Амилорид: применение при гипертонии, отеках и циррозе печени.

Medication

Amiloride, sold under the trade name Midamor among others, is a medication typically used with other medications to treat high blood pressure or swelling due to heart failure or cirrhosis of the liver. Amiloride is classified as a potassium sparing diuretic. Amiloride is often used together with another diuretic, such as a thiazide or loop diuretic. which both reduces absorption of sodium ion from the lumen of the nephron and reduces excretion of potassium ion into the lumen. It is on the World Health Organization's List of Essential Medicines.

Amiloride 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 amiloride 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 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 amiloride (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 amiloride had positive effects on blood pressure and blood sugar tolerance. Amiloride 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). Amiloride 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, amiloride is useful as an ENaC channel inhibitor due to its promotion of sodium excretion and its potassium sparing effects, restoring potassium to normal levels. Amiloride 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 amiloride 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 amiloride isn't a preferred drug due to cost and lack of efficacy.

People with diabetes are at higher risk for kidney problems, which increases their risk for hyperkalemia (high blood potassium). The use of amiloride in people with diabetes requires careful potassium and kidney function monitoring to prevent toxicity. Amiloride must be discontinued for at least 3 days prior to glucose tolerance testing, due to the risk for fatal hyperkalemia.

Data from the use of amiloride 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, amiloride 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 is contraindicated in people with kidney problems (e. g. anuria, acute or chronic kidney disease, or diabetic nephropathy), elevated blood potassium (≥5.5 mEq/L), or people that are hypersensitive to amiloride or any ingredients within the specific formulation. Use is also contraindicated in people that are already taking potassium sparing drugs (e. g. spironolactone and triamterene) or who are taking potassium supplements (e. g. potassium chloride) in most circumstances.

Amiloride may have important drug drug interactions when combined with other medications that also increase potassium levels in the blood, leading to hyperkalemia. For example, the combination of amiloride with angiotensin converting enzyme (ACE) inhibitors like lisinopril, or angiotensin II receptor type 1 (AT1) antagonists like losartan, may lead to high levels of potassium in the blood, requiring frequent monitoring. 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.

A fraction of the effects of amiloride is inhibition of cyclic GMP gated cation channels in the inner medullary collecting duct. Amiloride has a second action on the heart, blocking Na+/H+ exchangers such as sodium–hydrogen antiporter 1 (NHE 1). Amiloride 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. Amiloride 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, amiloride also blocks the reabsorption of Na, and thereby water in the intestines. Amiloride 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.

Amiloride 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 amiloride that is absorbed by the body by about 30%, though it does not affect the rate of absorption. However, taking amiloride with food helps to reduce the incidence of its gastrointestinal side effects. After being taken, amiloride's diuretic effect occurs within 2 hours, with peak diuresis within 6–10 hours. The diuretic effects of amiloride persist for about 24 hours after administration.

Amiloride is a pyrazinoylguanidine, composed of a substituted pyrazine ring structure with a carbonylguanidinium substituent.

Amiloride was first synthesized and discovered by the Merck Sharp and Dohme Research Laboratories in the late 1960s. The drug was discovered as part of a screening process of chemicals that reversed the effects of mineralocorticoids in vivo.

It is on the World Health Organization's List of Essential Medicines. Diuretics like amiloride act as masking agents by reducing the concentration of other doping agents due to promoting diuresis, increasing the total volume of the urine.

Amiloride is an inhibitor of NHE 1, which helps to maintain normal pH within cells. Cancer cells in leukemia, a type of blood cancer, have higher pH compared to normal cells. Amiloride affects the splicing and regulation of multiple genes involved in cancer, though they do not appear to be directly related to its effects on pH. Amiloride has been tested in vitro as an adjunct to the anticancer drug imatinib, which appeared to show a synergistic effect. Modified versions of amiloride, known as 5' (N,N dimethyl) amiloride (DMA), 5 N ethyl N isopropyl amiloride (EIPA), and 5 (N,N hexamethylene) amiloride (HMA), are being studied for the treatment of leukemia. Cystic fibrosis is a genetic disorder due to a mutation in the CFTR gene, which encodes for the CFTR chloride channel. However, longer acting ENaC inhibitors (i. e. benzamil) have also failed clinical trials, despite an improvement in both the solubility and potency of the drugs. research name "552 02"), with better pharmacokinetic properties, is being studied. Pain induced by exposure to acid is attenuated by amiloride in human trials, which may indicate a role for amiloride in the treatment of pain in the future.