Impaired Renal Efficiency

The place of ACE inhibitors in the treatment of hypertension

Hadzegova Blalovna Alla PhD. med. The introduction of Sc-converting enzyme (ACE) inhibitors in the treatment of arterial hypertension (AH) is a monument of the century. Currently, there are a large number of ACE inhibitors and a mechanism of action - inhibition of the renin-angiotensin-converting enzyme, resulting in reduced formation of angiotensin II. On the chemical composition of ACE inhibitors isolated containing the sulfhydryl (captopril), a carboxyl group (enalapril, lisinopril, ramipril, tsilazapril, etc.) and fosfonilnuyu group (fosinopril).Fosinopril is the most modern generation of ACE inhibitors. Active pharmaceutical forms are captopril, libenzapril, lisinopril and tseronapril, others - prodrugs, the effect occurs after metabolism in the liver and the formation of active metabolites. A very important feature of ACE inhibitors is the ability to accumulate in the tissues, namely lipophilicity, which determines the degree of tissue renin-angiotensin system blockade. Characterized by a high degree of lipophilicity fosinopril and quinapril least - Ramipril, etc.Our understanding of the ACE inhibitor largely formed on the basis of data from randomized trials, ALLHAT, CAPPP, ABCD, HOPE, FASET, SCAT, etc. The results of clinical studies have shown that the effectiveness of blood pressure (BP) and prevention of cardiovascular events, ACE inhibitors are not inferior to diuretics, beta-blockers and calcium antagonists.Meta-analysis of two studies of Russian - FLAG (fosinopril in the treatment of hypertension) and bassoon (pharmacoeconomic evaluation of the use of an ACE inhibitor (fosinopril) in the outpatient treatment of patients with hypertension complicated course) showed that the ACE inhibitor fosinopril is effective in the treatment of patients with hypertension. In a study in 2557 FLAG patients with essential hypertension I-III degree evaluated the effectiveness of three months of treatment with fosinopril at a dose of 10-20 mg / day. alone or in combination with hydrochlorothiazide (12.5-25 mg / d).. Found that fosinopril can effectively control blood pressure in 89% of patients, a goal of reducing blood pressure (140/90 mmHg) was achieved in 62.1% of patients. In this case, fosinopril has been well tolerated and highly secure, which recommends this treatment regimen for hypertension. The study group composed of key FAGOT 1777 patients who received fosinopril at a dose of 10-20 mg / day. with the addition of hydrochlorothiazide if necessary, at a dose of 12.5 mg (802 patients). The control group consisted of 819 patients, 81% of patients received beta-blockers, 56% - diuretics, and 33% - calcium antagonists.The study, fosinopril monotherapy is effective in more than 50% of patients. BP target in the intervention group was achieved in 67.8% of patients. In this case, noted that the effectiveness of the treatment of hypertension under the influence of fosinopril is not different in patients according to age and therapy than with beta-blockers and diuretics.Moreover, the results of multicenter studies FACET (Fosinopril) randomized ABCD (enalapril) showed that in patients with hypertension and diabetes mellitus type II, ACE inhibitors prevent the development of cardiovascular complications vascular significantly more effective than calcium antagonists. By their ability to provide organoprotective ACE inhibitors are superior to other antihypertensive agents. Most expressed their effects on the heart and kidneys. Shown that regression of left ventricular hypertrophy was more pronounced under the action of ACE inhibitors. Thus, the study sample use lisinopril 20 mg / day.contributed to a decrease in left ventricular mass by 15.8%. According to the results of a meta-analysis, which summarizes the results of 102 studies, ACE inhibitors 15% reduction of left ventricular mass, while other drugs showed 1.5-2 times less pronounced effect . ACE inhibitors - first-line drugs for the treatment of patients with renal disease. The search for drugs with properties nephroprotektive dictated by the fact that AG reduced levels of BP did not prevent renal dysfunction.Surveys (Euclid, ABCD, Prevenda IT), in which it was shown that ACE inhibitors slow the progression of kidney disease by reducing the pressure vnutriglomerulyarnogo, membrane permeability and proteinuria. However, when the drug is necessary to consider ways of disposal, or renal failure, it can be cumulative. Unlike most ACE inhibitors, which have a kidney or a predominantly renal route of excretion, the safer is the fosinopril, which has a dual route of elimination.In the normal liver and renal excretion of fosinopril is done in equal proportions, with the proportion of the increase in liver kidney road, preventing the accumulation of the drug. In patients with renal disease, the accumulation index is lower in fosinopril three times that of both enalapril and 6 to that of lisinopril. The study on the FOPS 757 elderly patients with renal failure, the efficacy and safety of fosinopril. The study Prevenda it was confirmed nephroprotective effects of fosinopril in patients with microalbuminuria and a normal blood pressure.With this group of fosinopril have been reported cases much less cardiovascular mortality and rehospitalization for myocardial infarction and heart failure. Patients treated with pravastatin, the incidence of cardiovascular events, death and readmission rates were 13% lower than in the control group, but higher than in the fosinopril. No less important properties of ACE inhibitors are well tolerated and safe, they do not affect the metabolism of fats, carbohydrates and purines, not cause impotence. It is these properties is defined as their wide application in the world.Thus, according to a study health survey for England in 1994 in England for the treatment of hypertension, ACE inhibitors, used in 26% of patients in 1998, the number of these patients had almost doubled to 50.8% - the highest figure among the different classes of antihypertensive funds. The most common side effect of limiting the use of ACE inhibitors is a dry cough that occurs due to increased levels of bradykinin. The frequency of this complication, according to various estimates, 5-50%. Coughing often occurs in women and nonsmokers. Among the ACE inhibitors fosinopril distinguished by the fact that rarely causes a cough.In controlled studies, treatment with fosinopril the appearance of dry cough observed in only 2% of patients. In addition, there is evidence that the frequency and intensity of cough caused by other ACE inhibitors, fosinopril reduced replacement. With mild to moderate hypertension, the ACE inhibitors prescribed as monotherapy, is effective in about 50% of patients. When the lack of effectiveness can be combined with other groups of drugs, especially diuretics and calcium channel blockers.In recent years, for the treatment of hypertension are widely used fixed combinations of ACE inhibitors with diuretics, which are capable of reaching the target blood pressure level in more than 80% of cases. The main cons-indications for the appointment of ACE inhibitors bilateral renal artery stenosis or artery stenosis to a solitary kidney, severe aortic stenosis, hyperkalemia greater than 5.5 mmol / L, pregnancy and breastfeeding.Thus, ACE inhibitors are among the major antihypertensive drugs, especially in patients post-myocardial cardiosclerosis with chronic heart failure and diabetic nephropathy, due to prolonged use, they have a marked effect renoprotective, reducing the risk of cardiovascular morbidity and mortality. When choosing an ACE inhibitor should be preferred drugs, which are characterized by high efficiency, long-acting, lack of accumulation to have a double track livestock and few side effects .

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