Amiloride

Last updated
Amiloride
Amilorid - Amiloride.svg
Clinical data
Trade names Midamor, others
Other namesMK-870
AHFS/Drugs.com Monograph
Pregnancy
category
  • AU:C
Routes of
administration 		By mouth
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
  • US: ℞-only
Pharmacokinetic data
Bioavailability Readily absorbed, 15–25%
Protein binding ~23%
Metabolism Nil
Onset of action 2 hours (peak at 6–10 hours, duration ~24 hours)
Elimination half-life 6 to 9 hours
Excretion urine (20–50%), feces (40%)
Identifiers
  • 3,5-diamino-6-chloro-N-(diaminomethylene)pyrazine-2-carboxamide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.018.205 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C6H8ClN7O
Molar mass 229.63 g·mol−1
3D model (JSmol)
Melting point 240.5 to 241.5 °C (464.9 to 466.7 °F)
  • Clc1nc(C(=O)\N=C(/N)N)c(nc1N)N
  • InChI=1S/C6H8ClN7O/c7-2-4(9)13-3(8)1(12-2)5(15)14-6(10)11/h(H4,8,9,13)(H4,10,11,14,15) Yes check.svgY
  • Key:XSDQTOBWRPYKKA-UHFFFAOYSA-N Yes check.svgY
   (verify)

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. [1] [2] Amiloride is classified as a potassium-sparing diuretic. Amiloride is often used together with another diuretic, such as a thiazide or loop diuretic. [2] It is taken by mouth. [1] Onset of action is about two hours and it lasts for about a day. [2]

Contents

Common side effects include high blood potassium, vomiting, loss of appetite, rash, and headache. [1] The risk of high blood potassium is greater in those with kidney problems, diabetes, and those who are older. [1] Amiloride blocks the epithelial sodium channel (ENaC) in the late distal tubule, connecting tubule, and collecting duct of the nephron, [3] which both reduces absorption of sodium ion from the lumen of the nephron and reduces excretion of potassium ion into the lumen. [2]

Amiloride was developed in 1967. [4] It is on the World Health Organization's List of Essential Medicines. [5]

Medical uses

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. [6] 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. [6] The 2017 clinical practice guidelines of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines list amiloride as a "secondary" oral antihypertensive, with minimal efficacy. [7] 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). [8] When combined with hydrochlorothiazide, the addition of amiloride had positive effects on blood pressure and blood sugar tolerance. [9] 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). [10]

Amiloride is the treatment of choice for Liddle phenotype, [11] 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. [12] 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. [13]

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. [6] 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. [14]

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 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. [6]

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. [6]

Lactation

There is no data on the use of amiloride in women that are breastfeeding. While diuretics can make lactation difficult, it is unlikely that amiloride would induce this effect in the absence of other diuretics. [15]

Pregnancy

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. [16]

Contraindications

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 whom are taking potassium supplements (e.g. potassium chloride) in most circumstances. [1]

Adverse effects

Amiloride is generally well tolerated. [17] Common adverse effects to the use of amiloride include elevated blood potassium, mild skin rashes, headaches, and gastrointestinal side effects (nausea, vomiting, diarrhea, decreased appetite, flatulence, and abdominal pain). [1] Mild symptoms of high blood potassium concentrations include unusual skin sensations, muscle weakness, or fatigue, but more severe symptoms such as flaccid paralysis of the limbs, slow heart rate, and even shock can occur. [1]

Overdose

There exists no overdose data on amiloride in humans, though it is expected than an overdose would produce effects consistent with its therapeutic effects; e.g. dehydration due to over-diuresis, and electrolyte disturbances related to hyperkalemia. It is unknown if amiloride can be dialyzed off, and no specific antidote against it exists. Treatment is generally supportive, though hyperkalemia can be treated. [17]

Interactions

Amiloride may have important drug-drug interactions when combined with other medications that also increase potassium levels in the blood, leading to hyperkalemia. [18] 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. [18]

Pharmacology

Mechanism of action

Diuresis

Amiloride works by directly blocking the epithelial sodium channel (ENaC) with an IC50 around 0.1 μM, indicating potent blockade. [19] Antagonism of ENaC thereby inhibits sodium reabsorption in the late distal convoluted tubules, connecting tubules, and collecting ducts in the nephron. [20] 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 amiloride is inhibition of cyclic GMP-gated cation channels in the inner medullary collecting duct. [21]

Amiloride has a second action on the heart, blocking Na+/H+ exchangers sodium–hydrogen antiporter 1 or 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. [22] Note that 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. [23]

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. [24]

Pharmacokinetics

Absorption

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. [1]

Distribution

Amiloride cross the placenta and distributes into breast milk in vivo. [1]

Metabolism

Amiloride is not metabolized by the liver. [1] In comparison, the ENaC inhibitor triamterene is metabolized by the liver. [25]

Excretion

About 50% of amiloride is excreted unchanged by the kidneys, while around 40% is excreted in the feces (likely drug that wasn't absorbed). The half-life of amiloride in humans is between 6 and 9 hours, which may be prolonged in people with poor kidney function. [1]

Pharmacogenomics

A single nucleotide polymorphism (SNP) in the protein NEDD4L may impact how amiloride affects a person's blood pressure in people with high blood pressure. [26]

Chemistry

A photograph of pure amiloride HCl powder. Amilorid-HCl substance photo.jpg
A photograph of pure amiloride HCl powder.

Amiloride is a pyrazinoylguanidine, composed of a substituted pyrazine ring structure with a carbonylguanidinium substituent. [27] Amiloride's pKa is 8.67, which is due to the guanidinium group. [27] In high pH (alkaline, low hydrogen concentration) environments, the guanidinium group is deprotonated and the compound is rendered neutral, depleting its activity on sodium channels. [27] Amiloride, as a pure substance, is highly fluorescent, with excitation wavelengths at 215, 288, and 360 nm, emitting light at 420 nm. [28]

Light at wavelength 420nm. This is the emission wavelength for light due to amiloride fluorescence. Light wavelength 420nm.jpg
Light at wavelength 420nm. This is the emission wavelength for light due to amiloride fluorescence.

History

Amiloride was first synthesized and discovered by the Merck Sharp and Dohme Research Laboratories in the late 1960s. [27] The drug was discovered as part of a screening process of chemicals that reversed the effects of mineralocorticoids in vivo. [27] Amiloride was the only drug in the screen that was capable of causing the excretion of sodium (natriuresis) without a concomitant urinary excretion of potassium (kaliuresis). [27] Thousands of amiloride analogues have been studied since its initial discovery, which have been used to study the effects of sodium transporters. [27]

Amiloride was approved by the U.S. Food and Drug Administration (FDA) on October 5, 1981. [29]

Society and culture

It is on the World Health Organization's List of Essential Medicines. [5]

Amiloride is on the World Anti-Doping Agency's list of banned substances, as it is considered a masking agent. [30] 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. [25] The list includes other potassium-sparing diuretics, such as triamterene and spironolactone. [30] In 2008, amiloride and the potassium-sparing diuretic triamterene were found in 3% of positive diuretic doping samples. [25]

Formulations and trade names

Research

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. [31]

AmilorideAnalogues.jpg

Cystic fibrosis is a genetic disorder due to a mutation in the CFTR gene, which encodes for the CFTR chloride channel. [19] There is evidence that suggests that the molecular target of amiloride, ENaC, is also implicated in cystic fibrosis due to its effects on mucus in the lungs. [19] Aerosolized formulations of amiloride have been tested in clinical trials, though long-term clinical trials have failed to show much utility. [19] Due to its short duration of action, it was thought that longer-acting ENaC inhibitors may prove more effective. [32] 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. [19] A third generation amiloride analogue (N-(3,5-diamino-6-chloropyrazine-2-carbonyl)-N'-4-[4-(2,3-dihydroxypropoxy)phenyl]butyl-guanidine methanesulfonate, [33] research name "552-02"), with better pharmacokinetic properties, is being studied. [19]

Amiloride55202.jpg

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. [19]

Related Research Articles

<span class="mw-page-title-main">Aldosterone</span> Mineralocorticoid steroid hormone

Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon. It plays a central role in the homeostatic regulation of blood pressure, plasma sodium (Na+), and potassium (K+) levels. It does so primarily by acting on the mineralocorticoid receptors in the distal tubules and collecting ducts of the nephron. It influences the reabsorption of sodium and excretion of potassium (from and into the tubular fluids, respectively) of the kidney, thereby indirectly influencing water retention or loss, blood pressure, and blood volume. When dysregulated, aldosterone is pathogenic and contributes to the development and progression of cardiovascular and kidney disease. Aldosterone has exactly the opposite function of the atrial natriuretic hormone secreted by the heart.

<span class="mw-page-title-main">Distal convoluted tubule</span>

The distal convoluted tubule (DCT) is a portion of kidney nephron between the loop of Henle and the collecting tubule.

<span class="mw-page-title-main">Hydrochlorothiazide</span> Diuretic medication

Hydrochlorothiazide, sold under the brand name Hydrodiuril among others, is a diuretic medication used to treat hypertension and swelling due to fluid build-up. Other uses include treating diabetes insipidus and renal tubular acidosis and to decrease the risk of kidney stones in those with a high calcium level in the urine. Hydrochlorothiazide is taken by mouth and may be combined with other blood pressure medications as a single pill to increase effectiveness. Hydrochlorothiazide is a thiazide medication which inhibits reabsorption of sodium and chloride ions from the distal convoluted tubules of the kidneys, causing a natriuresis. This initially increases urine volume and lowers blood volume. It is believed to reduce peripheral vascular resistance.

Antihypertensives are a class of drugs that are used to treat hypertension. Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke, heart failure, kidney failure and myocardial infarction. Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34% and of ischaemic heart disease by 21%, and can reduce the likelihood of dementia, heart failure, and mortality from cardiovascular disease. There are many classes of antihypertensives, which lower blood pressure by different means. Among the most important and most widely used medications are thiazide diuretics, calcium channel blockers, ACE inhibitors, angiotensin II receptor antagonists (ARBs), and beta blockers.

<span class="mw-page-title-main">Hyperkalemia</span> Medical condition with excess potassium

Hyperkalemia is an elevated level of potassium (K+) in the blood. Normal potassium levels are between 3.5 and 5.0 mmol/L (3.5 and 5.0 mEq/L) with levels above 5.5 mmol/L defined as hyperkalemia. Typically hyperkalemia does not cause symptoms. Occasionally when severe it can cause palpitations, muscle pain, muscle weakness, or numbness. Hyperkalemia can cause an abnormal heart rhythm which can result in cardiac arrest and death.

<span class="mw-page-title-main">Loop diuretic</span> Diuretics that act at the ascending limb of the loop of Henle in the kidney

Loop diuretics are diuretics that act on the Na-K-Cl cotransporter along the thick ascending limb of the loop of Henle in nephrons of the kidneys. They are primarily used in medicine to treat hypertension and edema often due to congestive heart failure or chronic kidney disease. While thiazide diuretics are more effective in patients with normal kidney function, loop diuretics are more effective in patients with impaired kidney function.

<span class="mw-page-title-main">Chlortalidone</span> Thiazide-like diuretic drug

Chlortalidone, also known as chlorthalidone, is a thiazide-like diuretic drug used to treat high blood pressure, swelling, diabetes insipidus, and renal tubular acidosis. Because chlortalidone is reliably effective in most patients with high blood pressure, it is considered a preferred initial treatment. It is also used to prevent calcium-based kidney stones. It is taken by mouth. Effects generally begin within three hours and last for up to three days. Long-term treatment with chlortalidone is more effective than hydrochlorothiazide for prevention of heart attack or stroke.

<span class="mw-page-title-main">Thiazide</span> Class of chemical compounds

Thiazide refers to both a class of sulfur-containing organic molecules and a class of diuretics based on the chemical structure of benzothiadiazine. The thiazide drug class was discovered and developed at Merck and Co. in the 1950s. The first approved drug of this class, chlorothiazide, was marketed under the trade name Diuril beginning in 1958. In most countries, thiazides are the least expensive antihypertensive drugs available.

<span class="mw-page-title-main">Gitelman syndrome</span> Medical condition

Gitelman syndrome (GS) is an autosomal recessive kidney tubule disorder characterized by low blood levels of potassium and magnesium, decreased excretion of calcium in the urine, and elevated blood pH. It is the most frequent hereditary salt-losing tubulopathy. Gitelman syndrome is caused by disease-causing variants on both alleles of the SLC12A3 gene. The SLC12A3 gene encodes the thiazide-sensitive sodium-chloride cotransporter, which can be found in the distal convoluted tubule of the kidney.

<span class="mw-page-title-main">Potassium-sparing diuretic</span> Drugs that cause diuresis without causing potassium loss in the urine and leading to hyperkalemia

Potassium-sparing diuretics refers to drugs that cause diuresis without causing potassium loss in the urine. They are typically used as an adjunct in management of hypertension, cirrhosis, and congestive heart failure. The steroidal aldosterone antagonists can also be used for treatment of primary hyperaldosteronism. Spironolactone, a steroidal aldosterone antagonist, is also used in management of female hirsutism and acne from PCOS or other causes.

<span class="mw-page-title-main">Triamterene</span> Chemical compound

Triamterene is a potassium-sparing diuretic often used in combination with thiazide diuretics for the treatment of high blood pressure or swelling. The combination with hydrochlorothiazide, is known as hydrochlorothiazide/triamterene.

<span class="mw-page-title-main">Metabolic alkalosis</span> Medical condition

Metabolic alkalosis is a metabolic condition in which the pH of tissue is elevated beyond the normal range (7.35–7.45). This is the result of decreased hydrogen ion concentration, leading to increased bicarbonate, or alternatively a direct result of increased bicarbonate concentrations. The condition typically cannot last long if the kidneys are functioning properly.

<span class="mw-page-title-main">Metolazone</span> Chemical compound

Metolazone is a thiazide-like diuretic marketed under the brand names Zytanix, Metoz, Zaroxolyn, and Mykrox. It is primarily used to treat congestive heart failure and high blood pressure. Metolazone indirectly decreases the amount of water reabsorbed into the bloodstream by the kidney, so that blood volume decreases and urine volume increases. This lowers blood pressure and prevents excess fluid accumulation in heart failure. Metolazone is sometimes used together with loop diuretics such as furosemide or bumetanide, but these highly effective combinations can lead to dehydration and electrolyte abnormalities.

<span class="mw-page-title-main">Antimineralocorticoid</span> Drug class

An antimineralocorticoid, also known as a mineralocorticoid receptor antagonist or aldosterone antagonist, is a diuretic drug which antagonizes the action of aldosterone at mineralocorticoid receptors. This group of drugs is often used as adjunctive therapy, in combination with other drugs, for the management of chronic heart failure. Spironolactone, the first member of the class, is also used in the management of hyperaldosteronism and female hirsutism. Most antimineralocorticoids, including spironolactone, are steroidal spirolactones. Finerenone is a nonsteroidal antimineralocorticoid.

<span class="mw-page-title-main">Liddle's syndrome</span> Medical condition

Liddle's syndrome, also called Liddle syndrome, is a genetic disorder inherited in an autosomal dominant manner that is characterized by early, and frequently severe, high blood pressure associated with low plasma renin activity, metabolic alkalosis, low blood potassium, and normal to low levels of aldosterone. Liddle syndrome involves abnormal kidney function, with excess reabsorption of sodium and loss of potassium from the renal tubule, and is treated with a combination of low sodium diet and potassium-sparing diuretics. It is extremely rare, with fewer than 30 pedigrees or isolated cases having been reported worldwide as of 2008.

<span class="mw-page-title-main">Bartter syndrome</span> Medical condition

Bartter syndrome (BS) is a rare inherited disease characterised by a defect in the thick ascending limb of the loop of Henle, which results in low potassium levels (hypokalemia), increased blood pH (alkalosis), and normal to low blood pressure. There are two types of Bartter syndrome: neonatal and classic. A closely associated disorder, Gitelman syndrome, is milder than both subtypes of Bartter syndrome.

Pseudohyperaldosteronism is a medical condition which mimics the effects of elevated aldosterone (hyperaldosteronism) by presenting with high blood pressure (hypertension), low blood potassium levels (hypokalemia), metabolic alkalosis, and low levels of plasma renin activity (PRA). However, unlike hyperaldosteronism, this conditions exhibits low or normal levels of aldosterone in the blood. Causes include genetic disorders, acquired conditions, metabolic disorders, and dietary imbalances including excessive consumption of licorice. Confirmatory diagnosis depends on the specific root cause and may involve blood tests, urine tests, or genetic testing; however, all forms of this condition exhibit abnormally low concentrations of both plasma renin activity (PRA) and plasma aldosterone concentration (PAC) which differentiates this group of conditions from other forms of secondary hypertension. Treatment is tailored to the specific cause and focuses on symptom control, blood pressure management, and avoidance of triggers.

<span class="mw-page-title-main">Epithelial sodium channel</span> Group of membrane proteins

The epithelial sodium channel(ENaC), (also known as amiloride-sensitive sodium channel) is a membrane-bound ion channel that is selectively permeable to sodium ions (Na+). It is assembled as a heterotrimer composed of three homologous subunits α or δ, β, and γ, These subunits are encoded by four genes: SCNN1A, SCNN1B, SCNN1G, and SCNN1D. The ENaC is involved primarily in the reabsorption of sodium ions at the collecting ducts of the kidney's nephrons. In addition to being implicated in diseases where fluid balance across epithelial membranes is perturbed, including pulmonary edema, cystic fibrosis, COPD and COVID-19, proteolyzed forms of ENaC function as the human salt taste receptor.

<span class="mw-page-title-main">Benzamil</span> Chemical compound

Benzamil or benzyl amiloride is a potent blocker of the ENaC channel and also a sodium-calcium exchange blocker. It is a potent analog of amiloride, and is marketed as the hydrochloride salt. As amiloride, benzamil has been studied as a possible treatment for cystic fibrosis, although with disappointing results.

<span class="mw-page-title-main">Diuretic</span> Substance that promotes the production of urine

A diuretic is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. A diuretic tablet is sometimes colloquially called a water tablet. There are several categories of diuretics. All diuretics increase the excretion of water from the body, through the kidneys. There exist several classes of diuretic, and each works in a distinct way. Alternatively, an antidiuretic, such as vasopressin, is an agent or drug which reduces the excretion of water in urine.

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