A short-acting APF inhibitor is. List of ACE inhibitors - drugs of the latest generation, conditions of use

»» No.1 1999 PROFESSOR Yu.N. CHERNOV, HEAD OF THE DEPARTMENT OF CLINICAL PHARMACOLOGY WITH THE COURSE OF FUV, VORONEZH MEDICAL ACADEMY NAMED AFTER N.N. BURDENKO

G.A. BATISHCHEVA, HEAD OF THE COURSE OF CLINICAL PHARMACOLOGY, CANDIDATE OF MEDICAL SCIENCES

PROFESSOR V.M. PROVOTOROV, HEAD OF THE DEPARTMENT OF FACULTY THERAPY, LAUREATE OF THE PRIZE OF THE COUNCIL OF MINISTERS OF THE USSR

S.Yu. CHERNOV, STUDENT OF THE DEPARTMENT OF FACULTY THERAPY

Angiotensin converting enzyme (ACE) inhibitors are a group of drugs, the use of which since the early 70s has made it possible to achieve certain success in the treatment of patients with cardiovascular pathology.

Currently, about 50 drugs of the ACE inhibitor group are used. The experience of their use in arterial hypertension, heart failure, coronary heart disease, diabetic nephrology simultaneously raises questions related to the optimization of pharmacotherapy. First of all, this is the determination of the characteristics of the individual reaction to the administration of ACE inhibitors, the prognosis of the treatment, clear contraindications, the development of a monitoring system for pharmacodynamic effects, and the definition of withdrawal criteria.

The pharmacological action of ACE inhibitors is due to their effect on the functional state of the renin-angiotensin-aldosterone system. In this case, ACE inhibitors have the necessary structure that allows them to interact with the zinc atom in the angiotensin-converting enzyme molecule. This is accompanied by its inactivation and suppression of the activity of the circulating (plasma) and tissue (local) angiotensin systems.

The drugs of the group differ in the severity and duration of the inhibitory effect on angiotensin I-converting enzyme: in particular, ramipril in the body turns into an active metabolite - ramiprilat, the affinity of which for angiotensin I-converting enzyme is 42 times higher, and the ramipril-enzyme complex is 72 times higher more stable than captopril enzyme.

The affinity of the active metabolite of quinapril, quinaprilat, for angiotensin I-converting enzyme is 30-300 times stronger than that of lisinopril, ramiprilat or fosinoprilat.

The inhibition of angiotensin I-converting enzyme is dose-dependent. In particular, perindopril at a dose of 2 mg inhibits angiotensin I-converting enzyme by 80% at the peak of action and by 60% after 24 hours. With an increase in the dose of perindopril to 8 mg, its inhibitory ability increases to 95% and 75%, respectively.

The blockade of the production of local angiotensin II may depend on the degree of penetration of drugs into the tissues - ACE inhibitors, which have high lipophilicity, more easily penetrate into tissues and suppress the activity of the angiotensin I-converting enzyme.

When studying the ability of ACE inhibitors to inhibit angiotensin I-converting enzyme in the tissues of the lungs, heart, kidneys, adrenal glands and in the aorta, it was found that trandalopril, ramipril and perindopril are superior to enalapril in their ability to reduce the formation of angiotensin II in the tissues of these organs.

According to M. Ondetti (1988), the highest lipophilicity index for the active metabolite of quinapril, quinaprilat, compared to enalaprilat, ramiprilat, perindoprilat. In this case, quinaprilat inhibits the activity of angiotensin I-converting enzyme in plasma, lungs, kidneys, heart, without changing the activity of angiotensin I-converting enzyme in the brain and testes.

Another ACE inhibitor, perindopril (or its active form), crosses the blood-brain barrier, reducing the activity of ACE in the brain.

The pharmacological action of ACE inhibitors, causing inhibition of the conversion of angiotensin I into active vasoconstrictor angiotensin II, leads to a decrease in the level of angiotensin II in plasma with a decrease in the release of norepinephrine from the presynaptic endings of sympathetic nerve fibers.

The blockade of the effects of angiotensin II limits the release of calcium from the sarcoplasmic reticulum, which reduces the vasoconstrictor response of smooth muscle cells.

When treated with ACE inhibitors, the balance of vasoactive compounds changes in favor of vasodilating biologically active substances, which is achieved by limiting the activity of kininase, identical to ACE, and increasing the level of bradykinin.

The effect of bradykinin on the bradykinin receptors of the vascular endothelium promotes the release of an endothelium-dependent relaxing factor - nitric oxide and vasodilating prostaglandins (prostaglandin E2, prostacyclin).

In the mechanism of the hypotensive action of ACE inhibitors, it is important to reduce the production and release of aldosterone from the adrenal glands, which affects the regulation of potassium-sodium metabolism and the content of fluid in the body. This effect of ACE inhibitors leads to a decrease in sodium accumulation in vascular smooth muscle cells and to the limitation of excessive vasoconstriction, which is especially pronounced in salt-dependent arterial hypertension.

Considering that the content of ACE in the vascular endothelium is much higher than that in the circulating blood, it is assumed that the vascular endothelium is the main point of application of ACE inhibitors. Course therapy with drugs of the group causes structural changes in the arterial wall: a decrease in smooth muscle cell hypertrophy with a limitation of the amount of excess collagen. The lumen of peripheral arteries significantly increases, hypertrophy of the muscular membrane of the arteries and arterioles undergoes reverse development, which is associated with inhibition of migration and proliferation of smooth muscle cells, with a decrease in the formation of endothelin in the vascular endothelium, which affects the production of endothelial growth factor.

The tissue effects of ACE inhibitors are manifested by a decrease in myocardial hypertrophy with a change in the ratio of myocytes and collagen in favor of myocytes.

Clinical observations have established that the vasodilating effect of ACE inhibitors can manifest itself in various vascular basins at the level of arterioles, venules, and microcirculation vessels.

The possibility of reducing vascular resistance in the pulmonary circulation, in the portal blood flow system, and in the regional circulation in the kidneys has been established.

An increase in the diameter of large peripheral arteries (from 13% to 21%) was noted while taking captopril and ramipril. In this case, ramipril led to a pronounced increase in the volumetric blood flow velocity. Improvement of the function of the endothelium of the coronary vessels is shown with prolonged, 6-month administration of quinapril.

The systemic hapotensive effect of the drugs of the group is manifested in a decrease in systolic and diastolic blood pressure while restoring the chronostructure of daily blood pressure.

Clinical studies have shown that a single daily intake of enalapril (ednit) leads to an improvement in the indicators of daily blood pressure monitoring. With pharmacotherapy with ramipril, systolic blood pressure decreases mainly in the daytime, and diastolic blood pressure - both during the day and at night. The course use of moexipril in patients with mild and moderate arterial hypertension reduces the average daily blood pressure without changing the nature of the blood pressure curve and heart rate variability. In this case, the effect of the drug is more pronounced in the daytime.

It is important that the higher the affinity of the drug for ACE, the lower its therapeutic dose, the longer the hypotensive effect, and the less fluctuations in blood pressure during the day.

The short-acting ACE inhibitor captopril has an antihypertensive effect within the first hour after administration, and the total duration of action of the drug is 6 hours. The maximum chronosensitivity to captopril (kapoten) was detected in the morning, at noon and in the early evening hours.

Due to the rapid development of the hypotensive effect, captopril can be used as a remedy for the relief of hypertensive crises. In this case, the effect of the drug appears in 5-7 minutes, and the decrease in blood pressure after 15 minutes.

In contrast to captopril, second-generation ACE inhibitors have an antihypertensive effect for up to 24 hours. The maximum effect of enalapril is observed in 4-6 hours, lisinopril in 4-10 hours, quinapril in 2-4 hours after administration.

An individual peculiarity of the blood pressure reaction was noted when prescribing ACE inhibitors in patients with heart failure: with a three-month course of therapy, a positive dynamics of daily blood pressure was observed in patients with heart failure with arterial hypertension, while during pharmacotherapy of patients without arterial hypertension, there were no significant changes in the daily blood pressure profile.

The individual response of blood pressure to the administration of ACE inhibitors in patients with arterial hypertension may depend on the level of daily secretion of aldosterone, adrenaline, norepinephrine.

The antihypertensive effect on taking enalapril (renitec) is more pronounced in patients with high rates of excretion of aldosterone, adrenaline, norepinephrine with a decrease in the concentration of aldosterone and sodium in the blood plasma. On the contrary, in patients without an antihypertensive effect, the level of hormones in the blood and urine by the end of the two-week treatment did not differ significantly from the initial one, and sodium excretion in the urine even decreased. Insufficient hypotensive effect of ACE inhibitors is also noted in patients with an increase in body mass index, in these cases, higher doses of drugs are required.

It is assumed that with low sodium reabsorption and a high level of circulating renin, the degree of the hypotensive effect of ACE inhibitors should be higher, since in this case a decrease in peripheral vasoconstriction is associated with a decrease in the formation of circulating angiotensin II.

The cardiovascular effects of ACE inhibitors, along with a decrease in the tone of arterioles, include a venodilating effect with a redistribution of blood to the vessels of the lower extremities. At the same time, in patients, the reaction to the orthostatic test may increase with the appearance of postural hypotension.

A decrease in systemic blood pressure with a decrease in post-load simultaneously with a decrease in venous return of blood to the heart causes a decrease in ventricular filling pressure. The cardioprotective effect of ACE inhibitors is also due to their effect on the local renin-angiotensin system with an effect on hypertrophy, dilation, myocardial remodeling, as well as on the structure of the vascular wall of the coronary arteries.

ACE inhibitors increase the coronary reserve by reducing the hypertrophy of the medial layer of the intramural coronary arteries, and the course therapy with captopril improves the relaxation properties of the myocardium, reducing myocardial hypoperfusion during the dipyridamole injection test (according to the results of stress myocardial scintigraphy).

The appointment of ACE inhibitors in patients with chronic heart failure (CHF) increases the speed and strength of contraction of the subendo- and subepicardial layers, increasing the rate of early diastolic filling of the left ventricle, which contributes to an increase in exercise tolerance.

Trandalopril (hopten) in the treatment of patients with CHF not only improves hemodynamic parameters, but also reduces asynchrony and increases sensitivity to nitroglycerin.

There is evidence of a more favorable course of remodeling in patients who received ACE inhibitor therapy in the first 24 hours after myocardial infarction.

Clinical studies have shown that enalapril (ednit) after 16 weeks of therapy, along with a decrease in the average daily values \u200b\u200bof systolic and diastolic blood pressure, contributes to a decrease in the mass of the left ventricular myocardium.

ACE inhibitors are the only group of drugs that are known to be able to improve the life prognosis of patients with chronic heart failure: according to 32 randomized trials, the use of ACE inhibitors reduced mortality by an average of 23% and decreased the total number of hospitalizations due to CHF decompensation by 35%. Comparative studies have shown the advantage of therapy with ACE inhibitors (enalapril) compared with pharmacotherapy with digoxin. Moreover, the use of ACE inhibitors in the treatment of CHF makes it possible to achieve positive dynamics of the condition with previous ineffective therapy.

The use of ramipril, enalapril in the early stages of heart failure eliminates diastolic dysfunction of the myocardium due to the period of early filling, contributing to the preservation of left ventricular function with prolonged use.

Long-term course therapy with ACE inhibitors improves myocardial contractile function, significantly reducing the end-diastolic volume and end-systolic volume with an increase in cardiac output and ejection fraction. At the same time, the correction of pathological asynchrony of the myocardium of the right and left ventricles was noted.

ACE inhibitors are used in patients with acromegaly when eliminating hypersomatotropinemia before and after radical treatment, since the possibility of regression of left ventricular hypertrophy has been shown.

The use of captopril makes it possible to increase the efficiency of electrical stimulation cardiomyoplasty in patients with severe heart failure in the long-term follow-up - after 6-12 months, leading to a decrease in transient and stable defects in myocardial perfusion. Evaluation of the individual response of patients to the use of ACE inhibitors made it possible to establish that the effect on the regression of left ventricular hypertrophy is the greater, the higher the initial myocardial mass, and the effectiveness of the use of ACE inhibitors in CHF II-III class is most pronounced in patients with initially low ejection fraction.

Of clinical interest is the fact that in the treatment of chronic cor pulmonale, the use of ACE inhibitors (prestarium in a daily dose of 2-4 mg) is also more effective in patients with initially enlarged sizes of the right atrium and right ventricle with hypokinetic type of hemodynamics.

An improvement in the parameters of the contractile function of the myocardium of the right heart, along with a decrease in pressure in the pulmonary artery, is shown when taking captopril, prestarium, ramipril, lisinopril. A significant improvement in the contractility of the myocardium of the right heart is accompanied by an improvement in the function of external respiration with an increase in the indices of the Tiffno test.

Six-month administration of perindopril in patients with CHF improves bronchial patency of large, medium and small bronchi. At the same time, the increase in patency in small bronchi is more pronounced in smoking patients.

The authors associate the positive dynamics of the function of external respiration in the treatment of CHF in patients with rheumatic heart defects with a decrease in venous stasis in the pulmonary circulation as a result of a decrease in pre- and afterload.

There is evidence that ACE inhibitors can reduce hypoxic vasoconstriction, however, the appearance of irritative cough as one of the side effects may limit their use.

In addition, when taking ACE inhibitors, in some cases in patients with bronchopulmonary pathology, the course of the disease may worsen.

Treatment with enalapril of arterial hypertension in patients with concomitant exacerbation of chronic bronchitis can increase obstruction of the middle and small bronchi, which is partly due to cholinergic imbalance, and the use of prestarium in patients with hyperkinetic type of hemodynamics can increase the pressure in the pulmonary artery.

In the clinical use of ACE inhibitors, it is also necessary to take into account the state of renal function, since all components of the tissue renin-angiotensin system are present in the kidneys, and a decrease in the formation of circulating and local angiotensin II with a decrease in the tone of the efferent arterioles affects the glomerular filtration rate.

Shown is the nephroprotective effect of ACE inhibitors in the treatment of patients with diabetic nephropathy, arterial pruritus, glomerulonephritis, lupus nephritis, scleroderma.

When prescribing ACE inhibitors, the corrective effect of drugs on the level of systemic and glomerular hypertension, as well as the duration of the antiproteinuric effect after their withdrawal, is important. This effect can last up to 6 months, which determines the need for a repeated course of pharmacotherapy with ACE inhibitors at least twice a year.

Clinical observations substantiated the need for preliminary monitoring of the state of the functional renal reserve (FPR) and determining the presence of microalbuminuria when prescribing ACE inhibitors. Pharmacotherapy is prognostically unfavorable if the patient has a reduced FPR and renal isozymes of carboxylic esterases are found in the urine, which indicates ischemia of the proximal renal tubules.

Care should be taken to prescribe ACE inhibitors to patients with reduced FPR and normoalbuminuria, which indicates the functioning of the kidneys in conditions of a high gradient of intraglomerular hydrostatic pressure, and a decrease in systemic and glomerular pressure when using ACE inhibitors in such patients can cause deterioration of renal perfusion.

There is a point of view that the appointment of ACE inhibitors is not indicated for the prevention of diabetic nephropathy, since in patients with preserved FPR and normoalbuminuria, the administration of drugs of this group can lead to hyperfiltration and deterioration of the functional state of the kidneys.

The use of ACE inhibitors for renovascular stenosis can be an alternative to surgical intervention in the case of monolateral stenosis, which is accompanied by renin-dependent hypertension.

In case of bilateral stenosis, the administration of ACE inhibitors is excluded because of the danger of pre- and post-glomerular vasodilation and the risk of a critical decrease in local renal blood flow.

The effect of ACE inhibitors on the state of regional blood circulation was also noted in relation to portal blood flow. In particular, the course therapy with captopril, enalapril, perindopril in patients with portal gastropathy leads to a decrease in the vulnerability and bleeding of the mucous membrane with the disappearance of erosions and ulcers.

ACE inhibitors can affect the state of the microvasculature: course therapy with captopril limits the manifestations of venous stasis with a decrease in the diameter of the venules and an increase in the arterio-venular ratio to 1: 3. At the same time, along with the acceleration of blood flow, a positive hemorheological effect of captopril (tensiomin) was revealed: a decrease in intravascular aggregation with a significant decrease in ADP-induced aggregation, a decrease in the level of soluble fibrin-monomer complexes, fibrinogen-fibrin degradation products.

An increase in the fibrinolytic activity of the blood was also found against the background of 6-month intake of perindopril. Course therapy with prestarium in a daily dose of 4 mg, affects the plasma and vascular-platelet link of hemostasis, reducing the activity of von Willebrant factor, and short-term use of enalapril in healthy people limits changes in hemostasis on physical activity.

Along with a positive effect on hemostasis indicators, ACE inhibitors contribute to the normalization of water metabolism, including the content of free and bound water, potassium and sodium ions in blood fractions.

Among the pharmacological effects of ACE inhibitors, the possibility of influencing lipid, carbohydrate and purine metabolism can be noted.

Treatment with ACE inhibitors leads to a decrease in insulin resistance and an improvement in glucose metabolism, which is associated with an increase in the formation of bradykinin and an improvement in microcirculation.

Optimization of insulin and glucose transport to tissues with an increase in the sensitivity of cells to insulin and an increase in glucose utilization under the influence of pharmacotherapy with ACE inhibitors can be so pronounced that it requires glycemic control.

The positive effect of ACE inhibitors on lipid metabolism in patients with arterial hypertension with diabetes mellitus, in the treatment of patients with postmenopausal hypertension, is manifested by a moderate tendency to decrease the level of cholesterol, triglycerides with a decrease in the atherogenic index. ACE inhibitors can promote metabolic support (LDH, G-6-FDG) of oxygen transport, activating the synthesis of high-energy compounds in erythrocytes.

ACE inhibitors increase the excretion of urate by the kidneys, therefore they are the first choice drugs in patients with arterial hypertension in combination with gout. However, the peculiarities of the individual reaction to their intake in individual patients can lead to the formation of gouty stones.

The drug interactions of ACE inhibitors have not yet been adequately studied. An increase in the antihypertensive effect was noted with a combination of ACE inhibitors with hypothiazide, with a three-component scheme: corinfar-retard + cordanum + captopril, with combined therapy: enalapril + beta-blockers or in combination with 2nd generation calcium antagonists (isradipine, amlodipine).

The simultaneous administration of enalapril and losartan is accompanied by a decrease in the activity of natriuretic peptide (by 17.8%) and endothelein (by 24.4%).

In the post-hospital period of myocardial infarction, to limit the progression of heart failure, combination therapy with enalapril in combination with beta-blockers is most effective.

The combination of kapoten with amiodarone allows to increase the antiarrhythmic effect to 93.8%, while the "runs" of ventricular tachycardia disappear and the frequency of ventricular extrasystoles is significantly reduced.

Speaking about the adverse drug interactions of ACE inhibitors, it should be noted that, along with lithium and potassium preparations, the side effects of ACE inhibitors can enhance cytostatics and interferon, when combined with which, the incidence of neutropenia and agranulocytosis increases.

NSAID therapy, leading, due to inhibition of prostaglandin synthesis, to constriction in the kidneys of the afferent arteriole, in combination with ACE inhibitors, which eliminate the narrowing of the outflow arteriole, impairs glomerular filtration and leads to renal dysfunction.

Among the side effects of ACE inhibitors, the appearance of cough (0.7-25%), angioedema (0.1-0.2%), skin rash (1-5%), a violation of taste and the syndrome of "burnt tongue" (0, 1-0.3%).

Zinc deficiency associated with liver pathology predisposes to violations of taste sensations during pharmacotherapy with ACE inhibitors.

Among the side effects, weakness, nausea, dizziness, constipation are often noted, but they do not cause the drug to be discontinued, adjusting the dose and blood pressure level can eliminate these phenomena.

Arterial hypotension on the first dose is observed in 10% of patients, especially in the presence of CHF, however, with pharmacotherapy with perindopril, the hypotensive effect of the first dose is absent.

The occurrence of proteinuria on the administration of ACE inhibitors is observed in 3.5% of patients taking captopril, 0.72% - receiving moexipril, and 1.4% - taking enalapril, which is usually associated with a decrease in intraglomerular pressure. The drug of choice is spirapril, when administered, the creatinine level does not change, even if the clearance is less than 30 ml / min. Rare side effects of ACE inhibitors include neutropenia and agranulocytosis. Cases of aplastic anemia on the administration of lisinopril are described.

ACE inhibitors are contraindicated in pregnancy, as they lead to a lack of amniotic fluid, neonatal anemia and pulmonary hypoplasia in the fetus. In the first three months of pregnancy, fetotoxic effects are possible.

The possibility of developing kidney anomalies with the introduction of enalapril in the neonatal period has been experimentally proved.

In the clinical use of ACE inhibitors, it is important to take into account the characteristics of pharmacokinetics. So, when prescribing second-generation drugs (prodrugs) in patients with concomitant liver pathology, the time during which the drug concentration in plasma reaches its maximum is lengthened.

The relationship between oxidative metabolism and the severity of the hypertensive effect of ACE inhibitors has been established. At the same time, a monthly course of pharmacotherapy with enalapril does not give an effect in 45% of patients who are "slow oxidants".

Among the many questions regarding the use of ACE inhibitors, the tactics of drug withdrawal are not completely clear, which is associated with an increase in plasma renin activity against the background of pharmacotherapy with ACE inhibitors and the possibility of a withdrawal syndrome.

The aspect of prophylactic administration of ACE inhibitors in persons with genetically determined elevated ACE activity requires further research, since these people are considered as a risk group for developing coronary artery disease.

A difficult task is to determine the criteria for predicting the effectiveness of therapy with ACE inhibitors, which is especially important for second-generation drugs, the clinical use of which allows assessing the effect not earlier than 4 weeks of course therapy. Given the high cost of second-generation drugs, this also has socio-economic significance.

Further study of the pharmacological action of ACE inhibitors in relation to the determination of lipid peroxidation parameters, the state of the antioxidant system and the level of eicosanoids in the body is promising.

In conclusion, it can be noted that the problem of effective use of ACE inhibitors has not been fully resolved. Clarification of the individual characteristics of the reaction to the administration of ACE inhibitors is necessary for choosing the tactics of prescribing drugs in order to optimize pharmacotherapy.

Literature

1. Alexandrov A.A. ACE inhibitors: clinical age of majority. In the world of drugs. 1998, 1, p. 21.
2. Arutyunov G.P., Vershinin A.A., Stepanova L.V. et al. The effect of long-term therapy with an ACE inhibitor enalapril (renitek) on the post-hospital period of acute myocardial infarction. Clinical pharmacology and pharmacotherapy. 1998, 2, p. 36-40.
3. Akhmedova D.A., Kazanbiev N.K., Ataeva 3.N. et al. The effect of combination therapy on the remodeling of the left ventricle of the hypertensive heart. Abstracts of the Fifth Russian National Congress "Man and Medicine". Moscow, 1998, p. fifteen.
4. Balakhonova N.P., Avdeev V.G., Kuznetsov N.Ye. and others. The use of captopril (acetyne of the company "Wockhardt") in hypertension and congestive heart failure. Clinical medicine. 1997, 75, 1, p. 42-43.
5. Belousov Yu.B., Tkhostova E.B. Clinical use of the angiotensin-converting enzyme inhibitors Berlipril® 5. M. "Universum Publishing". 1997, p. 28.
6. Borisenko A.P., Gvozdev Yu.N., Aksenova T.N. et al. Amiodarone and kapoten in the treatment of prognostically dangerous arrhythmias in patients with chronic circulatory failure. Abstracts of the Fifth Russian National Congress "Man and Medicine". Moscow, 1998, p. 28.
7. Bugrova O.V., Bagirova V.V., Rybina O.I. Influence of renitek on the state of the renal functional reserve in patients with systemic lupus erythematosus and systemic scleroderma. Abstracts of the Fifth Russian National Congress "Man and Medicine". Moscow, 1998, p. 34.
8. Gilyarovsky S.P., Orlov V.A. Therapeutic tactics in the event of side effects of ACE inhibitors. Clinical pharmacology and pharmacotherapy. 1997, 4, p. 74-83.
9. Gukova S.P., Fomicheva E.V., Kovalev Yu.R. The role of structural polymorphism of the angiotensin-converting enzyme gene in the development of myocardial infarction. Clinical medicine. 1997, 75.9, p. 36-38.
10. Gurgenyan S.V., Adalyan K.G., Vatinyan S.Kh. et al. Regression of left ventricular hypertrophy under the influence of the angiotensin-converting enzyme inhibitor enalapril in hypertensive patients. Cardiology. 1998, 38, 7, p. 7-11.
11. Demidova I.V., Tereshchenko S.N., Moiseev B.C. et al. The effect of the ACE inhibitor perindopril on the function of external respiration in patients with chronic heart failure. Abstracts of the Fifth Russian National Congress "Man and Medicine". Moscow, 1998, p. 58.
12. Dityatkov A.E., Tikhonov V.A., Evstafiev Yu.A. and other The use of ramipril in the treatment of pulmonary hypertension in tuberculosis. Abstracts of the Fifth Russian National Congress "Man and Medicine". Moscow, 1998, p. 61.
13. Zonis B.Ya. Antihypertensive therapy in patients with diabetes mellitus. Russian medical journal. 1997, 6, 9, p. 548-553.
14. Ivleva A.Ya. Clinical use of angiotensin-converting enzyme inhibitors and angiotensin II antagonists. M., 1998, from "Miklos", p. 158.
15. Kakaliya E., Belousov Yu.B., Bykov A.V. et al. The effectiveness of captopril (tensiomin) in long-term treatment of arterial hypertension. Soviet medicine. 1991, 10, p. 45-48.
16. Karpov R.S., Pavlyukova E.N., Taranov S.V. and others. Experience of long-term therapy of patients with syndrome X. Abstracts of the Fifth Russian National Congress "Man and Medicine". Moscow, 1998, p. 90.
17. Kakhnovsky I.M., Fomina M.G., Ostroumov E.N. et al. Gopten (trandolapril) in the treatment of chronic heart failure in patients with ischemic heart disease. Therapeutic archive. 1998, 70, 8, p. 29-33.
18. Sour N.D., Ponomarev V.G., Malik M.A. et al. ACE inhibitors in patients with portal gastropathy. Clinical pharmacology and pharmacotherapy. 1997, 2, p. 42-43.
19. Kobalava Zh.D., Moryleva ON, Kotovskaya Yu.V. et al. Postmenopausal hypertension: treatment with an ACE inhibitor moexipril. Clinical pharmacology and pharmacotherapy. 1997.4, p. 63-74.
20. Korotkov N.I., Efimova E.G., Shutemova E.A. et al. Influence of prestarium on the hemodynamic state of patients with chronic obstructive bronchitis. Abstracts of the Fifth Russian National Congress "Man and Medicine". Moscow, 1998, p. 103.
21. Kots Ya.I., Vdovenko L.G., Badamshina N.B. et al. Diastolic function of the left ventricle in patients with heart failure during treatment with an angiotensin-converting enzyme inhibitor ramipril and an angiotensin II receptor antagonist kosaar. Abstracts of the Fifth Russian National Congress "Man and Medicine". Moscow, 1998, p. 105.
22. Kukes V.G., Ignatiev V.G., Pavlova L.I. et al. Clinical efficacy of Corinfar-retard in combination with cordanum, triampur, kapoten in patients with arterial hypertension. Clinical medicine. 1996, 74, 2, p. 20-22.
23. Kukushkin S.K., Lebedev A.V., Manoshkina E.N. et al. Comparative evaluation of the antihypertensive effect of ramipril and captopril by the method of 24-hour ambulatory blood pressure monitoring. Clinical pharmacology and pharmacotherapy. 1997.3, p. 27-28.
24. Kutyrina I.M., Tareeva I.E., Shvetsov M.Yu. et al. Experience of using ramipril in patients with lupus nephritis. Clinical pharmacology and pharmacotherapy. 1997, 2, p. 25-26.
25. Mazur N.A. Organ lesions, metabolic disorders in arterial hypertension and the effect of antihypertensive therapy on them. Therapeutic archive. 1995, 67, 6, p. 3-5.
26. Malanina K.S., Nekrutenko L.A., Khlynova O.V. Influence of prestarium on vascular-platelet hemostasis in hypertensive patients. Abstracts of the Fifth Russian National Congress "Man and Medicine". Moscow, 1998, p. 130.
27. Markov V.A., Gavina A.V., Kolodin M.I. et al. The effect of perindopril in combination with thrombolysis on the size of the left ventricle and the clinical course of myocardial infarction. Clinical pharmacology and pharmacotherapy. 1997, 1, p. 30-31.
28. Moiseev B.C. ACE inhibitors and nephropathy. Clinical pharmacology and pharmacotherapy. 1997, 4, p. 67-69.
29. Olbinskaya L.I., Pinskaya E.V., Bolshakova T.D. and others. Activity of some systems of neurohumoral regulation, electrolyte balance and clinical efficacy of renitek in patients with essential hypertension. Therapeutic archive. 1996, 68, 4, p. 54-57.
30. Olbinskaya L.I., Andrushishina T.B., Zakharova V.L. Antihypertensive efficacy according to 24-hour blood pressure monitoring data, safety and effect on the morphofunctional parameters of the heart of the angiotensin-converting enzyme inhibitor ednit in hypertensive patients. Cardiology. 1997, 37, 9, p. 26-29.
31. Olbinskaya L.I., Andrushishina T.B. Effect of a new angiotensin-converting enzyme inhibitor moexipril on circadian rhythms of arterial pressure in hypertensive patients. Therapeutic archive. 1997, 69, 3, p. 58-61.
32. Olbinskaya LI, Sizova J., Tsarkov I. Treatment of chronic heart failure with angiotensin-converting enzyme inhibitors. Doctor. 1998, 8, p. 11-15.
33. Orlova L.A., Mareev V.Yu., Sinitsyn V.G. et al. Effect of angiotensin-converting enzyme inhibitor enalapril and cardiac glycoside digoxin on left ventricular remodeling. Cardiology. 1997, 37, 2, p. 4-9.
34. Pekarskaya M.V., Akhmedov Sh.D., Krivoshchekov E.V. etc. The use of kapoten in the treatment of patients who underwent electrostimulation cardiomyoplasty. Cardiology. 1998, 38, 7, p. 21-23.
35. Pekarsky S.E., Vorottsova I.N., Mordovyan V.F. Reduction of left ventricular hypertrophy and dynamics of parameters of daily monitoring of blood pressure under the influence of ramipril in patients with essential arterial hypertension. Therapeutic archive. 1997, 69, 4, p. 18-20.
36. Pekarsky S.E., Krivonogov N.G., Griss S.V. and other Features of the renoprotective effect of ramipril in patients with essential hypertension. Clinical pharmacology and pharmacotherapy. 1997, 1, p. 26-29.
37. Ryazanova S.E. Treatment of heart failure in patients with chronic cor pulmonale. Russian medical journal. 1997, 3, p. 57-62.
38. Savenkov M.P., Ivanov S.N. Changes in the function of external respiration in patients with chronic bronchitis when using enalapril and losartan. Abstracts of the Third Russian National Congress "Man and Medicine". Moscow, 1996, p. 197.
39. Sviridov A.A., Pogonchenkova I.V., Zadionchenko V.A. Hemodynamic effects of sinopril in the treatment of patients with chronic cor pulmonale. Abstracts of the Fifth Russian National Congress "Man and Medicine". Moscow, 1998, p. 188.
40. Silorenko BA, Sopoleva Yu. V. Angiotensin-converting enzyme inhibitor moexipril in the treatment of hypertension in postmenopausal women. Cardiology. 1997, 37, 6, p. 87-92.
41. Sidorenko V.A., Preobrazhensky D.V. The range of clinical application of the angiotensin-converting enzyme inhibitor quinapril. Cardiology. 1998, 3, p. 85-90.
42. Smirnova I.Yu., Dementyeva N.G., Malykhin A.Yu. et al. Pharmacokinetic approach to optimization of antihypertensive therapy with enalapril. Vseros. scientific. conf. "From materia medica to modern medical technologies". 1998, p. 163.
43. Sotnikova T.I., Fedorova T.A., Rybakova M.K. et al. The effectiveness of tensiomin in the treatment of patients with chronic heart failure. Abstracts of the Fifth Russian National Congress "Man and Medicine". Moscow, 1998, p. 201.
44. Stipakov E.G., Stipakova A.V., Shutemova E.A. et al. Prestarium in the treatment of systemic and pulmonary hypertension in patients with chronic obstructive pulmonary diseases. Abstracts of the Fifth Russian National Congress "Man and Medicine". Moscow, 1998, p. 205.
45. Tereshchenko S.N., Drozdov V.N., Levchuk N.N. et al. Changes in the plasma hemostasis in the treatment of perindopril in patients with congestive heart failure. Clinical pharmacology and pharmacotherapy. 1997, 4, p. 83-87.
46. \u200b\u200bTereshchenko S.N., Drozdov V.N., Demidova I.V. and other Angiotensin-converting enzyme inhibitor perindopril in the treatment of congestive heart failure. Therapeutic archive. 1997, 69, 7, p. 53-56.
47. Tereshchenko S.N., Kobalava Zh.D., Demidova I.V. et al. Changes in the daily blood pressure profile in patients with congestive heart failure during therapy with an angiotensin-converting enzyme inhibitor perindopril. Therapeutic archive. 1997, 69, 12, p. 40-43.
48. Tikhonov V.P., Turenko E.V. The effectiveness of treatment with kapoten in patients with arterial hypertension, depending on the state of the kidneys. Abstracts of the Third Russian National Congress "Man and Medicine". Moscow, 1996, p. 220.
49. Tkhostova E.B., Pronin A.Yu., Belousov Yu.B. The use of enalapril in patients with mild and moderate arterial hypertension according to the data of daily monitoring of blood pressure. Cardiology. 1997, 37, 10, p. 30-33.
50. Fatenkov VN, Fatenkov OV, Shchukin Yu.V. and other Angiotensin-converting enzyme inhibitors in the treatment of heart failure in patients with coronary artery disease. Abstracts of the Fifth Russian National Congress "Man and Medicine". Moscow, 1998, p. 223.
51. Fazulzyanov A.A., Andreev V.M., Fazulzyanova G.N. Respiratory mechanics, alveolar ventilation, ventilation-perfusion relations in the correction of heart failure with strophanthin and kapoten. Kazan Medical Journal. 1995, LXXVI, 6, pp. 417-419.
52. Fedorova T.A., Sotnikova T.I., Rybakova M.K. and other Clinical, hemodynamic and hemorheological effects of captopril in heart failure. Cardiology. 1998, 38.5, p. 49-53.
53. Filatova N.P. The use of perindopril (prestarium) for arterial hypertension. Therapeutic archive. 1995, 67, 9, p. 81-83.
54. Filatova E.V., Vikhert O.A., Rogoza N.M. et al. Comparison of the effect of capoten (captopril) and ramipril on the daily blood pressure profile and peripheral hemodynamics in hypertensive patients in combination with diabetes mellitus. Therapeutic archive. 1996, 68, 5, p. 67-70.
55. Fuchs A.R. Influence of lomir and enap on left ventricular diastolic function in patients with arterial hypertension. Clinical pharmacology and pharmacotherapy. 1997, 1, p. 27-28.
56. Khlynova OV, Guev AV, Schekotov VV Dynamics of venous and central circulation indicators in patients with arterial hypertension treated with enalapril. Clinical pharmacology and pharmacotherapy. 1998, 1, p. 59-61.
57. Shestakova M.V., Sheremetyeva S.V., Dedov I.I. Tactics of using renitek (angiotensin-converting enzyme inhibitor) for the treatment and prevention of diabetic nephropathy. Clinical medicine. 1995, 73, 3, p. 96-99.
58. Shustov S.B., Baranov V.L., Kadin D.V. The effect of the angiotensin-converting enzyme inhibitor perindopril on the state of the left ventricular myocardium in patients with acromegaly after radical treatment. Cardiology. 1998, 38, 6, p. 51-54.
59. Shcherban N.N., Pakhomova S.P., Kalensky V.Kh. et al. Comparison of the efficacy of sublingual application of capoten and prazosin in the treatment of hypertensive crises. Clinical medicine. 1995, 73, 2, p. 60.
60. Bertoli L., Lo Cicero S., Busnardo I. et al. Effects of captopril on hemodynamics and blood gases in chronic obstructive lung disease with pulmonary hypertension. Respiration 49, 251-256, 1986.
61. Campese V. M. Salt sensitivity in hypertension. Renae and cardiovascular implications. Hypertension 23,531-550,1994.
62. Derkx F H M., Tan-Thong L., Wenting G. J. et al. Assynchronous changes in prorenin and renin secretion after captopril in patients with renal artery stenosis. Hypertension 5, 244-256, 1983.
63. Fabris B., Chen B., Pupie V. et al. Inhibition of angiotensin-converting enzyme (ACE) in plasma and tissue. J. Cardiovasc Pharmacol, 1990,15, Suppl. 6-13.
64. Gibbons G.H. Endotelial function as a determinant of vascular function and structure: A new therapeutic target. Am J. Cardiol 1997,79,5a 3-8.
65. Glasser Stephen P. The time course of left ventricular remodeling after acute myocardial infarction. Am. J. Cardial 1997, 80, 4, 506-507.
66. Guron Gregor, Adams Michael A., Sundelin Brigitta, Friberg Peter. Neonatal angiotensin-converting enzyme inhibition in the rat induces persistent abnormalities in renal function and hystology. Hypertension 1997, 29, 1, Pt 1, 91-97.
67. Ikeda Uichi, Shimada Kazujuki. NO and cardiac failure. Clin. Cardiol, 1997, 20, 10, 837-841.
68. Johnston C.I. Tissue angiotensin converting enzyme in cardie and vascular hypertrophy, repair and remodeling. Hypertension 1994, 23, 258-268.
69. Johnston C. I., Fabris B., Yamada A. et al. Comparative studies off tissue inhibition by angiotensin-converting enzyme inhibitors. J. Hypertens, 1989, 7, Suppl. 5, 11-16.
70. Lindpaintner K., Jin M., Wilhelm M. J. et al. Intracardiac generation of angiotensin and its physiologic role. Circulacion, 77, (Suppl. 1), 1988, 1-18.
71. Luseher T., Wensel R., Morean P., Tacase H. Vascular protective effects of SCE inhibitors and calcium antagonists: Theoretical basis for a combination therapy in hypertension and ofther cardiovascular diseases. Cardiovasc Drugs Ther, 1995, 9, 509-523.
72. Mancini G. B. J .; Henry G. P., Macay C. et al Angiotensin converting enzyme inhibition with quinapril improves endothclial vasomotor dysfunction in patients with coronary artery disease. The TREND study. Circulation, 1996, 94, 258-265.
73. Me Areavey D., Robertson J.I.S. Angiotensin converting enzyme inhibitors and moderate hypertension. Drugs, 1990, 40, 326-345.
74. Morgan K.G. The role of calcium in the control of vascular tone as assessed by the Ca ++ indicator aequorin. Cardiovasc Drugs Ther 4, 1990, 1355-1362.
75. Ondetti M.A. Structural relationships of angiotensin-converting enzyme inhibitors to pharmacological activity. Circulation, 1988, -77, Suppl. 1, 74-78.
76. Pedram Ali, Razandi Mahnaz, An Ren-Ming. Vasoactive peptides modulate vascular endothelial cell growth factor production and endothelial cell proliferation and invasion. J. Biol. Chem. 1997, 272, 27, 17097-17103.
77. Perella M. A., Hildebrand G.F.L. Margulis K.B. Endotelium - derived relaxing factor in regulation of basal cardio - pulmonary and renal function. Am J. Physiology, 261, 1991, 323-328.
78. Pratt R.E. ltoh H., Gibbons G.H., Dzan V. J. Role of angiotensine in the control of vascular smooth muscle cell growth. J. Of Vsc. Med. And Biol., 1991, 3, 25-29.
79. Prisco D., Paniccia R., Bandinelli B. Short-term ACE inhibition may influence exercise-induced changes in haemostasis in healthy subjects. Fibrinolysis, 1997, 11, 4, 187-192.
80. Schror K. Role of prostaglandins in the cardiovascular effects of bradykinine and the angiotensin-converting enzyme inhibitors. J. Cardiovasc Pharmacol, 1992, 20 (Suppl. 9), 68, 73.
81. Simpson P. C. Kariya K., Kams L. R. et. al. Adrenergic hormones and control of cardiac myocyte growth. Mollecular and Cellular Biochem, 1991, 104, 35-43.
82. Van Belle Eric, Vallet Beno Jt, Anffray Jean-Luc, Bauters Christophe et al. NO syntehesis is involved in structural and functional effects of ACE inhibitors in injured arteries. Am J. Physiology 1997,270,1,2,298-305.

An integrated approach is used in the treatment of hypertension. Monotherapy is justified only at the initial stages of the development of the disease. One of the first-line drugs are ACE inhibitors - drugs that act directly on adrenal hormones, which provoke an increase in blood pressure due to fluid retention in the body.

ACE inhibitors are medicines that act on the angiotensin-converting enzyme. Under the influence of angiotensin, the production of aldesterone increases, which entails an increase in vascular tone and fluid retention in the body, as a result of which blood pressure rises.

Angiotensin-converting enzyme inhibitors inhibit the synthesis of specific hormones that cause the development of hypertension. To date, drugs in this group are prescribed to almost all patients in the absence of contraindications as a means to control blood pressure.

The mechanism of action of drugs in this group is manifested in two stages. One side,

Drugs in this group are almost always included in the treatment regimen

aCE inhibitors affect the synthesis of angiotensin, which increases vascular tone. Angiotensin, in turn, provokes an increased production of aldesterone. This hormone is synthesized by the adrenal glands and causes fluid retention in the body in response to salt intake. Slowing down the production of aldesterone reduces edema and reduces the pressure of blood on the walls of blood vessels, while a decrease in angiotensin leads to a normalization of the frequency of contractions of the heart muscle and a decrease in vascular tone.

In addition, ACE inhibitors significantly increase the effectiveness of diuretics by reducing the synthesis of the hormone that causes edema. Thus, they are indicated as part of complex therapy for hypertension of 2 and 3 degrees, but not as an independent remedy.

The mechanism of action of the latest generation ACE inhibitors affects the normalization of the cardiovascular system, including the heart itself, and the urinary system. In addition, drugs in this group can reduce the risk of damage to target organs with an increase in blood pressure above 180 mm Hg.

Classification of drugs

ACE inhibitors are divided into synthetic and natural. The drugs used in the treatment of hypertension are precisely synthetic drugs. Natural inhibitors are released from a specific reaction between whey and casein.

ACE inhibitors are divided into three groups, depending on the active ingredient. Distinguish:

• sulfhydryl group preparations;
• carboxyl group drugs;
• phosphonate ACE inhibitors.

The mechanism of action of drugs, regardless of the group, is exactly the same. These drugs are complete analogues of each other, as they have the same effect on the cardiovascular system. The only difference between ACE inhibitors of different groups is the mechanism of excretion of the active substance after taking the pill. This must be taken into account when prescribing medication for patients with renal failure.

Some ACE inhibitors are excreted by the kidneys, others are processed in the liver - this must be taken into account in case of pathologies of these organs

List of drugs of the sulfhydryl group

The list of drugs-ACE inhibitors of the sulfhydryl group is quite wide, but most often they are used:

• captopril;
• benazepril;
• zofenopril.

One of the most popular and used drugs for the treatment of hypertension is captopril. The active ingredient has the following trade names - Captopril, Kapoten, Bokordil.

A feature of this group of drugs is the lack of prolonged action. The taken pill is active for no more than six hours, so the drug is taken 2-3 times a day. Drugs in this group are prescribed for arterial hypertension against the background of coronary heart disease, often combined with diuretics.

The advantage of drugs of the sulfhydryl group is good tolerance by the body. They can be taken for diabetes and heart failure.

The recommended dosage of Captopril is up to 100 mg per day. It is taken one hour before meals, 1 or 2 tablets, depending on the amount of active ingredient in one tablet. When prescribing a medicine, it is taken into account that it is excreted by the kidneys, therefore, in case of renal failure, the drug is not prescribed.

Benazepril is taken a maximum of twice a day, since the active substance is released slowly. The recommended dosage regimen is one tablet in the morning and in the evening at regular intervals.

Zofenopril is also taken two tablets a day. Unlike other drugs of the sulfhydryl group, this drug has less stress on the kidneys, but in case of renal failure it can only be used under medical supervision.

Captopril is among the most popular drugs

Carboxyl group drugs

ACE inhibitors of the carboxyl group are drugs with the following active ingredients in the composition:

• Quinapril;
• Renitek;
• Ramipril;
• Lisinopril.

The list of drugs in this group is very wide and includes more than 15 active substances. They all have a similar mechanism of action, contraindications and indications for use.

Features of drugs of the carboxyl group:

• prolonged action;
• pronounced vasodilating effect;

The metabolism of the active substance occurs mainly in the liver, which can significantly reduce the load on the kidneys. Medicines have a pronounced vasodilator effect, due to which a rapid decrease in blood pressure occurs. These properties of drugs of the carboxyl group should be taken into account when taken by patients with hypertension grade 3. In this case, rapid normalization of blood pressure can negatively affect the work of the heart muscle.

Due to the prolonged action, such drugs are taken 1 time per day. The release of the active substance occurs slowly, which allows for a long-term and sustained therapeutic effect.

It is enough to take these preparations once a day.

Phosphinyl group preparations

The third group of ACE inhibitors includes two active ingredients - fosinopril and ceronapril. These drugs are intended more likely to control the morning surges in blood pressure in hypertension, rather than as a complex treatment. As an independent agent, phosphinyl group preparations are not effective enough.

Feature of drugs - prolonged action, which allows you to control the level of blood pressure even during a night's rest. The metabolism of these drugs is carried out simultaneously in the kidneys and liver, which makes it possible to prescribe a drug in case of impaired renal function in older patients.

Another feature is a convenient reception scheme. It is enough to take the drug only once a day in the morning to ensure a stable therapeutic effect.

New generation combination medicines

Drugs of the third group belong to a new generation of drugs for hypertension, along with combined drugs.

Their advantages:

• prolonged action;
• ease of use;
• good tolerance;
• complex action.

Due to the peculiarities of the metabolism of the active substance, the new generation drugs can be used to treat patients with renal failure and diabetes mellitus. This is very important, since hypertension is diagnosed mainly at an older age against the background of concomitant chronic diseases.

Combined drugs can be taken for hypertensive patients with diabetes mellitus

Combination drugs include drugs containing calcium channel blockers and ACE inhibitors, or diuretics and ACE inhibitors. These drugs are very convenient because you can take just one drug to control your blood pressure.

Combination of an ACE inhibitor and a diuretic:

• Caposide;
• Ramazid N;
• Fozikard N.

Such drugs have a more pronounced hypotensive effect, while they can be used as monotherapy for hypertension of 1 and 2 degrees. In addition, they are convenient to take - only 1 tablet a day to ensure a stable therapeutic effect throughout the day.

At an older age, there is a violation of the elasticity of large arteries. This is due to physiological changes against the background of constantly high blood pressure. When the vessels lose flexibility and their permeability is impaired, treatment is carried out with combination drugs that contain an ACE inhibitor and a calcium antagonist. The list of such funds:

• Triapin;
• Tarka;
• Egipres;
• Coripren.

In most cases, Coripren is prescribed. It is advisable to use such drugs for the treatment of hypertension in the case when other drugs, including ACE inhibitors as an independent agent, are ineffective. Usually they are prescribed to patients over 65 years of age with an increased risk of blood clots and myocardial infarction.

Features of use for hypertension

ACE inhibitors are prescribed mainly for hypertension. However, this is not the only area of \u200b\u200bapplication of this group of drugs.

The peculiarity of drugs of the ACE inhibitor group consists in a positive effect on target organs. Taking such drugs allows you to minimize the risk of developing dangerous consequences, such as stroke or myocardial infarction.

With hypertension of 1 degree, there is a steady, but insignificant increase in blood pressure, not higher than 140 mm Hg. If the disease develops against the background of any chronic diseases and the cardiologist has reason to believe that the disease will progress rapidly, ACE inhibitors are prescribed as monotherapy. The combination of drugs of this group with a diet, rejection of bad habits and normalization of the daily regimen, allows you to achieve a steady decrease in blood pressure in half of the patients taking the medicine.

Stage 2 hypertension is characterized by a steady increase in blood pressure up to 160 mm Hg. and higher. This increases the risk of damage to any organ. Usually, vision is affected first (angiopathy develops) or kidneys. With such pressure, diet therapy and reducing the load are no longer enough, it is necessary to take medications. At the same time, drugs of the ACE inhibitor group pursue two goals - to achieve a stable decrease in pressure and avoid the development of complications. Usually, complex therapy is used, including a diuretic, calcium antagonists and ACE inhibitors. Timely treatment allows achieving a stable hypotensive effect in 70% of cases and preventing the development of dangerous complications.

With grade 3 hypertension, blood pressure rises above 160 mm Hg. Taking diuretics and calcium antagonists as monotherapy shows low results, therefore, new generation combined agents are used for treatment. The danger of hypertension of the 3rd degree is the development of hypertensive crises, disruption of the work of two or more target organs (heart, kidneys, brain, organs of vision). Usually, severe hypertension occurs against the background of diabetes mellitus, vascular atherosclerosis or other chronic diseases. In this case, the drugs must be taken for life.

In the initial stages of hypertension, ACE inhibitors are taken as the main drug, in the later stages - as part of complex therapy

Application for heart failure

Among the indications for the use of ACE inhibitors is any form of heart failure. The drugs in this group help:

• To avoid the progression of the disease;
• Reduce the load on blood vessels and heart;
• Prevent the development of myocardial infarction.

The use of an ACE inhibitor in patients with heart failure made it possible to reduce the risk of sudden death as a result of the cessation of cardiac activity by 2.5 times. In addition, according to the patients themselves, drugs in this group significantly improve the quality of life with such a diagnosis.

With heart failure, drugs are taken with caution. At the beginning of treatment, the administration of reduced dosages is indicated, no more than ¼ of the recommended amount given in the instructions. This precautionary measure is due to the risk of a sudden drop in blood pressure to critical values. As the body gets used to the drug, the dosage gradually increases, eventually reaching the recommended one.

In addition, drugs in this group can be used during the recovery period after myocardial infarction.

ACE inhibitors for renal failure

In renal failure, ACE inhibitors help reduce the rate of progression of the disease. They are prescribed, among other things, for impaired renal function in the presence of diabetes mellitus. At the same time, it is important to select a drug taking into account its metabolism and excretion from the body. For the treatment and control of kidney function, drugs that are metabolized in the liver should be selected. This is an important condition for achieving a sustainable therapeutic effect.

In case of kidney damage, drugs are selected that are excreted by the liver

Contraindications

Only a doctor should prescribe drugs of the ACE inhibitor group, after taking a history and a detailed examination of the patient. Before starting treatment, the patient is advised to read the instructions for the drug again. The following diseases and conditions are contraindications:

• Rheumatoid arthritis;
• Lupus erythematosus;
• Pregnancy;
• Lactation period.

ACE inhibitors should not be taken in case of individual intolerance. Special instructions may vary, depending on the specific drug, so it is important to carefully study the instructions.

Taking drugs of this group during pregnancy can provoke fetal malformations that are incompatible with life.

Reception of ACE inhibitors with hypotension is categorically contraindicated, otherwise there is a risk of coma due to a decrease in blood pressure to critical values.

Side effects

If the medicine is selected correctly, the patient follows the doctor's recommendations and does not exceed the dosages, the development of side effects is unlikely, since the drugs of the ACE inhibitor group are well tolerated by the body.

Nevertheless, with hypersensitivity and violation of the intake regimen, the development of undesirable phenomena is possible:

• hypotension;
• dry cough that is difficult to treat;
• retention of potassium in the body (hyperkalemia);
• the formation of protein compounds in the urine;
• impaired renal function;
• excretion of glucose in the urine;
• allergic rash and angioedema.

The most common side effect is persistent cough

The most common dry cough when taking drugs in this group. This side effect is observed in about 1/5 of patients taking an ACE inhibitor to control blood pressure. It is difficult to get rid of a cough with the help of special drugs, but it goes away on its own within a few days after the abolition of ACE inhibitors.

With individual drug intolerance, a severe allergic reaction and Quincke's edema may develop. Such complications are very rare, but pose a serious danger not only to health, but also to the patient's life.

With a decrease in blood pressure to dangerous values \u200b\u200band the development of hypotension, it is necessary to consult a doctor about changing the dosage regimen or reducing the dosage. Usually this phenomenon is observed when taking too large doses of the drug against the background of heart failure.

As a rule, all complications when taking ACE inhibitors are reversible, or go away on their own after discontinuation of the drug. However, it is recommended that you inform your doctor about any changes in your health after starting a new medication.

Drug interactions

The drugs used for the treatment of gastritis and heartburn, which have an enveloping effect (Maalox, Gaviscon), significantly reduce the absorption of inhibitors by the stomach, which reduces their bioavailability and therapeutic effect. With the simultaneous administration of an ACE inhibitor with such drugs, it may be necessary to adjust the regimen for taking antihypertensive drugs.

The hypertensive effect of an ACE inhibitor is reduced when taken simultaneously with anti-inflammatory drugs of the nonsteroidal group (Ibuprofen, Nimesulide, Diclofenac). The simultaneous administration of acetylsalicylic acid and ACE inhibitors reduces the effectiveness of the latter.

A complete list of drug interactions and important indications is given in the instructions for use of the drug, which should be carefully studied before starting treatment.

For questions about the need to increase or decrease the dosage of the drugs taken, you should contact your cardiologist, but do not try to change the treatment regimen yourself. It is important to remember that any drugs for the treatment of hypertension, if taken incorrectly, can lead to irreversible consequences, so you should trust your doctor, but do not try to treat the disease yourself.

Diabetes mellitus is another pathology in which antiotensin-converting enzyme inhibitors are mandatory. Even if the patient has normal blood pressure without a tendency to fluctuate, it will still be necessary to drink these pills, but the drug will be taken systematically, regardless of the patient's condition and any other factors.

Renal pathologies - chronic pyelonephritis and glomerulonephritis, as well as various systemic pathologies.

In this case, the appointment is possible only after the patient is examined by a nephrologist and undergoes a number of additional medical examinations.

A number of additional studies include ultrasound of the kidneys, general urine analysis, biochemical blood test with the determination of the renal and hepatic complex.

Modern inhibitors - list of drugs

It will be necessary to divide the drugs of the given pharmacological group into two categories - drugs and prodrugs.

The fundamental difference between them is that in the first case, when the drug itself is already a medicinal compound, it enters the body and immediately begins to act.

In other words, its clinical effect manifests itself rather quickly, which makes it possible to use such pills as an emergency aid. And can be used as emergency drugs.

Captopril and Lisinopril are used for (in the overwhelming majority of cases, it is prescribed - a combination of captopril with hydrochlorothiazide, a diuretic).

Captopril tablets

For routine administration, it is recommended to use prodrugs - these are compounds that by themselves do not have biochemical activity in the human body, but when ingested, they are converted into substrates that can have a pronounced clinical effect.

There are a great many examples of prodrugs from the ACE inhibitors group: Ramipril, Fosinopril and many others. There is no fundamental difference between them if we consider biochemically active molecules with substances identical in mass.

One can reasonably argue - why, then, in some cases, there is a high efficiency of antiotensin-converting enzyme inhibitors (ACE inhibitors), while in others it leaves much to be desired?

Provided that the same dosages of drugs are used, and the results of the use were established on the same people?

The answer is on the surface - everything is determined by the drug manufacturer. Not all manufacturers that are represented on the pharmacological market today have the required certificates of conformity, but, nevertheless, they continue to function safely, supplying patients with low-quality but cheap products.

Medicines from the ACE inhibitor group act quickly, which makes it possible to provide emergency assistance in the shortest possible time, however, their duration of exposure is short, which excludes the possibility of their use at normal blood pressure, although antihypertensive drugs are drunk systematically.

You shouldn't try to save money on medicines. Moreover, now the cost of original drugs is not much higher than the price of generic drugs, the effectiveness of which is highly questionable.

Indications and contraindications

Modern ACE inhibitors are prescribed for the treatment of pathologies such as:

1. hypertonic disease;
2. heart failure;
3. diabetes;
4. renal pathologies - chronic pyelonephritis and glomerulonephritis;
5. metabolic systemic disorders.

ACE inhibitors are drugs that are contraindicated for use in the following cases:

1. individual intolerance to the drug;
2. pregnancy at any stage of gestation and breastfeeding of the child.

Groups

What are ACE inhibitors?

There are several classifications of drugs belonging to the ACE inhibitors group.

However, the only one that is significant is their conditional division into drugs and prodrugs (this subdivision has already been given above).

Natural ACE inhibitors

In fact, there are no such natural remedies. Angiotensin-converting enzyme inhibitors are drugs that are synthetic, but this moment in no way affects their clinical efficacy.

It's worth noting that the best ACE inhibitor is the one prescribed by your doctor. You cannot engage in self-medication.

Related Videos

What are ACE inhibitors? The list of drugs and their pharmacological characteristics in the video:

The basis for the complex treatment of arterial hypertension is ACE inhibitors - angiotensin-converting enzyme blockers. Together with diuretics, they stabilize blood pressure in a short time, and keep it within normal limits for a long time.

ACE inhibitors are used to treat arterial hypertension

ACE inhibitors - what are they?

Angiotensin-converting inhibitors - These are natural and synthetic substances that inhibit the production of the vasoconstrictor enzyme angiotensin in the kidneys.

This action makes it possible to use drugs for:

• decrease in blood flow to the heart, which reduces the load on a vital organ;
• protect the kidneys from pressure surges (hypertension) and excess sugar in the body (diabetes).

Modern antihypertensive drugs of the ACE inhibitor group have a long-term effect and a stable effect. Medicines have a minimal list of side effects and are easy to use.

Classification of ACE inhibitors

Depending on the chemical composition, angiotensin-converting inhibitors include several main groups - carboxyl, phosphinyl, sulfhydryl. All of them have different degrees of elimination from the body and differences in assimilation. There is a difference in the dosage, but it depends on the characteristics of the disease and is calculated by the doctor.

Table "Comparative characteristics of the groups of modern angiotensin-converting enzyme inhibitors"

According to the duration of the therapeutic action, drugs for pressure also have several groups:

1. Short-acting drugs (captopril). Such inhibitors should be taken 3-4 times a day.
2. Medium duration drugs (Benazepril, Zofenopril, Enalapril). It is enough to take such medicines at least 2 times a day.
3. Long-acting ACE blockers (Cilazapril, Lisinopril, Quinapril, Fosinopril). Medication is good for relieving pressure with one dose per day.

The list of drugs belongs to the latest generation drugs and contributes to the suppression of ACE in blood, tissues (kidneys, heart, vessels). At the same time, the new generation angiotensin-converting enzyme inhibitors not only reduce high blood pressure, but also protect the internal organs of a person - they have a positive effect on the heart muscle and strengthen the walls of the vessels of the brain and kidneys.

Action of ACE inhibitors

The mechanism of ACE blockers is to inhibit the production of a vasoconstrictor enzyme produced by the kidneys (angiotensin). The drug affects the renin-angiotenson system, prevents the conversion of angiotensin 1 into angiotensin 2 (a provocateur of hypertension), which leads to the normalization of blood pressure.

With the release of nitric oxide, angiotensin receptor blockers slow the breakdown of bradykinin, which is responsible for vascular wall dilation. As a result, the main therapeutic effect is achieved in hypertension - blocking angiotensin 2 receptors, relieving high tone in the arteries and stabilizing pressure.

Indications for angiotensin-converting enzyme inhibitors

Antihypertensive drugs of the last generation ACE blockers group are complex drugs.

This allows them to be used in the following states:

• with hypertension of various etymologies;
• with heart failure (decreased ejection fraction of the left ventricle or hypertrophy);
• with renal failure (glomerulonephritis, pyelonephritis, diabetic nephropathy, hypertensive nephropathy);
• after a stroke with pressure surges upward;
• with a previous myocardial infarction.

The use of ACE blockers is limited or replaced by other drugs in the case of a strong decrease in creatinine clearance (it happens in renal failure and threatens with hyperkalemia).

Features of the use of ACE inhibitors

Antihypertensive drugs will produce a higher therapeutic effect if the main features of their use are taken into account:

1. Inhibitors should be taken one hour before meals, observing the dosage and number of doses indicated by the doctor.
2. Do not use salt substitutes. Such food analogues contain potassium, which is already accumulated in the body during treatment with ACE blockers. For the same reason, it is not recommended to abuse foods containing potassium (cabbage, lettuce, oranges, bananas, apricots).
3. You can not take anti-inflammatory drugs of non-steroidal origin (ibuprofen, nurofen, brufen) in parallel with inhibitors. Such drugs delay the excretion of water and sodium from the body, which reduces the effect of angiotensin-converting enzyme blockers.
4. Constantly monitor the pressure and kidney function.
5. Do not interrupt the course of treatment without the knowledge of the doctor.

Do not take with inhibitors Ibuprofen and similar medications

Contraindications

Along with widespread use in the treatment of arterial hypertension, ACE blockers have many contraindications. They can be conditionally divided into absolute (strictly prohibited for use) and relative (application depends on the clinical picture, when the result justifies the possible harm).

Table "Main contraindications to the use of angiotensin-converting enzyme inhibitors"

It is important to understand that ACE inhibitor drugs are serious drugs that can be harmful as well as beneficial. Therefore, it is necessary to strictly adhere to the recommendations of a specialist and not ignore contraindications.

Side effects of ACE inhibitors

ACE receptor blockers have a positive effect on the human body in the treatment of hypertension.

Despite this, drugs can cause certain negative reactions from vital systems:

1. Cough. There are no such ACE inhibitors that do not cause cough. To one degree or another, antihypertensive drugs cause a similar symptom. If it is severe, it is better to consult a doctor.
2. Disorders in the digestive tract in the form of severe vomiting and prolonged diarrhea.
3. Itching and redness of the skin.
4. An increase in the amount of potassium in the blood, which is accompanied by a disturbance in the rhythm of the heart, shortness of breath, tingling in the limbs, irritability, confusion.
5. Swelling of the throat, tongue, face. Temperature, sore throat, chest discomfort, swelling of the lower extremities.

Puffiness in the throat may appear when taking inhibitors

The first time you take this medicine, you may experience a metallic or salty taste in your mouth. In addition, at the beginning of therapy, dizziness will be most pronounced, and a breakdown is possible.

Another important side effect of using ACE inhibitors is renal impairment. This happens when renal failure occurs in an acute stage.

In the treatment of hypertension, ACE inhibitors are considered the most effective drugs. Medicines inhibit the production of angiotensin by the kidneys and, thereby, help to normalize blood pressure. Due to the broad mechanism of action, such drugs are used for heart and renal failure, in the treatment of arterial hypertension of various origins. The main thing is not to self-medicate and be able to report all changes to the doctor. This will help avoid negative consequences.

ACE inhibitors are drugs that effectively lower blood pressure, preventing the onset and progression of structural changes in the heart and blood vessels that accompany hypertension. Their effect on comorbidities is also beneficial. Drugs in this group reduce blood pressure in patients with hypertension. The decrease in pressure is associated with a decrease in peripheral vascular resistance. Unlike direct vasodilators, a decrease in blood pressure with an ACE inhibitor is not accompanied by reflex tachycardia or a decrease in cardiac output. Compared to a number of other drugs used, they have other advantages: they have a beneficial effect on insulin resistance, slow the progression of diabetic nephropathy, prevent potassium loss during diuretic therapy, prevent cardiac dilatation, and reduce mortality in heart disease.

ACE inhibitor belongs to a group of drugs that are used to treat a wide range of diseases. Their literal name is angiotensin-converting enzyme blockers, but the abbreviation is more often used - ACE inhibitors.

The latest drugs in this group block the production of a hormone called angiotensin II in the body. It does this by blocking an enzyme that converts angiotensin. Consequently, vasodilation of the blood vessels occurs and water is absorbed back into the vascular bed in the kidneys. This process leads to a decrease in pressure, as indicated above.

The human body has many ways to regulate pressure. However, there are two main areas that can be used. One of them is vascular resistance (resistance). If the vessels contract, the resistance increases; if they expand, it decreases. When considering the same volume of blood flowing through the blood vessels - blood pressure will rise if the blood vessel narrows.

Another way the body uses to control pressure is to reduce the volume of blood released by the heart into the body. The multiplication of heart rate and heart rate is equal to the value of cardiac output. Blood pressure results from a combination of these two main areas, namely the regulation of vascular resistance and the volume of blood pumped by the heart. ACE inhibitors act in both directions.

Blood is made up of blood cells such as blood cells and plasma. The kidneys are the organ that controls the fluid in the body, and the kidneys themselves are able to regulate the amount of fluid. Increased water reabsorption decreases urine volume and increases blood pressure. In a normal physiological state, pressure regulation works as follows. When the kidneys are under increased pressure, they release the hormone renin into the bloodstream. Renin converts angiotensinogen to angiotensin I, which is converted to angiotensin II using an angiotensin-converting enzyme.

Angiotensin

Angiotensin II is an active hormone that has three main effects:

• narrowing of blood vessels;
• reabsorption of water in the kidneys;
• release of the hormone aldosterone, which also causes increased reabsorption of water in the kidneys.

ACE inhibitors are inhibitors of the conversion of angiotensin I to angiotensin II, which reduce its level. The result is the induction of vasodilatation. The amount of water absorbed by the kidneys back into the bloodstream is reduced. This leads to a decrease in pressure. Hence:

• with hypertension, ACE inhibitors are reduced;
• with heart failure, there is a reduction in the volume of blood that pumps the heart. This makes it easier for the heart to work, thereby reducing the progression of heart failure.

There is another group of drugs on the market called angiotensin II receptor antagonists (eg, Candesart, Lozatran). They act on the same principle as ACE inhibitors, and can be used in cases where a patient has negative reactions when taking drugs of this group.

List of drugs

The list of drugs belonging to the considered group of ACE inhibitors is relatively wide. Let's consider some of the first drugs used for therapeutic purposes.

Drugs - ACE inhibitors - list of first line drugs:

• Captopril;
• Cilazapril;
• Enalapril;
• Fozinopril;
• Imidapril;
• Lisinopril;
• Moexipril;
• Perindopril;
• Quinapril;
• Ramipril;
• Trandolapril.

Next-generation ACE inhibitors are found in a number of commercial drugs, present in drugs in combination with other active substances.

Classification

ACE inhibitors differ in their effects, bioavailability, biological half-life and elimination. Most drugs are prodrugs, so they are absorbed as natural ineffective substances, acting only after esterification in the liver. The active substances produced by prodrugs have typical multiphase elimination kinetics. The strong terminal binding of the inhibitor to ACE is responsible for the long terminal phase.

The classification of ACE inhibitors is determined according to the structure of the ligand. In this regard, 3 groups of inhibitors are divided:

• sulfhydryl;
• carboxyl;
• phosphoryl (Fosinopril tablets).

However, from a practical point of view, comparative characteristics of ACE inhibitors in accordance with their pharmacological properties are more advantageous:

• a drug that is absorbed as an active, then converting metabolite;
• an inactive drug that is activated only after esterification in the liver;
• hydrophilic, directly active and non-metabolizable drug.

Specialized studies show that the effectiveness of all ACE inhibitors is approximately the same. With hypertension, it does not matter which drug the person takes. For heart failure, the following medicines are suitable: Enalapril, Lisinopril, Ramipril. People with renal insufficiency can take Alapril, Lisinopril, Ramipril.

Scope of application

Shown aCE activity with hypertension - the pressure in hypertension decreases due to a decrease in peripheral vascular resistance, which is not accompanied by reflex tachycardia or a decrease in cardiac output. Of all the drugs used for hypertension, an ACE inhibitor is the most effective treatment for reducing cardiac hypertrophy and interstitial fibrosis. These drugs do not affect the metabolism of lipids or sugars; on the contrary, they have a beneficial effect on insulin resistance and slow the progression of diabetic neuropathy. Concomitant diuretic therapy makes an ACE inhibitor a group capable of preventing potassium loss.

The drugs reduce mortality in patients with cardiac dysfunction. These patients have a reduced risk of fatal myocardial infarction. The use of an ACE inhibitor in the acute phase of the disease reduces the activity of the renin-angiotensin and sympathomadric systems. These medications should be administered within the first 24 hours.

In coronary artery disease without manifestations of heart failure, ACE inhibitors also reduce the risk of mortality.

Drugs in this group reduce the risk of nephropathy in diabetics without proteinuria and are used as prevention of secondary stroke in patients with hypertensive and normotensive exercise.

Important! Before prescribing drugs of this group, it is advisable to conduct a blood test for ACE.

The main indications for the use of ACE inhibitors are the following conditions:

• hypertension;
• heart failure;
• myocardial infarction;
• diabetic nephropathy.

How to use ACE inhibitors correctly?

How it is appropriate to use a particular medicine and in what dosage are questions that should be resolved with your doctor. Typically, you start with lower doses that are gradually increased. This method is chosen to closely monitor the body's response to the active substance. For some people, the first dose can cause a rapid drop in blood pressure.

If you are taking diuretics, you should stop taking them the day before taking ACE inhibitors.

After taking the first dose of medication:

• stay at home for 4 hours, in some cases nausea may occur after taking;
• if you are not feeling well, sit or lie down;
• if the condition worsens, see your doctor.

Arterial hypertension

ACE inhibitors belong to 6 main groups of drugs, defined by WHO as first-line drugs for the treatment of hypertension (hypertension, high blood pressure).

ACEs of the latest generation have an antihypertensive effect comparable to other antihypertensive agents. So far, mortality studies have not been conducted that demonstrate a greater effect of these drugs on reducing mortality than, for example, diuretics, beta-blockers or calcium channel blockers. The largest comparative study to date has been the STOP 2 (Swedish Trial in Old Patients with Hypertension-2 study).

In patients with arterial hypertension with left ventricular hypertrophy, the goal of therapy is not only to sufficiently reduce pressure, but also to reduce the weight of the left ventricle. The most suitable drugs are ACE or calcium channel blockers.

Patients with arterial hypertension with a low response rate to monotherapy require combination therapy. Its base is ACE-I, supplemented by antihypertensive drugs from other groups of drugs.

Heart failure

Inhibitors reduce the force that strains the heart muscle, reducing blood volume and dilating blood vessels. All of this reduces the force the heart generates to release blood into the bloodstream.

Cases of heart failure (chronic cardiovascular failure) in European countries are recorded in 2% of the population, with a significant increase in older age groups. And, although mortality from cardiovascular diseases in the civilized world is decreasing, the prevalence of the problem is constantly growing.

This clinical syndrome has a worse prognosis than some types of cancer, more than 10% of patients die within one year after the development of clinical signs, more than 50% of patients die within 5 years. The combination of ACE-I and beta-blockers used in modern medicine is the basis for the treatment of heart failure and possible concomitant hypertension. This combination prolongs and improves life.

Myocardial infarction

Recently, there have been a number of studies examining the effect of ACE on conditions after myocardial infarction. Their results have significantly contributed to the widespread use of drugs of this group in patients with acute myocardial infarction. Based on research results, angiotensin-converting enzyme inhibition is given to all patients with myocardial infarction even if they do not have hypertension or heart failure.

Stroke prevention

In a recently completed ACE trial, Perindopril was administered to patients with a history of stroke. The study included 6105 patients, 64% of whom were hypertensive. The average outgoing pressure was 147/86, after the use of "Peridopril" it decreased by about 9/4 compared with the control group that did not take this drug. The total number of heart attacks decreased by 28%, the number of deaths - by 38%, the number of hemorrhagic conditions - by 48%, ischemia - by 24%. The incidence of myocardial infarction ACE-blocker "Perindopril" reduced by 38%.

Chronic renal failure

In chronic renal disease, ACE inhibitors slow down the course of the disease.

To slow down the progression of renal failure as much as possible, especially in patients with elevated blood levels, a decrease in blood pressure to 130/80 is required. ACE-I slows down the progression of diabetic nephropathy to a greater extent than other antihypertensive drugs already at a pressure of 140/90. Numerous clinical trials have been conducted to evaluate the effect of ACE-I on non-diabetic kidney disease. It has been shown that drugs in this group reduce blood pressure and reduce the secretion of protein in the urine.

Possible side effects

Common possible side effects include hypotension (low blood pressure). It either does not appear at all, or is manifested by dizziness. If this symptom occurs, along with the pharmacological effects of the drug, inform your doctor about it. In about 10% of people, the mechanism of action of an ACE inhibitor causes a dry cough. A very small percentage of people suffer from edema (swelling of the lips, eyes, tongue). Some drugs can interact with ACE inhibitors. In particular, NSAIDs, diuretics, lithium.

Contraindications for use

A complete list of contraindications and diseases that prohibit the use of a drug that converts a converting enzyme is presented in the instructions for use. Read the package insert carefully to prevent complications from developing.

The main contraindications are as follows:

• pregnancy, breastfeeding;
• allergy to drugs in this group;
• angioedema;
• renal artery stenosis.

In all other cases, the use of an ACE inhibitor is allowed, however, the appointment is prescribed exclusively by a doctor! Treatment is carried out under the supervision of a specialist.