Amlodipine: the original or a generic medication?

Calcium antagonists (AA) are presented in the Republic of Belarus, a large number of drugs a few generations. Each new generation of AC has significantly improved pharmacokinetic properties, more optimal parameters of therapeutic efficacy and safety.

The literature contains a large number of publications on the use of AK in the practice of general practitioner (1-3, 6, 8). The classification was proposed by AK T.Toyo-Oka and W. Nayler in 1996. Based on our long experience in the use of AK in cardiology, drugs I generation (nifedipine, diltiazem, verapamil) were gradually replaced from medical practice in relation to the severity of side effects (eg, nifedipine causes excessive activation of the sympathetic-adrenal system, verapamil - a negative foreign-and chronotropic effects), as well as short term of their actions. Therapeutic use of AK I generation, seems to be confined to emergency cardiology (hypertensive crises, paroxysmal cardiac arrhythmia) (6).

AK II generation, despite the improved pharmacokinetic properties, tissue selectivity, distinguished by a lack of predictability, wide fluctuations in drug concentration in plasma during the "mezhdozovogo" interval, a sudden termination, which can lead to undesirable clinical effects (1,6).

Antagonist of slow calcium channels of the III generation is characterized by selectivity of amlodipine in vascular smooth muscle cells, which determines the hypertensive effect - decrease in peripheral vascular resistance in the absence or slight decrease in cardiac output. Amlodipine lowers the tone of arteries and arterioles of the pulmonary circulation - because this is not observed significant tachycardia. In addition, the drug does not affect the circadian rhythm of blood pressure, no significant effect on sinus node function, conduction (5 - 8).

Unlike other calcium channel blockers, amlodipine has a long enough period of elimination: T _{1 / 2} of 35-40 hours, which allows you to take it 1 time a day (6).

Because blood pressure is reduced slowly (peak attained within 6 hours after admission) and persists for more than 24 hours, amlodipine is shown as a means of long-term treatment of patients with arterial hypertension (AH). In contrast to the AK I and II generations amlodipine, which is very important, does not cause withdrawal symptoms (4 and 6, 8).

As shown by comparative studies of tolerability of antihypertensive therapy (TOMHS), amlodipine showed better results than chlorthalidone, doxazosin, and enalapril atsebutalol (3, 8). Proved the advantage of amlodipine in reducing the risk of cardiovascular complications. Thus, the total mortality in the treatment of amlodipine was 4.1 / 1,000 patient-years, with use of drugs other groups - 6.7 / 1,000 patient-years, the treatment with nifedipine - 23.8 / 1000. Cardiovascular mortality was respectively 1 / 1000, 4,4 / 1,000 and 15.9 / 1,000 person-years (3).

Therapy with amlodipine reduces myocardial mass and reduce the dilatation of the left ventricle, the drug prevents the remodeling of the heart and arteries (7,8).

There is evidence of hyperactivation in the early hours of the renin-angiotensin system and, therefore, increase the risk of cardiovascular complications (2, 4). The problem of the morning increase in blood pressure (BP) has become particularly urgent in light of a significant increase in risk of myocardial infarction, sudden death, patients with hypertension was morning, the first 3 hours after awakening. One of the main causes of these serious complications - an excessive increase in blood pressure and heart rate in the morning in response to physical activation of patients and, consequently, the activation of metabolic processes (3). All this justifies the need for more careful monitoring of blood pressure is in the morning hours. Unfortunately, identified by SMAD morning of blood pressure and not go beyond the scope of research and not adequately addressed in practice. Therefore, an additional criterion for choosing a calcium antagonist amlodipine generation III is its ability to effectively control blood pressure in the morning.

In the appointment of medicines for the treatment of any disease, including hypertension, before the clinician is the problem of selection of original or generic products. An active policy of companies - manufacturers of original drugs contributes to a negative attitude toward the very notion of "generic". However, according to some researchers, such a position for no reason (OB Taliban, 2006). By assigning a generic, the clinician should have information about its pharmaceutical and therapeutic equivalence of the original drug. ═

Aim of this study was to evaluate the efficacy and tolerability of morning rise in blood pressure in patients with arterial hypertension (AH) on an outpatient basis amlodipine company Pfizer (Norvasc) amlodipine and the company Pharmacare Int. Co (Vaskopin).

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Materials and methods

We examined 148 patients with essential hypertension I-II degree (according to WHO criteria, 1999) using casual blood pressure measurements and diurnal blood pressure monitoring (SMAD). We selected 48 patients with persistent elevated blood pressure in the morning, which were divided into 2 groups of 24 patients in each group. The disease duration was, on average for both groups of 11,9 ╠ 1,8 years. Each patient included in the study prior to the appointment of the above drugs was administered weekly break from medication. Patients first group (17 men and 7 women, mean age 52,2 ╠ 1,8 years) within 2 months of receiving amlodipine Rfizer (Norvasc), 10 mg per day dose. Patients second group (16 men and 8 women, mean age 51,8 ╠ 1,7 years) and for 2 months to 10 mg per day administered amlodipine of Pharmacare Int. Co (Vaskopin).

If at this dose therapeutic effect was not achieved (diastolic blood pressure (DBP) did not decrease to 90 mm Hg or by at least 10% of baseline), a dose of both drugs was increased to 15 mg per day. Expression of blood pressure in the morning hours was evaluated at 2, 4, 6, 8 weeks of treatment. Therapeutic effectiveness, prescribed therapy was considered good for the normalization of blood pressure (DBP reduction to 90 mmHg), satisfactory - with a decrease in diastolic blood pressure by at least 10%, but not back to normal, and poor - with a decrease in DBP in the morning, less than 10 % from baseline.

The study excluded patients with symptomatic hypertension, chronic cardiovascular failure, myocardial infarction, acute cerebral blood circulation in the last 12 months, sick sinus syndrome, atrioventricular block, diabetes, comorbid conditions requiring more medication use and make it difficult to assess the effectiveness of conducted antigipertenzionnoy therapy and its tolerability. Were excluded patients with individual intolerance to calcium antagonists.

Titration of doses of the drugs was performed during the first week by casual BP control. Prior to the beginning and after 2, 4, 6, 8 weeks of supplementation conducted daily monitoring of blood pressure monitor "Kardiotehnika - 4000 AD" (St. Petersburg). SMAD during the following time intervals used changes in BP: morning period (the first 90 minutes after you wake up and rise from the bed) - 10 minutes a day period - 15 minutes a night time - 30 minutes. In the morning time SMAD was carried out with more frequent measurement, and we conventionally call "morning blood pressure monitoring" - UMAD. In this case, we separately calculated the index of time (% of the time the morning of the period during which there was an increase of blood pressure above 140/90 mm Hg) and the index area (area under the curve value, graphically reflecting the degree of increase of blood pressure above 140/90 mm Hg. Art..)

Statistical data processing carried out using the program Statgraphics (version 2.6) methods of variation statistics using paired t-test.

Results and Discussion

The main characteristics of patients is presented in Table 1.

Table 1. Characteristics of examined patients with hypertension

As can be seen from Table 1 in the study in both groups included both men and women in equal proportion, predominantly of working age (40-50 years) with mainly average risk of cardiovascular complications (respectively, 58.3% and 54.1%). At 8 people. (33.3%) in Group 1 and 9 people. (37.5%) in group 2 there was a high risk of cardiovascular complications. Only in 2 patients in the 1st and 2nd groups marked by a very high risk of cardiovascular complications and was diagnosed with coronary heart disease. Left ventricular hypertrophy occurred in 8 patients of group 1 (33.3%) and 9 patients in group 2 (37.5%). All patients showed an drug therapy. Prior to prescribing only 16.9% of patients in Group 1 and 12.5% ​​in group 2 regularly took antihypertensive drugs. Most patients in both groups (83.1% and 85.7% respectively) were taking medications only sporadically and mainly in the sharp rise in blood pressure and deterioration of general health. A significant number of patients as the 1st (37.4%) and 2nd group (33.3%) as the preferred antihypertensive therapy clonidine. Frequent hypertensive crises (2 times per year) were observed in only one (4.1%) patients in group 2, one in a hypertensive crisis were recorded in 4 (16.9%) patients in Group 1 and 3 - x (12.5%) in group 2. Over the entire period of the disease, one hypertensive crisis was observed in 8 (33.3%) patients in Group 1 and in 7 (29.1%) in group 2. Depending on the initial circadian blood pressure profile curve types were isolated circadian rhythm of blood pressure. With a normal circadian rhythm and adequate blood pressure reduction at night (dippers; daily index - SI = 10-20%) in group 1 was 14 (58.3%) patients in the 2 nd - 15 (62.5% .) Lack of or insufficient blood pressure reduction at night (non-dippers; Cu20%) (see Table 1.).

Table 2 shows the dynamics of the traditional indicators of SMAD in the treatment of patients with arterial nipertenziey Norvasc and in askopinom.

Table 2. Changes in SMAD after treatment Norvasc and in askopinom

* - Statistically significant (P <0.05) change in the before and after treatment.

When applied alone Norvasc good and satisfactory effect was achieved in 21 patients (87.5%), while taking vaskopina - in 20 patients (83.3%). Every third patient, both the 1st and 2nd groups to achieve a sustained reduction in blood pressure (below 140/90 mm Hg) during the day, including during the morning hours, the dose of both drugs had increased to 15 mg / day. In 6 patients (25.0%) as the 1st and 2nd group, which according to the SMAD, a decrease of blood pressure at night (over-dippers), as Norvasc and vaskopin a daily dose of 10 mg did not cause a significant reduction blood pressure at night, ie, dose adjustments of drugs is not required.

All patients in both groups as Norvasc and vaskopin caused a statistically significant decrease in average systolic and diastolic blood pressure at night, with daytime and nighttime periods, as well as a significant decrease in the indices of time and space. The variability of blood pressure, heart rate under the influence of treatment Norvasc and vaskopinom during the day, as well as daytime and nighttime periods remained unchanged. Tachycardia (heart rate> 90/min.) Was observed only in 3 (12.5%) patients in Group 1 and 4 (16.9%) patients in group 2, which makes these patients had to appoint metoprolol 50 mg / day.

Dynamics of changes in indicators UMAD in patients with hypertension treatment Norvasc is presented in Table 3.

Table 3. Dynamics of changes in indicators UMAD in patients with hypertension treatment Norvasc

** - Statistically significant (P <0.05) change in the before and after treatment.

Significant decrease in the average of both systolic and diastolic blood pressure, reducing time index and the area was observed only at the end of the 2nd week of treatment Norvasc. The most pronounced antihypertensive effect was observed at 4 to 6 weeks, especially significant - by the end of a two-month course of treatment (reduction in mean morning blood pressure below 140/90 mm Hg and morning time index less than 40%) (Table 3). Norvasc, according to UMAD, did not cause changes in blood pressure and heart rate variability. Unidirectional changes in the values ​​UMAD occurred and patients in group 2, treated as an antihypertensive therapy vaskopin (Table 4).

Table 4. Dynamics of changes in indicators UMAD patients with hypertension in treatment vaskopinom

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* - Statistically significant (P <0.05) change in the before and after treatment.

As shown in Table. 4, the dynamics of changes in the values ​​UMAD in patients with hypertension after treatment vaskopinom had the same character as that of patients receiving antihypertensive therapy as Norvasc. Morning hypotensive effect when taking vaskopina (group 2) was achieved in the overwhelming number of patients (83.3%). Decrease in blood pressure, an index of time and space in the morning as well as in group 1, was observed only at the end of second week of treatment. The most pronounced therapeutic effect in patients vaskopina manifested in 4 to 6 weeks, and most important - the end of the eighth week of treatment. In all patients, the drug did not cause changes in blood pressure and heart rate variability.

Thus, the morning antihypertensive effect was achieved in the overwhelming majority of hypertensive patients receiving Norvasc (87.5%) and vaskopin (83.3%). All patients in both groups by the end of treatment significantly decreased the index space and time, at the same time the variability of blood pressure and heart rate remained unchanged. Only in 3 patients of group 1 and 4 patients in group 2 with medication, there was tachycardia (heart rate> 90/min.), In connection with which he was appointed an additional dose of metoprolol 50mg/sutki.

Our investigations have shown, taking both Norvasc and vaskopina well tolerated. The overwhelming number of patients in Group 1 (75%) and 2 (71%) side effects were absent. In 20.8% of patients in Group 1 and 25% of patients in group 2 side effects occurred in the early days of treatment and were generally of short duration, were independently and did not require discontinuation. Only one patient in Group 1 and 2 patients in group 2 refused the drugs due to the fact that they have observed persistent swelling of the legs that have not been at lower doses of drugs. In the analysis of ECG, clinical blood and urine after treatment with significant changes from the original data was not observed.

The action of both drugs takes 24 hours, as evidenced by a significant decrease in average systolic and diastolic blood pressure in these times, registered with SMAD and UMAD.

The results of this study indicate that Norvasc and vaskopin equally possess the ability to effectively control blood pressure both during the day and into the morning hours.

Conclusions:

1. Therapy vaskopinom company Pharmacare Int. Co, and Pfizer's Norvasc is in equally high, preventing the increase in blood pressure in the morning.

2. Vaskopin and Norvasc may be used as a means of monotherapy in patients with mild to moderate hypertension.

3. При лечении больных, у которых ночью самостоятельно снижается АД, необходимо осуществлять тщательный подбор доз препаратов в целях профилактики ночной гипотензии.

4. Лечение больных АГ целесообразно проводить под контролем суточного и утреннего мониторирования АД.

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