APF inhibitors effectiveness. ACE inhibitors: classification and list of drugs. Organoprotective effects of ACE inhibitors

In pharmacology, a drug group is distinguished - ACE inhibitors, the list of drugs of the latest generation is constantly being updated. In short, the main focus of these drugs is blood pressure. Medicines have a common mechanism of action, but differ in structure, composition, duration of work, method of excretion. In medical practice, there is no single classification of ACE inhibitors, therefore, the division into types is conditional.

General information

Inhibitors are pharmacological nephroprotective drugs that are blockers of enzymes that cause hypertension. They have a beneficial effect on the body with various pathologies:

cardiovascular diseases;
hypertension;
chronic heart failure (CHF).

According to statistics, these funds are considered leaders in the treatment of vascular diseases, their mild action has a positive effect on all organs and systems. The following advantages are highlighted in the treatment with inhibitors:

drugs do not negatively affect the excretory system, kidneys;
do not disturb carbohydrate metabolism;
they are allowed to be taken by people with diabetes mellitus, patients of age suffering from chronic diseases.

Many drugs have a combined composition, therefore, replace other drugs. In this direction, treatment with one drug is actively used, this method is relevant and in demand today. Inhibitors are able to combine with other pharmacological agents, providing a broader effect on the body. This feature is indispensable for the elderly, who often suffer from concomitant diseases.

Enalapril - an inhibitor in combination with a calcium channel blocker

The mechanism of action of drugs

The mechanism and scheme of action of ACE inhibitors is aimed at blocking an enzyme that traps fluid and chemical compounds, which leads to an increase in pressure. The composition of the preparations includes elements that are able to penetrate into soft tissues. A distinctive feature of the constituent components is the ability to dissolve well in fats. It is on this indicator that the positive effect of the drug depends.

In addition to all these positive aspects, ACE drugs slow down the breakdown of certain chemical compounds, which helps to dilate blood vessels and stabilize pressure. Systematic and long-term intake of funds from the ACE group contributes to such changes in the body:

the walls of blood vessels are strengthened;
blood pressure stabilizes;
improves blood circulation in the kidneys;
the use of funds reduces the risk of developing arrhythmias.

These drugs affect the protective functions of the body by stimulating them and helping to protect the myocardium. This method allows you to prevent hypertensive crisis and strengthen the heart muscle. ACE inhibitors are used for hypertrophy of the heart muscles, they strengthen the walls of blood vessels and stabilize the condition of the heart chambers.

Inhibition is effective in heart failure, does not have a detrimental effect on the kidneys, the human liver, which becomes an important advantage of therapy.

To slow down platelet aggregation, it is recommended to take a Cardiomagnyl inhibitor

Indications for use

The pricing policy of inhibitors makes them available to all patients in need of narrow-profile treatment. The therapy has become affordable and effective, which is why it is used in modern medicine. ACE inhibitors have been a leader in the treatment of hypertension for 30 years. The main advantage of this therapy is the minimal effect on internal organs, there are no complications after a long course of treatment.

Indications for the use of ACE inhibitors:

the period after a stroke, when unstable pressure is noted;
the post-infarction period, due to which the pressure rises, left ventricular dysfunction is diagnosed;
renal pathology;
high blood pressure due to the development of diabetes mellitus, diabetic nephrosclerosis syndrome;
dysfunction of the left ventricle, serious disturbances in the work of the heart and circulatory system.

These diseases and age-related changes, which are associated with an increase in blood pressure, are corrected with inhibitors. Based on the diagnostic results, the attending physician prescribes a therapy that is aimed at stabilizing the pathological condition, gives a beneficial effect on all organs and systems of vital activity.

In the picture, the drug Concor, prescribed as a beta-blocker for hypertension

Classification

Due to the lack of clinical relevance, there is no generally known drug classification. The separation of inhibitors occurs according to their chemical structural components:

based on fosinopril, phosphonyl group;
katopril - sulfhydral group;
enalapril - carboxyl group;
group of natural.

There are differences in the duration of the action. In most cases, the daily frequency of taking the drug is 1 time per day. Their use for a month or more can prolong the effect of drugs.

These funds are also divided according to their bioavailability, which is due to a narrow range of influence. There are 2 groups, which are distributed according to molecular components:

hydrophilic agents are those drugs that are instantly absorbed into the plasma and provide a quick therapeutic effect;
hydrophobic agents - this group includes most of the inhibitors, the action of which occurs at the cellular level, which contributes to a pronounced effect.

A large list of drugs needs careful study and comparison with the general clinical picture of the patient. There is also a third classifier:

active agents that are processed in the liver while having a biologically active structure.
prodrugs, their action begins after absorption into the soft tissues of the stomach, intestines and conversion into metabolites.

Effectiveness depends on many indicators, including human tolerance to drugs. Therefore, it is important to undergo a complete diagnostic examination, and then start taking funds with an active substance recommended by a doctor.

New generation inhibitor names

Features of reception

The main advantage of ACE inhibitors is considered to be their beneficial effect on the vital systems and internal organs of a person. The specific composition of inhibitors directly affects the site of localization of the disease, thereby leaving other organs intact.

Indications for use, and how to use the drugs correctly, the doctor will tell you at the reception. A list of recommendations is highlighted that should be taken into account when taking ACE:

drugs are recommended to be taken 1-1.5 hours before meals;
only a doctor can indicate the exact number of appointments per day;
it is worth giving up salt, sugar substitutes;
pay attention to the daily diet, eat only natural products;
give up food rich in potassium.

Doctors pay special attention to the patient's diet when treating an ACE inhibitor. The patient is advised to give up many foods that can affect blood pressure and those that contain large amounts of potassium.

When treating this group of drugs, you should be careful about taking other drugs, especially anti-inflammatory, antipyretic and pain relievers. Frequent use of such medications reduces the effectiveness of the inhibitors.

Hospitalization of the patient is used only in case of serious disorders and progression of concomitant diseases. In the treatment of ACE inhibitors, constant monitoring is needed regarding the state of the excretory system and surges in blood pressure. You can not independently cancel and prescribe drugs. It is worth remembering that only a long course of therapy will give the desired result and normalize blood pressure.

Tablets of various brands for the long-term treatment of hypertension

Contraindications

Inhibitors, like other pharmacological agents, have their own contraindications, they are divided into absolute and relative:

the period of pregnancy, feeding the baby with breast milk;
age under 18;
hyperkalemia;
individual intolerance to the components;
aortic stenosis;
low pressure.

Serious liver disease, kidney disease, anemia, hepatitis require careful attention from a doctor when treating with inhibitors. Self-medication is strictly prohibited - health should be treated carefully and factors provoking complications should be excluded.

With prolonged use of Cardipril, the health of patients improves every day.

Before starting treatment with inhibitors, it is worth excluding the fact of pregnancy, otherwise the active substances can adversely affect the fetus. When breastfeeding, the doctor must balance the possible risk with the necessary care for the woman.

Side effects of drugs

ACE inhibitors are well absorbed by the body, but still have certain side effects and effects. If you experience unpleasant symptoms, then in order to prevent it, you should stop taking medications and visit a doctor.

There is a list of such side effects:

dry, persistent cough;
dizziness, chronic fatigue;
hyperkalemia;
cardiopalmus;
disorders of the digestive system;
changes in the qualitative composition of blood;
decreased work of the excretory system;
a sharp change in blood pressure.

Side effects and effects are purely individual manifestations, therefore, some people may experience allergic reactions in the form of skin rashes. When correcting blood pressure with inhibitors, it is recommended to regularly take a complete blood count to monitor any changes.

Therapy with pharmacological agents from the ACE inhibitor group is a good prevention of diseases of the circulatory system. The only and main rule that should be taken into account during treatment is strict adherence to all the recommendations and prescriptions of the doctor.

Rational pharmacotherapy of arterial hypertension: angiotensin-converting enzyme inhibitors and angiotensin-II receptor blockers

S. Yu. Shtrygol, Ph.D. honey. Sciences, prof.
National University of Pharmacy, Kharkov

The drugs considered in this report are among the modern and most effective antihypertensive drugs with valuable pharmacological properties.

Angiotensin-converting enzyme (ACE) inhibitors

The drugs in this group are subdivided into two generations.

First generation:

captopril (captopril-KMP, kapoten)

Second generation:

enalapril (renitek, enam)
quinapril (acupo)
lisinopril (diroton, lisopress, lisoril)
ramipril (tritace)
perindopril (prestarium)
moexipril (moex)
fosinopril (monopril)
cilazapril (inhibace)

There are also ready-made combinations of ACE inhibitors with thiazide diuretics - for example, captopril with hydrochlorothiazide (caposide), enalapril with hydrochlorothiazide (enap-N, enap-HL).

Mechanism of action and pharmacological properties of ACE inhibitors. The first drug of this group (captopril) appeared about 30 years ago, but a wide range of ACE inhibitors with different properties was created relatively recently, and their special place among cardiovascular drugs was determined only in recent years. ACE inhibitors are used mainly for various forms of arterial hypertension and chronic heart failure. There is also the first evidence of the high efficacy of these drugs in IHD and cerebrovascular accidents.

The mechanism of action of ACE inhibitors is that they disrupt the formation of one of the most powerful vasoconstrictor substances (angiotensin II) as follows:

As a result of a significant decrease or cessation of the formation of angiotensin-II, the following most important effects are sharply weakened or eliminated:

pressor effect on blood vessels;
activation of the sympathetic nervous system;
hypertrophy of cardiomyocytes and smooth muscle cells of the vascular wall;
increased formation of aldosterone in the adrenal glands, sodium and water retention in the body;
increased secretion of vasopressin, ACTH, prolactin in the pituitary gland.

In addition, the function of ACE is not only the formation of angiotensin-II, but also the destruction of bradykinin, a vasodilator, therefore, when ACE is inhibited, bradykinin accumulates, which contributes to a decrease in vascular tone. The destruction of natriuretic hormone also decreases.

As a result of the action of ACE inhibitors, peripheral vascular resistance decreases, the pre- and afterload on the myocardium decreases. Blood flow in the heart, brain, kidneys increases, diuresis increases moderately. It is very important that the hypertrophy of the myocardium and vascular walls (the so-called remodeling) is reduced.

Of all the drugs, only captopril and lisinopril inhibit ACE directly themselves, and the rest are "prodrugs", that is, they are converted in the liver into active metabolites, which inhibit the enzyme.

All ACE inhibitors are well absorbed in the gastrointestinal tract, they are taken per os, but injectable forms of lisinopril and enalapril (vazotek) have also been created.

Captopril has significant disadvantages: short action, as a result of which the drug should be prescribed 3-4 times a day (2 hours before meals); the presence of sulfhydryl groups, which contribute to autoimmunization and provoke a persistent dry cough. In addition, captopril has the lowest activity among all ACE inhibitors.

The rest of the drugs (second generation) have the following advantages: high activity, significant duration of action (can be prescribed once a day, regardless of food intake); lack of sulfhydryl groups, good tolerance.

ACE inhibitors compare favorably with other antihypertensive drugs in the following properties:

no withdrawal syndrome, such as clonidine;
lack of depression of the central nervous system, inherent, for example, clonidine, reserpine and preparations containing it;
effective reduction of left ventricular hypertrophy, which eliminates the risk factor for the development of myocardial ischemia;
lack of influence on the metabolism of carbohydrates, due to which it is advisable to prescribe them when arterial hypertension is combined with diabetes mellitus (in these patients, they are preferable); Moreover, ACE inhibitors are important in the treatment of diabetic nephropathy and the prevention of chronic renal failure, because they reduce intraglomerular pressure and inhibit the development of glomerulosclerosis (while β-blockers increase drug hypoglycemia, thiazide diuretics cause hyperglycemia, impair carbohydrate tolerance);
the absence of impaired cholesterol metabolism, while β-blockers and thiazide diuretics cause a redistribution of cholesterol, increase its content in atherogenic fractions and can enhance atherosclerotic vascular lesions;
absence or minimal severity of oppression of sexual function, which is usually caused, for example, by thiazide diuretics, adrenergic blockers, sympatholytics (reserpine, octadine, methyldopa);
improving the quality of life of patients, established in numerous studies.

Special pharmacological properties are inherent, in particular, in moexipril (moex), which, along with the hypotensive effect, effectively increases the density of bone tissue, improves its mineralization. Therefore, moex is especially indicated for concomitant osteoporosis, especially in menopausal women (in this case, moex should be considered the drug of choice). Perindopril helps to reduce collagen synthesis, sclerotic changes in the myocardium.

Features of the appointment of ACE inhibitors. For the first dose, blood pressure should not decrease by more than 10/5 mm Hg. Art. in a standing position. 2-3 days before transferring the patient to ACE inhibitors, it is advisable to stop taking other antihypertensive drugs. Begin treatment with a minimum dose, gradually increasing it. With concomitant liver diseases, it is necessary to prescribe those ACE inhibitors that themselves inhibit this enzyme (preferably lisinopril), since the conversion of other drugs into active metabolites is disturbed.

Dosage regimen

With arterial hypertension:

Captopril- an initial dose of 12.5 mg 3 times a day (2 hours before meals), if necessary, a single dose is increased to 50 mg, the maximum daily dose is 300 mg
Capozid, Kaptopres-Darnitsa- a combined preparation; an initial dose of 1/2 tablet, then - 1 tablet 1 time per day in the morning (1 tablet contains 50 mg of captopril and 25 mg of hydrochlorothiazide, the significant duration of the action of the diuretic makes more frequent administration irrational during the day)
Caposid-KMP- 1 tablet contains 50 mg of captopril and 12.5 mg of hydrochlorothiazide. Take 1 tablet per day, if necessary, 2 tablets per day.
Lisinopril- initial dose of 5 mg (if treatment is carried out against the background of diuretics) or 10 mg 1 time per day, then - 20 mg, maximum - 40 mg per day
Enalapril- initial dose of 5 mg once a day (against the background of diuretics - 2.5 mg, with renovascular hypertension - 1.25 mg), then 10–20 mg, maximum - 40 mg per day (in 1–2 doses)
Enap-N, enap-NL- combination preparations (in 1 tablet "Enap-N" - 10 mg of enalapril maleate and 25 mg of hydrochlorothiazide, in 1 tablet of "Enap-HL" - 10 mg of enalapril maleate and 12.5 mg of hydrochlorothiazide), are administered orally once a day for 1 tablet (enap-N) or 1-2 tablets each (enap-HL)
Perindopril- an initial dose of 4 mg once a day, with insufficient effect, it increases to 8 mg.
Quinapril- initial dose of 5 mg once a day, then - 10-20 mg
Ramipril- an initial dose of 1.25–2.5 mg 1 time per day, with insufficient effect up to 5–10 mg 1 time per day.
Moexipril- the initial dose is 3.75–7.5 mg once a day, with insufficient effect - 15 mg per day (maximum 30 mg).
Cilazapril- an initial dose of 1 mg once a day, then 2.5 mg, it is possible to increase the dose to 5 mg per day.
Fosinopril- an initial dose of 10 mg once a day, then, if necessary, 20 mg (maximum 40 mg).

The dose of ACE inhibitors for hypertension is increased gradually, usually over 3 weeks. The duration of the course of treatment is determined individually under the control of blood pressure, ECG and, as a rule, is at least 1-2 months.

In chronic heart failure, the dose of ACE inhibitors is usually 2 times lower on average than in uncomplicated arterial hypertension. This is important to prevent a decrease in blood pressure and an energetically and hemodynamically unfavorable reflex tachycardia. Duration of treatment - up to several months, it is recommended to visit a doctor 1-2 times a month, blood pressure, heart rate, ECG are monitored.

Side effects. They are relatively rare. After the first doses of the drug, dizziness, reflex tachycardia (especially when taking captopril) may develop. Dyspepsia in the form of slight dry mouth, changes in taste. An increase in the activity of hepatic transaminases is possible. Dry cough that cannot be corrected (especially often on captopril due to the presence of sulfhydryl groups, as well as as a result of the accumulation of bradykinin, which sensitizes the receptors of the cough reflex), prevails in women. Rarely - skin rash, itching, swelling of the nasal mucosa (mainly on captopril). Possible hyperkalemia and proteinuria (with an initial impairment of renal function).

Contraindications Hyperkalemia (plasma potassium levels more than 5.5 mmol / L), stenosis (thrombosis) of the renal arteries (including a single kidney), increasing azotemia, pregnancy (especially the second and third trimesters due to the risk of teratogenic effects) and breastfeeding , leukopenia, thrombocytopenia (especially for captopril).

Interaction with other drugs

Rational combinations. ACE inhibitors in a significant number of cases can be used as monotherapy. However, they work well with calcium channel blockers of various groups (verapamil, fenigidin, diltiazem and others), β-blockers (propranolol, metoprolol and others), furosemide, thiazide diuretics (as already noted, there are ready-made combined preparations with dihydrochlorothiazide, erythiazide: -N, etc.), with other diuretics, with α-blockers (for example, with prazosin). In heart failure, ACE inhibitors can be combined with cardiac glycosides.

Irrational and dangerous combinations. You can not combine ACE inhibitors with any potassium preparations (Panangin, asparkam, potassium chloride, etc.); combinations with potassium-sparing diuretics (veroshpiron, triamterene, amiloride) are also dangerous, as there is a risk of hyperkalemia. It is irrational to prescribe glucocorticoid hormones and any NSAIDs (acetylsalicylic acid, diclofenac sodium, indomethacin, ibuprofen, etc.) simultaneously with ACE inhibitors, since these drugs disrupt the synthesis of prostaglandins through which bradykinin acts, which is necessary for the vasodilating effect of ACE inhibitors; as a result, the effectiveness of ACE inhibitors is reduced.

Pharmacoeconomic aspects. Among ACE inhibitors, captopril and enalapril are most common, which is associated with the traditional adherence to cheaper drugs without assessing the cost-effectiveness and cost-benefit ratios. However, specially conducted studies have shown that the target daily dose (the dose at the level of application of which it is advisable to reach) of the drug enalapril - renitek (20 mg) reaches 66% of patients, and the target daily dose of perindopril - prestarium (4 mg) - 90% of patients, with the cost of a daily dose of prestarium is about 15% lower than that of a renitek. And the total costs for all therapy in a group of 100 people per patient who reached the target dose were 37% lower for the more expensive prestarium than for the cheaper renitek.

Summing up, it should be noted that ACE inhibitors have significant advantages over many other antihypertensive drugs. These advantages are due to the efficacy and safety, metabolic inertness and a favorable effect on the blood supply to organs, the absence of replacing one risk factor with another, relatively infrequent side effects and complications, the possibility of monotherapy, and, if necessary, good compatibility with most antihypertensive drugs.

In modern conditions, when there is a significant selection of drugs, it is advisable not to be limited to the usual and, as it seems only at first glance, more economically more profitable for the patient, relatively inexpensive drugs captopril and enalapril. So, enalapril, excreted from the body mainly by the renal route, is risky to prescribe in case of impaired renal excretory function because of the danger of cumulation.

Lisinopril (diroton) is the drug of choice in patients with concomitant liver disease, when other ACE inhibitors cannot be converted to the active form. But with renal failure, it, excreted unchanged in the urine, can accumulate.

Moexipirl (moex), along with renal excretion, is excreted to a large extent in the bile. Therefore, when using it in patients with renal insufficiency, the risk of cumulation is reduced. The drug can be considered especially indicated in concomitant osteoporosis, especially in older women.

Perindopril (prestarium) and ramipril (tritace) are excreted primarily by the hepatic route. These drugs are well tolerated. It is advisable to prescribe them for cardiosclerosis.

Fosinopril (monopril) and ramipril (tritace), as established in a comparative study of 24 ACE inhibitors, have the maximum coefficient of the so-called end-peak action, which indicates the highest efficacy in the treatment of arterial hypertension with these drugs.

Angiotensin receptor blockers

Like ACE inhibitors, these drugs reduce the activity of the renin-angiotensin-aldosterone system, but have a different point of application. They do not reduce the formation of angiotensin-II, but prevent its effect on receptors for it (type 1) in the vessels, heart, kidneys and other organs. This eliminates the effects of angiotensin II. The main effect is hypotensive. These drugs are especially effective in reducing the total peripheral vascular resistance, reducing myocardial afterload and pressure in the pulmonary circulation. Angiotensin receptor blockers in modern conditions are of great importance in the treatment of arterial hypertension. Begin to use them in chronic heart failure.

The first drug in this group was saralazin, created more than 30 years ago. Now it is not used, because it acts very briefly, it is injected only into a vein (being a peptide, it is destroyed in the stomach), it can cause a paradoxical increase in blood pressure (since sometimes it causes excitation of receptors instead of blockade) and is very allergic. Therefore, convenient in use non-peptide inhibitors of angiotensin receptors have been synthesized: losartan (kosaar, brozaar), created in 1988, and later valsartan, irbesartan, eprozartan.

The most common and well-proven drug in this group is losartan. It works for a long time (about 24 hours), therefore it is prescribed 1 time per day (regardless of food intake). Its hypotensive effect develops within 5-6 hours. The therapeutic effect increases gradually and reaches a maximum after 3-4 weeks of treatment. An important feature of the pharmacokinetics of losartan is the elimination of the drug and its metabolites through the liver (with bile), therefore, even with renal failure, it does not cumulate and can be prescribed in the usual dosage, but in case of liver pathology, the dose must be reduced. Losartan metabolites reduce the level of uric acid in the blood, which is often increased by diuretics.

Angiotensin receptor blockers have the same pharmacotherapeutic advantages that distinguish them favorably from other antihypertensive drugs, as do ACE inhibitors. The disadvantage is the relatively high cost of angiotensin receptor blockers.

Indications. Hypertension (especially with poor tolerance of ACE inhibitors), renovascular arterial hypertension. Chronic heart failure.

Features of the appointment. The initial dose of losartan for hypertension is 0.05–0.1 g (50–100 mg) per day (regardless of food intake). If the patient is receiving dehydration therapy, the dose of losartan is reduced to 25 mg (1/2 tablet) per day. In heart failure, the initial dose is 12.5 mg (1/4 tablet) once a day. The tablet can be divided into parts and chewed. Angiotensin receptor blockers can be prescribed in case of insufficient effectiveness of ACE inhibitors after the latter is discontinued. Monitoring of blood pressure, ECG is carried out.

Side effects. They are relatively rare. Dizziness, headache are possible. Sometimes, sensitive patients develop orthostatic hypotension, tachycardia (these effects are dose dependent). Hyperkalemia may develop, transaminase activity may increase. Dry cough is very rare, since the exchange of bradykinin is not disturbed.

Contraindications Individual increased sensitivity. Pregnancy (teratogenic properties, fetal death may occur) and lactation, childhood. In case of liver diseases with impaired function (even in history), it is necessary to take into account the increase in the concentration of the drug in the blood and reduce the dose.

Interaction with other drugs. Like ACE inhibitors, angiotensin receptor blockers are incompatible with potassium supplements. The combination with potassium-sparing diuretics is also not recommended (the threat of hyperkalemia). When combined with diuretics, especially those prescribed in high doses, caution is needed, since the hypotensive effect of angiotensin receptor blockers is significantly enhanced.

Literature

Gayevy M. D., Galenko-Yaroshevsky P. A. Petrov V. I. et al. Pharmacotherapy with the basics of clinical pharmacology / Ed. V. I. Petrov. - Volgograd, 1998. - 451 p.
Gorokhova S.G., Vorobiev P.A., Avksentyeva M.V. Markov modeling in calculating the cost / efficiency ratio for some ACE inhibitors // Problems of standardization in health care: Scientific and practical peer-reviewed journal.- M: Nyudiamed, 2001 .- No. 4.- P. 103.
Drogovoz S.M. Pharmacology on the palms.- Kharkov, 2002.- 120 p.
Mikhailov I.B. Clinical Pharmacology.- St. Petersburg: Foliant, 1998.- 496 p.
Olbinskaya L. I., Andrushchishina T. B. Rational pharmacotherapy of arterial hypertension // Russian medical journal.-2001.- T. 9, No. 15.- P. 615-621.
Solyanik E.V., Belyaeva L.A., Geltser B.I. P. 129.

Operating principle

ACE inhibitors inhibit the action of the angiotensin-converting enzyme, which converts biologically inactive angiotensin I into the hormone angiotensin II, which has a vasoconstrictor effect. As a result of the effect on the renin-angiotensin system, as well as the enhancement of the effects of the kallikrein-kinin system ACE inhibitors have a hypotensive effect.

ACE inhibitors slow the breakdown of bradykinin, a powerful vasodilator that stimulates blood vessel dilation through the release of nitric oxide (NO) and prostacyclin (prostaglandin I2).

Classification of ACE inhibitors

Preparations containing sulfhydryl groups: captopril, zofenopril.
Dicarboxylate-containing drugs: enalapril, ramipril, quinapril, perindopril, lisinopril, benazepril.
Phosphonate-containing drugs: fosinopril.
Natural ACE inhibitors.

Casokinins and lactokinins are the breakdown products of casein and whey that naturally occur after consuming dairy products. The role in lowering blood pressure is unclear. Lactotripeptides Val-Pro-Pro and Ile-Pro-Pro are produced by probiotics Lactobacillus helveticus or are breakdown products of casein and have an antihypertensive effect. ACE inhibitors reduce blood pressure by reducing total peripheral vascular resistance. Cardiac output and heart rate do not change much. These drugs do not induce the reflex tachycardia associated with direct vasodilators. The absence of reflex tachycardia is achieved by setting the level of activation of baroreceptors to a lower level or by activating the parasympathetic nervous system.

Clinical benefits of ACE inhibitors

Side effects

ACE inhibitors are well tolerated as they induce fewer idiosyncratic reactions and have no metabolic side effects compared to beta-blockers and diuretics.

Canadian researchers report that the use of ACE inhibitors increases the risk of falls and fractures in patients by 53%. It is assumed that this effect of drugs can be associated with both changes in the structure of bones and the likelihood of a significant decrease in pressure when changing body position.

Application of ACE inhibitors in Russia

The use of ACE inhibitors in Russia has expanded after the Government of the Russian Federation adopted Decree No. 1387 dated 05.11.1997 "On measures to stabilize and develop healthcare and medical science in the Russian Federation", which approved the concept of developing healthcare and medical science in the Russian Federation, within the framework of which The Ministry of Health was instructed to create and implement the program "Prevention and treatment of arterial hypertension in the Russian Federation", which the Ministry of Health of the Russian Federation did. During the period of this program in 2002-2008, about 3.6 billion rubles were spent on its implementation from the budget. Both the program itself and its implementation have been criticized. Critics point to the fact that during the period of implementation of this program the incidence of coronary heart disease increased by 26%, cerebrovascular diseases and strokes - by 40%, and argue that the implementation of the program was aimed at stealing money from the state budget, and not at improving people's health. ... However, critics ignore the following facts:

the existence of cheap ACE inhibitors that do not have the negative effects of expensive drugs,
increased intracranial pressure with prolonged use of the old vasodilators protected by them,
the danger of overdose, which also exists with older drugs, not only ACE inhibitors,
the positive effect of ACE inhibitors on reducing overall morbidity and mortality, as a result of which people die at an older age from diseases of old age.

Notes (edit)

Links

Modern treatment of arterial hypertension. Choice of treatment. Part 1.
Modern treatment of arterial hypertension. Choice of treatment. Part 2.
Modern treatment of arterial hypertension. ACE inhibitors.

Drugs affecting the renin-angiotensin system ( C09.)
ACE inhibitors	Captopril Enalapril Lisinopril Perindopril Ramipril Quinapril Benazepril * Cilazapril Fosinopril Trandolapril Spirapril Delapril * Moexipril Temocapril * Zofenopril Imidapril *
ACE inhibitors in combination with diuretics	Combinations of captopril and diuretics Combinations of enalapril and diuretics
ACE inhibitors in combination with calcium channel blockers	Combination of enalapril and lercanidipine Combination of lisinopril and amlodipine Combination of perindopril and amlodipine Combination of ramipril and felodipine Combination of trandolapril and verapamil Combination of delapril and manidipine
Angiotensin II antagonists	Losartan Eprosartan Valsartan Irbesartan Tazosartan * Candesartan Telmisartan Olmesartan medoxomil
Angiotensin II antagonists in combination with calcium channel blockers	Combination of valsartan and amlodipine Combination of olmesartan medoxomil and amlodipine Combination of telmisartan and amlodipine
Angiotensin II antagonists in other combinations	Combination of valsartan, amlodipine and hydrochlorothiazide Combination of valsartan and aliskiren
Renin secretion inhibitors	Remikiren * Aliskiren Combination of aliskiren and hydrochlorothiazide
* - the drug is not registered in Russia

Wikimedia Foundation. 2010.

See what "ACE inhibitors" are in other dictionaries:

Active ingredient ›› Hydrochlorothiazide * + Ramipril * (Hydrochlorothiazide * + Ramipril *) Latin name Hartil D ATC: ›› C09BA05 Ramipril in combination with diuretics Pharmacological group: ACE inhibitors in combinations Nosological ... ...

- (Greek anti against + hyper + lat. tensio tension; synonyms: antihypertensive drugs) drugs of different pharmacological classes that have a common property to reduce high systemic blood pressure and have found application ... ... Medical encyclopedia

Active ingredient ›› Hydrochlorothiazide * + Quinapril * (Hydrochlorothiazide * + Quinapril *) Latin name Accuzide ATC: ›› C09BA06 Quinapril in combination with diuretics Pharmacological group: ACE inhibitors in combinations Nosological ... ... Dictionary of Medicines

Active ingredient ›› Lisinopril * (Lisinopril *) Latin name Lisinopril Stada ATX: ›› C09AA03 Lisinopril Pharmacological group: ACE inhibitors Nosological classification (ICD 10) ›› I10 I15 Diseases characterized by increased ... ... Dictionary of Medicines

Active ingredient ›› Perindopril * + Indapamide * (Perindopril * + Indapamide *) Latin name Noliprel ATX: ›› C09BA04 Perindopril in combination with diuretics Pharmacological group: ACE inhibitors in combinations Nosological classification ... ... Dictionary of Medicines

Angiotensin-converting enzyme, abbreviated as ACE, is a protein that is found in the extracellular fluid and stimulates the breakdown of angiotensin 1 to angiotensin 2. Both of these forms are involved in the regulation of blood pressure (BP), increasing its level, but it is the second (angiotensin 2) that is active.

A large group of drugs related to ACE inhibitors are used to treat hypertension, since they block this leading mechanism of vasoconstriction and the growth of their resistance.

📌 Read in this article

Mechanism of action of ACE inhibitors

The main point of application of medicines is an enzyme capable of activating angiotensin 1 by cleaving a part of the molecule from it. Formed as a result of the reaction, angiotensin 2 has the property of causing vasospasm, sodium and water retention in the body.

A feature of drugs is the suppression of ACE, which is found in the blood plasma, as well as in the extracellular fluid of the tissues of the kidneys, myocardium and blood vessels. Therefore, not only the situational level of pressure (stress, physical activity) decreases, but also the basal level, which determines the value of blood pressure at rest.

The advantage of drugs is the ability to protect the heart muscle from overload. This is manifested by the following effects:

improve relaxation of the walls of the left ventricle during diastole,
reduce the severity of myocardial hypertrophy,
reduce the size of the heart chambers,
reduce the need for oxygen in the heart muscle.

This leads to a positive effect on ventricular contractility, which means it prevents the progression of ischemic events in the heart muscle.

The protective properties of ACE inhibitors are also manifested in relation to renal tissue. They are most effective with increased urinary protein loss. This is due to the effect on the growth factors of nephrons (a structural unit of the kidneys).

When prescribed to patients with renal insufficiency, filtration is improved and the pressure in the renal arteries normalizes.

In addition, there are also less used in standard treatment regimens, but no less interesting effects of this group of medicines:

decreases tissue resistance to insulin (important in type 2 diabetes mellitus, obesity, metabolic syndrome),
the content of potassium in the blood rises (loss of potassium leads to metabolic disorders in the myocardium, arrhythmias),
increase the elasticity of the vascular wall, restore the protective properties of the inner shell, preventing atherosclerosis,
protect the myocardium from exposure to ionizing radiation.

Classification

Since there is no single approach to the separation of ACE inhibitors, they often use the isolation of groups according to the chemical structure of the molecule:

sulfridryl - Captopril, Benazepril;
carboxyl - Enalapril, Lisinopril, Ramipril;
phosphinyl - Fosinopril.

The drugs of the first group, as well as Enalapril, differ from all the others in that they need to be taken 2 times a day, and Captopril even 3. All the others have a long-term effect, which is not only convenient for use, but also protects the heart and blood vessels from sudden fluctuations pressure throughout the day, since the frequency of admission is once a day.

Most drugs belong to a prodrug, that is, they are converted into an active compound, passing through the digestive system. But there are also initially acting, without transformation - Captopril and Lisinopril.

Latest generation drugs

The allocation of generations for these medicines is very conditional, but in order to understand their special properties acquired by new compounds in the process of scientific development, drugs are divided into:

"Old", first generations - Captopril and Enalapril,
the latest generation - Fosinopril, Zofenopril, Spirapril, Perindopril, Ramipril.

The rest of the drugs are classified as the second generation.

Fozinopril (Monopril)

It can be excreted not only by the kidneys, but also by the liver, therefore it can be used for renal insufficiency, has a minimum of side effects, including the characteristic cough characteristic of ACE inhibitors.

Zofenopril (Zokardis)

It has a long half-life, acts as an antioxidant, protects the membrane of muscle fibers of the heart and blood vessels from damage, is effective in concomitant ischemic disease, and is prescribed in the acute stage.

Spirapril (Quadropril)

It has a uniform profile of action over 38 hours, which helps to maintain stable pressure in the morning hours, when the risk of vascular complications is higher.

Perinopril ()

It is used for the prevention of recurrent strokes and heart attacks, has a pronounced vasodilator effect, reduces the risk of circulatory failure, is well tolerated by most patients.

Ramipril (Ampril)

Long lasting powerful drug. It is used for cardiac insufficiency, reduces the risk of sudden cardiac arrest, mortality from heart attack and stroke, and is effective in diabetic nephropathy.

Indications for use

The main action of the drugs is aimed at lowering blood pressure, so they are indicated for primary and secondary. But since the clinical spectrum of their pharmacodynamic properties is much wider, they are prescribed for hypertensive patients with such concomitant pathologies:

circulatory failure
dysfunction of the left ventricle and its walls,
diabetes mellitus (except for Enalapril),
renal hypertension with glomerulo- and pyelonephritis, unilateral renal artery stenosis,
, ischemic disease,
nephropathy,
suffered myocardial infarction, stroke,
metabolic syndrome, obesity.

Watch the video on the action of ACE inhibitors:

Contraindications

bilateral renal artery stenosis,
severe kidney failure
increased potassium in the blood,
low blood pressure.

Use drugs with caution in children, with cirrhosis or hepatitis. With combined treatment, there may be drug incompatibility (antipsychotics, Rasilez, potassium-sparing diuretics, Allopurinol).

Can I use during pregnancy and lactation?

ACE inhibitors are not prescribed during pregnancy, and if it was detected during treatment, then they must be urgently canceled. This is due to such actions on the fetus:

congenital malformations,
impaired renal function,
hypotension,
increased potassium in the blood,
delayed bone formation.

Although a small amount of medicines passes into breast milk, they are not recommended for breastfeeding because of the risk of impaired blood circulation and renal filtration in a baby.

Cough and other side effects

ACE inhibitors differ from other antihypertensive drugs in that they do not change metabolic processes - the content of uric acid, cholesterol and blood sugar, and some even have a beneficial effect, preventing their increase. A decrease in blood coagulation activity was also noted with prolonged use of drugs.

Thus, these funds help to eliminate the main causes of the progression of atherosclerosis and its consequence - hypertension.

Despite good tolerance, even in old age, most patients eventually complain of a persistent dry cough. This is due to the fact that ACE inhibitors increase the sensitivity of the bronchi to the action of any irritants - dust, plant pollen, animal hair, a pair of chemical compounds.

When ACE is blocked, bradykinin accumulates, which relaxes arterial vessels, but stimulates receptors in the bronchial tract. Coughing causes hoarseness, vomiting, and urine flow during an attack. It can occur even with small doses; when drugs are discontinued, it passes without consequences for the patient.

In addition to coughing, side effects of drugs that block ACE are:

pressure drop below normal,
high potassium in the blood,
decreased kidney function,
allergic edema,
violation of taste sensations,
skin rash
impaired liver function,
low rates of immune defense.

Which is better - ACE inhibitors or diuretics?

Patients with newly diagnosed hypertension are most often prescribed diuretics, and if they are ineffective or have contraindications, they are transferred to ACE inhibitors. The most optimal is the combination of these two groups of medicines, since the effect of their combined use is much higher than their separate use. At the same time, ACE blockers reduce the loss of potassium in the urine, characteristic of.

How to use drugs

The frequency of admission and the dose is selected individually by the doctor after a complete examination, but there are a number of rules that must be followed when treating with ACE inhibitors:

drugs are taken one hour before meals (preferably at the same time every day);
it is forbidden to use preparations or salt substitutes containing potassium;
many pain relievers (Iburofen, Indomethacin) cause water retention in the body and reduce the effect of treatment;
you cannot abruptly stop taking ACE inhibitors on your own, as this provokes a pressure surge.

For many patients, treatment is recommended for a long time, even for life, so you should regularly visit a doctor to adjust the dose and check the functioning of the kidneys and heart during the course of treatment. If the drugs are prescribed to women of childbearing age, then during the period of taking them, it is advisable to protect themselves from pregnancy.

High potassium levels in the blood are a serious complication when taking ACE inhibitors. Its symptoms:

muscle weakness
violation of the rhythm of the pulse,
numbness of fingers and toes
labored breathing,
heaviness in the legs.

If any of these signs appear, you need to undergo a blood test for potassium content, as well as an EGC study.

ACE inhibitors are a large group of drugs that act on the main mechanism of vasoconstriction in hypertension. Their use is advisable when high blood pressure is combined with circulatory failure, pathology of cerebral hemodynamics, nephropathy, arrhythmia, diabetes and obesity. It is not recommended to take during pregnancy and lactation.

The most common side effects are coughing and increased potassium levels in the blood. The latest generation of drugs is distinguished by good tolerance and a long period of action. Most patients report an improvement in the quality of life and an increase in exercise tolerance after a course of taking ACE inhibitors. Activation of the brain during therapy allows them to be widely used in the elderly.

Classification of ACE inhibitors

Compounds containing a sulfhydryl group: captopril, fentiapril, pivalopril, zofenopril, alacepril.
Drugs with a carboxy group: enalapril, lisinopril, benazepril, quinapril, moexipril, ramipril, spirapril, perindopril, pentopril, cilazapril, trandolapril.
Phosphorus-containing compounds: fosinopril.

Many angiotensin-converting enzyme blockers are esters that are 100-1000 times less active than their active metabolites, but have higher oral bioavailability.

Representatives of this pharmaceutical group differ according to three criteria:

activity;
original form: a precursor of an active compound (prodrug) or an active substance;
pharmacokinetics (degree of absorption from the digestive system, the effect of food on the bioavailability of the drug, half-life, tissue distribution, elimination mechanisms).

None of the ACE inhibitors has significant advantages over other representatives of this class: they all effectively suppress the synthesis of angiotensin II from angiotensinIhave similar indications, contraindications and side effects... However, these drugs differ significantly in the nature of distribution in tissues. However, it is not yet known if this will bring any new benefits.

With the exception of fosinopril and spirapril, which are equally eliminated by the liver and kidneys, angiotensin-converting enzyme blockers are mainly excreted in the urine. Consequently, with renal dysfunction, excretion of most of these drugs is reduced, and their dose in such patients should be reduced.

List of trade names of ACE inhibitors

Captopril: Angiopril®, Blockordil, Kapoten®, Katopil, etc.
Enalapril: Bagopril®, Berlipril®, Vasolapril, Invoril®, Corandil, Myopril, Renipril®, Renitek, Ednit®, Enalakor, Enam®, Enap®, Enarenal®, Enapharm, Envipril, etc.
Lisinopril: Dapril®, Diropress®, Diroton®, Zonixem®, Irumed®, Lizacard, Lizigamma®, Lizinoton®, Lisiprex®, Lisonorm, Listril®, Litan®, Prinivil, Rileis-Sanovel, Sinopril, etc.
Perindopril: Arentopres, Hypernik, Parnavel, Perineva®, Perinpress, Prestarium®, Stopress, etc.
Ramipril: Amprilan®, Vasolong, Dilaprel®, Corpril®, Pyramil®, Ramepress®, Ramigamma, Ramicardia, Tritace®, Hartil®, etc.
Quinapril: Accupro®.
Zofenopril: Zocardis®.
Moexipril: Moex®.
Spirapril: Quadropril®.
Trandolapril: Gopten®.
Cilazapril: Inhibase®, Prilazid.
Fosinopril: Monopril®, Fozikard®, Fosinap, Fozinotek, etc.

There are also drugs that are ready-made combinations of ACE inhibitors with diuretics and / or calcium antagonists.

Scope of application

Arterial hypertension

These drugs are widely used as antihypertensive drugs, since they lower blood pressure in all forms of hypertension, with the exception of primary hyperaldosteronism. Monotherapy with ACE inhibitors normalizes blood pressure in about 50% of patients with mild to moderate hypertension.

Representatives of this class reduce the risk of cardiovascular complications in hypertension to a greater extent in comparison with other antihypertensive drugs.

Angiotensin-converting enzyme blockers are the drugs of choice for hypertension associated with diabetes mellitus (inhibit the progression of diabetic nephropathy) and left ventricular hypertrophy. They are also recommended when hypertension is combined with coronary artery disease.

Heart failure

ACE inhibitors are prescribed for any degree of heart failure, since these drugs prevent or inhibit its development, reduce the likelihood of sudden death and myocardial infarction, and improve the quality of life. Treatment begins with low doses, since in these patients a sharp drop in blood pressure is possible, especially against the background of a decrease in the mass of circulating blood. In addition, they reduce the dilatation (expansion) of the left ventricle and to some extent restore the normal ellipsoidal shape of the heart.

Myocardial infarction

ACE inhibitors reduce mortality when given in the early period of myocardial infarction. They are especially effective when combined with hypertension and diabetes mellitus. If there are no contraindications (cardiogenic shock, severe arterial hypotension), they should be prescribed immediately together with thrombolytics (enzymes that destroy an already formed blood clot), antiplatelet agents (aspirin, cardiomagnyl) and β-blockers. Patients at risk (major myocardial infarction, heart failure) should take these drugs for a long time.

Stroke prevention

ACE inhibitors shift the balance between the coagulation and fibrinolytic blood systems towards the latter. Scientific studies have shown that they significantly reduce the incidence of heart attack, stroke, mortality in patients with vascular pathology, diabetes mellitus and other risk factors for cerebral circulation disorders.

Chronic renal failure (CRF)

Angiotensin-converting enzyme blockers prevent or slow down kidney damage in diabetes mellitus. They not only prevent diabetic nephropathy, but also inhibit the development of retinopathy in insulin-dependent diabetes mellitus. ACE inhibitors inhibit the progression of chronic renal failure and other renal pathology, including severe.

Side effect

Serious side effects of representatives of this pharmaceutical group are quite rare, they are usually well tolerated.

Arterial hypotension. The first intake of the drug can lead to a sharp drop in blood pressure in patients with increased plasma renin activity, i.e.:
with Na + deficiency;
receiving combined antihypertensive therapy;
with heart failure.

In such cases, they start with very low doses of ACE inhibitors or, before starting therapy, it is recommended that the patient increase their salt intake and stop diuretics.

Cough. About 5-20% of patients taking drugs of this pharmaceutical group complain of persistent dry cough. This side effect usually does not depend on the dose, it occurs more often in women, usually within 1 week to 6 months from the start of admission. After the abolition of the ACE blocker, the cough disappears on average in 4 days.
Hyperkalemia. In individuals with normally functioning kidneys, significant potassium retention is rare. However, ACE inhibitors can cause hyperkalemia in patients with renal failure, as well as in those taking potassium-sparing diuretics (amiloride, triamterene, spironolactone), potassium preparations, β-blockers, or nonsteroidal anti-inflammatory drugs (NSAIDs).
Acute renal failure (ARF). Can lead to acute renal failure with narrowing of the renal arteries on both sides, narrowing of an artery of a single kidney, heart failure, or a decrease in the mass of circulating blood due to diarrhea or taking diuretics. The likelihood of acute renal failure is especially high in elderly patients with heart failure. However, if treatment is started promptly and correctly, renal function will completely normalize in almost all patients.
Effects on the fetus. They do not affect the fetus during the period of organogenesis (I trimester), but their intake in the II and III trimesters can lead to oligohydramnios, underdevelopment of the skull and lungs, intrauterine growth retardation, fetal and newborn death. Thus, drugs of this pharmaceutical group are not contraindicated in women of childbearing age, but as soon as it becomes known that a woman is pregnant, angiotensin-converting enzyme inhibitors should be immediately canceled. If this is done in the first trimester, the risk of negative effects on the fetus is reduced to zero.
Rash. Members of this group sometimes cause maculopapular rash, which may be accompanied by itching. It disappears on its own or after a decrease in the dose of an ACE blocker or a short course of antihistamines (diphenhydramine, suprastin, tavegil, etc.).
Proteinuria (excretion of protein in the urine). Patients taking drugs of this pharmaceutical group sometimes develop proteinuria (more than 1 g / day), but it is rather difficult to prove its connection with the use of ACE inhibitors. It is believed that proteinuria is not a contraindication to their appointment - on the contrary, these drugs are recommended for certain kidney diseases accompanied by proteinuria (for example, diabetic nephropathy).
Quincke's edema. In 0.1-0.2% of patients, representatives of this pharmaceutical group cause angioedema. This side effect is independent of the dose and usually occurs within a few hours after the first dose. In severe cases, airway obstruction and respiratory problems develop, which can be fatal. When the drug is discontinued, Quincke's edema disappears in a few hours; during this time, measures are taken to maintain airway patency, if necessary, adrenaline, antihistamines and glucocorticosteroids (dexamethasone, hydrocortisone, prednisolone) are administered. In blacks, the likelihood of angioedema with ACE inhibitors is 4.5 times higher than in whites.
Disturbances in taste. Patients taking drugs of this pharmaceutical group sometimes notice a decrease or loss of taste. This side effect is reversible and is more common with captopril.
Neutropenia. This is a rare but severe side effect of ACE blockers. It is observed mainly when hypertension is combined with collagenoses or parenchymal kidney disease. If the serum creatinine concentration is 2 mg or more, the dose of the drug should be reduced.
A very rare and reversible side effect of ACE inhibitors is glucosuria (the presence of sugar in the urine) in the absence of hyperglycemia (high blood sugar). The mechanism is not known.
Hepatotoxic action. It is also an extremely rare, reversible complication. It usually presents with cholestasis (bile stasis). The mechanism is not known.

Drug interactions

Antacids (maalox, almagel, etc.) reduce the bioavailability of ACE blockers. Capsaicin (an alkaloid of hot peppers) increases the cough caused by drugs in this group. NSAIDs, including aspirin, reduce their antihypertensive effect. Potassium-sparing diuretics and potassium supplements in combination with ACE inhibitors can lead to hyperkalemia. Members of this group increase serum digoxin and lithium levels and increase the allergic response to allopurinol (an anti-gout agent).