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Hydrochlorothiazide, enalapril (Enalapril N) 25 mg + 10 mg – [20 tablets]

$12.42

Combined hypotensive agent (diuretic + ace inhibitor)

SKU: 63403 Category:

Description

Enalapril N 25 mg + 10 mg Pharmacodynamics
Hydrochlorthiazide
Hydrochlorothiazide belongs to the diuretics of thiazide series and has a diuretic effect by inhibiting sodium reabsorption in the distal convoluted renal tubules of the renal cortical layer. It enhances excretion of sodium and chlorine ions and, to a lesser extent, potassium and magnesium ions, increasing urine volume and contributing to BP reduction. Diuretic effect occurs 2 hours after ingestion of hydrochlorothiazide, reaching a maximum after 4 hours and lasting 6 to 12 hours.

Enalapril
Enalapril is a derivative of two amino acids, L-alanine and L-proline. Enalapril is a prodrug: its hydrolysis results in enalaprilate, which is a highly specific and long-acting ACE inhibitor that does not contain a sulfhydryl group.
ACE (peptidyl dipeptidase A) catalyzes the conversion of angiotensin I into the pressor peptide angiotensin II. After absorption, enalapril is hydrolyzed to enalaprilate, which inhibits ACE. Its mechanism of action is related to the reduction of angiotensin II formation from angiotensin I, which results in increased plasma renin activity (due to the elimination of negative feedback in response to renin release) and decreased aldosterone release. ACE is identical to the enzyme kininase II, so enalapril can also block the degradation of bradykinin, a peptide with a marked vasodilatory effect. The significance of this effect in the therapeutic effect of enalapril needs to be clarified.

Despite the fact that the main mechanism of antihypertensive action of enalapril is considered to be inhibition of renin-angiotensin-aldosterone system (RAAS) activity, which plays an important role in blood pressure (BP) regulation, enalapril shows antihypertensive effect also in patients with decreased blood plasma renin activity.
Enalapril administration in patients with arterial hypertension leads to a decrease in BP in both standing and lying position without a significant increase in heart rate (HR).

Symptomatic postural hypotension develops infrequently. In some patients, it may take several weeks of therapy to achieve optimal BP reduction. Interruption of therapy with enalapril does not cause a sharp rise in BP.

Effective inhibition of ACE activity is usually observed 2-4 hours after a single oral dose of enalapril.
Antihypertensive effect develops within 1 hour, the maximum BP reduction is observed 4-6 hours after oral administration. The duration of action depends on the dose taken. When using the recommended doses of enalapril, the antihypertensive effect and hemodynamic effects are maintained for 24 hours.
In clinical trials in patients with essential hypertension, a decrease in BP was accompanied by a decrease in total peripheral vascular resistance, an increase in cardiac output and no or little change in HR.

After enalapril administration, an increase in renal blood flow was observed. The glomerular filtration rate did not change. No signs of sodium or fluid retention were observed during enalapril administration. However, in patients with initially decreased glomerular filtration its rate usually increased.
Hypotensive therapy with enalapril leads to significant regression of left ventricular hypertrophy and preservation of systolic function.

Enalapril N 25 mg + 10 mg therapy is accompanied by favorable effects on plasma lipoprotein fraction ratios and no or favorable effects on serum total cholesterol concentrations.
Combination of enalapril and hydrochlorothiazide
In clinical studies it has been shown that the use of hydrochlorothiazide and enalapril combination results in a more pronounced BP reduction compared to monotherapy of each of drugs separately and allows to maintain the antihypertensive effect of Enalapril N 25 mg + 10 mg for at least 24 hours. Enalapril reduces the loss of potassium ions due to the use of hydrochlorothiazide.

Indications
Arterial hypertension (patients who are indicated for combination therapy).
Contraindications
Hydrochlorothiazide
Hydrochlorothiazide is rapidly absorbed in the gastrointestinal tract after oral administration. The degree of absorption when taken orally is approximately 80%. Simultaneous intake of food has little effect on the degree of absorption.
The TCmax in plasma is 2-5 hours after oral administration. Binding with plasma proteins (mainly with albumin) is about 40-60%, the main part of hydrochlorothiazide is accumulated in erythrocytes.
Hydrochlorothiazide is not metabolized and is almost completely (more than 95%) excreted unchanged by the kidneys. T1/2 is 5-15 hours.
Special patient groups
The limited data available indicate that in patients over 65 years of age (both healthy and with arterial hypertension) the systemic clearance of hydrochlorothiazide was decreased compared to young healthy volunteers.
In patients with impaired renal function, an increased T1/2 of hydrochlorothiazide was noted.
The presence of hepatic impairment has no significant effect on the pharmacokinetics of hydrochlorothiazide.
Hydrochlorthiazide crosses the placental barrier, but does not cross the blood-brain barrier.
Dosage and administration
  • Orally.
  • Enalapril N should be taken regularly at the same time, preferably in the morning, regardless of meal time, without chewing, with small amount of liquid, 1 time per day.
  • The recommended dose is 1 tablet per day, which is the maximum daily dose.
  • At the beginning of Enalapril N therapy, symptomatic arterial hypotension may develop, which occurs more often in patients with water-electrolyte balance disorders (including those due to previous diuretic therapy, diarrhea and/or vomiting), in patients with severe heart failure, severe arterial hypertension, renovascular hypertension. The above patients should be monitored for 8 hours after the first dose of the drug. Diuretics should be discontinued 2-3 days before starting therapy with Enalapril N.
  • Renal function should be assessed before starting treatment. The duration of treatment is determined by the physician.
  • Administration in patients with impaired renal function
  • In patients with renal insufficiency with CK 30-80 ml/min the drug should be used only after prior titration of enalapril and hydrochlorothiazide doses separately, according to the doses in Enalapril N combination preparation.
  • In patients with renal insufficiency (CK greater than 30 ml/min, but not less than 80 ml/min), the recommended starting dose of enalapril when used in monotherapy is 5 to 10 mg.
  • In patients with severe renal insufficiency (CKR less than 30 ml/min) the use of Enalapril N is contraindicated.
  • Administration in elderly patients
  • Clinical studies of efficacy and safety of concomitant use of hydrochlorothiazide and enalapril were similar in elderly (over 65 years) and younger patients with arterial hypertension. The initial dose of Enalapril H is not required for elderly patients.