Rational Pharmacotherapy in Cardiology

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Vol 2, No 3 (2006)
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4-11 366

Aim. To evaluate antihypertensive efficiency of benasepril therapy (Lotensin, Novartis) and its effects on microcirculation, endothelium function, system of cytoprotection, ophthalmoscopic and functional characteristics of eye retina in patients with arterial hypertension (AH). Material and methods. 40 patients with AH of 1-3 degree (AH1, AH2, and AH3) were studied. After wash-out period all patients were prescribed benasepril 5-10 mg daily. If necessary, hydrochlorothiazide 12,5 mg daily was added. Treatment lasted during 6 months. Patients were examined at the beginning and at the end of the study. Ambulatory blood pressure (BP) monitoring was carried out. Microcirculation was assessed by method of laser Doppler flowmetry. Stable plasma metabolites of nitric oxide (NO) were determined by spectral photometry. Cytoprotection was assessed by content of heat shock proteins (HSP70) in leucocytes of peripheral blood. Ophthalmoscopy, color and contrast static campimetry with evaluation of sensory-motor reaction (SMR) time in different fields of vision were carried out. Results. Therapy with benasepril allowed to improve daily profile of BP and to reach its target level in all AH patients. Number of patients with spastic type of microcirculation decreased. Functional condition of endothelium improved which revealed in normalization of endothelial production of NO. Therapy with benasepril resulted in intracellular HSP70 level decrease which testified restriction of cellular destruction. The cytoprotective effect of benasepril was stronger in patient with severe AH. Therapy with benasepril resulted in SMR time decrease which signifies its positive influence on retinal blood flow. Evaluation of contrast and color sensitiveness of retina allowed to reveal and quantitatively assess earlier dysfunctions of retinal tissue perfusion, compared to ophthalmoscopy. Conclusion. Benasepril is an efficient antihypertensive drug which improves microcirculation, endothelium function and retinal perfusion, has cytoprotective effect. Color and contrast static campimetry is an adequate method for quantitative assessment of retinal perfusion and allows objectively to evaluate damage of eye as target organ of AH.

12-18 488

Aim. To evaluate the influence of carvedilol (Talliton, Egis, Hungary) on daily profile of blood pressure (BP), anatomical and functional conditions of left ventricle (LV) and cerebral circulation in patients with arterial hypertension (AH), stage II-III. Material and methods. 30 patients (10 men, 20 women, average age 51,9±7,9 y.o.) with AH II-III stage ( RSSC,2004) and with initially affected daily profile of BP, cerebral circulation, anatomical and functional disorders of LV took carvedilol 25-75 mg/d during 6 months. Hemodynamics was estimated by ambulatory BP monitoring, Doppler Echocardiography, and ultrasound Dopplerography of extra cranial vessels. Results. A normalizing effect of carvedilol on abnormal daily profile of BP and cerebral circulation was determined. The treatment resulted in the regress of LV hypertrophy with predominant reduction of interventricular septum thickness and also the transformation of concentrical LV hypertrophy in excentrical one. Conclusion. Long-term therapy with carvedilol in patients with AH II-III stage provides a stable BP control and cardioprotective effect, improves cerebral circulation.

19-25 830

Aim. To evaluate the effecacy of enalapril (Enam, Dr.Reddy’s, India) and atenolol (Tenormin, AstraZeneca, UK) and their influence on processes of cardiovascular system remodeling in comparative research in patients with arterial hypertension. Material and methods. 38 patients with arterial hypertension stage II were examined. 21 patients were treated with enalapril (10-40 mg\d) and 17 – with atenolol (50-100 mg\d). Duration of therapy was 24 weeks.  A daily monitoring of blood pressure and echocardiography were made before and after the treatment. Spontaneous erythrocyte aggregation and deformability, spontaneous platelet aggregation and adhesive property of neutrophils were also estimated. A number of leucocytes carrying activation markers and expressing adhesive molecules was calculated. The plasma concentration of adhesive molecules (ICAM-1) and von Willebrand protein as well as serum concentration of N-terminal peptide of procollagen type III was also estimated. Results. Enalapril versus atenolol improved blood rheology, reduced functional leucocytes activity, plasma concentration of von Willebrand protein and intercellular adhesive molecules. The reduction in collagen III synthesis activity in enalapril therapy was proved. A significant regress of left ventricle hypertrophy due to enalapril treatment was related with favorable non-hemodynamic effects. Conclusion. The research revealed that the blockage of tissue rennin-angiotensin system is very important in prevention of cardiovascular complications especially in high risk patients.

26-31 3355

Aim. To asses effects of amlodipin and metoprolol on autonomic system in emotional and cold tests in hypertensive patients with different psychological profile (PP) Material and methods. 61 patients with arterial hypertension of II grade were observed. Therapy with amlodipin or metoprolol was prescribed and allowed to reach target blood pressure (BP) level in all the patients. Patients were divided into 2 groups: 1-st one – patients with normal PP, 2-nd group – patients with subclinical depression. Patients were examined before and 30 days after therapy. Examination included ambulatory BP monitoring, assessment of autonomic status by variational intervalometry and spectral analysis of heart rate variability (HRV) in cold and emotional tests. Depression and anxiety levels were determined with Bek’s and HADS scales.  Results. Treatment with amlodipin  and metoprolol can result in improvement, worsening or unchanging of PP.  In hypertensive patients with subclinical depression improving their PP resulted in autonomic reaction change: sympathetic activity increases and reaction on stress becomes more adequate. If subclinical depression occurred in hypertensive patients because of amlodipin and metoprolol therapy, sympathetic system stress-reaction decreased and parasympathetic influence increased. Conclusion. The study results show necessity of psychometric examination of hypertensive patients in order to reveal subclinical depression and anxiety.  

32-36 499

Aim. To investigate the effects of cytoprotection with mildronate (Grindex, Latvia) on oxidative processes and endothelial function in elderly patients with ischemic heart disease (IHD). Material and methods. 117 elderly (upwards 60 y.o.) patients with IHD were included into controlled study. They were also suffering from heart failure II-III functional class (according to NYHA classification) and from arterial hypertension (AH). All patients were randomized into 2 groups: 1) 67 patients (75,4±0,5 y. o.) were treated with mildronate 500 mg/day simultaneously with basic therapy during 12 weeks (the main group) and 2) 50 patients (74,0±0,6 y. o.) were treated only with basic therapy during 12 weeks (the compare group). Total cholesterol (CH), triglycerides (TG), low density lipoprotein cholesterol (LDL), high density lipoprotein CH (HDL), LDL antioxidant potential (concentration of α-tocopherol and retinol in LDL), initial level of lipid peroxidation (LPO) products in LDL, LDL resistance to oxidation and blood level of NO metabolites were determined before and after 4 and 12 weeks of the therapy. Results. Mildronate did not have any effect on the blood lipid profile in elderly patients with IHD. The initial level of LPO products in LDL was decreased by 33% and LDL resistance to oxidation was increased by 26% in the main group after 12 weeks of therapy in comparison with the same parameters before the study and in comparison with control group of patients (p<0,05). The blood level of NO metabolites was 1,4 fold higher in the main group of patients after 12 weeks of therapy in comparison with the same parameters before therapy and in comparison with control group of patients (p<0,05). More prominent growth of LDL resistance to oxidation after 12 week therapy with mildronate was revealed in men than in women, in patients with angina II class than in patients with angina III class, in patients with heart failure II class than in patients with heart failure III class. Conclusion. Some antiatherogenic effects of mildronate are observed in elderly patients with IHD. These are the decrease in LPO activity in LDL and the increase in synthesis of NO.


37-45 715

Mechanisms of atherothrombosis in atherosclerosis of coronary arteries are described. Mechanism of action and clinical efficiency of antithrombotic and antiplatelet medicines such as acetylsalicylic acid, warfarin, ticlopidine and clopidogrel are discussed. Study data on new antiplatelet drugs are given: selective thromboxane inhibitors, antagonists of thromboxane receptors, blockers of platelet receptors for glycoproteins GPIIb/IIIa. Possibility of clinical use of additional antiplatelet features of statines is discussed, as well as their connection to stimulation of nitrate oxide production, powerful endogenous antiplatelet factor. Examples of other donators of nitrate oxide and activators of its endogenous synthesis are given.

46-50 394

Atherothrombosis is a complication of ischemic heart disease, and it leads to development of acute coronary syndrome. Atherothrombosis is characterized by sudden destruction of atherosclerotic plaque, which results into platelets activation and thrombus formation. Aspirin - one of the most widely used antiaggregate drugs, prevents development of the recurring myocardium infarction, stroke, sudden coronary death. But in number of patients aspirin is not efficient. Development of repeated thrombotic complications with aspirin therapy or resistance to aspirin is independent predictor of high coronary risk. There are controversial data about aspirin resistance incidence, which varies from 5 to 48%. Possible reasons for this are discussed: low compliance with treatment, peculiarities of functional condition of platelets, genetically given variability of platelet receptors etc. Different methods, based on estimation of platelets activity are proposed to assess the possibility of repeated thrombotic complications, caused by resistance to aspirin. Further researches including valid number of patients are needed to assess incidence of aspirin resistance and to reveal mechanisms of its development.

51-55 524

The anticoagulants of indirect action during many years serve drugs of basic prophylaxis and therapy of thromboembolic episodes at cardiovascular , neurological, oncology, orthopaedic and other diseases, after surgical interventions and traumas, and also large bunch of the generically caused and acquired (secondary) thrombophilie. The contents of vitamin К1 in nutrition depend on a method of product preparation. The highest concentrations are found in dark green vegetables and grass: parsley, spinach, green turnip, and also in cabbage and lettuce. For achievement stable hypocoagulation at assignment of anticoagulants of indirect action the daily entering with nutrition of constant amounts of vitamin K (at a level 65-80 mkg/day) is necessary. Thus, a doctor at assignment of anticoagulants, is obliged to pay attention to character of a food and to inform patient about possible undesirable consequences at the use of products keeping high levels of vitamin К1.


56-64 881

Results of randomized clinical trials on the usage of calcium antagonists (CA) in order to prevent perioperative complications during aortocoronary bypass procedure and operations on heart valves are analyzed. CA reduced the risk of perioperative myocardial infarctions and episodes of reversible myocardial ischemia. After angioplasty of coronary arteries CA (particularly amlodipine) show positive effects on restenosis incidence and reduce about 3 times a number of repeated angioplasty and aortocoronary bypass operations. The use of CA was accompanied by more often need in heart electro stimulation without any subclass differences. It is also registered that nimodipine can strengthen intraoperative blood loss. It is concluded, that CA have significant evident base that allows recommending them to patients undertaken by cardiological surgery.

65-68 578

The metabolism, classification, biomedical implication and clinical application of polyunsaturated fatty acids (PUFAs) were analyzed. It was proved that PUFAs class omega-3 have positive effects on cardiovascular system. First of all, this is an antiarrhythmogenic action, which is accompanied by the increase in variability of heart rhythm. Omega-3 PUFAs cause the reduction in platelet activity and vasoactive mediator release (serotonin, thromboxane A2), vasodilatation, the reduction in inflammatory mediators release and endothelium permeability, the rising of endothelium dependent dilatation of vessels, the depression of vascular response on angiotensine П and noradrenalin. Omega-3 PUFAs are responsible for the reduction in blood pressure, the increase in erythrocytes elasticity, the fall of fibrinogen concentration and normalization of plasma lipid profile. Omega-3 PUFAs in large dozes show antiatherosclerotic effect. Clinical data showing that Omega-3 PUFAs increase in life time due to reduction in sudden death incidence were provided. It is suggested to use Omega-3 PUFAs (OMAKOR) for secondary prevention of ischemic heart disease and treatment of hypertriglyceridemia.


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