Pharmacological action

Combined antihypertensive drug. It has pronounced antihypertensive and antianginal effects due to the complementary action of two active substances: slow calcium channel blocker (BCCC) - amlodipine and selective beta 1-adrenoblocker - bisoprolol.

Amlodipine

Amlodipine blocks the calcium channels, reduces the transmembrane transition of calcium ions into the cell (mostly in the smooth muscle cells of the vessels than in the cardiomyocytes).

The antihypertensive effect of amlodipine is due to a direct relaxing effect on the smooth muscle cells of the vessels, which leads to a decrease in the resistance of peripheral vessels.

The mechanism of antianginal action is not fully understood, perhaps it is associated with the following two effects.

1. Expansion of peripheral arterioles reduces OPSS, i.e. afterloading. Since amlodipine does not cause reflex tachycardia, the consumption of energy and oxygen by the myocardium decreases.

2. Expansion of large coronary arteries and coronary arterioles improves the supply of oxygen to both normal and ischemic zones of the myocardium. Due to these effects, the supply of oxygen to the myocardium improves, even with spasm of the coronary arteries (Prinzmetal angina or unstable angina).

In patients with hypertension, taking the drug 1 time / day causes a clinically significant decrease in blood pressure in the supine position and standing during the entire 24-hour interval between doses of the drug. Due to the slow development of the antihypertensive effect of amlodipine, it does not cause acute arterial hypotension.

In patients with angina, taking the drug 1 time / day increases the total exercise time, the time before the onset of angina attack, as well as the time to a significant decrease in the ST interval, and also reduces the frequency of angina attacks and the need for sublingual nitroglycerin intake.

There was no negative effect of amlodipine on the exchange of blood plasma lipids, blood glucose and serum uric acid.

Bisoprolol

Bisoprolol is a selective beta 1-blocker, without its own sympathomimetic activity, does not have a membrane-stabilizing effect.

It has only a slight affinity for the c2-adrenergic receptors of the smooth muscles of the bronchi and vessels, as well as for the β2-adrenoreceptors involved in the regulation of metabolism. Consequently, bisoprolol as a whole does not affect the resistance of the respiratory tract and the metabolic processes in which β2-adrenergic receptors are involved.

The selective effect of the drug on β1-adrenergic receptors persists beyond the therapeutic range.

Bisoprolol does not have a pronounced negative inotropic effect.

The maximum effect of the drug is achieved 3-4 hours after ingestion. Even with the appointment of bisoprolol 1 time / day, its therapeutic effect persists for 24 hours due to 10-12 h T1 / 2 from the blood plasma. Typically, the maximum antihypertensive effect is achieved 2 weeks after the start of treatment.

Bisoprolol reduces the activity of the sympathoadrenal system (CAS) by blocking the β1-adrenergic receptor of the heart.

With a single admission in patients with IHD without signs of chronic heart failure, bisoprolol reduces heart rate, reduces stroke volume of the heart and, as a result, reduces the ejection fraction and myocardial oxygen demand. With prolonged therapy, the initially increased OPSS decreases. Reduction of renin activity in blood plasma is considered as one of the components of antihypertensive action of beta-blockers

Indications

- Arterial hypertension: substitution of therapy with monocomponent drugs amlodipine and bisoprolol in the same doses.