Amiloride, sold under the trade name Midamor, 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.
Trade name Midamor
Pregnancy category AU: C
Routes of administration: By mouth
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%)
Amiloride is often used together with another diuretic, such as a thiazide or loop diuretic.
Onset of action is about two hours and it lasts for about a day.
Side effects include high blood potassium, vomiting, loss of appetite, rash, and headache.
Amiloride blocks the epithelial sodium channel (ENaC) in the late distal tubule, connecting tubule, and collecting duct of the nephron.
It reduces absorption of sodium ion from the lumen of the nephron and reduces excretion of potassium ion into the lumen.
The potassium-sparing effects of amiloride offset the low blood potassium often induced by thiazides or loop diuretics.
It is a secondary oral antihypertensive, with minimal efficacy, it may be be useful for preventing the metabolic side effects of thiazide diuretics, allowing for the use of higher thiazide doses.
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, located in the apical membrane of polarized epithelial cells in the late distal tubule and collecting duct of the kidney.
It leads to retention of sodium and water and to hypokalemia, and 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.
It can be used as a monotherapy or an adjunctive therapy alongside other diuretics.
Can be used to treat ascites in place of spironolactone if it is not tolerated.
People with poor kidney function are at high risk for hyperkalemia.
Limited 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.
Contraindicated in people with kidney problems, elevated blood potassium,
in people that are already taking potassium-sparing drugs, spironolactone and triamterene, or whom are taking potassium supplements.
Common adverse effects: elevated blood potassium, mild skin rashes, headaches, and gastrointestinal side effects of nausea, vomiting, diarrhea, decreased appetite, flatulence, and abdominal pain.
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.
It is expected than an overdose would produce effects consistent with its therapeutic effects; dehydration due to over-diuresis, and electrolyte disturbances related to hyperkalemia.
Amiloride may have drug-drug interactions when combined with other medications that also increase potassium levels in the blood.
Thebcombination 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.
Amiloride works by directly blocking the epithelial sodium channel (ENaC).
Amiloride antagonizes the epithelial sodium channel (ENaC), inhibiting sodium reabsorption in the late distal convoluted tubules, connecting tubules, and collecting ducts in the nephron.
It promotes the loss of sodium and water from the body, and reduces potassium excretion.
Amiloride is inhibition of cyclic GMP-gated cation channels in the inner medullary collecting duct.
In the heart it blocks the Na+/H+ exchangers sodium–hydrogen antiporter 1 or NHE-1.
It 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.
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.
It 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%, but taking amiloride with food helps to reduce the incidence of its gastrointestinal side effects.
Its 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 crosses the placenta and distributes into breast milk.
Amiloride is not metabolized by the liver.
About 50% of amiloride is excreted unchanged by the kidneys, while around 40% is excreted in the feces.
Half-life of amiloride in humans is between 6 and 9 hours, which may be prolonged in people with poor kidney function.
The single nucleotide polymorphism (SNP) in the protein NEDD4L may impact how amiloride affects blood pressure.
Amiloride is on list of banned substances, as it is considered a masking agent.