Mechanism of action Diuresis<unk>  works by directly blocking the epithelial sodium channel (ENaC) with an IC50 around 0.1 μM, indicating potent blockade. Antagonism of ENaC thereby inhibits sodium reabsorption in the late distal convoluted tubules, connecting tubules, and collecting ducts in the nephron. This promotes the loss of sodium and water from the body, and reduces potassium excretion. The drug is often used in conjunction with a thiazide diuretic to counteract with a potassium-losing effect. Due to its potassium-sparing capacities, hyperkalemia (elevated potassium concentration in the blood) can occur. The risk of developing hyperkalemia is increased in patients who are also taking ACE inhibitors, angiotensin II receptor antagonists, other potassium-sparing diuretics, or any potassium-containing supplements. Miscellaneous A fraction of the effects of<unk>  is inhibition of cyclic GMP-gated cation channels in the inner medullary collecting duct.<unk>  has a second action on the heart, blocking Na+/H+ exchangers sodium–hydrogen antiporter 1 or NHE-1.<unk>  also blocks the Na+/H+ antiporter on the apical surface of the proximal tubule cells in the nephron, abolishing more than 80% of the action of angiotensin II on the secretion of hydrogen ions in proximal tubule cells. Note that<unk>  is not an angiotensin II receptor blocker (like losartan, for example). The Na-H transporter is also found in the Jejunum of the small intestine, as a result,<unk>  also blocks the reabsorption of Na, and thereby water in the intestines.<unk>  is considered to be a reversible, pan-acid-sensing ion channel (ASIC) inhibitor that prevents the transient flow of ions but not the sustained flow of ions. ASICs are members of the ENaC family of protein channels, and are found in the nervous system, the cardiovascular system, the gastrointestinal system, and the skin. Broadly, ASICs are involved in harm detection, chemosensation (pH changes specifically), and touch. Pharmacokinetics Absorption<unk>  has an oral bioavailability of 50%, meaning that about 50% of an oral dose is absorbed into the blood stream. Coadministration with food reduces the amount of<unk>  that is absorbed by the body by about 30%, though it does not affect the rate of absorption. However, taking<unk>  with food helps to reduce the incidence of its gastrointestinal side effects. After being taken,<unk> 's diuretic effect occurs within 2 hours, with peak diuresis within 6–10 hours. The diuretic effects of<unk>  persist for about 24 hours after administration. Distribution<unk>  cross the placenta and distributes into breast milk in vivo. Metabolism<unk>  is not metabolized by the liver. In comparison, the ENaC inhibitor triamterene is metabolized by the liver. Excretion About 50% of<unk>  is excreted unchanged by the kidneys, while around 40% is excreted in the feces (likely drug that wasn't absorbed). The half-life of<unk>  in humans is between 6 and 9 hours, which may be prolonged in people with poor kidney function. Pharmacogenomics A single nucleotide polymorphism (SNP) in the protein NEDD4L may impact how<unk>  affects a person's blood pressure in people with high blood pressure.
Amiloride
Bumetanide
Chlorothiazide
Furosemide
Cyclothiazide
Tolvaptan
Torasemide
Spironolactone