Amiloride

BRAND NAMES

• Midamor: This is the most common brand name for amiloride sold as a single active ingredient.

MECHANISM OF ACTION

Amiloride works by blocking epithelial sodium channels (ENaC) in the distal tubules and collecting ducts of the kidneys, which reduces the reabsorption of sodium and water. By preventing sodium from entering the tubular cells, it lowers the electrical gradient that typically promotes potassium secretion. This results in a "potassium-sparing" diuretic effect, making the drug effective in treating conditions such as high blood pressure and heart failure.

PHARMACOKINETICS:

Absorption

Amiloride is readily but incompletely absorbed from the gastrointestinal (GI) tract after oral administration, with an average bioavailability of about 50%. This means that approximately half of a dose is absorbed into the bloodstream.

Distribution

Amiloride has a large volume of distribution (350–380 L), suggesting extensive distribution beyond the plasma into body tissues. It is not metabolized by the liver and is eliminated unchanged by the kidneys. In individuals with normal renal function, its half-life ranges from 6 to 9 hours. Around 50% of the drug is excreted in the urine, while approximately 40% is eliminated via the feces.

Metabolism

Amiloride is not metabolized by the liver and is primarily eliminated unchanged by the kidneys, with a portion also excreted in the stool. Within 72 hours of an oral dose, approximately 50% is excreted in the urine and around 40% in the feces. The drug has a typical half-life of 6 to 9 hours.

Excretion

Amiloride is eliminated unchanged in both urine and feces, with approximately 50% of a dose excreted in the urine and about 40% in the stool within 72 hours. Since it is not metabolized by the liver, the drug is excreted in its original form.

PHARMACODYNAMICS

Amiloride is a potassium-sparing diuretic that acts by inhibiting epithelial sodium channels (ENaC) in the distal convoluted tubules and collecting ducts of the kidney, thereby reducing sodium reabsorption. This results in a modest increase in the excretion of sodium and water, while simultaneously decreasing the urinary secretion of potassium and hydrogen ions—hence its classification as "potassium-sparing." Its action does not depend on the presence of aldosterone.

ADMINISTRATION

Amiloride is an oral medication categorized as a potassium-sparing diuretic, commonly known as a "water pill." It is primarily prescribed to help control high blood pressure (hypertension) and manage fluid retention (edema) associated with conditions like heart failure, liver cirrhosis, and certain kidney disorders. Amiloride works by promoting the elimination of excess sodium and water through the urine while helping the body retain potassium, which is essential for maintaining a healthy electrolyte balance. 

DOSAGE AND STRENGTH

Amiloride is an oral tablet primarily available in a strength of 5 mg. It is a potassium-sparing diuretic used alone or with other diuretics to treat conditions such as high blood pressure and edema. The dosage of amiloride varies depending on the medical condition and whether it is used alone or with other medications. It is typically taken once daily with food. 

Dosages

The dosage of amiloride is determined by a healthcare professional based on the specific medical condition being treated, whether the medication is being used alone or in combination with other drugs, and the individual patient's response.

Strengths

• Amiloride HCl oral tablet: 5 mg.

• Amiloride in combination products: It is also available in combination with other diuretics, most commonly hydrochlorothiazide. An example includes tablets containing 5 mg of amiloride and 50 mg of hydrochlorothiazide.

DRUG INTERACTIONS

A drug interactionhappens when another substance affects how a medication works, potentially increasing side effects or reducing its effectiveness. According to the U.S. Food and Drug Administration (FDA), such interactions can occur with prescription or over-the-counter medications, alcohol, certain foods and beverages (such as grapefruit juice), herbal remedies or dietary supplements (like St. John’s Wort), and even underlying health conditions.

FOOD INTERACTIONS

The primary food-related interactions with amiloride are linked to its impact on potassium levels and are more influenced by dietary patterns and supplements than by specific meals. As a potassium-sparing diuretic, amiloride helps the body retain potassium, so consuming a potassium-rich diet can increase the risk of developing hyperkalemia-a potentially dangerous condition caused by excess potassium in the blood.

CONTRAINDICATIONS

Amiloride is not recommended for use in individuals with certain kidney conditions, such as anuria, acute or chronic kidney disease, or diabetic nephropathy. It is also contraindicated in those with elevated blood potassium levels (≥5.5 mEq/L) or in individuals who are allergic to amiloride or any component of its formulation. In most cases, amiloride should not be used alongside other potassium-sparing medications (such as spironolactone or triamterene) or potassium supplements (like potassium chloride), as this can significantly increase the risk of hyperkalemia.

SIDE EFFECTS

Common side effects

• Nausea and vomiting

• Diarrhea or other gastrointestinal upset, including gas, abdominal pain, or loss of appetite

• Headache

• Dizziness, drowsiness, or fatigue

• Weakness or muscle cramps

• Mild skin rash

Serious side effects

• Abdominal pain

• Confusion

• Irregular or slow heartbeat

• Tingling or numbness in the hands, feet, or lips.

• Weakness or heaviness in the legs 

OVER DOSE

An overdose of amiloride is a medical emergency that requires immediate attention. It can lead to severe dehydration, dangerously high potassium levels (hyperkalemia), andlow blood pressure (hypotension). As there is no specific antidote for amiloride overdose, treatment primarily involves supportive care, focusing on relieving symptoms and restoring normal electrolyte balance.

TOXICITY

The primary toxicity concern associated with amiloride is hyperkalemia (elevated blood potassium levels), which can be life-threatening and may cause irregular heart rhythms. Other possible side effects include nausea, vomiting, diarrhea, dizziness, headache, muscle cramps, and fatigue. In more severe cases, toxicity may result in liver damage, kidney impairment, or serious allergic reactions. Therefore, amiloride should be avoided in individuals with impaired kidney function or significantly elevated potassium levels.