Ami-Hydro

Ami-Hydro Uses, Dosage, Side Effects, Food Interaction and all others data.

Amiloride is a weak diuretic which acts mainly on the distal renal tubules. It increases the excretion of Na and reduces the excretion of K. It diminishes kaliuretic effects of other diuretics, and may produce an additional natriuretic effect.

Hydrochlorothiazide inhibits the reabsorption of Na in the distal tubules causing increased excretion of Na and water including K and hydrogen ions.

Trade Name Ami-Hydro
Generic Hydrochlorothiazide + Amiloride
Type
Therapeutic Class Thiazide diuretics & related drugs
Manufacturer
Available Country Canada, United States
Last Updated: September 19, 2023 at 7:00 am
Ami-Hydro
Ami-Hydro

Uses

Treatment of hypertension or congestive heart failure in patients who develop hypokalemia when thiazide or other kaliuretic diuretics are used alone, or in patients in whom maintenance of normal serum potassium levels is clinically important (eg, digitalized patients); alone or as adjunctive treatment with other antihypertensive agents.

Ami-Hydro is also used to associated treatment for these conditions: Ascites, Calcium Nephrolithiasis, Congestive Heart Failure (CHF), High Blood Pressure (Hypertension), Hypokalemia, Metabolic Alkalosis, PolyuriaAcidosis, Renal Tubular, Calcium Nephrolithiasis, Cirrhosis of the Liver, Congestive Heart Failure (CHF), Diabetes Insipidus, Edema, High Blood Pressure (Hypertension), Hypertension,Essential, Hypokalemia caused by diuretics, Nephrotic Syndrome, Premenstrual tension with edema, Sodium retention, Stroke, Prophylaxis of preeclampsia

How Ami-Hydro works

Amiloride works by inhibiting sodium reabsorption in the distal convoluted tubules and collecting ducts in the kidneys by binding to the amiloride-sensitive sodium channels. This promotes the loss of sodium and water from the body, but without depleting potassium. Amiloride exerts its potassium sparing effect through the inhibition of sodium reabsorption at the distal convoluted tubule, cortical collecting tubule and collecting duct; this decreases the net negative potential of the tubular lumen and reduces both potassium and hydrogen secretion and their subsequent excretion. Amiloride is not an aldosterone antagonist and its effects are seen even in the absence of aldosterone.

Hydrochlorothiazide is transported from the circulation into epithelial cells of the distal convoluted tubule by the organic anion transporters OAT1, OAT3, and OAT4. From these cells, hydrochlorothiazide is transported to the lumen of the tubule by multidrug resistance associated protein 4 (MRP4).

Normally, sodium is reabsorbed into epithelial cells of the distal convoluted tubule and pumped into the basolateral interstitium by a sodium-potassium ATPase, creating a concentration gradient between the epithelial cell and the distal convoluted tubule that promotes the reabsorption of water.

Hydrochlorothiazide acts on the proximal region of the distal convoluted tubule, inhibiting reabsorption by the sodium-chloride symporter, also known as Solute Carrier Family 12 Member 3 (SLC12A3). Inhibition of SLC12A3 reduces the magnitude of the concentration gradient between the epithelial cell and distal convoluted tubule, reducing the reabsorption of water.

Dosage

Ami-Hydro dosage

Adult: 1-2 tablets (5 mg amiloride & 50 mg hydrochlorothiazide) daily in single or divided doses, increasing if necessary to maximum 4 tablets.

Children: Safety and efficacy not established.

Side Effects

  • Cardiovascular: Arrhythmia, tachycardia, palpitations (amiloride).
  • CNS: Headache, fatigue, tiredness, weakness, dizziness, encephalopathy, tremors, decreased libido (amiloride); restlessness (hydrochlorothiazide).
  • Dermatologic: Mild skin rash, pruritus, alopecia (amiloride); urticaria, purpura (hydrochlorothiazide).
  • EENT (eye, ear, nose, and throat): Increased ocular pressure, tinnitus (amiloride); transient blurred vision, xanthopsia (hydrochlorothiazide).
  • GI: Nausea, anorexia, GI and abdominal pain, flatulence, activation of peptic ulcer, dyspepsia, heartburn, dry mouth (amiloride); pancreatitis, cramping, GI irritation, sialadenitis (hydrochlorothiazide).
  • Genitourinary: Bladder spasm, polyuria, urinary frequency (amiloride); interstitial nephritis (hydrochlorothiazide).
  • Hematologic: Aplastic anemia, neutropenia (amiloride); agranulocytosis, leukopenia, hemolytic anemia, thrombocytopenia (hydrochlorothiazide).
  • Hepatic: Jaundice.
  • Metabolic: Hyperkalemia, hyperglycemia, glucosuria, hyperuricemia (hydrochlorothiazide).
  • Respiratory: Shortness of breath, cough (amiloride); respiratory distress, including pneumonitis and pulmonary edema (hydrochlorothiazide).

Toxicity

No data are available in regard to overdosage in humans. The oral LD50 of amiloride hydrochloride (calculated as the base) is 56 mg/kg in mice and 36 to 85 mg/kg in rats, depending on the strain. The most likely signs and symptoms to be expected with overdosage are dehydration and electrolyte imbalance.

The oral LD50 of hydrochlorothiazide is >10g/kg in mice and rats.

Patients experiencing an overdose may present with hypokalemia, hypochloremia, and hyponatremia. Treat patients with symptomatic and supportive treatment including fluids and electrolytes. Vasopressors may be administered to treat hypotension and oxygen may be given for respiratory impairment.

Precaution

Thiazides should be used with caution in patients with severe renal disease, impaired hepatic function or progressive liver disease and gout.

Interaction

  • Amiloride ACE inhibitors (eg, captopril): May result in severely elevated potassium levels.
  • Potassium preparations: May severely increase serum potassium levels, possibly resulting in cardiac arrhythmias or cardiac arrest. Do not coadminister.
  • Hydrochlorothiazide Bile acid sequestrants: May reduce thiazide absorption; give thiazide at least 2 h before sequestrant.
  • Diazoxide: May cause hyperglycemia.
  • Digitalis glycosides: Diuretic-induced hypokalemia and hypomagnesemia may lead to digitalis-induced arrhythmias.
  • Lithium: Renal excretion of lithium may be reduced.
  • Loop diuretics (eg, furosemide): Synergistic effects may occur, resulting in profound diuresis and serious electrolyte abnormalities.
  • Sulfonylureas (eg, chlorpropamide): Hypoglycemic effect of sulfonylurea may be decreased, necessitating an increase in sulfonylurea dosage.

Volume of Distribution

The volume of distribution varies widely from one study to another with values of 0.83-4.19L/kg.

Elimination Route

Readily absorbed following oral administration.

An oral dose of hydrochlorothiazide is 65-75% bioavailable, with a Tmax of 1-5 hours, and a Cmax of 70-490ng/mL following doses of 12.5-100mg. When taken with a meal, bioavailability is 10% lower, Cmax is 20% lower, and Tmax increases from 1.6 to 2.9 hours.

Half Life

Plasma half-life varies from 6 to 9 hours.

The plasma half life of hydrochlorothiazide is 5.6-14.8h.

Clearance

The renal clearance of hydrochlorothiazide in patients with normal renal function is 285mL/min. Patients with a creatinine clearance of 31-80mL/min have an average hydroxychlorothiazide renal clearance of 75mL/min, and patients with a creatinine clearance of ≤30mL/min have an average hydroxychlorothiazide renal clearance of 17mL/min.

Elimination Route

Amiloride HCl is not metabolized by the liver but is excreted unchanged by the kidneys. About 50 percent of a 20 mg dose of amiloride HCl is excreted in the urine and 40 percent in the stool within 72 hours.

Hydrochlorothiazide is eliminated in the urine as unchanged hydrochlorothiazide.

Pregnancy & Breastfeeding use

Pregnancy Category B

Lactation:

  • Amiloride: undetermined
  • hydrochlorothiazide: excreted in breast milk.

Contraindication

Hyperkalemia (serum potassium levels greater than 5.5 mEq/L); concurrently with other potassium-sparing diuretics (eg, spironolactone), potassium supplements (including potassium-rich diet) except in severe or refractory cases of hypokalemia; impaired renal function; sensitivity to any components of product.

Special Warning

Elderly: in some patients specially the elderly an initial dose of 12.5 mg daily may be sufficient.

Children: An initial dose for children has been 1 to 2 mg per kg body-weight in 2 divided doses. Infants under 6 months may need doses upto 3 mg per kg daily.

Acute Overdose

Symptoms: Dehydration, electrolyte imbalance (eg, hyperkalemia), electrolyte depletion (hypokalemia, hypochloremia, hyponatremia).

Storage Condition

Store tablets at controlled room temperature (59° to 86°F). Protect from moisture, freezing, and excessive heat.

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*** Taking medicines without doctor's advice can cause long-term problems.
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