Ampril (Ramipril) HD tablets 5 mg/25 mg. №30

active substance: 1 tablet contains 5 mg of ramipril and 25 mg of hydrochlorothiazide;

excipients : sodium bicarbonate, lactose monohydrate, croscarmellose sodium, pregelatinized starch, sodium stearyl fumarate.

Tablets.

Main physico-chemical properties: flat tablets without coating, in the form of capsules, white or almost white in color with a line on one side and the mark “25” on the other side. The tablet can be divided into two equal parts.

Combined drugs of angiotensin-converting enzyme inhibitors. Ramipril and diuretics. ATX code C09V A05.

Mechanism of action

Ramipril

Ramiprilat, the active metabolite of ramipril, inhibits the enzyme dipeptidyl carboxypeptidase I (angiotensin-converting enzyme or kininase II).

In blood plasma and tissues, this enzyme catalyzes the conversion of angiotensin I into the active vasoconstrictor substance angiotensin II, and also causes the destruction of the active vasodilator bradykinin. A decrease in the formation of angiotensin II and inhibition of the destruction of bradykinin leads to vasodilation.

Since angiotensin II also stimulates the release of aldosterone, ramiprilat causes a decrease in aldosterone secretion. In patients of Negroid race (Afro-Caribbean descent) with arterial hypertension (generally, the population is characterized by a low level of renin activity), the response to monotherapy with angiotensin-converting enzyme (ACE) inhibitors was, on average, less pronounced than in patients of other races.

Hydrochlorothiazide

Hydrochlorothiazide is a thiazide diuretic. The mechanism of antihypertensive action of thiazide diuretics has not yet been fully elucidated. They slow down the reabsorption of sodium and chlorine ions in the distal tubules. Increased excretion of these ions through the kidneys is accompanied by an increase in urine production (due to osmotic binding of water). The excretion of potassium and magnesium increases, the excretion of uric acid decreases. Possible mechanisms of the antihypertensive effect of hydrochlorothiazide can be: a changed sodium balance, a decrease in the extracellular volume of water and plasma, a change in the resistance of kidney vessels, as well as a decrease in sensitivity to angiotensin II.

Pharmacodynamic effect.

Ramipril

The use of ramipril causes a significant decrease in the peripheral resistance of arteries. As a rule, there are no significant changes in renal plasma flow and glomerular filtration rate. In patients with arterial hypertension, the appointment of ramipril leads to a decrease in blood pressure in a standing and lying position without a compensatory increase in heart rate. In most patients, the onset of the hypotensive effect after a single dose occurs 1-2 hours after oral administration. The peak effect of a single dose is usually achieved within 3-6 hours after oral administration. The hypotensive effect of a single dose usually lasts for 24 hours. With long-term treatment with ramipril, the maximum antihypertensive effect is usually achieved after 3-4 weeks of treatment. It has been proven that with long-term therapy, the antihypertensive effect persists for 2 years. Abrupt discontinuation of ramipril does not cause a rapid and excessive increase in blood pressure.

Hydrochlorothiazide

When taking hydrochlorothiazide, the beginning of the diuretic effect occurs after 2 hours, and its peak – after about 4 hours, the effect lasts for 6-12 hours.

The hypotensive effect occurs on the 3rd-4th day after the start of therapy and can last for 1 week after stopping treatment.

The blood pressure lowering effect is accompanied by a slight increase in glomerular filtration rate, renal vascular resistance, and plasma renin activity.

Simultaneous use of ramipril-hydrochlorothiazide

In the course of clinical studies, it was established that the use of the combination leads to a more significant reduction in blood pressure than the use of individual components. Perhaps due to the blockade of the renin-angiotensin-aldosterone system, the simultaneous use of ramipril with hydrochlorothiazide reduces the loss of potassium, which accompanies the diuretic effect. Combining an ACE inhibitor with a thiazide diuretic causes a synergistic effect and also reduces the risk of hypokalemia caused by the use of the diuretic itself.

Double blockade of the renin-angiotensin-aldosterone system (RAAS)

Two large randomized controlled trials (ONTARGET (telmisartan alone and in combination with ramipril) and VA NEPHRON-D (patients with diabetic nephropathy)) of the combination of an ACE inhibitor with an angiotensin II receptor blocker have been reported.

The ONTARGET study was conducted in patients with cardiovascular or cerebrovascular diseases or type 2 diabetes accompanied by signs of target organ damage. The VA NEPHRON-D study was conducted in patients with type 2 diabetes and diabetic nephropathy.

These studies did not show a positive effect on renal function and/or cardiovascular complications and mortality, but an increased risk of hyperkalemia, acute kidney injury, and/or hypotension was observed compared with monotherapy. Given the similar pharmacodynamic properties, these results are also applicable to other ACE inhibitors and angiotensin II receptor blockers.

ACE inhibitors and angiotensin II receptor blockers should not be used simultaneously in patients with diabetic nephropathy.

The ALTITUDE study (use of aliskiren in type 2 diabetes with cardiovascular and renal endpoints) tested the benefits of adding aliskiren to standard therapy with ACE inhibitors or angiotensin II receptor blockers in patients with type 2 diabetes and chronic kidney disease, cardiovascular disease -vascular diseases, or both. The study was terminated early due to an increased risk of developing adverse effects. Cardiovascular death, stroke, and serious adverse events (hyperkalemia, hypotension, and renal disease) were more common with aliskiren than with placebo.