ATC Group: C09B ACE inhibitors, combinations

Fixed dose combination of delapril, an inhibitor of the angiotensin conversion enzyme, and manidipine, a dyhydropyridine calcium-antagonist with antihypertensive activity and nephroprotecting properties. The combination of these active ingredients through complementary mechanisms of action produces a synergistic antihypertensive effect, reducing blood pressure in a greater measure than with the single constituents.

Fixed combination of an ACE-inhibitor, enalapril, and a calcium channel blocker, lercanidipine, two antihypertensive compounds with complementary mechanism of action to control blood pressure in patients with essential hypertension. The combination of these substances has an additive antihypertensive effect, reducing blood pressure to a greater degree than either component alone.

The two active substances have a complementary antihypertensive effect. Once absorbed, enalapril is hydrolyzed to enalaprilat, a substance that inhibits ACE. This inhibition results in a decrease in plasma angiotensin II, which leads to an increase in plasma renin activity and a decrease in aldosterone secretion. Enalapril has an antihypertensive effect even in cases of hypertension with low renin. Nitrendipine is a calcium antagonist of the 1-4 dihydropyridine group that acts as an antihypertensive agent. The mechanism of action of nitrendipine is based on the inhibition of the flow of calcium ions in the smooth muscle fibers of the vessels.

Perindopril is an inhibitor of the enzyme that converts angiotensin I into angiotensin II (Angiotensin Converting Enzyme ACE). Perindopril is active in all grades of hypertension: mild, moderate, severe; a reduction in systolic and diastolic blood pressures in both supine and standing positions is observed. Amlodipine is a calcium ion influx inhibitor of the dihydropyridine group and inhibits the transmembrane influx of calcium ions into cardiac and vascular smooth muscle. The mechanism of the antihypertensive action of amlodipine is due to a direct relaxant effect on vascular smooth muscle.

Perindopril is an inhibitor of the enzyme that converts angiotensin I into angiotensin II (ACE). Inhibition of ACE results in a reduction of angiotensin II in the plasma, which leads to increased plasma renin activity and reduced secretion of aldosterone. Since ACE inactivates bradykinin, inhibition of ACE also results in an increased activity of circulating and local kallikrein-kinin systems. It is possible that this mechanism contributes to the blood pressure-lowering action of ACE inhibitors. Bisoprolol is a highly beta1-selective-adrenoceptor blocking agent, lacking intrinsic stimulating and relevant membrane stabilising activity. Bisoprolol is generally not to be expected to influence the airway resistance and beta2-mediated metabolic effects.

Combination of three antihypertensive components with complementary mechanisms to control blood pressure in patient with hypertension. Perindopril is an angiotensin converting enzyme inhibitor, indapamide, a chlorosulphamoyl diuretic and amlodipine, a calcium ion flux inhibitor of the dihydropyridine group.

Ramiprilat, the active metabolite of the prodrug ramipril, catalyses the conversion of angiotensin I to the active vasoconstrictor substance angiotensin II, as well as the breakdown of the active vasodilator bradykinin. Reduced angiotensin II formation and inhibition of bradykinin breakdown lead to vasodilatation. Amlodipine dilates peripheral arterioles and thus, reduces the total peripheral resistance (afterload) against which the heart works. Since the heart rate remains stable, this unloading of the heart reduces myocardial energy consumption and oxygen requirements. The mechanism of action of amlodipine also probably involves dilatation of the main coronary arteries and coronary arterioles, both in normal and ischaemic regions.

Both the calcium antagonist felodipine and the ACE inhibitor ramipril reduce blood pressure by dilation of the peripheral blood vessels. Calcium antagonists dilate the arterial beds while ACE inhibitors dilate both arterial and venous beds. Vasodilatation and thereby reduction of blood pressure may lead to activation of the sympathetic nervous system and the renin-angiotensin system. Inhibition of ACE results in decreased plasma angiotensin II.

Ramiprilat, the active metabolite of the prodrug ramipril, inhibits the enzyme dipeptidylcarboxypeptidase I. Decreased formation of angiotensin II and inhibition of bradykinin degradation lead to vasodilation. Amlodipine is a calcium ion influx inhibitor of the dihydropyridine group and inhibits the entry of calcium ions through the cell membrane into cardiac cells and smooth muscle fibers. Hydrochlorothiazide is a thiazide diuretic. The mechanism of antihypertensive action of thiazide diuretics is not fully understood.