Each Zepres Plus tablet contains 10 mg of enalapril maleate and 25 mg of hydrochlorothiazide.
MECHANISM OF ACTION
Zepres Plus provides anti-hypertensive and diuretic activity. Enalapril maleate and hydrochlorothiazide have been used singly and concomitantly for the treatment of hypertension. The anti-hypertensive effects of these two agents are additive and are sustained for at least 24 hours.
Enalapril, after hydrolysis to enalaprilat, inhibits angiotensin-converting enzyme (ACE). The mechanism through which enalapril lowers blood pressure is believed to be primarily suppression of the renin-angiotensin-aldosterone system. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex. Inhibition of ACE results in decreased plasma angiotensin II, which leads to decreased vasopressor activity and to decreased aldosterone secretion. In patients treated with enalapril maleate plus a thiazide diuretic, there was essentially no change in serum potassium.
Hydrochlorothiazide is a thiazide diuretic. 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.
Absorption: Following oral administration of enalapril maleate, peak serum concentrations of enalapril occur within about one hour. The extent of absorption of enalapril is approximately 60%. Enalapril absorption is not influenced by the presence of food in the gastrointestinal tract.
Metabolism: Following absorption, enalapril is hydrolyzed to enalaprilat, which is a more potent angiotensin converting enzyme inhibitor than enalapril.
Distribution: Peak serum concentrations of enalaprilat occur three to four hours after an oral dose of enalapril maleate.
Excretion: Excretion of enalaprilat and enalapril is primarily renal. Approximately 94% of the dose is recovered in the urine and feces as enalaprilat or enalapril. The principal components in urine are enalaprilat, accounting for about 40% of the dose, and intact enalapril.
In most patients studied, after oral administration of a single dose of enalapril maleate, onset of antihypertensive activity was seen at one hour with peak reduction of blood pressure achieved by four to six hours. At recommended doses, antihypertensive effects of enalapril maleate monotherapy have been maintained for at least 24 hours. In some patients the effects may diminish toward the end of the dosing interval; this was less frequently observed with concomitant administration of enalapril maleate and hydrochlorothiazide. Achievement of optimal blood pressure reduction may require several weeks of enalapril therapy in some patients. The antihypertensive effects of enalapril have continued during long-term therapy. Abrupt withdrawal of enalapril has not been associated with a rapid increase in blood pressure.
After oral use diuresis begins within two hours, peaks in about four hours and lasts about 6 to 12 hours.
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.
Distribution: Hydrochlorothiazide crosses the placental but not the blood-brain barrier.
Metabolism and Elimination: Hydrochlorothiazide is not metabolized but is eliminated rapidly by the kidney. At least 61% of the oral dose is eliminated unchanged within 24 hours. Hydrochlorothiazide crosses the placental but not the blood-brain barrier.