Dihydropyridine calcium antagonists in the treatment of gestational hypertension

The most studied according to numerous studies conducted in pregnant women with different clinical types of arterial hypertension (AH), a nifedipine. The drug is well established as a rapid means for the treatment of acute severe hypertension, including in pre-eclampsia (PE).

The report of the Working Group on high blood pressure during pregnancy, National Institutes of Health U.S. National Heart, Lung, and Blood USA (2000) [25] showed that the expressed variations of blood pressure during the day in prescribing short-acting may worsen feto- placental blood flow, which led to recommendations on the need to smooth blood pressure reduction. From this perspective, the most preferred among DAC drugs with prolonged action, such as sustained-release nifedipine, felodipine [17], nicardipine [26], isradipine [4], amlodipine [8, 9].

Since amlodipine in pregnant women was carried out several studies [3, 8, 9]. The drug not only leads to normalization of blood pressure, but also reduce the frequency of hypertensive, hemodynamic dissociation by reducing total peripheral vascular resistance and cardiac index, and to improve perinatal outcomes [8]. In IM Davidovich et al [3] showed that the use of amlodipine in gestational hypertension (GH) has contributed, along with normalization of blood pressure, restoration of impaired endothelium-dependent vasodilation of brachial artery.

YY is the most common type of clinical hypertension in pregnancy and a rise in blood pressure, was first recorded in the second half of pregnancy (after 20 weeks of gestation) in normotensive women and is not accompanied by proteinuria [25].

However, the application of calcium antagonists remain a number of issues that can lead to improved treatment of complications during pregnancy and reducing perinatal morbidity and mortality [7].

In view of this study was to evaluate the efficacy and safety of DAK - amlodipine in pregnant women with mild course of GH, which developed in the III trimester of gestation.

Material and methods

We undertook a clinical and instrumental examination 32 pregnant women with HS. The diagnosis of GH on the International Classification of Diseases revision 10 corresponded to category O13 - pregnancy-induced hypertension without proteinuria significantly [6]. All women mentioned for mild HS, ie, increased blood pressure in the range of 140-159/90-99 mm Hg. of Art. The average age of women was 30,84 ╠ 7,14 years (range 21 to 45 years). Development was observed with GH III trimester of pregnancy - increased blood pressure in the middle began to 34,06 ╠ 3,88 week. As an antihypertensive therapy used amlodipine (Vaskopin, the company ╚Pharmacare╩) in monotherapy, which was administered at a daily dose of 5-10 mg in 1-2 doses. The average daily dose was 6,09 ╠ 2,1 mg. Effective level of control GH was considered to achieve blood pressure below 140/90 mm Hg. of Art. in office measurements and less than 130/80 mm Hg. of Art. - Daily average for daily monitoring of blood pressure [19, 25]. Daily monitoring of blood pressure (SMAD) was performed using a monitor OXFORD Medilog dX (UK) by standard methods [23, 29, 30], as applicable, including pregnant women [14] twice (before the appointment of antihypertensive therapy and after 7-10 days from start of treatment). Safety of the drug was assessed by the number of such gestational and perinatal complications, such as the incidence of premature birth, cerebral ischemia infants born preterm and low birthweight for gestational age children, weight loss and growth of infants. The incidence of gestational and perinatal complications were compared with a group of 30 pregnant women with HS located in non-drug therapy.

Results and Discussion

Question of antihypertensive treatment GH is still open: first, do not determine whether the destination of antihypertensive drugs, and secondly, blood pressure is unknown to the start of treatment. According to the literature [13] considered the unanimous opinion that the appointment of antihypertensive drugs is a major component of drug treatment of severe HS, avoiding complications in mother and fetus. With controlled blood pressure medication should be kept at 130-140/80-90 mm Hg. of Art. as a more pronounced reduction in blood pressure can lead to a breach of perfusion of internal organs, including the placenta, followed by the deterioration of the fetus. Application of the same drug therapy for mild HS is doubtful, as suitable for a mother's blood pressure reduction may lead to poor utero-placental blood flow, disruption of hemodynamics of the fetus and intrauterine fetal development [27]. In addition, it is known that the prognosis for women with GH favorable.

On the other hand, some authors [3, 5, 16, 25] believe that the mild HS, which developed before the 34th week of pregnancy, you should use pharmacological antihypertensive therapy, which allows you to prolong pregnancy and improve the functional status of the fetus. Feasibility of using drugs for non-severe HS, which began later in gestation, has not been established.

Experts in the recommendations of the European Society of Cardiology 2003 and 2007. diagnosis and treatment of pregnant women with hypertension [19, 30, 31] propose to start drug therapy with GH, developed after 28 weeks' gestation with blood pressure levels above 150/95 mm Hg. of Art.

Prescribing antihypertensive therapy for pregnant women is a responsible step, as affect the interests of not only mothers, but fruit. Also keep in mind the type of clinical hypertension during pregnancy, because there are significant differences in the pathogenesis of elevated BP. For example, it is known that gestational hypertension types (PE and GH) are accompanied by increased tone of peripheral vessels, including endothelial dysfunction due to [1, 10]. Thus, the treatment is justified in the use of GH DAC, which not only have a vasodilating effect, but also have a positive effect on endothelial function. Moreover, reducing the concentration of Ca2 + in the cytosol and vasodilation in patients receiving calcium antagonists caused a decrease in transmembrane receipt of Ca2 + in smooth muscle cells and NO-cyclic guanosine monophosphate-mediated stimulation of the release of endothelial cells and platelet-NO, a potent vasodilator mechanism in endothelial cells. In addition, calcium antagonists inhibit the formation of free radicals that deplete NO. The effect of AIBN on endothelial function in patients with hypertension have demonstrated in studies of PREVENT (amlodipine) [24], INSIGHT (with nifedipine GITS) [22], ELSA (with latsidipinom) [20]. In IV Tumbaeva [12] have shown nifedipine not only effectively reduced blood pressure in pregnant women, but endothelium-dependent vasodilation and increased the brachial artery. In addition, according to X. Zhang et al [33], amlodipine, unlike nifedipine and diltiazem, dose-dependently generated NO in blood vessels. According to some reports [18], increase the synthesis of another DAC vasodilator - bradykinin. In studies of A. Manninen [21] have shown that pregnant women with hypertension nifedipine reduces the production of platelet thromboxane A2.

Despite the numerous studies that demonstrate the safe use of DAC in the treatment of hypertension in pregnant women, finally they can be used during the period of gestation has not been established. This class of drugs is a category C drug safety for the fetus to use during pregnancy (FDA, 2004 [28]). This means that when using the DAC in animals showed adverse effects on the fetus, but adequate and well controlled studies in pregnant women has not been conducted. Nevertheless, despite the potential risk to the fetus, the expected therapeutic effect of the drug may justify his appointment [2, 11].

Safety of amlodipine use in pregnancy or breast-feeding information to pharmaceutical reference also not been established. Amlodipine showed no toxicity in studies in pregnant animals except for the delay childbirth and to increase contractions in rats at a dose 50 times higher than the maximum recommended dose for humans. Accordingly, its use during pregnancy is recommended only in cases where the intended benefits to the mother and the child will prevail over the potential risk.

In the surveyed group of pregnant women with GH baseline blood pressure according to the SMAD was 140,42 ╠ 3,59 mm Hg. of Art. for systolic blood pressure and 90,83 ╠ 3,59 mm Hg. of Art. for diastolic blood pressure. When you SMAD had significantly (p <0.05) decrease in both systolic blood pressure - up to 127,97 ╠ 5,66 mm Hg. of Art. and diastolic blood pressure - up to 83,28 ╠ 5,48 mm Hg. of Art. With SMAD in patients receiving amlodipine (Vaskopina, the company ╚Pharmacare╩) noted the smooth and sustained blood pressure reduction, with no significant fluctuations in the diurnal blood pressure profile. Reaching the target blood pressure according to the intake of SMAD Vaskopina noted in 66% of cases.

A comparison group of pregnant women surveyed, with patients receiving non-pharmacological treatment SG on any indicator that characterizes the development of gestational and perinatal complications, there were no significant differences.

Thus, based on available data, we can say that:

1. The use of AIBN with long-acting GH pathogenetically the most appropriate for comparison with other antihypertensive drugs used during pregnancy;

2. Amlodipine (Vaskopin, the company ╚Pharmacare╩) proved to be an effective antihypertensive agent in HS;

3. Application Vaskopina in the III trimester of pregnancy is not accompanied by an increase in the number of gestational and perinatal complications.

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