View source for Chemistry:Potassium-sparing diuretic

{{short description|Drugs that cause diuresis without causing potassium loss in the urine and leading to hyperkalemia}}
[[Image:Potassium-sparing diuretics.svg|thumb|Structural formula of the potassium-sparing diuretics. Click to enlarge.]]

'''Potassium-sparing diuretics''' refers to drugs that cause [[Medicine:Diuresis|diuresis]] without causing [[Chemistry:Potassium|potassium]] loss in the [[Biology:Urine|urine]].<ref name="pmid2002648">{{cite journal |vauthors=Rose BD |title=Diuretics |journal=Kidney Int. |volume=39 |issue=2 |pages=336–52 |date=February 1991 |pmid=2002648 |doi=10.1038/ki.1991.43 |doi-access=free}}</ref> They are typically used as an adjunct in management of [[Medicine:Hypertension|hypertension]], [[Medicine:Cirrhosis|cirrhosis]], and congestive heart failure.<ref>{{cite journal |vauthors=Weber KT, Villarreal D |title=Aldosterone and antialdosterone therapy in congestive heart failure |journal=The American Journal of Cardiology |date=January 1993 |volume=71 |issue=3 |pages=A3–A11 |doi=10.1016/0002-9149(93)90238-8|pmid=8422002 }}</ref> The steroidal aldosterone antagonists can also be used for treatment of primary hyperaldosteronism. [[Biology:Spironolactone|Spironolactone]], a steroidal aldosterone antagonist, is also used in management of female hirsutism and [[Engineering:Acne|acne]] from PCOS or other causes.<ref>{{cite journal |vauthors=Martin KA, Anderson RB, Chang RJ, Ehrmann DA, Lobo RA, Murad MH, Pugeat MM, Rosenfield RL |title=Evaluation and Treatment of Hirsutism in Premenopausal Women: An Endocrine Society* Clinical Practice Guideline |journal=The Journal of Clinical Endocrinology & Metabolism |date=1 April 2018 |volume=103 |issue=4 |pages=1233–1257 |doi=10.1210/jc.2018-00241 |pmid=29522147 |display-authors = 2|doi-access=free }}</ref><ref>{{cite journal |vauthors=Grandhi R, Alikhan A |title=Spironolactone for the Treatment of Acne: A 4-Year Retrospective Study |journal=Dermatology |date=2017 |volume=233 |issue=2–3 |pages=141–144 |doi=10.1159/000471799|pmid=28472793 |doi-access=free }}</ref>

==Types of potassium-sparing diuretics==
* [[Biology:Epithelial sodium channel|Epithelial sodium channel]] blockers:<ref>{{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 }}</ref>
** [[Chemistry:Amiloride|Amiloride]]{{snd}} better tolerated than triamterene
** [[Chemistry:Triamterene|Triamterene]]{{snd}} increased renal side-effects
* Aldosterone antagonists, also known as [[Chemistry:Mineralocorticoid receptor antagonist|mineralocorticoid receptor antagonist]]s:<ref>{{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}}</ref>
** [[Biology:Spironolactone|Spironolactone]]{{snd}} most widespread use, inexpensive
** [[Chemistry:Eplerenone|Eplerenone]]{{snd}} more selective so reduced side-effects but more expensive and less potent
** [[Chemistry:Finerenone|Finerenone]]{{snd}} non-steroidal, more selective and potent than spironolactone and eplerenone
** [[Chemistry:Canrenone|Canrenone]]{{snd}} very limited use

==Mechanism of action==

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<sup>+</sup>) into the lumen/ urine in exchange.<ref name="pmid2002648" /> Sodium reabsorption also causes water retention.{{cn|date=April 2021}}

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<sup>+</sup> in the urine and can lead to clinically significant decreases, termed [[Medicine:Hypokalemia|hypokalemia]]. Increased sodium reabsorption also increases water retention.{{cn|date=April 2021}}

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<sup>+</sup> in urine and decreased retention of water, preventing hypokalemia.<ref>{{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 }}</ref>

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.<ref name="hropot">{{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 }}</ref> 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 [[Biology:Furosemide|furosemide]]) to treat fluid retention in congestive heart failure and [[Medicine:Ascites|ascites]] in [[Medicine:Cirrhosis|cirrhosis]].<ref name="hropot"/>

==Adverse effects==

On their own this group of drugs may raise potassium levels beyond the normal range, termed [[Medicine:Hyperkalemia|hyperkalemia]], which risks potentially fatal [[Medicine:Heart arrhythmia|arrhythmia]]s. Triamterene, specifically, is a potential nephrotoxin and up to half of the patients on it can have crystalluria or urinary casts.<ref>{{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}}</ref><ref>{{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}}</ref> Spironolactone can cause gynecomastia, menstrual abnormalities, impotence, and decreased libido by binding non-selective estrogen and progesterone receptors.{{citation needed|date=October 2020}}

==Other diuretics==
While not classically considered potassium-sparing diuretics, ACE inhibitors (ACEis) and angiotensin receptor blockers (ARBs) are anti-hypertensive drugs with diuretic effects that decrease renal excretion of potassium. They work by inhibiting either the production (ACEis) or effects (ARBs) of angiotensin 2. This results in a decrease in aldosterone release, which causes potassium-sparing-diuretic-like effects similar to those of the aldosterone antagonists, spironolactone, and eplerenone.{{cn|date=April 2021}}

==See also==
* [[Chemistry:ATC code C03#C03D Potassium-sparing agents|C03D Potassium-sparing agents]]

==References==
{{reflist}}

==External links==
* {{MeshName|Potassium+Sparing+Diuretics}}

{{Diuretics}}

[[Category:Potassium-sparing diuretics]]
[[Category:Cardiology]]

{{Sourceattribution|Potassium-sparing diuretic}}