Capabilities calcium antagonist Norvasc in the treatment of cardiovascular diseases

heart diseaseCurrently, cardiovascular disease (heart disease) is called an epidemic of the twentieth century, but in the beginning of the third millennium, they remain a threat to the health of the population of developed countries.

Today it is hard to imagine that that 60 years ago doctors do not pay attention to high blood pressure, and treatment prescribed, as a rule, only at a significant severity of symptoms. According to WHO 15-20% of the adult population suffers from hypertension, which is one of the causes of mortality from cardiovascular disease, the cause of disability and related costs. It is well known that hypertension is one of the major risk factors for coronary heart disease (CHD) and vascular lesions of the brain.

The end of the twentieth century was marked by intensive development of ideas about the pathogenetic basis of hypertension, critical revision of many causes, mechanisms and treatment of this disease, the creation of new classes of antihypertensive drugs and the formation of a new approach for evaluating the effectiveness of treatment – medicines based on evidence. One of the most difficult tasks for the clinician is the selection of the optimal drug for the treatment of hypertensive patients. The problem was that, in the absence of specific indications there are several classes of effective antihypertensive agents, which can be applied in this situation. Numerous randomized studies have found no significant benefit in any of the six classes of antihypertensive drugs on the severity of blood pressure reduction. It becomes clear that the attention given the ability of drugs to reduce cardiovascular morbidity and mortality while maintaining good quality of life.

In methodical recommendations of WHO / ISH was expected that the most important differences between classes of antihypertensive agents (diuretics, b-blockers, calcium antagonists, a-blockers, ACE inhibitors, angiotensin-converting enzyme and angiotensin receptors) are the presence or absence of evidence from randomized clinical trials that studied the effect of these drugs on morbidity and mortality in hypertensive patients.

Calcium antagonists have been used in cardiology for over 35 years. Their widespread use in clinical practice promotes high antiischemic and antianginal efficacy and tolerability established in large clinical trials. The main point of application of this group of drugs at the cellular level are slow calcium channels which calcium ions pass through into the smooth muscle cells of blood vessels and the heart. In the presence of calcium ions the interaction of actin and myosin occurs and provides contractility of smooth muscle cells. In addition, calcium channels are involved in the generation of pacemaker activity in the cells of the sinus node and atrioventricular conduction of an impulse on-ventricular node. The mechanism of action fo calcium antagonists is as follows:

1)  reduction in afterload due to their peripheral vasodilator effect and reduce systemic vascular resistance

2) direct negative inotropic effect on the myocardium

3) improved myocardial perfusion during ischemia due to edema and prevent coronary artery spasm and reduce their resistance

It has been established that the vasodilating effect induced by calcium antagonists, is carried out not only by direct action on smooth muscles of the vascular wall, but indirectly, through the release of nitric oxide potentiation of vascular endothelium. This phenomenon was found in the majority of dihydropyridines isradipine and, to a lesser degree – in nifedipine preparations. The first generation of calcium antagonists: verapamil, diltiazem, nifedipine, felodipine, isradipine, nicardipine, nitrendipine. The second generation of calcium antagonists (modified release) verapamil SR, Diltiazem CD, nifedipine XL, felodipine ER, isradipine CR. The third generation of calcium antagonists (long-acting drugs): Norvasc, Lacipil, lercanidipine. Preparations of 2nd and 3rd generations are more active and specifical for particular organs and tissues, have longer effect (amlodipine, nisoldipine, felodipine, etc.). The positive properties of these calcium channel blockers include: greater specificity to organs and vascular areas suitable for prophylactic use, the weakening of many of the side effects typical of drugs 1st generation, as well as the emergence of new drugs with additional properties, such as antiagregatnoy activity against platelets (trapidil). The 3rd generation preparations are increasingly used in the clinic. These drugs have a long antihypertensive effect with minimal impact on myocardial contractility and intracardiac conduction.

Application of amlodipine in patients with  hypertension

Vasodilation in patients receiving amlodipine is due to not only the blockade of calcium channels, but also the stimulation of endothelial cells release nitric oxide (NO), which is a powerful natural vasodilator, as well as increased release of bradykinin.

Hypotensive effect of amlodipine develops gradually, has dose-dependent effect, not causes serious reflex increase in heart rate (HR), no drug tolerance develops with prolonged use.