Calcium antagonists in the treatment of hypertension

Under arterial hypertension (AH) understand chronic disease proceeding, the main manifestation of which is to increase the numbers of blood pressure (BP) is an equal and / or above 140/90 mm ​​Hg

Intrigue hypertension is that, flowing for a long time, it may be asymptomatic or have minor symptoms. AG is considered as one of the most powerful factors that can damage the vascular wall of any location. With the accession of hypertension atherosclerosis occurs early and at an accelerated pace, and the defeat of cerebral vessels contributes to poor blood supply to the brain (1).

Hypertension causes damage to target organs and development of associated clinical conditions. Among the associated clinical conditions leading cerebrovascular disease. In cerebrovascular diseases or complications were allocated 2 groups: 1) acute ischemic, and 2) chronic ischemic (14). For acute ischemic stroke include ischemic (cerebral infarction), hemorrhagic stroke (intracerebral, subarachnoid hemorrhage) and transient ischemic attack ((TIA) - a transient or dynamic cerebral blood flow). Chronic vascular pathology are hypertensive encephalopathy, which contributes to the progression of diffuse and focal lesions of the brain, as well as the initial manifestation of heart failure. According to the WHO in 2002 in the world of stroke (MI), 5.5 million people died. AG is a leading cause of 70% of all types of MI (8). That hypertension 3-4 times greater than the risk of cerebral circulation. The risk of MI is directly related to systolic (SBP) and diastolic blood pressure (DBP) (4). Cerebrovascular depend not only on the level of blood pressure, but also on the duration of the current AG. The important fact is the increase in risk of MI even with a slight increase in blood pressure. As a result, we can assume that inadequate treatment of hypertension is a major cause of mortality from cardiovascular diseases and in particular from the MI (2).

WHO has identified hypertension as the leading risk factor for development of modified acute and chronic forms of cardiovascular complications. Therefore, to reduce premature mortality from cardiovascular disease may be adequate treatment of hypertension.

заключается в блокаде входа свободного кальция в гладкомышечные клетки. Calcium antagonists (AA) - ​​one of the major classes of drugs used in kardionevrologii (5). The mechanism of action is blockade of the AK entrance of free calcium in smooth muscle cells. The result is relaxation of smooth muscle and dilation of arteries and arterioles. The walls of the cell membranes have a special time - the channels through which the transport of calcium ions. There are three main types of calcium channels: L, T, N. L type channels located in the heart cells, skeletal muscle and vascular smooth muscle. AK is affected by this type calcium channels. The result is a steady decline in the tone of smooth muscle cells of the vascular wall of large arteries and arterioles, which leads to permanent reduction in peripheral vascular resistance and systemic systolic and diastolic blood pressure (6).

AK is widely used in cardiology from the mid 70s of the 20th century. By the mid-90s they were one of the most chastonaznachaemyh drugs. 20 to 25 million patients with hypertension in the United States take a quarter of AK (13). According to global statistics, AK market is much larger market of other antihypertensive drugs: ACE inhibitors, angiotensin receptor antagonists II, beta-blockers and diuretics even. This is attributed, on one hand - with their high clinical efficacy, metabolic neutrality, on the other hand - with relatively few contraindications to the appointment, and relatively few side effects they cause (14).

AK is divided into two subgroups: the dihydropyridine (nifedipine, felodipine, latsedipin, amlodipine) and nedigidropiridinovye (verapamil and diltiazem). Between a subgroup of the above vary widely in the pharmacological properties, which causes different approaches of their application in clinical practice. In addition, AK is divided into first-and second-generation. The first generation of tablets include drugs that are commonly prescribed to maintain the therapeutic effect of three or four times a day. AK the second generation - it is long-acting drugs that can be given 2 or 1 per day. Prolonged effect is due to different chemical structure of drugs that are able to more long-circulating in the blood (amlodipine, felodipine) or a specific product with a slow and controlled release of drugs (verapamil, nifedipine) (9, 10).

Dihydropyridine AK operate mainly in the peripheral vessels, causing a vasodilator effect, which leads to lower blood pressure. In addition dihydropyridine AK, causing vasodilator effect on coronary arteries, have anti-ischemic effect, but this group of drugs does not affect the conducting system of the heart, and, in consequence, have no anti-arrhythmic effect. As a result, the effect of vasodilating dihydropyridine AK increased tone of the sympathetic nervous system, which contributes to increased rates of heart rate. This subgroup is also called diminishing pulse AK.

Nedigidropiridinovye AK as a result of the blockade of L-channels, blocking the release of calcium from the sarcoplasmic reticulum, which contributes to a lack of calcium concentration and inability to connect with troponin C and the activation of the reduction process. The result of this is inhibition of myocardial contractility (negative inotropic effect). Blockade of L-channels sinus leads to inhibition of pacemaker activity of sinus node - negative effect bathmotropic. Blockade of L-channel AV node leads to the inhibition of conduction in the AV node (negative dromotropic effect) (10, 11). Nedigidropiridinovye AK due to the direct effect on the sinus node, conducting system, as well as myocardial contractility, reduce the tone of the sympathetic nervous system and thereby reduce the heart rate - they are called which reduce heart rate of AK (10).

AK long-acting dihydropyridine provide adequate therapeutic effect in patients who do not always regularly taking antihypertensive medications. We prove that the omission in the reception of amlodipine leads only to a small reduction in the hypotensive effect (5). That's the AK should serve the drugs of choice in old age, isolated systolic hypertension, the presence of angina, atherosclerosis, peripheral arterial disease, carotid atherosclerosis. Dihydropyridine AK is that group of drugs that the doctor can prescribe to pregnant women with hypertension.

Dihydropyridine AK, in particular, amlodipine at a dose of 5-10 mg per day for 20 weeks led to a significant decrease in left ventricular mass. We prove that the left ventricular hypertrophy increases the overall mortality rate 4 times, and mortality from cardiovascular causes - in 7-9 times. The influence of left ventricular hypertrophy on the prognosis of cardiovascular disease is more significant at younger ages. Appointment of Amlodipine resulted in a significant decrease in the thickness of the interventricular septum, posterior wall of the left ventricle, with significant changes in the size of the cavities of the heart and lower ejection fraction did not (17). AK dihydropyridine reduce proteinuria. They have renoprotektivnoe effect, it is especially shown their use in chronic renal failure (such as amlodipine and latsedipina). The three-year, randomized, placebo-controlled study examined the effect of amlodipine Prevent on clinical outcomes of carotid atherosclerosis and coronary artery disease and. In 825 patients with coronary artery disease amlodipine had no effect on the progression of coronary artery atherosclerosis. At the same time noted that amlodipine caused a significant decrease in the rate of progression of atherosclerotic carotid arteries (in terms of intima-media thickness) and a significant decrease in the incidence of unstable angina and the need for different methods of myocardial revascularization.

Dihydropyridine AK can be given as bronchial asthma, marked peripheral blood flow disorders, type 1 diabetes, as well as when there are contraindications and undesirable beta-blockers: severe sinus bradycardia (less than 50 beats per minute), sick sinus syndrome, severe degree atrioventricular blockade (grade 2 or more).

наиболее характерные для дигидропиридинов: головная боль, сердцебиение, головокружение, ощущение жара. AK have few contraindications to dihydropyridine AK virtually there exists no absolute contraindications, relative contraindications are all types of tachyarrhythmias, congestive heart failure. Side effects are most characteristic of dihydropyridines: headache, palpitations, dizziness, sensation of heat. There is a difference in side effects of drugs in the first and second generation. For second-generation drugs (amlodipine) - the appearance of edema in the legs, associated with the violation of the capillary circulation. In many cases the development of edema in the legs can prevent the associated appointment of ACE inhibitors (1).

Thus, AK is one of the main groups of drugs with proven activity in the achievement of the antihypertensive effect, and also has several additional effects: regression of left ventricular hypertrophy, nefroprotektivnoe action, metabolic neutrality, reduced atherogenic blood.

Practitioners are not always easy to understand variety of antihypertensive drugs and in particular AK. At the present time in Russia, registered 20 generic amlodipine and they all have different names (9). We have studied the AK vaskopin dihydropyridine (amlodipine) produced by ╚Pharmacare Int. Co. ╩In the treatment of hypertension.
═

Materials and Methods. The study included 34 patients with hypertension (18zhenschin and 16 men) aged 37 to 68 years (mean age 51,3 ╠ 3,4 years). Duration of illness from 1 year to 12 years. Systolic blood pressure (SBP) was 150 - 210 mm. Hg. of Art. and diastolic blood pressure - 90 to 110 mm. Hg. of Art. The first group included 12 patients with SBP 150 -159 mm. Hg. of Art., diastolic blood pressure 90 -99 mm. Hg. of Art., the second of 14 patients with SBP 160 - 179 mm. Hg. of Art., DBP 100 -109 mm. Hg. Art and the third group consisted of 8 patients with SBP 180 - 210 mm. Hg. of Art., diastolic blood pressure 110 - 125 mm. Hg. of Art. Were excluded patients with severe kidney disease, decompensated liver disease, patients taking steroids and contraceptives. In all patients within a few days prior to study entry canceled prior antihypertensive therapy. The therapeutic dose was adjusted individually vaskopina. The initial dose was 2.5 mg. Dose titrated from 2.5 mg to 10 mg to achieve the target values ​​of patients in blood pressure (140/90 mm. Hg. Art..) With little effect added to the treatment of diuretic (indapamimd) and an ACE inhibitor. Vaskopin 2.5 mg per day taken 9 patients, 5 mg per day - 11 patients, 10 mg per day - 14 patients. Efficacy and tolerability of treatment was evaluated on the basis of the dynamics of clinical symptoms and hemodynamic parameters: BP was measured at Korotkoff was recorded heart rate (HR), recorded the electrocardiogram (ECG) in the dynamics, defined by total cholesterol (LDL) and glucose in the blood before treatment and 12 weeks of active treatment.

The hypotensive effect vaskopina evaluated on the 7th day of treatment and every 14 days for 3 months. In all patients after 7 days was noted a tendency towards a stable reduction of blood pressure after 14 days of blood pressure has stabilized, 48% of patients were transferred to a maintenance dose vaskopina 5 mg / day. Dynamics of blood pressure and heart rate is presented in Table 1.

Table 1. Dynamics of blood pressure and heart rate in patients on background 7 - day course of treatment vaskopinom

Note: * - P <0.05 compared with baseline.

The absence of sharp drops in blood pressure during treatment. This side effect is dizziness was observed in 4 patients and were stopped after 7 days of therapy without the drug. Peripheral edema while taking vaskopina absent. The dynamics of ECG parameters did not change. There was no effect of the drug on carbohydrate and lipid metabolism. Dynamics of lipid and glucose in patients with hypertension in treatment vaskopinom shown in Table 2.

Table 2. Dynamics of lipid and glucose in patients with hypertension in treatment vaskopinom

Thus, vaskopin an effective, safe, metabolically neutral drug. Can be administered as monotherapy in patients with hypertension I-II century. At AG II-III century. with prolonged duration of disease - in the form of combination therapy (in combination with diuretics and ACE inhibitors). Vaskopin does not require lengthy dose titration, as the dose of 5-10 mg is effective in most patients with hypertension.

References:
1. Kabalava Railway, Gudkov, KM Secrets of hypertension: Answers to your questions. - Moscow, 2004
2. Martsevich SJ Is it possible to prevent cerebral stroke in hypertensive patients? / / Directory of outpatient physician. - 2006. - T.4, № 1.
3. Mac Mahon S, Peto R, Cutler J et al. Blood pressure, stroke and coronary eart desease. Part 1. Prolonged differences in blood pressure: prospective observation studies corrected for the regression delution bias. - Lancet, 1990. - 335: 765-74.
4. Suslin ZA, Geraskin LA, Fonyakin A. and so on cerebral blood flow and cognitive function in patients with cerebrovascular pathology in the treatment of tevetenom / / Atmosphere. Nervous Diseases, 2005. - № 2. - S. 2-7.
5. Kukes VG Ostroumov, OD, Starodubtseva AK etc. The modern view of the clinical and pharmacological characteristics of hypertension / / Good clinical practice, 2005. - № 1. - S. 97-104.
6. Karpov Yu.A., Sorokin, EV Pharmacotherapy in Cardiology: the position of calcium antagonists / / Consilium medicum, 2004. - T.6., № 5.
7. Pristrom MS, Sushinsky VE Arterial hypertension in the elderly. Current issues of therapy. - Minsk: Asobny, 2006. - 112.
8. Martsevich SJ Prevention of stroke: the possibilities of modern therapy / / Consilium medicum, 2004. - T. 10, № 2.
9. Martsevich SJ The role of calcium antagonists in the modern treatment of cardiovascular diseases / / Russian Journal of Medicine, 2003. - T. 11, № 9.
10. Kukes VG, VP Fisenko Clinical Pharmacology. - London: Remedium, 2003. - 86 sec.
11. Kukes VG Clinical Pharmacology. - London: GOEOTARMeditsina, 2000. - S. 133 - 145, 166-167.
12. Oshchepkova EV Hypertensive encephalopathy / / Consilium medicum, 2004 .- T. 3, № 3.
13. Maholio TA, Cutler JA, Furberg CD et al. Trends in pharmacologic management of hypertention in United States / / Arch. Intern. Med, 1995 / - 155: 1829 - 37.
14. Epstein M. calcium antagonist in management of hypertension. In: Epstein M, editor calcium antagonist in clinical medicine 3rd edition. Philadelphia: Hanley and Belfus, 2002. - P. 293-313.
15. Schmeider RE, Shilachi MP, Klingbeil et al. Update reversal of left ventricular hypertrophy in essential hypertension (a metaanalysis of all randomized double-blind studies unt; December 1996) / / Nephral Dial Transplant, 1998; 13: 564-9.
16. Fonyakin AV Geraskin LA Hypertension, cerebrovascular pathology and vascular cognitive impairment. Topical issues. - Moscow, 2006. - 48.
17. AO Konradi Treatment of hypertension. Left ventricular hypertrophy / / Consilium medicum, 2005. - T. 11, № 2.