ACE inhibitors, or angiotensional enzyme inhibitors, is a group of drugs that reduce the concentration of angiotensin II in the blood and tissues, and also increase the content of bradykinin, due to which the tone of the vessels and blood pressure decreases. They are used to treat both light and heavy hypertension and are particularly effective in patients with high renin activity, as well as those who use diuretics, since diuretics increase the level of renin and the activity of the renin-angiotensin system in the blood.

In 1967, it was found that angiotensin I turns into angiotensin II when passing through a small circle of blood circulation, and a year later it was possible to show that Bradykin also disappears almost completely at the first pass through the small circle. K.k. NG and J. Vane suggested that carboxypeptidase, inactivating bradykin, and an enzyme converting angiotensin I in angiotensin II in the lungs - ACE, identical. The assumption has become a proven fact when 1968 it was shown that dipeptidyl carboxypeptidase, which converts A-I in A-II, is able to inactivate Bradykin. Here the Branches of the Brazil Snake, which causes a hard spasm of the intestines. Ferreira has proven that the serpentine poison enhances the effect of Bradykinin, destroying the enzyme inhibiting Bradykinin. The next step was made by Bakhl in 1968 - he urged that the serpentine poison was able to destroy - ACE. This information was the interest of two researchers D. Caushman and M. Ondetti, having spent numerous tests, they were isolated from the serpentine poison a purified substance inhibiting ACE, a peptide consisting of nine amino acid radicals. Inserted intravenously, it provided, as expected, an energetic antihypertensive effect. In 1975, under the leadership of D. Caushman and M. Ondetti, a captitor was synthesized, which became the first representative of the large group medicinal preparationsknown as APE inhibitors.

ACE Inhibitors Action Mechanism

The mechanism of action of ACE inhibitors is due to the main effect caused by these drugs (implied in their name), namely the ability to inhibit the activity of the key enzyme renin-angiotensin system of ACE. The oppression of ACE activity leads to a number of consequences, which ensure the hypotensive effect of these drugs:

• inhibition of vasoconstrictor and sodium-holding effects of angiotensin II by reducing its formation from angiotensin I;
• braking inactivation of bradykinin and promoting the manifestation of its positive vasodilatory and sodium-system properties;
• an increase in the synthesis of powerful vasodilating factors: nitrogen oxide (II) and prostacyclin;
• an increase in the synthesis of angiotensin with vasodilative and sodium systemic activity;
• infertility of the formation of angiotensin III, catecholamines, vasopressin, aldosterone and endothelin-1.

Classification of APF inhibitors

Depending on the chemical structure, ACE inhibitors are divided into four main groups:

• sulfhydryl (captopril, benazepril);
• carboxyl (quinapril, leaser, perindopril, ramipril, enalapril);
• phosphate (fozinopril);
• hydroxam (Idrapril).

Depending on the ability to dissolve in lipids or water, the inhibitors of ACE pharmacokinetically divide into three classes:

• Class I - Lipophilic Medicines: Kaptopril, Alaceptril, FentaPril.
• Class II - lipophilic prodrugs.
• The subclass IIA is preparations, active metabolites of which are highlighted mainly by the kidneys: Benazepril, quinapril, perindopril, cilaproil, enalapril.
• Subclass IIB - drugs, the active metabolites of which are inherent in the two ways of elimination - through the kidneys with urine, as well as through the liver with a bile and digestive channel with a feet: moaxipril, rampril, spirapril, translapril, fozinopril.
• Class III - Hydrophilic Medicines: Lisinopril, Libenpal, Cranapril.

Lipophilicity is a very important property. medical agents, characterizes their ability to penetrate the tissue through the lipid membrane and coagulate the activity of the ACE directly in the targets (kidney, myocardium, endothelium vessels).

The preparations of the second generation differ from the first integer number of features: greater activity, less frequency of adoption of undesirable effects and the absence of sulfhydryl groups in the chemical structure that promotes autochemunization.

Communion - preparation of 1st grade with nephroprotector action, but it is short-range (6-8 hours), therefore it is prescribed 3-4 times a day. The preparations of the 2nd class have a longer half-life (18-24 hours) they will be appointed 1-2 times a day.

However, they are all prodrug, enter the body in inactive condition, need metabolic activation in the liver. The preparations of the 3rd class are active metabolites of the 2nd grade drugs, which are valid for 24 hours and provide a soft, stable antihypertensive effect.

ACE inhibitors Indication for purpose:

• Arterial hypertension;
• Heart failure;
• Renal pathology;
• Moved myocardial infarction;
• High coronary risk;
• Prevention of re-strokes.

In the treatment of arterial hypertension, preference should be given inhibitors of ACE in such cases:

• Concomitant heart failure;
• Asymptomatic violation of the systolic function of the left ventricle;
• Accompanying diabetes;
• Left ventricular hypertrophy;
• Coronary artery disease;
• Atherosclerosis of sleepy arteries;
• The presence of microalbuminuria;
• Chronic kidney disease (hypertensive or diabetic nephropathy).

ACF inhibitors Contraindication

Among the contraindications to the use of ACF inhibitors are distinguished by absolute contraindications:

• a tendency to angioorem edema;
• periods of pregnancy and lactation;
• bilateral stenosis of the renal arteries or stenosis of the artery of the only kidney;
• severe chronic renal failure;
• pronounced hypercalemia;
• hypertrophic cardiomyopathy with a pronounced obstruction of the left ventricular route;
• hemodynamically weighty stenosis of aortic or mitral valve;
• constrictive pericarditis;
• chronic pulmonary heart in the decompensation stage;
• porphyry;
• leukopenia;
• heavy anemia.

Relative contraindications:

• moderate chronic renal failure;
• moderate hypercalemia;
• cirrhosis of the liver or chronically active hepatitis;
• chronic pulmonary heart in the compensation stage;
• severe obstructive lung diseases;
• padagric kidney;
• condition after kidney transplantation;
• combination of this drug with indomethacin, potassium-holder diuretics, phenothiazines, rifampicin, allopurinol and lithium salts.

What are the side effects of APF inhibitors?

• dry cough;
• headache, dizziness and general weakness;
• arterial hypotension;
• infections of the upper respiratory tract;
• increase in blood potassium concentration;
• increasing the content of creatinine in the blood;
• proteinuria;
• toxic and imuneopathological effect on the kidneys;
• allergic reactions;
• neutropenia, anemia and thrombocytopenia;
• change in digestion organs (manifested by distorting taste, nausea, vomiting, the aphthous rash on the mucous membrane of the mouth, impaired liver function);
• paradoxical increase in blood pressure with one-sided stenosis of the renal artery.

ACE inhibitors are peculiar to the effect of the "first dose" - an excessive decrease in blood pressure, with a threat of imposition in the collapse, the occurrence of dizziness, the possibility of fainting in the first 2-4 hours after receiving the full dose of the drug. This is especially dangerous for IHD patients and discirculatory cerebral insufficiency. Therefore, captopril, and enalapril type inhibitors are prescribed initially in a significantly reduced dose of 1/4-1 / 2 tablets. The exception is perindopril, which does not cause the first dose hypotension.

What an ACF inhibitor is better?

Among the ACE inhibitors, the pretarium preparation has the best qualities. This drug In a dose of 4-8 mg, when taking 1 time per day, it ensures an effective dose-dependent reduction in blood pressure from the first week of treatment. Preshaum consistently controls blood pressure over the day with a single reception. Among all ACE inhibitors, the PRESA has the highest T / P ratio (the ratio of the final efficiency of the drug to the maximum), which is confirmed by the FDA (the United States Food and Medicine Control Office) and the consensus of the European Cardiology Society. Due to this, the prestarium provides true control of blood pressure over 24 hours and reliably protects against the rise of blood pressure in the most "dangerous" morning timeWhen the risk of such complications as a heart attack or stroke is particularly high.

According to the ratio of "Price - Quality", it should be noted the drug Berripril as one of high-quality generics in the treatment of ACE inhibitors.

Catad_Tema Arterial Hypertension - Articles

Inhibitors of angiotensin glossing enzyme and treatment of arterial hypertension

Yu.A. Karkov

RKNPKMZ RF, Moscow

The decrease in the increased blood pressure (AD) is definitely an important task of treating patients with arterial hypertension (AG), and proper pressure control is still an essential tool in the treatment of this extremely common disease. Today, the choice of antihypertensive drugs is large enough - from diuretics to drugs blocking the activity of the renin-angiotensin system (RAC) at different levels. However, the most attractive drugs possessing beyond the ad-reduction action, additional, primarily organoprotective properties, which ultimately should ensure improvement of the forecast in patients with ag in their long-term use. In this regard, the targeted creation of an angiotensin surgery enzyme inhibitors (ACE) is a huge achievement in the treatment of hypertension and other cardiovascular diseases. This class of drugs combines the advantages of high antihypertensive efficacy and good tolerability with the provision of high quality of life with a proven cardio, vasculo and renoprotective action and, especially important, decrease in the frequency of cardiovascular complications and an increase in the life expectancy of patients with their long-term use.

Mechanism of action.

ACE inhibitors act, competitive way related to the active catalytic fragment of this enzyme and blocking, thereby, the transition of angiotensin I to the biologically active peptide angiotensin II (AII). Initially created for the inhibition of ACE in plasma and reducing the level AII in plasma, this class of drugs has a hypotensive effect, probably through other mechanisms.

It has been proven that in various organs there are all components for the formation of AII locally (APE is produced by endothelial cells of vessels, as well as cells of such organs, like heart, kidney, brain and adrenal glands), which received the name of fabric or local races.

In addition to controlling AII products from angiotensin I, ACE is one of the enzymes responsible for bradykinine degradation, which is not only a powerful direct vasodilator, but also contributes to the release of the endothelial cells of the two other dlyators - endotheliums of the produced relaxing factor (nitrogen oxide - N0) and Prostaglandinov. However, until recently, it remains unclear how the antihypertensive effect of ACE inhibitors is connected with Bradykinin. The estimated anti-theterosclerotic effect of ACE inhibitors may be due to the suppression of the synthesis AII and the activation of the N0 system and prostaglandins through the bradykinin system.

ACE inhibitors also reduce the sympathetic activity, which allows them to be considered as indirect anti-adverergic substances, and prevent the salt and water delay due to a decrease in the level of aldosterone. Thus, under the influence of ACE inhibitors, there is a decrease in AII products and the secretion of aldosterone, AI, Bradykinin and Renin increase.

The main representatives of the class of ACE inhibitors.

Despite the belonging to one class, ACE inhibitors (more than a dozen of the original drugs are currently registered) differ from each other by the type of binding and strength of binding to the enzyme, the presence or absence of prodrug, the degree of lipophilicity, the duration of action, elimination or excretion paths (table ). Captopril has a ligand binding to an ACE, a sulfhydryl group, is an active medicine that has an action without conversion in the liver, and is excreted by the kidneys. Most ACE inhibitors represent prodrugs that, as a result of esterification in the liver, are transformed into an active metabolite. Due to more stable relations with ACE, they have a longer hypotensive effect. The table indicates the drug Spirapril, with which most doctors of our country are not familiar with the preparation. Spirapril is a carboxyl-containing drug (prodrug), to whose features a long half-life (about 40 h) can be attributed, which provides 24-hour control over the level of blood pressure in a single reception of 6 mg per day.

The main pharmacokinetic characteristics of ACE inhibitors (by LH. Opie with modifications)

It should be noted that at present there is no reason to assume that antihypertensive mechanisms differ in different ACE inhibitors.

Since all APE inhibitors are derived mainly by the kidneys, their doses should be reduced in the elderly and in patients with impaired kidney function and an elevated level of serum creatinine. For example, when renal failure, the dose of Enalapril should be reduced by half, if creatinine clearance drops below 30 ml / min. The exceptions are Fozinopil and Spirapril, the correction of doses of which is not required during renal failure. Pharmacokinetics Spirapril studied in 34 patients with kidney damage various severity Clementine clearance from 11 to 126 ml / min [&]. All patients involved in the study were divided into 4 groups depending on creatinine clearance. Although there was an increase in the maximum of the concentration and the area under the curve "The concentration of the drug in the plasma - time" (AUC) in accordance with the decrease in the speed of glomerular filtration, it was not possible to detect a reliable increase in the minimum concentration of the drug in the plasma, both after one-time heating of the spirapel of 6 mg and After 4 weekly trees in this dose. The data of this study indicate the lack of cumulation of the drug even in patients with creatinine clearance below 20 ml / min.

Antihypertensive efficiency of ACE inhibitors and clinical use.

As a monotherapy, the ACE inhibitors normalize or significantly reduce blood pressure in 60-70% of the hypertension, which is quite comparable to other antihypertensive drugs. The speed of the antihypertensive action of the captopril makes it possible to use it to relieve a hypertensive crisis, including when taking a tongue. Reducing the blood pressure When using other representatives of this class, it is observed in the first hours after taking the drug, but it is possible to judge the antihypertensive effect only in a few weeks of regular reception. For example, in one of the studies, the spirapel in the daily dose of 6 mg once already on the 2nd week of treatment reduced systolic and diastolic blood pressure (-12 mm Hg. Art. And 11 mm Hg. Art.), At 8 week, the decline was more pronounced (-18 mm Hg and -17 mm Hg. Art. respectively).

The effectiveness of APE inhibitors is proved in patients with mild, moderate and severe ag (increased blood pressure I, II, III degree in WHO, 1999), as well as in the treatment of malignant AG. The severity of the antihypertensive effect depends on the individual characteristics of the development of AG, the state of the RAC (vasorenal hypertension or its hyperactivity on the background of the long-term use of diuretics), compliance with the restriction of salt (increased effect), concomitant therapy (nonsteroidal anti-inflammatory drugs reduce the effect) and other factors.

In recent years, a number of studies have been conducted on the assessment of the antihypertensive effect of ACE inhibitors in real clinical practice, one of these studies is quadriga - quadropryl (spirapril) in patients with essential ag, which recently ended in 11 regions of our country. This open incomparable study included 235 patients (128 women) aged 25 to 74 years (average age 51 years) with ag 1 and 2 degree of increase in blood pressure. During the 3-month observation on the background of the spirapel in a dose of 6 mg once a day (with an insufficient effect, the hydrochlorodiazide is possible 12.5-25 mg), the Hell decreased from 158/98 to 132/83 mm RT. Article .. Thus, in this major study, high antihypertensive efficacy and good portability of the spirapel in patients with AG was demonstrated, which is quite consistent with the results of other work by this drug conducted in our country and abroad.

With an insufficient antihypertensive effect, a combination of ACE inhibitors is primarily recommended with diuretics, as well as with calcium antagonists, beta-blockers and preparations. central action . Perspectively combination with type 1 angiotensin receptors, but further research is needed.

It is important to note that the heart rate, the shock volume and the minute volume of the heart remain unchanged when using ACE inhibitors in patients with ag.

Clinical advantages of the IAPF.

ACE inhibitors do not have negative influence For a number of important metabolic indicators and have additional favorable effects, some of which are not associated with a decrease in blood pressure.

When appropriate this class, a good quality of life is maintained (normal sexual activity, a physical activity reaction), including elderly people. Improving cognitive functions against the background of ACE inhibitors in old age allows them to be more widely used in this category of patients.

ACE inhibitors are metabolically neutral: against the background of their use there are no changes in lipid profile, uric acid, blood glucose level and insulinistance (the latest indicators for some data can even improve). The favorable effect of ACE inhibitors on some parameters of hemostasis (decrease in the level of plasminogen tissue activator inhibitor) is assumed. Thus, ACE inhibitors have either neutral or a beneficial effect on classic and new risk factors for cardiovascular diseases.

Extensive experience of clinical use showed that ACE inhibitors are characterized by good tolerance with a total frequency of unwanted effects less than 10%. Cough is the most commonly informed side effect of ACE inhibitors, which, according to different estimates, is found in 2-6% of cases. It, as a rule, appears during the first weeks of treatment, is gradually enhanced and may require complete cancellation of the drug. In other cases, its severity can gradually decrease until complete termination. With a persistently persisting cough, it is advisable to transfer the patient to the treatment of type I angiotensive receptors for treatment.

An angioedema edema refers to life-hazardous complications of therapy of ACE inhibitors, requiring immediate cancellation of the drug. In the future, such a patient (this is a rather rare complication - about 0.04%) the purpose of ACE inhibitors is absolutely contraindicated, and the possibility of application in these cases AII receptor blockers is still unclear.

The organoprotective effects of ACE inhibitors.

Cardioprotective. It has been established that the presence of hypertrophy of the myocardial of the left ventricle (GLB) significantly worsens the forecast with the AG. According to the Framingham study, the rate of development of myocardial and death infarction was several times higher in the presence of a GLB, compared with those without it. The relative risk of death from all causes is increased by 1.5 times in men and 2 times in women with an increase in the mass of the myocardial of the left ventricle for every 50 g / m 2.

ACE inhibitors according to all represented meta-analyzes reduce the mass of hypertrophied left ventricular myocardium to a greater extent, compared with other antihypertensive preparations for every 1 mm Hg. Art. Reduced blood pressure. This suggests that the regression of the GLF in the treatment of ACE inhibitors is connected not only with the Hell-reduction action, but also by other mechanisms.

In one of the studies, the effect of long-term intake (for 3 years) spirals on the GLB was studied (the mass of myocardial myocardials of the left ventricle\u003e 240 g according to ECCG) and hemodynamic parameters of 11 men aged from 41 to 60 years with AG (diastolic blood pressure from 100 to 120 mm Hg. Art.). During the study, it was possible to achieve a significant decrease in the blood pressure from 161/107 to 135/87 mm Hg. Art. (36 months). The mass of myocardial left ventricle decreased from 340 to 298 g (p< 0,05). Сердечный выброс не изменился, значительно уменьшилось системное артериолярное сопротивление. Таким образом, достигнутый и, что весьма важно, сохранившийся в последующем регресс ГЛЖ на 12 %, был связан, в основном, с уменьшением толщины задней стенки левого желудочка и системным артериолярным сопротивлением.

Nephroprotective. These properties of ACE inhibitors are specific, associated with the peculiarities of their action on the structural and functional characteristics of the kidneys and depend not only on antihypertensive effects. The main mechanisms of nephroprotection of this class are a decrease in increased intraccurry pressure and antiproteinurically, which, according to clinical studiesis implemented in preventing and slowing down the rate of incidence of glomerular filtration and the development of terminal renal failure.

Vasculotovative.The estimated specific role of AII in damage to the vascular wall and the process of remodeling small and resistive arteries, creates prerequisites for a new direction in the use of ACE inhibitors. It was shown that the drugs of this group improve the elastic characteristics of large arteries; Overcome vascular remodeling (the restoration of normal ratio is the thickness of the vascular wall / clearance of the vessel), normalize the impaired endothelial function (4).

It should be noted that the first clinical evidence of a long-proposed anti-studosclerotic action of ACE inhibitors was obtained in the Study of Nore (15). It was demonstrated that the appointment of an ACE inhibitor Ramipril patients with a high risk of developing cardiovascular complications (IBS, AG, diabetes mellitus, the defeat of the peripheral arteries, etc.) significantly by 20-31% reduces the frequency of death, myocardial infarction and brain stroke, comparison with placebo. An important step in studying the potential of ACE inhibitors was the results of the Progress study, in which the therapy based on perindopril led to a 28% reduction in the risk of re-cerebral development in patients with cerebrovascular diseases in history, and, regardless of the presence or absence of AG (16). The data of these studies give clinical confirmation of the anti-theterosclerotic effects of ACE inhibitors (4).

Specific readings.

In accordance with international and domestic recommendations (1; 2), ACE inhibitors can be prescribed by the patient AG as a monotherapy as the first medicine. However, taking into account the above circumstances, the drugs of this class should be given preference with the combination of hypertension with clinical manifestations of blood circulation deficiency and dysfunction of the left ventricle, after the myocardial infarction, in the presence of diabetic nephropathy. The previously favorable cardio and nephroprotective effects of ACE inhibitors make it possible to make a choice in favor of this class if patients with GLB and proteinuria.

Impact on the prognosis of patients with ag.

In the recently recent meta analysis (5) comparing the efficiency of modes medical treatment With the use of ACE inhibitors against the main on diuretics or beta-blockers (SARRR, STOP-2, UKPDS; This is proof of a favorable impact on the prognosis of patients with agply treatment of ACE inhibitors.

Thus, the results of the latest studies make it possible to assume that the ACE inhibitors in the future will occupy the position of the "drug of choice" for the treatment of patients with AG, regardless of the presence or absence of their previously specified readings. The emergence of a new indication for the appointment of ACE inhibitors is predicted - prevention and treatment of atherosclerosis (15), as well as the prevention of repeated cerebral stroke (16).

Contraindications and caution when using ACE inhibitors.

Preparations are absolutely contraindicated for the treatment of AG in pregnant women. This fully applies to the instructions on angioedema edema and similar allergic manifestations in the past. Currently, there is no clinical experience in using ACE inhibitors in children.

To prevent the first dose hypotension in patients with high-activated races (long diuretic therapy, hyponatremia, renal artery stenosis) to pre-cancel 1-2 days of diuretics, fill the loss of fluid and use small doses.

In patients with fixed heart emissions (pronounced mitral or aortic stenosis), when used inhibitors of ACE, an uncontrolled drop of blood pressure may occur, since the decrease in peripheral resistance cannot be compensated due to the impossibility of increasing heart emission.

It should be paid attention to hyperkalemia, especially in cases of renal failure, which can increase when appointing ACE inhibitors or may first appear after their destination. In the latter situation, the cause of the previously unrecognized two-sided stenosis of the renal arteries can be.

Conclusion.

As emphasized in methodological recommendations for the management of patients with arterial hypertension of WHO / Moag (2.), AG is not only not so much a violation of hemodynamics in the form of increased blood pressure. This disease is characterized by a set of functional, structural, hormonal, metabolic and other violations. Major events at AG are developing in a vascular wall. These changes, resulting in the further development of atherosclerosis with the damage to large arteries of the heart and brain, largely determine the prognosis of the patient with AG. The widespread use of ACE inhibitors in clinical practice will help not only carry out proper control over the level of blood pressure, but also to improve the prognosis of this category of patients, including through non-hemodynamic factors.

Quadropryl® - Dossier drug

Literature
1. All-Russian Scientific Society of Cardiologists (Inect). National Recommendations on the diagnosis and treatment of arterial hypertension. 2001
2.Nguidelines subcommitee. 1999 World Health Organization. - International Society of Hypertension Guidelines for the Management of Hypertension. J. Hypertension. - 1999; 17: 151-183.
3. Opie L.h. Angiotensin Converting Enzyme Inhibitors. The Advance Continues. 3 EDITION. Authors "Publishing House, NEW-York, 1999, p. 275.
4. DZAU V., BERNSTEIN K., CELERMAIER D., ET AL. The Relevance of Tissue Angiotensin- Converting Enzyme: Manifestations in Mechanistic and Endpoint Data. Am. J. Cardiol. - 2001; 88 (Suppl. L): 1 -20.
5. Blood Pressure Lowering Treatment Trialasts "Collaboration. Effects of Ace Inhibitors, Calcium Antagonists, and Other Blood-Pressure-Lowering Drugs: Results of Prospectively Designed Overviews of Randomized Trials. Lancet. - 2000; 355: 1955-1964.
6. GRASS P., GERBEAN C, KUTZ K. SPIRAPRIL: PHARMACOKINETIC PROPERTIES AND DRUG INTERACTION. Blood Pressure. - 1994; 3 (Suppl. 2): 7-12.
7.Guitard C, Lohmann F.W., Alfiero R., et al. COMPARISON OF EFFICACY OF SPIRAPRIL AND ENALAPRIL IN CONTROL OF MILD-TO-MODERATE HYPERTENSION. Cardiovasc. Drugs. Ther. - 1997; 11: 453-461.
8. Meredith P.A., Grass P., Guitard C, et al. Pharmacokinoetics of Spirapril in Renal Impairment. Blood Pressure. - 1993; 3 (Suppl. 2): 14-19.
9. YUKUSEVICH V.V., Mozheko M.E., Paleutin Shh., Et al. Spirapril is a new inhibitor of a long-term ACE: efficiency and safety in patients with hypertension in combination with diabetes and impaired kidney function. Therapeutic archive. -2000; 10: 6-14.
10. Shalyanov S.A., Martsevich S.Yu., Deev A.D., et al. Comparative study The effectiveness of the spiral (quadropryl) and amlodipine. The results of a randomized study in patients with soft and moderate ag. Therapeutic archive. - 2000; 10: 10-13.
11. Schmidt I., Korole X. The use of spirapril in patients with ag-clinical experience in Germany. Therapeutic archive. -2000; 10: 14-18.
12. Fogari R., Mugellini A., Zoppi A., et al. Effect of Losartan and Perindopril on Plasma PAI-1 and Fibrinogen in Hypertensive Type 2 Diabetic Patients. J. Hypertens. - 1999; 17 (Suppl. 3): 1-34.
13.LEVY D.Y Garrison R.J., Savage D.D., et al. Prognostic Implications of Echocardiographically Determined Left Ventricular Mass In The Framingham Heart Study. N. engl. J. Med. - 1990; 322: 1561-1566.
14. Otterstad J.e, Froyend G. Changes in Left Ventricular Dimensions and Haemodynamics During Antiypertensive Treatment with Spirapril for 36 months. Blood Pressure. - 1994; 3 (Suppl. 2): 69-72.
15. The Hope Study Investigators. Effects of An Angiotensin-Converting Enzyme Inhibitor, Ramipril, On Death From Cardiovascular Causes, Myocardial Infarction, and Stroke in High-Risk Patients. N. engl. J. Med. 2000; 342: 145-53.
16. PROGRESS COLLABORATIVE GROUP. Randomised Trial of PerindoprilBased Blood-Pressure-Lowering Regimen Among 6105 Individuals With Previous Stroke and Transient Ischaemic Attack. Lancet. - 2001; 358: 1033-1041.

3
1 FGAOU in the first MGMU them. THEM. Siechenov Ministry of Health of Russia (Sechenovsky University), Moscow
2 FGAOU WITH "First MGMU them. THEM. Sechenov "Ministry of Health of Russia, Moscow
3 KGMA - branch of FGBOU DPO RMPOO of the Ministry of Health of Russia, Kazan

Citation:Yermolaeva A.S., Dralova O.V., Maksimov M.L. The third-generation ACF inhibitor Fozinopil in the treatment of patients with cardiovascular diseases // RMW. 2014. №12. P. 906.

Cardiovascular diseases are the main cause of death Veverops energize more than 4.3 million deaths annually. Arterial hypertension (AG) refers to the dasch of the most common cardiovascular diseases (about 40% of the adult population RFIMEN ENDED AD) is exposed to the most important risk factor for the development of basic cardiovascular complications, such as myocardial infarction Iostrian violation of cerebral circulation, determining high mortality of breeding .

Renin-angiotensin-aldosterone system (RAAS) is considered as the main factor in the regulation of blood pressure and homeostasis, plays a central role in the emergence of AG and its consequences, acts as an indispensable participant in the cardiovascular continuum, starting from the stage of influence of risk factors, potency of atherosclerosis, endothelial dysfunction ischemic Disease Hearts (IBS), LV Hypertrophy, myocardial remodeling and completing final heart failure, as well as development chronic disease kidney (HBP).

Currently, 5 main classes of antihypertensive drugs are recommended for treating AH: angiotensin-plating enzyme inhibitors (IAPF), angiotensin II receptor blockers (s), block plants of slow calcium channels (BMKK), B-adrenoblays (Bab), diuretics. Against the background of antihypertensive therapy, a change in the activity of Raas is possible. One of the ways to reduce its activity is to suppress the synthesis of angiotensin II.

the IAPF is highly efficient drugs widely used in the treatment of cardiovascular diseases: ag, coronary artery disease, chronic heart failure (CHHN). The relevance of their use in the practice of treating diseases of the cardiovascular system is due to the effects of the blockade of neurohumoral systems, vase, cardio and nephroprotective properties.

Over the past years, the number of IAPFs, differentiating the pharmacokinetic properties, the duration of the action, the activity of the initial preparation and the degree of tissue bioavailability, is steadily growing. According to the chemical structure, drugs differ by what a chemical group (sulfhydryl, carboxyalkyl, phosphinyl or hydroxam) in their molecule is associated with zinc ion in the active centers of angiotensin glider enzyme.

At the heart of the clinically significant pharmacological effects of the IAPF lies their ability to suppress the activity of the enzyme (ACE or kininosis II), converting angiotensin I c. Angiotenzine II, and thus influence the functioning of Raas. Angiotensin II is considered the main effector link of Raas. Angiotensin II, activating AT1 receptors, has a powerful vasoconstrictor action. Under the influence of angiotensin II, the smooth muscle cells occur, the reduction of myocardials increases, the production of aldosterone increases, as well as the excretion of catecholamines from the brainstones of adrenal glands and the sympathetic nerve endings. Angiotensin II also regulates sodium transport using intestinal and kidney epithelocytes. In addition to physiological functions Locally produced angiotensin II causes inflammation, cell proliferation, mitosis, apoptosis, migration and differentiation of cells, regulates the gene expression of bioactive substances and activates multiple intracellular signaling pathways, many of which contribute to tissue damage.

the IAPF reduce the secretion of aldosterone and vasopressin, prevent the destruction of Bradikinin. Bradykin, accumulating in endothelium, acting through the β 2-receptors of Brudikinin, causes the relaxation of the smooth muscles of the vessels and contributes to the release of the relaxing factor dependent on the endothelium (prostacycline and prostaglandin of E2). In addition, under the influence of the IAPF, the synthesis of other vasoconstrictor and anti-zeothetic substances (norepinephrine, arginine-vasopressin, endotheline-1), which participate in the pathogenesis of cardiac dysfunction and AG has been reduced. The main organophestructive effects of the IAPF are due to the Blocade of ACE in various tissues (for example, vessels, kidneys, heart).

Distinguish the following main pharmacological effects IAPF: hemodynamic, neurohumoral, antiproliferative, kidney, etc.

The hemodynamic effect of the IAPF is implemented through their ability to reduce the total peripheral vascular resistance, cause sodium effect, but the effect on the heart rate is small. A decrease in the tone of peripheral vessels also occurs as a result of the blockade of the tissue ACE, which leads to a decrease in the content of angiotensin II B. target organs (for example, vascular wall). In patients with normal and increased blood pressure without heart failure, the IAPF practically does not affect the minute volume of the heart and shock volume. In contrast to other Vasodilators, the IAPF does not cause reflex tachycardia, apparently due to the impact on baroreceptors, amplification of parasympathetic activity and, possibly, reduce sympathetic activity. There is also no changes in the heart rate during exercise. The use of the IAPF improves the ability of cardiomyocytes to relaxation. The JEAPF reduce hypertrophy of the left hearts in patients with IBS, AGs suffering from insulin-independent diabetes diabetes (SD) and heart failure. Also, the IAPF reduce endothelial dysfunction. This property is binding to the weakening of vasoconstriction and increased nitrogen oxide as a result of an increase in bradykinin education at ACE blockade.

In patients with HSN, IAPF improves clinical symptoms, quality of life, slow down the progression of the disease and improve the forecast, and also prevent the onset of clinically pronounced decompensation. This is due to their ability to cause both arterial and venous vasodilation. Venenous vasodilatation increases the capacity of Vulus, reduces the load on the right atrium, as a result of this, the pressure in the pulmonary vein decreases, the load of the left ventricle decreases and the stagnation is reduced by a small circulation of blood circulation.

Arterial vasodulation leads to a decrease in peripheral vascular resistance and increasing heart Emission. The short rate of intake of the IAPF is accompanied by a decrease in the content of angiotensin II, the emission of renin and the level of angiotensin I is increasing, and the level of angiotensin I. Angiotensin II has a powerful vasoconstrictor effect on the muscles of smooth muscle cells, strengthens the reduction of myocardium, stimulates the products of aldosterone, activates the excretion of catecholamines from adrenal brainstones and from sympathetic nerve endings, stimulates sympathetic nervous system, Strengthens thirst and the desire to eat salty food. Also angiotensin II regulates sodium transport using intestinal and kidney epithelocytes. In addition, the IAPF reduce the content in the plasma of epinephrine, norepinephrine and vasopressin.

In addition, an increase in the level of angiotensin I gives an increase in the concentration of bradykinin, as well as the activation of alternative paths of turning angiotensin I c. angiotensin II. Thus, the use of IAPF increases the level of kinines, prostacyclin and nitrogen oxide. With prolonged use of the IAPF, the production of aldosterone decreases, normally stimulated by hypercalemia, hypermagniasia and ACTH, which leads to an increase in the removal of sodium and water.

With prolonged use of the IAPF, an antiproliferative effect occurs: a decrease in the hypertrophy of the muscular layer of the vascular wall and myocardium, a decrease in the proliferation of the extracellular matrix. Possible mechanisms of the ACAP to reduce myocardial hypertrophy are considered: a mechanical cause due to reducing preload and post-loading, as well as a decrease in sympathetic activity and reduced growth stimulation. In addition, the IAPF reduce the formation of collagen by reducing the content of angiotensin II, which acts both directly on the fibroblasts and indirectly due to stimulation of the secretion of aldosterone. Braking growth and proliferation of smooth muscle cells and fibroblasts in media arteries leads to an increase in their lumen, as well as restoration and improvement of the elasticity of the arterial wall. Thus, the central hemodynamics is normalized and peripheral vascular resistance is reduced.

There are relatively new data on the explanation of the antifibrotic effect of the IAPF on myocardium with AG. Researchers believe that this EAPF effect is the result of the blockade of hydrolysis of N-acetyl-serinal-aspartyl-lysyl proline, leading to a decrease in the proliferation of fibroblasts, inflammatory cells, expressing the transforming growth factor and collagen deposition. In addition, the JAPP prevents the apoptosis of cardiomyocytes.

the IAPF has a favorable effect on the kidneys, since it is expanding predominantly efferent arterioles and less affect the afferent. Thus, intracluded pressure decreases, proteinuria decreases, renal blood flow increases with a minor change in glomerular filtration rate. Despite the decrease in the vascular resistance in the glomers, the speed of glomerular filtration remains unchanged or increased together with the filtration fraction. As a result of improving the renal hemodynamics, sodium is increased, the production of aldosterone decreases, which leads to a slowdown in the progression of nephropathy.

Raas plays an important role in the pathogenesis and progression of atherosclerosis. Thus, at the appointment of the IAPF, the development of atherosclerosis is slowed down due to the blockade of angiotensin II formation and an increase in the concentration of bradykinin and nitrogen oxide, which improve the endothelial function.

In the published comparative analysis of three studies (Hope, Europa, Peace) on the effect of the EAPP in 29 805 patients with atherosclerosis, but without dysfunction of the left ventricle, the total mortality rates, fatal and non-infamous cardiovascular events are shown that the assignment of the IAPP leads to a reliable Reducing the total (7.8 against 8.9%, p \u003d 0.0004) and cardiovascular (4.3 versus 5.2%, p \u003d 0.0002) mortality, nefatal myocardial infarction (5.3 against 6, 4%, p \u003d 0.0001), brain strokes (2.2 versus 2.8%, p \u003d 0.0004), heart failure (2.1 versus 2.7%, p \u003d 0.0007) and conducting an aortocortonary Shunting (6.0 versus 6.9%, p \u003d 0.0036). The authors concluded that the assignment of the IAPF should be considered in all patients with an intermediate risk in the presence of an atherosclerotic process.

Thus, the IAPF is shown for the treatment of AG (class IA). In patients with hypertension, the initial purpose of treatment is control of blood pressure, which can be achieved by various drugsreducing the risk of cardiovascular complications with long-term therapy. The JAPP is also considered as a means of the first line in patients with heart failure, systolic dysfunction of the left ventricle or the SD, who have suffered or stroke, as well as in patients of high-risk coronary heart disease.

Over the past decades, more than 30 chemical compoundsbelonging to the IAPF class. One of the most effective, safe and economical IAPF is fosinopril sodium (monophil). The clinically important difference in fosinopril from many other IAPF is the presence in its chemical formula of phosphinic acid residues. This feature of the structure gives the drug a number of unique properties that distinguish it from other drugs of this class, and allows it to be attributed to the third, most modern, IAPF generation.

Fozinopril is a prodrug and acts after suction and transformation (in the liver, mucous membranes, kidney, bloodstream) into active metabolite - fozinospota, which binds to plasma proteins (95-98%). The half-life of the fosinopoid is 12-15 hours, which causes its long-term antihypertensive effect and reception 1 r. / Day. The drug is distinguished by extremely high lipophilicity - the lipophilicity index Fozin coat is more than 2.0 units, while Enalaprilalate is 0.108. This makes it easier to penetrate the fozin coating through cell membranes and allows you to suppress the activity of not only circulating, but also the tissue Raas in the heart, lungs, kidneys and the brain. It is experimentally shown that fozin coil inhibits the ACE in the heart muscle to a greater extent than ramiprilates and enalaprilat, which underlies the more pronounced (compared to other IAPFs) hypotensive and cardioprotective effects. Unlike other IAPF (captopril, Enalapril, Leisinopril, etc.), which are removed from the body mainly by the kidneys, for fozinopril are characterized by two main routes of elimination - renal and hepatic (with bile) in a 1: 1 ratio. Moreover, with a decrease in the kidney function, the excretion of an active metabolite with biliary increases and, on the contrary, its excretion with urine increases during liver failure. This makes the drug most effective in the elderly, as well as in patients with liver and kidney pathology.

The clinically significant advantage of Fozinopril, distinguishing it from most other IAPF, is good tolerability. So, in patients with HSN II-IV functional class according to the NYHA classification, the frequency of side effects with the use of fozinopril and placebo was practically no difference. There is an extremely low frequency of dry cough. It is noted that the dry cough caused by other JAPPs weakens or even completely disappears when moving to fozinopril. Thus, in a double-blind comparative study with Enalapril, a reliably more rare cough occurrence was shown when the fosinopoid appointment. This study included 179 patients who had already ceased to receive an AAPF due to cough development. The attempt to resume treatment was much more successful when choosing a fozinopril - the re-development of cough was observed more than twice as much as Eanalapril. Also, when it is applied, a smaller number of clinical and biochemical side effects is observed, especially in "Risk groups" - in the elderly hypertensive or sick patients. Fozinopid distinguishes and convenient dosing mode - a single reception provides 24-hour control control (the ratio of the residual effect to the peak effect is 64%) and prevents its increase in the early morning watches. The initial daily dose of fosinopril at AG is 10 mg once with a possible subsequent increase of up to 20-40 mg. With CHN, the initial daily dose - 5-10 mg (in patients with hypotension - 2.5-5 mg), the average therapeutic - 10-20 mg, the maximum - 20-40 mg.

In the FOPS study (757 patients over 60), the target level of hell for 12 weeks. Fozin colation treatment was achieved in 80% of patients, with parts of them additionally prescribed 12.5 mg of hydrochlorothiazide to achieve a better therapeutic result. In the Flight study (19,432 patients with AG, 989 of them - over 75 years old) after 12 weeks. From the beginning of treatment, the target hell was achieved in 79.8% of patients. It was noted that the antihypertensive activity of Fozinopril gradually increases in the first few weeks of treatment, hell more often reaches target levels without manifestations of compensatory heart rate disorders, and the abolition of the drug does not lead to a rapid rise of blood pressure. The effect of fosinopril, as a rule, does not depend on age-sex features and body weight of patients.

When conducting the Russian program, the flag (fozinopril in the treatment of arterial hypertension) was assessed by the likelihood of achieving target levels of blood pressure in patients with soft and moderate hypers in the outpatient conditions for monotherapy with fosinopril (10-20 mg / day) or its combination with hydrochlorothiazide. In total, 2557 patients were included in the study, of which 26.7% amounted to persons over 60 years. Targeted adhesion achieved in 62.1% of patients. Side effects 8.3% of patients were marked, and only 5.2% had the abolition of drugs.

In the study of the FAGOT (pharmacoeconomic assessment of the use of the Pozinopoid IAPF in the outpatient treatment of patients with arterial hypertension of complicated flow), 2596 patients with soft or moderate hyperen and the presence of two risk factors for cardiovascular complications were included. The effectiveness of the monotherapy of the fozin arrival or its combination with hydrochlorothiazide and generally accepted therapy (diuretics, women, calcium antagonists) in patients of different ages has been compared. The target ad when taking fozinopril and hydrochlorothiazide was achieved in 67.8% of patients. It is shown that the rate of achieving the hypotensive effect and its severity in the use of fozinopril does not differ in patients of elderly and young age, but higher than when using the traditional treatment regimen. Compared to other drugs, Fozinopil has beneficially distinguished the simplicity of admission and costly efficiency.

Fozinopril is effective in the prevention and reverse development of left ventricular hypertrophy (LV) with AG, i.e. it not only reduces blood pressure, but also contributes to the regression of structural remodeling of the heart chambers. For 9 months. The mass of myocardial LV decreases in persons with pronounced hypertrophy of 5 g, and in the comparison group it increases. Such observation is very important, since hypertrophy of the LV wall is one of the key predictors of cardiovascular disasters. The drug also has favorably affects atherosclerosis of carotid arteries. It is shown that the thickness of the intima-media complex in this segment of the vascular bed after 36 weeks. Regular drug intake is reduced by 0.0278 ± 0.03 mm, while outside the reception of the fozinopril, this indicator only increases.

The results of the double-blind placebo-controlled PhylLis study demonstrated the inhibitory effect of the therapy with fozinopril (20 mg / day) on the progression of atherosclerosis of the carotide basin vessels, i.e. anti-theaterogenic effect. The study involved 508 patients with hypertension with asymptomatic atherosclerotic damage to the carotid arteries and their large branches. The average observation period was 2.6 years. The thickness of the intima-media complex, as well as an atherosclerotic lesion zone, in patients who took fozinopid, reliably and similarly decreased. Thus, in several studies, it was demonstrated that the fosinopril has anti-studary effect in patients with hypertension, at least in certain sections of the vascular bed.

Fozinopid is also able to improve the diastolic function of LV in young people with a soft hypertension without hypertrophy of the LV wall. The study was attended by 66 young people (average age of 36 years) with an average duration of AG, according to medical records, 5.4 years. The dose of fosinopril was 20 mg / day. The control group obtained a combination of hydrochlorothiazide and hydralazine. The monotherapy Fozinopril demonstrated the indisputable advantages in the normalization of the diastolic function of the LV and the prevention of LV hypertrophy.

To confirm the own nephroprotective effect of Fozinopril, not related to the decline in blood pressure, the Prevend IT study was conducted (Prevenion of Renal Vascular End-Stage Disease Intervention Trial). The study included 854 patients with microalbuminuria, which were prescribed 2 drugs for 46 months .: Rhustatin and Fozinopid, each of which had placebo control. The main purpose of this study was an assessment of the effect of fosinopril and pravastatin on cardiovascular complications and renal failure in patients with microalbuminuria, normal level Hell and total cholesterol. For the first 3 months. The level of albuminuria has significantly decreased in patients who received fozinopil, which remained for 4 years of observation. The use of pravastatin was not accompanied by a change in microalbuminuria. In comparison with Placebo Fozinopil reduced the risk of stroke, but did not affect the risk of myocardial infarction.

The use of fozinopril - a long-acting IAPF, characterized by mutually compensated ways of excretion with urine and bile, is associated with minimal risk of cumulation in chronic renal failure, including expressed (extrogenic creatinine clearance<30 мл/мин). Аргументом в пользу выбора именно этого препарата у больных ХСН с исходными гиперкреатининемией и/или снижением СКФ является установленный в клинических исследованиях минимальный по сравнению с другими иАПФ риск нарастания сывороточных концентраций креатинина и калия. У пожилых больных с изолированной систолической АГ (исследование FOPS), у которых вероятность провокации ухудшения функции почек иАПФ максимальна, применение фозиноприла не было сопряжено с появлением признаков почечной недостаточности. Безопасность фозиноприла с точки зрения влияния на функцию почек установлена и в крупных отечественных контролируемых исследованиях (проект «Три Ф») .

When comparing fosinopril and nifedipine in the form of a long-acting gastrointestinal therapeutic system (GITS) in 241 patients with parenchymathous diseases of the kidneys and chronic renal failure, in which the bloodstream level of the creatinine level was observed for the previous year, treatment was treated with fozinopril 10-20 mg / day With nifedipine extended 30-60 mg / day. The end points in the study were the doubling of the level of creatinine and the need for hemodialysis. After 3 years of observation of 36% of patients in a group receiving nifedipine, and 21% of patients (P<0,05) в группе, получавшей фозиноприл, достигли конечной точки. При этом уровень протеинурии на фоне лечения фозиноприлом уменьшился на 57% от исходного, в группе терапии нифедипином — возрос на 7% .

Conclusion. IAPF Fozinopil (Monophil) is an effective modern drug that allows not only to achieve the target level of blood pressure in patients with ag, but also has proven cardio-, vase and nephroprotective effects and is able to inhibit the atherosclerotic process. Fozinopil (Monophil) can serve as a drug of choice as hypotensive therapy of hypertension in people of all age groups. To ensure the optimal organoprotective effect, fosinopril can be successfully used both in monotherapy and in combination, including tiazide diuretics or calcium antagonists. Connecting a versatile efficiency, good tolerability and ease of use, the fozinopril can be recommended for therapy of patients with AG, including in combination with HBS, IBS and CXN.

Literature

1. Diagnosis and treatment of arterial hypertension: Russian recommendations (fourth revision) // Systemic hypertension. 2010. No. 3. P. 5-26.
2. Chazov I.E., Ratova L. G. Combined therapy of arterial hypertension: Arterial Hypertension Guide / Ed. E. I. Chazov, I. E. Chazova. M.: Media Media, 2005. P. 784.
3. Ostrumova OD, Maksimov M. L. Choice of a combination of APF inhibitors and diuretics in the treatment of arterial hypertension in the new edition of Russian recommendations: Focus on the treatment of elderly patients // Pharmatec. 2011. No. 8. P. 42-49.
4. Kobalava ZH.D., Kotovskaya Yu.V., Moiseev V.S. Arterial hypertension. Keys to diagnosis and treatment: a series of a "doctor-specialist library". M.: Gootar Media, 2009. 864 p.
5. Karpov Yu. A. Treatment of patients with cardiovascular diseases: The role of the blockade of the renin-angiotensin system with the help of sartans // RMW. 2009. No. 23. P. 1548-1554.
6. Mukhin N.A., Moiseev V.S., Kobalava Zh.d. et al. Cardiorenal interactions: clinical significance and role in the pathogenesis of diseases of the cardiovascular system and kidney // Ter. archive. 2004. No. 6. P. 39-47.
7. Medvedev I.N., Kumova T.A., Gamolina O. V. The role of a Renin-angiotensin-aldosterone system in the development of arterial hypertension // Russian Cardiology Journal. 2009. No. 4. P. 82-84.
8. Jacoby D.S., Rader D. J. Renin -Gangiotensin System and Atherothrombotic Disease: from Genes to Treatment // Arch. Intern. Med. 2003. Vol. 163 (10). P. 1155-1164.
9. Otrumova OD, Maksimov M. L. Place inhibitors of angiotensin-converting enzyme in the treatment of arterial hypertension in various groups of patients // Cardiovascular therapy and prevention. 2010. № 9 (7). P. 90-96.
10. ESH-ESC Guidelines Committee. 2013 Guidelines for the Management of Arterial Hypertension // J. Hypertens. 2013. Vol. 31. P. 1281-1357.
11. Clinical Pharmacology / Ed. V. G. Kukes. M.: Goeotar Media, 2013. 1056 p.
12. Chaz E.I., Chazov I. E. Arterial Hypertension Guide. M., 2005. 734 p.
13. Harutyunov G.P., Chernyavskaya T. K. Problems of nephroprotection in patients with arterial hypertension. The value of the microalbuminuria indicator for a general practitioner // Quality of life. Medicine. 2005. No. 3. P. 22-27.
14. Rational Pharmacotherapy of Cardiovascular Diseases: Hands. for practicing doctors / under total. ed. E. I. Chazov, Yu. N. Belenkova. M.: Litterra, 2005. 972 p. (Rational pharmacotherapy: gray hands. For practitioners doctors; T. 6).
15. TAYANOVSKAYA Yu.V., Lelyuk V.G., Kutuzov A.B. et al. Methodology and applied value of the study of the function of the endothelium in generally clinic practice and clinics of radiation medicine // Echography. 2001. T. 2, No. 4. P. 384-396.
16. Belenkov Yu.N., Mareev V.Yu., Ageev F. T. Endothelial dysfunction for heart failure: the possibilities of therapy inhibitors inhibitors of angiotensin glider enzyme // Cardiology. 2001. No. 5. P. 100-104.
17. Metelitsa V. I. Clinical Pharmacology of cardiovascular medicines. M.: Mia, 2005. 926 p.
18. Clinical Pharmacology: National Guide (National Guide Series). M.: Gootar Media, 2014. 976 p.
19. Stella A., Zanchetti A. Control of Renal Renin Release // Kidney Int. 1987. Vol. 31 (Suppl. 20). P. 89-94.
20. Diagnosis and treatment in cardiology: educational. Manual for studies Medvozzi / Ed. Michael H. Crawford; per. from English Yaz.; under total. ed. Acad. Ramne R. G. Oganova. M.: Medpress-Inform, 2007. 800 p.
21. Almazov V.A., Berkovich O.A., Sitnikova M.Yu. and others. Endothelial dysfunction in patients with the debut of coronary heart disease at different ages // Cardiology. 2001. No. 5. P. 26-29.
22. GRIENDLING K.K. et al. Angiotensin II Signaling in Vascular Smooth Muscle // New Concepts - HypeRtension. 1997. Vol. 29. P. 366-373.
23. Karpov Yu. A. Inhibitors of an angiotensin glider enzyme in mono- and combined therapy of arterial hypertension // RMG. 2009. No. 18. P. 1122-1127.
24. Taddei S., Virdis A., Chiadoni L., Salvetti A. The Role of Endothelium in Human Hypertension // Curr. Opin. NEPHROL. Hypertens. 1998. No. 7. R. 20-39.
25. Ratmanova A. Inhibitors of Raas in nephroprotection. Is the combination of ACF inhibitors and sconce? // Med. Review. 2008. № 3 (03). P. 74-80.
26. Freedman J.E., Loscalzo J. Nitric Oxide and Its Relationship to Thrombotic Disorders // J. Thromb. Haemost. 2003. Vol. 1 (6). R. 1183-1188.
27. Shishkin A.N., Lyandina M. L. Endothelial dysfunction and arterial hypertension // Arterial hypertension. 2008. T. 14. No. 4. P. 315-319.
28. Preobrazhensky D.V., Marevich A.V., Romanova E.I. et al. Microalbuminuria: diagnostic, clinical and prognostic value (part of the second) // Russian Cardiology Journal. 2000. № 4. P. 78-85.
29. S. A. Boytsov, A. M. Urinsky, R. L. Kuznetsov, Yu. M. Pozdnyakov Structure of risk factors, lesions of target organs and metabolic changes in patients with arterial hypertension in various age groups - Cardiology. - 2009. - № 4. - P. 19-24.
30. Belousov Yu.B., Leonova M.V., Tarasov A.V. et al. Evaluation of the organoprotective effects of modern antihypertensive drugs // Bulletin of RGMU. 2006. No. 4 (51). P. 22-27.
31. Preobrazhensky D.V., Savchenko M.V., Kectiews V.G., Sidorenko B. A. Fozinopril - First Representative of a new generation of angiotensin surgery enzyme inhibitors // Cardiology. 2000. No. 5. C. 75-81.
32. Krasnova E. A. Fozinopid in the treatment of arterial hypertension // RMH. 2006. No. 4.
33. Ostrokhova E. V. Fozinopid in the treatment and prevention of chronic heart failure in patients with arterial hypertension: the problem of the optimal choice of an angiotensin glittering enzyme inhibitor // Pharmatek. 2006. No. 20. P. 28-32.
34. Ageev F.T., Mareev V. Yu. Monophil (Fozinopril) in the treatment of cardiovascular diseases // RMG. 2000. T. 8. P. 11-16.
35. Geluk C.A., Asselbergs F.W., Hillege H.L. ET AT. Impact of Statins In Microalbuminuric Subjects with the Metabolic Syndrome: A Substudy of the prevend Intervention Trial // EUR. Heart J. 2005. Vol. 26 (13). P. 1314-1320.
36. Huang K., Dai G. The Effect and Mechanism of Forsinopril On Ventricular Hypertrophy of SHR and Left Ventricular Pressure Overloading Rat // J. Huazriong. Univ. Sci Technolog. Med. SCI. 2002. Vol. 22. P. 17-20.
37. HUI K.K., Duchin K.L., Kripalani K. et al. Pharmacokinoetics of Fosinopril in Patients with Various Degrees of Renal Function // Clin. Pharmacol. Ther. 1991. Vol. 49. P. 457-467.
38. Ford N.F. et al. Single-Dose and Steady-State Pharmacokinoetics of Fosinopril and Fosinoprilat in Patients with Hepatic Impairment // J. Clin. Pharmacol. 1995. Vol.35. P. 145-150.
39. Deedwania P. C. Clinical Profile of Fosinopril, A NOVEL PHOSPHINIC ACID ACE INHIBITOR, FOR THE TREATMENT OF HEART FAILURE // Heart Failure. 1995. Vol. 11. P. 3.
40. Levinson B., Graney W.F., Devault A.R. et al. Age Is not Reason for Dose Adjustment for Fosinopril in Hypertension. // am. J. Hypertens. 1989. Vol. 2 (PT2). 8A.
41. Tatti P., PaHor M., BYINGTON R.P. et al. Outcome Results of the Fosinipril VS Amlodipine Cardiovascular Events Randomized Trial (Facet) in Patients with Hypertension and Niddm // Diabetes Care. 1998. Vol. 21. P. 597-603.
42. Sturov N. V. The place of the ACE inhibitor of Fozinopril in the treatment of arterial hypertension // Hard patient. 2007. No. 2.
43. Vetter W. Treatment of Senile Hypertension: The Fosinopril in Old Patients Study (FOPS) // AJH. 1997. Vol. 10. S. 255-261.
44. Berdah J., Guest M., Salvador M. Study of the Efficacy and Safety of Fosinopril in General Practice in 19,435 Hypertensive Patients (Flight Study) // Ann. Cardiol. Angiol. 1998. Vol. 47 (3). P. 169-175.
45. Karpov Yu. A. Fozinopid when treating arterial hypertension (flag): Russian program for assessing the practical achievability of target levels of blood pressure // RMH. 2001. T. 9. No. 10. P. 406-410.
46. Chazov I. E. The first results of the study of the FAGOT // CONSIHUM MEDICUM. 2002. T. 4. No. 11. P. 596-598.
47. Tasic I.S., Mijalkovic D., Djordjevic D. et al. Effect of Fosinopril On Progresion of the Asymptomatic Carotid Atherosclerosis and Left Ventricular Hypertrophy in Hypertensive Patients // SRP. ARH. Celok. Lek. 2006. Vol. 134 (3-4). P. 106-113.
48. Zanchetti A. Crepaldi G., Bond M.G. et al. Different effects of antihypertensive regimens based on fosinopril or hydrochlorothiazide with or without lipid lowering by pravastatin on progression of asymptomatic carotid atherosclerosis: principal results of PHYLLIS- a randomized double-blind trial // Stroke. 2004. Vol. 35 (12). P. 2807-2812.
49. Chang N.c., Shih C.M., BI W.F. et al. Fosinopril Improves Left Ventricular Diastolic Function in Young Mildly Hypertensive Patients Without Hypertrophy // Cardiovasc. Drugs Ther. 2002. Vol. 16 (2). P. 141-147.
50. Mukhin N.A., Fomin V.V., Moiseev S.V., Khamhieeva M. S. Chronic heart failure and kidney defeat: treatment perspectives // Consilium Medicum. 2008. № 09.
51. SICA D.A., Cutler R.E., Parmer R.J. et al. COMPARISON OF THE STEADY-STATE PHARMACOKINETICS OF FOSINOPRIL, LISINOPRIL AND ENALAPRIL IN PATIENTS WITH CHRONIC HEPATIC AND RENAL INSUFFICIENCY // CLIN. Pharmacokinet. 1991. Vol. 20. P. 420-427.
52. Vetter W. Treatment of Senile Hypertension. The Fosinopril in Old Patiets Study (FOPS) // AM. J. Hypertens. 1997. Vol. 10. S. 255-261.
53. Karpov Yu.A., Mareev V.Yu., Chazov I. E. Russian programs for assessing the effectiveness of the treatment of fozinopril patients with arterial hypertension and heart failure. The project is three f (flag, style, baggage) // heart failure. 2003. No. 4 (5). P. 2-6.

Content

Hypertension is a common cardiovascular disease. Often, the increase in pressure provokes biologically inactive angiotensin I. To prevent its effect, the treatment scheme should include drugs that oppress the action of the hormone. Such means are inhibitors of angiotensin-converting enzyme.

What is AFF

Inhibitors of an angiotensin glider enzyme (ACE) - a group of natural and synthetic chemical compounds, the use of which helped achieve great success in the treatment of patients with cardiovascular pathologies. ACE has been used for more than 40 years. The first to preparation was captive. Further, the lysinopril and Enalapril were synthesized, the new generation inhibitors came to replace. In Cardiology, ACE drugs are used as the main tools that have a vasoconstrictor action.

The benefits of inhibitors consists in a long blocking of hormone angiotensin II - the main factor that has an impact on the increase of blood pressure. In addition, the means of angiotensification enzyme warn bradykinin decay, contribute to a decrease in the resistance of the efferent arteriole, the nitrogen oxide release is released, the vasodilating prostaglandin I2 increases (prostacyclin).

Preparations of ACE new generation

In the pharmacological group of drugs APF drugs with repeated reception (enalapril) are considered obsolete, because They do not provide the necessary complence. But at the same time, Enalapril remains the most popular tool that demonstrates excellent efficiency in the treatment of hypertension. In addition, there are no confirmed data that the Last Generation ACE blockers (perindopril, fozinopril, Ramipril, Zofensoid, Lisinopol) have more advantages over inhibitors released 40 years ago.

What medicines treat ACE inhibitors

The vasodilating powerful means of angiotensin glider enzyme in cardiology are often used to treat arterial hypertension. Comparative characteristics and list of ACE inhibitors, which are most popular among patients:

1. Enalapril

• The indirect cardioprotector quickly reduces blood pressure (diastolic, systolic) and reduces the load on the heart.
• Specifies up to 6 hours, excreted by the kidneys.
• It rarely cause impairment.
• Price - 200 rubles.

1. Captor

• Tool of short term.
• Well stabilizes the pressure, but the drug requires multiple reception. Only a doctor can install the dosage.
• It has antioxidant activity.
• It rarely provoke tachycardia.
• Price - 250 rubles.

1. Lysinopril

• The drug has a long exposure.
• It works independently, he does not need to be metabolized in the liver. Exchanged through the kidneys.
• The medicine is suitable for all patients, even those who suffer obese.
• You can use patients with chronic kidney disease.
• May cause headache, ataxia, drowsiness, tremor.
• The cost of the drug is 200 rubles.

1. Lottenzine

• Protect pressure reduction.
• It has vasodilative activity. Leads to a decrease in bradykinin.
• Contraindicated for nursing and pregnant women.
• Rarely can cause vomiting, nausea, diarrhea.
• Cost of medication within 100 rubles.

1. Monoph.

• Slows bradykinin metabolism. The volume of circulating blood does not change.
• The effect is achieved in three hours. The drug, as a rule, is not addictive.
• With caution, the remedy must be taken in patients with chronic kidney disease.
• Price - 500 rubles.

1. Ramipril.

• Cardioprotector produces ramiprilates.
• Reduces general vascular peripheral resistance.
• The use of meaningful hemodynamically arterial stenosis is contraindicated.
• The cost of funds is 350 rubles.

1. Accomplished.

• Promotes pressure reduction.
• Eliminates resistance in pulmonary vessels.
• Rarely the drug may cause vestibular disorders and loss of taste.
• Price - on average 200 rubles.

1. Perindopril.

• Helps to form an active metabolite in the body.
• Maximum efficiency is achieved after 3 hours after use.
• It rarely provoke diarrhea, nausea, dry mouth.
• The average cost of the drug in Russia is approximately 430 rubles.

1. Trandolapril.

• With long use reduces the severity of myocardial hypertrophy.
• Overdose may cause sharp hypotension and angioedema edema.
• Price - 500 rubles.

1. 
   Hinapril.

• Affects the renin angiotensin system.
• Significantly reduces the load on the heart.
• Rarely can cause allergic reactions.
• Price - 360 rubles.

Classification of APF inhibitors

There are several inhibitory classifications of ACE, their foundation includes a chemical group in a molecule that interacts with the ACE center; the path of removal from the body; Action activity. Based on the nature of the group, which is connected to the zinc atom, inhibitors are divided into 3 categories. In modern medicine, the chemical IAP-classification of drugs containing:

• sulfhydryl group;
• carboxyl group (dicarboxylate-containing drugs);
• phosphinyl group (phosphonate-containing drugs);
• group of natural compounds.

Sulfgidrile group

With the help of specific reagents, sulfhydryl groups of enzymes cause full or partial inhibition of activity of different enzymes. The means of this group are calcium antagonists. List of most famous means of sulfhydryl group of enzymes:

• Benazepril (potential drug);
• Captopril (means of Epsitron, Kozoten, Alkadil);
• Zofensoid (drug Zocardis).

ACE inhibitors with carboxyl group

Functional monovalent carboxyl group has a positive effect on the life of patients with hypertension. As a rule, dicarboxylate-containing drugs use only once a day. It is impossible to use such funds with ischemic heart disease, diabetes, renal failure. List of the most famous dicarboxylate-containing drugs:

• Perindopril (prescript);
• Enalapril (ENAP, Edith, Enam, Renipril, Berlipril, Rheniete);
• Lysinopol (dotroid, lysiotone);
• Ramipril (Tritacea, Hartil, Amprilan);
• Spirapril (quadropryl);
• QuinaPril;
• Transdolapril;
• Cilaproke.

Phosphonate-containing drugs

The phosphinyl group is associated with zinc ion in the active center of ACE, while inhibiting its activity. Treatments are used to treat renal failure and hypertension. Phosphonate-containing ACE preparations are usually considered to be the means of a new generation. They have a high ability to penetrate the tissue, so pressure stabilizes for a long period. The most popular preparations of ACE of this group:

• Fozinopid;
• Fozicard.

Natural Infibers APF.

The preparations of the ACE of natural origin were open when studying the peptides, which are contained in the roe of the flashers. Such means act as peculiar coordinators that limit the processes of strong tensile cells. Pressure is reduced by reducing peripheral vascular resistance. Natural ACE inhibitors that enter the organism with dairy products are called lactuineins and Kazokinins. In small quantities, they may be contained in garlic, hibiscus, serum.

ACE inhibitors - indications for use

Means with angiotensin gluttering enzymes are used even in plastic surgery. But, as a rule, it is most often prescribed to patients to reduce blood pressure and those patients who have violations in the activities of the cardiovascular system (for the treatment of arterial hypertension). It is not recommended to use drugs on our own, since these tools have many side effects and contraindications. The main indications for the use of ACE inhibitors:

• diabetic nephropathy;
• lV dysfunction (left ventricle) hearts;
• atherosclerosis of sleepy arteries;
• suffered myocardial infarction;
• diabetes;
• microalbuminuria;
• obstructive disease of the bronchi;
• atrial fibrillation;
• high activity of the renin-angiotensive system;
• metabolic syndrome.

ACF inhibitors with hypertension

APE drugs block an angiotensin-converting enzyme. These modern drugs have positive effects on human health, protecting his kidney and heart. In addition, an ACE inhibitors with diabetes have found a wide use of sugar diabetes. These drugs increase the sensitivity of cells to insulin, improve the absorption of glucose. As a rule, all means from hypertension must be accepted only a day. The list of drugs used in hypertension:

• MOOKSZHRIL;
• Lodzil (Dotroton, Lizoril);
• Ramipril (Tritacea);
• Talinolol (beta blocker);
• Fisinopril;
• Cilaproke.

ACE inhibitors in heart failure

Often the treatment of chronic heart failure involves the use of inhibitors. This cardioprotectory group in tissues and blood plasma prevents the transformation of inactive angiotensin I to active angiotensin II, thereby preventing its adverse effect on the heart, kidney, vascular peripherals, neurohumoral status. List of cardiosaped drugs that are allowed to take with heart failure:

• Enalapril;
• Captopril;
• antianginal verapamil;
• Lysinopril;
• Trandolapril.

ACE inhibitors with renal failure

For a long time it was believed that inhibitors poorly affect the work of the kidneys and therefore they were contraindicated even at the initial stage of renal failure. Today, these funds, on the contrary, prescribe patients to treat a violation of the function of the kidneys along with diuretics. The drugs of angiotensin-converting enzyme reduce proteinuria and improve the overall condition of the kidneys. You can take the following ACE inhibitors at CPN:

• Captopril;
• Lysinopril;
• Perindopril;
• Trandolapril.

ACE inhibitors - action mechanism

The mechanism of action of ACE inhibitors consists in reducing the activity of an angiotensin-converting enzyme, which accelerates the transition of biologically inactive angiotensin I to Active II, which has a vasopressor pronounced effect. APE preparations are constrained by the bradykinin decay, which is considered a powerful vasodilator. In addition, these funds reduce blood flow to the heart muscle, while reducing the load, protect the kidneys from the influence of diabetes and hypertension. Applying inhibitors, you can limit the activity of the kallicrein-kinin system.

Reception of APF inhibitors

Many patients with hypertension are often interested in how to take Blockers APF? The use of any drugs must be coordinated with a doctor. As a rule, inhibitors should be taken an hour before eating an empty stomach. Dosage, frequency of use, the gap between receptions must define a specialist. During treatment with the help of inhibitors, it is worth abandoning anti-inflammatory non-steroidal means (nurofen), substitutes of salt and products rich in potassium.

ACE inhibitors - Contraindications

List of relative contraindications of intake of inhibitors:

• arterial moderate hypotension;
• chronic severe renal failure;
• childhood;
• heavy anemia.

Absolute contraindications IAPF:

• hypersensitivity;
• lactation;
• bilateral stenosis of renal arteries;
• severe hypotension;
• aortic heavy stenosis;
• pregnancy;
• pronounced hypercalemia;
• porphyry;
• leukopenia.

Side Effects of ACE inhibitors

During the intake of inhibitors, it is necessary to remember the development of by-metabolic effects. Often, dizziness, angioedema edema, dry cough, potassium growth in blood can appear. These complications can be completely eliminated if you stop taking the drug. There are other side effects of ACE:

• itching, rash;
• weakness;
• hepatotoxicity;
• reducing libido;
• fetopathic potential;
• stomatitis, fever, rapid heartbeat;
• swelling of legs, neck, language, faces;
• there is a risk of falling and fractures;
• diarrhea or severe vomiting.

The price of APF inhibitors

You can buy inhibitors in the specialized department of the store or in any pharmacy of Moscow. Their price may differ, based on the form of release and manufacturer's company. Here is a small list of recent generation inhibitors and their approximate cost:

Video: APE drugs

Attention! The information presented in the article is familiarized. Article materials do not call for independent treatment. Only a qualified doctor may diagnose and give recommendations on treatment, based on the individual characteristics of a particular patient.

Discuss

ACE inhibitors - a list of drugs. The mechanism of action of ACE inhibitors of the new generation and contraindications

Hypertension (arterial hypertension) - the most common pathology of the cardiovascular system. Diseases are most susceptible to people over 60 years old. Hypertension is characterized by a resistant increase in blood pressure above the mark of 140 per 90 mm.rt.st.

The exact causes of hypertension are unknown. But doctors argue that there are a number of predisposing factors for the development of alert. So, hypertension is most susceptible to people suffering from overweight. Negatively affect the cardiovascular system and bad habits.

The addiction to alcohol and smoking increases the likelihood of progression of arterial hypertension by 30-60%. No less important aspect is nutrition. According to cardiologists, hypertension are most susceptible to people who use an excessive amount of pickles, black tea, coffee, oily dishes. It happens that arterial hypertension is a consequence of diseases of urinary or endocrine systems.

The characteristic symptoms of hypertensive disease are:

1. Pain in the chest area. Often pain syndrome is accompanied by a rapid heartbeat and a sense of tingling.
2. Dizziness and headaches. Moreover, the patient has increased sensitivity to external stimuli. Even minor noise can cause dizziness and cooler pain.
3. Eveny. Usually shouted hands and feet. Interesting is the fact that the swelling is much more often observed in women hypertensive.
4. Noise in the head. Usually this symptom appears only with increased pressure. If the adhesives of the hypertensive are normalized, the sign will disappear.
5. Memory disorder, increased fatigue, impairment of vision.
6. Nausea.

To diagnose hypertension, the patient needs to undergo a comprehensive diagnosis. The survey provides for tracking the stability of the increase in blood pressure. This is necessary to exclude the secondary hypertension. Diagnosis complements the ECG, the chest x-ray, surrendering urine and blood analysis. It is necessary to hand over the blood test to cholesterol, HDL, LDL.

Treatment of hypertension - Complex and symptomatic. It provides for the use of hypotonic drugs. Tiazide diuretics, sartans, ACE inhibitors, calcium antagonists, beta-adrenoblays are used.

Be sure to comply with the diet. Diet and therapy provides for the refusal of alcohol, oily meat, fried dishes, pickles, smoked meats, any semi-finished products and some spices. The diet should consist mainly of vegetables, fruits, berries, fresh greenery, low-fat meat, legumes, croup. It is allowed to use green tea and freshly squeezed horses.

To increase the effectiveness of therapy, it is necessary to add it moderate physical activity. Perfectly workflk, hiking, yoga, respiratory gymnastics, swimming. It is advisable to avoid increased physical exertion, and during classes to monitor the pulse and general well-being.