<unk>  may be used in combination with a thiazide diuretic for treatment of high blood pressure or (less commonly) in combination with a loop diuretic for treatment of heart failure. The potassium-sparing effects of<unk>  offset the low blood potassium (hypokalemia) that is often induced by thiazides or loop diuretics, which is of particular importance in people for whom maintaining a normal level of potassium is critically important. For example, people that are taking Digitalis (i.e. digoxin) are at higher risk for changes in heart rhythm if their potassium levels get too high. The 2017 clinical practice guidelines of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines list<unk>  as a "secondary" oral antihypertensive, with minimal efficacy. For people with resistant hypertension, already taking a thiazide diuretic, an angiotensin converting enzyme inhibitor (ACE-i) or an angiotensin II receptor blocker (ARB), and a calcium channel blocker, the addition of<unk>  (or spironolactone) was better at reducing blood pressure than adding a beta-blocker (bisoprolol) or an alpha-1 blocker (doxazosin). When combined with hydrochlorothiazide, the addition of<unk>  had positive effects on blood pressure and blood sugar tolerance.<unk>  may therefore be useful for preventing the metabolic side effects of thiazide diuretics, allowing for the use of higher thiazide doses (in line with how they were originally studied).<unk>  is the treatment of choice for Liddle phenotype, which is characterized by high blood pressure, low blood potassium, and metabolic alkalosis in conjunction with a low plasma renin activity and a low aldosterone. Some people with the Liddle phenotype have Liddle syndrome, which involves a genetic mutation resulting in upregulation of the epithelial sodium channel (ENaC), located in the apical membrane of polarized epithelial cells in the late distal tubule and collecting duct of the kidney. Because Liddle phenotype usually involves an upregulation of ENaC channels, leading to retention of sodium and water and to hypokalemia,<unk>  is useful as an ENaC channel inhibitor due to its promotion of sodium excretion and its potassium-sparing effects, restoring potassium to normal levels.<unk>  can be used as a monotherapy (single-drug therapy) or an adjunctive therapy alongside other diuretics (e.g. hydrochlorothiazide, furosemide) for the treatment of ascites and edema (swelling) due to cirrhosis of the liver. The 2012 clinical practice guidelines by the American Association for the Study of Liver Diseases (AASLD) states that<unk>  can be used to treat ascites in place of spironolactone if it isn't tolerated (e.g. due to the side effect of gynecomastia), though<unk>  isn't a preferred drug due to cost and lack of efficacy. Specific populations Diabetics People with diabetes are at higher risk for kidney problems, which increases their risk for hyperkalemia (high blood potassium). The use of<unk>  in people with diabetes requires careful potassium and kidney function monitoring to prevent toxicity.<unk>  must be discontinued for at least 3 days prior to glucose tolerance testing, due to the risk for fatal hyperkalemia. Poor kidney function People with poor kidney function (e.g. blood urea nitrogen >30 mg/dL, or serum creatinine >1.5 mg/dL) are at high risk for hyperkalemia. Lactation There is no data on the use of<unk>  in women that are breastfeeding. While diuretics can make lactation difficult, it is unlikely that<unk>  would induce this effect in the absence of other diuretics. Pregnancy Data from the use of<unk>  in animals suggests that it does not pose a risk to the developing fetus. However, when used in combination with the drug acetazolamide during the process of organ formation,<unk>  increases the risk for kidney and ureter abnormalities. Limited human data from use during pregnancy suggests an association with a specific congenital penis abnormality if taken during the first trimester, as well as a risk for mild intrauterine growth restriction if taken throughout pregnancy.
Amiloride
Bumetanide
Chlorothiazide
Furosemide
Cyclothiazide
Tolvaptan
Torasemide
Spironolactone