doi=10.1002/clc.20324 |issn=0160-9289 |pmc=6652937 |pmid=18404673 }}{{Cite journal |last1=Batterink |first1=Josh |last2=Stabler |first2=Sarah N |last3=Tejani |first3=Aaron M |last4=Fowkes |first4=Curt T |date=2010-08-04 |editor-last=Cochrane Hypertension Group |title=Spironolactone for hypertension |url=https://doi.wiley.com/10.1002/14651858.CD008169.pub2 |journal=Cochrane Database of Systematic Reviews |language=en |doi=10.1002/14651858.CD008169.pub2|url-access=subscription }}

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.

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.{{cite journal |vauthors=Horisberger J, Giebisch G |title=Potassium-Sparing Diuretics |journal=Kidney and Blood Pressure Research |date=1987 |volume=10 |issue=3–4 |pages=198–220 |doi=10.1159/000173130|pmid=2455308 }}

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.{{cite journal |vauthors=Hropot M, Fowler N, Karlmark B, Giebisch G |title=Tubular action of diuretics: Distal effects on electrolyte transport and acidification |journal=Kidney International |date=September 1985 |volume=28 |issue=3 |pages=477–489 |doi=10.1038/ki.1985.154 |pmid=4068482 |doi-access=free }} 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.

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.{{cite journal |vauthors=Modell JH, Graves SA, Ketover A |title=Clinical course of 91 consecutive near-drowning victims |journal=Chest |date=August 1976 |volume=70 |issue=2 |pages=231–8 |doi=10.1378/chest.70.2.231 |pmid=780069}}{{cite journal |vauthors=Fairley KF, Woo KT, Birch DF, Leaker BR, Ratnaike S |title=Triamterene-induced crystalluria and cylinduria: clinical and experimental studies. |journal=Clinical Nephrology |date=October 1986 |volume=26 |issue=4 |pages=169–73 |pmid=3780069}} 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.{{Cite journal |last1=Batterink |first1=Josh |last2=Stabler |first2=Sarah N |last3=Tejani |first3=Aaron M |last4=Fowkes |first4=Curt T |date=2010-08-04 |editor-last=Cochrane Hypertension Group |title=Spironolactone for hypertension |url=https://doi.wiley.com/10.1002/14651858.CD008169.pub2 |journal=Cochrane Database of Systematic Reviews |language=en |doi=10.1002/14651858.CD008169.pub2|url-access=subscription }} Spironolactone also causes hyperkalemia{{Cite journal |last1=Struthers |first1=Allan |last2=Krum |first2=Henry |last3=Williams |first3=Gordon H. |date=April 2008 |title=A Comparison of the Aldosterone-blocking Agents Eplerenone and Spironolactone |journal=Clinical Cardiology |language=en |volume=31 |issue=4 |pages=153–158 |doi=10.1002/clc.20324 |issn=0160-9289 |pmc=6652937 |pmid=18404673 }} and renal insufficiency.{{Cite journal |last=Marrs |first=Joel C |date=November 2010 |title=Spironolactone Management of Resistant Hypertension |url=http://journals.sagepub.com/doi/10.1345/aph.1P338 |journal=Annals of Pharmacotherapy |language=en |volume=44 |issue=11 |pages=1762–1769 |doi=10.1345/aph.1P338 |pmid=20978214 |issn=1060-0280 |via=National Library of Medicine|url-access=subscription }}

Spironolactone interacts with the following medications:{{Cite journal |last=Marrs |first=Joel C |date=November 2010 |title=Spironolactone Management of Resistant Hypertension |url=http://journals.sagepub.com/doi/10.1345/aph.1P338 |journal=Annals of Pharmacotherapy |language=en |volume=44 |issue=11 |pages=1762–1769 |doi=10.1345/aph.1P338 |pmid=20978214 |issn=1060-0280 |via=National Library of Medicine|url-access=subscription }}

- ACE inhibitors/ARBs: increases hyperkalemia risk

- Alcohol: risk of orthostatic hypotension

- Barbiturates: risk of orthostatic hypotension

- Narcotics: risk of orthostatic hypotension

- NSAIDs: increases hyperkalemia risk and decreases diuretic effect of potassium-sparing diuretics

- Digoxin: increases digoxin plasma concentrations, leading to increased toxicity

• C03D Potassium-sparing agents
• Kaliuresis

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• {{MeshName|Potassium+Sparing+Diuretics}}

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Category:Potassium-sparing diuretics

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