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MODURETIC (amiloride and hydrochlorothiazide) provides diuretic and antihypertensive activity (principally due to the hydrochlorothiazide component), while acting through the amiloride component to prevent the excessive potassium loss that may occur in patients receiving a thiazide diuretic. Due to its amiloride component, the urinary excretion of magnesium is less with MODURETIC (amiloride and hydrochlorothiazide) than with a thiazide or loop diuretic used alone (see PRECAUTIONS). The onset of the diuretic action of MODURETIC (amiloride and hydrochlorothiazide) is within 1 to 2 hours and this action appears to be sustained for approximately 24 hours.
Amiloride HCl is a potassium-conserving (antikaliuretic) drug that possesses weak (compared with thiazide diuretics) natriuretic, diuretic, and antihypertensive activity. These effects have been partially additive to the effects of thiazide diuretics in some clinical studies. Amiloride HCl has potassium-conserving activity in patients receiving kaliuretic-diuretic agents.
Amiloride HCl 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. This mechanism accounts in large part for the potassium sparing action of amiloride.
Amiloride HCl usually begins to act within 2 hours after an oral dose. Its effect on electrolyte excretion reaches a peak between 6 and 10 hours and lasts about 24 hours. Peak plasma levels are obtained in 3 to 4 hours and the plasma half-life varies from 6 to9 hours. Effects on electrolytes increase with single doses of amiloride HCl up to approximately 15 mg.
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. Amiloride HCl has little effect on glomerular filtration rate or renal blood flow. Because amiloride HCl is not metabolized by the liver, drug accumulation is not anticipated in patients with hepatic dysfunction, but accumulation can occur if the hepatorenal syndrome develops.
The mechanism of the antihypertensive effect of thiazides is unknown. Thiazides do not usually affect normal blood pressure.
Hydrochlorothiazide is a diuretic and antihypertensive. It affects the distal renal tubular mechanism of electrolyte reabsorption. Hydrochlorothiazide increases excretion of sodium and chloride in approximately equivalent amounts. Natriuresis may be accompanied by some loss of potassium and bicarbonate.
After oral use diuresis begins within two hours, peaks in about four hours and lasts about 6 to 12 hours.
Hydrochlorothiazide is not metabolized but is eliminated rapidly by the kidney. When plasma levels have been followed for at least 24 hours, the plasma half-life has been observed to vary between 5.6 and 14.8 hours. At least 61 percent of the oral dose is eliminated unchanged within 24 hours. Hydrochlorothiazide crosses the placental but not the blood-brain barrier and is excreted in breast milk.
Last reviewed on RxList: 4/24/2009
This monograph has been modified to include the generic and brand name in many instances.
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