Inhibiting drugs. ACE inhibitors (blockers): general characteristics of the pharmaceutical group

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 is used to treat hypertension, as they block this leading mechanism of vasoconstriction and an increase in their resistance.

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Mechanism of action of ACE inhibitors

The main point of application of medications is an enzyme that can activate angiotensin 1 by splitting off part of the molecule from it. Angiotensin 2 formed as a result of the reaction has the property of causing vasospasm, sodium and water retention in the body.

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

The advantage of the drugs is the ability to protect the heart muscle from overload. This manifests itself in 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, and therefore prevents the progression of ischemic phenomena in the heart muscle.

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

When prescribed to patients with renal failure, filtration improves and pressure in the renal arteries normalizes.

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

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

Classification

Since there is no single approach to separating ACE inhibitors, groups are more often used 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 times. All the others have a long-lasting 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 administration is once a day.

Most drugs are prodrugs, meaning they become active compounds as they pass through the digestive system. But there are also initially active ones, without transformation - Captopril and Lisinopril.

Latest generation drugs

The allocation of generations for these medications 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,
• latest generation - Fozinopril, Zofenopril, Spirapril, Perindopril, Ramipril.

The remaining drugs are classified as second generation.

Fosinopril (Monopril)

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

Zofenopril (Zocardis)

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

Spirapril (Quadropril)

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

Perinopril ()

Used to prevent recurrent strokes and heart attacks, has a pronounced vasodilating effect, reduces the risk of circulatory failure, and is well tolerated by most patients.

Ramipril (Ampril)

A powerful, long-lasting drug. Used for cardiac failure, reduces the risk of sudden cardiac arrest, mortality from heart attack and stroke, and is effective in diabetic nephropathy.

Indications for use

The main effect 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 to hypertensive patients with the following concomitant pathologies:

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

Watch the video about 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 (neuroleptics, Rasilez, potassium-sparing diuretics, Allopurinol).

Can it be used during pregnancy and lactation?

ACE inhibitors are not prescribed during pregnancy, and if pregnancy is detected during treatment, they should be discontinued immediately. This is due to the following actions on the fetus:

• congenital malformations,
• kidney dysfunction,
• hypotension,
• increased potassium in the blood,
• delayed bone formation.

Although a small amount of medications passes into breast milk, they are not recommended for nursing mothers due to the risk of circulatory and renal filtration problems in the child.

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 clotting activity was also noted with long-term use of the drugs.

Thus, these drugs help eliminate the main causes of the progression of atherosclerosis and its consequences - hypertension.

Despite good tolerability, 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, pollen, animal hair, chemical vapors.

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

In addition to cough, side effects of medications that block ACE are:

• pressure drop below normal,
• high potassium levels in the blood,
• decreased kidney function,
• allergic edema,
• disturbance of taste sensations,
• skin rash,
• liver dysfunction,
• low levels of immune protection.

Which is better - ACE inhibitors or diuretics?

Patients with newly diagnosed hypertension are most often prescribed diuretics, and if they are low in effectiveness or have contraindications, they are transferred to ACE inhibitors. The most optimal is the combination of these two groups of medications, 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, which is characteristic of.

How to use drugs

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

• medications are taken an hour before meals (preferably at the same time every day);
• It is prohibited to use preparations or salt substitutes containing potassium;
• many painkillers (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 surge in blood pressure.

For many patients, treatment is recommended for a long time, even lifelong, so you should regularly visit your doctor to adjust the dose and check your kidneys and heart function throughout the course of treatment. If drugs are prescribed to women of childbearing age, then it is advisable to protect against pregnancy while taking them.

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

• muscle weakness,
• irregular pulse rhythm,
• numbness of fingers and toes,
• difficulty 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 test.

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 breastfeeding.

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

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The drug enalapril for hypertension helps many patients. There are similar ACE inhibitors that can replace it in treatment - captopril, Enap. How often should I take it for blood pressure?

Indications for potassium-sparing diuretics include heart disease, ascites and even polycystic ovaries. The mechanism of action with ACE inhibitors is enhanced, so you can combine them under the supervision of a doctor. Latest generation drugs - Veroshpiron, Spironolactone.

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icosides, adding spironolactone (the dose can reach 250-300 mg/day) and/or an ACE inhibitor. In the most severe cases, ultrafiltration is performed, which makes it possible to remove up to several liters of fluid from the body.

Diuretics (primarily loop and thiazide) are first-line drugs in the treatment of heart failure (both mild and severe). They are an essential component of any therapy regimen. To overcome refractoriness to loop diuretics, ACE inhibitors and spironolactone are used. The possibility of combined use of the latter is discussed. In case of severe edematous syndrome, ultrafiltration may be performed.

ANGIOTENSIN CONVERTING ENZYME INHIBITORS

These drugs have taken a strong place in the arsenal of treatments for systolic heart failure. An ACE inhibitor in combination with a diuretic is indicated for all patients with heart failure. Extensive evidence suggests that ACE inhibitors improve

symptoms and increase the survival rate of patients with heart failure, therefore their administration is considered mandatory in all cases of systolic heart failure, regardless of the patient’s age.

ACE inhibitors increase physical performance. They significantly increase the survival of patients with heart failure: severe (CONSENSUS 1 study), mild or moderate (therapeutic arm of the SOLVD study) and mild or preclinical (SAVE study) (see Table 1). Recently, the AIRE (Acute Infarction Ramipril Efficacy) study showed that in a group of patients with clinical signs of heart failure after myocardial infarction, early (from day 2 to 9 of the disease) initiation of therapy with the ACE inhibitor ramipril contributed to a significant reduction in mortality and slowed disease progression.

It is important that doctors are aware of the possible side effects of ACE inhibitors, the development of arterial hypotension after taking the first dose of the drug, impaired renal function, and cough.

Hypotension requiring discontinuation of the drug occurs rarely during treatment with ACE inhibitors. Even in patients with severe heart failure, it is observed only in 56% of cases. However, after taking the first dose of the drug, the patient should be under the supervision of a nurse or someone from the family who can provide assistance if the patient complains of dizziness.

Renal function should be assessed before starting ACE inhibitor therapy and during the first week of treatment. A slight increase in plasma creatinine levels, observed quite often, does not require discontinuation of the drug, and only with a pronounced increase in this indicator is the ACE inhibitor discontinued.

Cough is a difficult symptom to evaluate because it occurs in up to 30% of patients with heart failure, regardless of treatment. It is very rare to discontinue an ACE inhibitor due to cough. In such cases, patients should be prescribed a combination of hydralazine and nitrates.

In patients at high risk of developing hypotension after taking the first dose of an ACE inhibitor, i.e. in those receiving 80 mg or more of furosemide per day with a plasma sodium level of less than 134 mmol/L or creatinine of 90 mmol/L or more, treatment with an ACE inhibitor is recommended to begin in the hospital. In other cases, it can be started on an outpatient basis, if adequate, competent monitoring of the patient is possible. In this case, there is no need to monitor blood pressure, since the patient’s complaints of sudden dizziness serve as a more accurate sign of a side effect of the drug.

ACE INHIBITORS

• 1st generation Captopril (Capoten)
• 2nd generation Enalapril (Renitec, Enap) Ramipril (Tritace) Perindopril (Prestarium) Lisinopril Cilazapril

The beneficial effect of ACE inhibitors in heart failure is explained by a decrease in total peripheral vascular resistance due to the elimination of the effect of angiotensin II on vascular receptors, as well as an increase in the content of bradykinin, which has a vasodilatory effect. Unlike many other vasodilators, ACE inhibitors, as a rule, do not cause reflex tachycardia. Drugs in this group not only reduce the content of angiotensin II in the blood plasma (endocrine function), but also have an effect on the local renin-angiotensin systems, which are found in various organs, including the heart (paracrine function). Due to this, ACE inhibitors prevent the progression of left ventricular dilatation and cause the reverse development of its hypertrophy.

In most studies of ACE inhibitors, drugs of this group were used for severe congestive heart failure in addition to diuretics and cardiac glycosides. Although the data obtained vary widely, in general, ACE inhibitors were effective in at least 2/3 of patients. They increased exercise tolerance, had a beneficial effect on hemodynamics (reduced pre- and afterload) and neurohumoral status (increased renin activity, decreased levels of angiotensin II, aldosterone, norepinephrine). However, the most important fact is that ACE inhibitors increased survival in patients with heart failure.

In general, the results of the studies demonstrate the feasibility of using ACE inhibitors in patients with low ejection fraction i

Angiotensin II is known to play a key role in the development of heart failure. The effectiveness of ACE inhibitors is explained by the fact that this group of drugs prevents the conversion of inactive angiotensin I into angiotensin P in the blood plasma and tissues, thereby preventing its adverse effects on the heart, peripheral vascular bed, kidneys, water-electrolyte balance and neurohumoral status.

ACE inhibitors in patients with heart failure increase the ejection fraction: from 0.8% (captopril) to 4.1% (lieinopril).

Cardiac hemodynamic effects of these drugs:

reduction in pre- and afterload, drop in blood pressure and heart rate.

Cardioprotective properties: regression of LV hypertrophy of the heart, reduction of its dilatation and prevention of LV remodeling in patients after myocardial infarction.

Antiarrhythmic effect: when taking captopril, the number of ventricular extrasystoles decreases by 4 times.

The diuretic effect of ACE inhibitors is comparable to diuretics. Electrolyte disturbances are normalized and prevented. Nephroprotective properties, especially in patients with arterial hypertension and diabetes mellitus, vasoprotection and antioxidant effect (captopril) were revealed.

The most important directions of action of ACE inhibitors: reduction in the level of norepinephrine, vasopressin, blockade of aldosterone synthesis, destruction and inactivation of bradykinin, suppression of baroreflexes.

Side effects: angioedema associated with the accumulation of bradykinin under the skin: appears either after the first dose or in the first 48 hours from the start of treatment. A cough (3-22% of cases), dry and often “barking”, can appear both at the beginning of treatment and much later, even after several months, sometimes forcing one to abandon the use of ACE inhibitors. There is evidence that the nonsteroidal anti-inflammatory drug sulindac (200 mg/day) prevents and inhibits the cough reflex.

Hypotension often occurs in severe heart failure and high-renin severe hypertension in elderly and senile patients with severe renal artery stenosis and when using large doses of diuretics. The risk of hypotension is reduced by low initial doses of captopril - 6.25 mg, enalapril - 2.5 mg. There is evidence that perindopril is preferable at a dose of 2 mg.

Severe arterial hypotension may limit the use of ACE inhibitors. If its cause is hypokalemia, hyponatremia, dehydration, usually associated with improper use of diuretics,

as well as various tachyarrhythmias, you should restore the water-electrolyte balance, normalize the heart rhythm, reduce the dose of diuretics, and only then try to use ACE inhibitors.

Initial hypotension is a manifestation of unrecognized pneumonia, recurrent pulmonary embolism, or the terminal phase of chronic heart failure.

Hyperkalemia, caused by blocking the release of aldosterone by the adrenal glands, most often develops when combined with potassium supplements and potassium-sparing diuretics.

The progression of renal failure occurs mainly with initially impaired renal function. An increase in creatinine and proteinuria makes it necessary to reduce the daily dose of the ACE inhibitor and carefully monitor the level of creatinine in the blood plasma and protein in the urine, especially in the first days and weeks of taking the drugs. For such patients, fosinopril is safer.

CAPTOPRIL (CAPOTEN) has become the “gold standard” among ACE inhibitors.

Contains a sulfhydryl group and is an active agent. Bioavailability - 60%, maximum concentration in blood plasma - after an hour when taken orally, when taken sublingually - much earlier. In the first 4 hours after administration, it is excreted in the urine. 2/3 of the drug taken, per day - 95%. The maximum concentration of free captopril not bound to proteins in blood plasma is 800 ng/ml, and the total (together with metabolites) is 1580 ng/ml.

After taking 12.5 mg of captopril, ACE activity in the blood plasma drops by 40%, the depression lasts up to 3 hours. In chronic heart failure, the optimal hemodynamic effect is achieved by a plasma concentration of 100-120 ng/ml of free captopril, which is achieved with an average effective dose of 53 mg/day.

To avoid side effects, treatment should begin with a dose of 6.25-12.5 mg 2-3 times a day, and if the patient is simultaneously receiving diuretics, the dose should be 6.25 mg 2-3 times a day, gradually increasing it to optimal.

For chronic renal failure (CRF) and creatinine clearance of 10-50 ml/min, the usual dose is given every 12-18 hours, and for clearance less than 10 ml/min - every 24 hours.

For patients with heart failure, the initial dose of captopril is 6.25 mg or lower with a gradual increase to 50-75 mg/day.

The addition of captopril or other ACE inhibitors to diuretic therapy in patients with heart failure increases its effectiveness.

In some patients with very severe heart failure, captopril may increase plasma digoxin levels by 25%, which is associated with renal dysfunction.

Contraindications: severe renal dysfunction, azotemia, hyperkalemia, bilateral renal artery stenosis or stenosis of a single renal artery, condition after kidney transplantation, primary hyperaldosteronism, aortic stenosis, hereditary angioedema, pregnancy, lactation, childhood, hypersensitivity to captopril and other ACE inhibitors.

Side effects specific to captopril are associated with the presence of a sulfhydryl group. Neutropenia is possible when using high doses, which experts have now abandoned. Proteinuria occurs in 1% of cases at a dose of 150 mg/day in patients who have had renal disease.

Perversion of taste and ulcers on the buccal mucosa are possible in 2-7% of cases, these phenomena are dose-dependent. High doses of captopril are associated with the appearance of collagen diseases, impaired immune response, and an increase in the titer of antinuclear antibodies.

ENALAPRIL is a second-generation non-sulfhydryl ACE inhibitor, which has a long-lasting effect.

After oral administration, the drug is rapidly absorbed and hydrolyzed to form enaprilat, a highly specific, long-acting non-sulfhydryl ACE inhibitor. T 1/2 - about 11 o'clock. Eliminated primarily in urine. Dose adjustment for chronic renal failure begins with glomerular filtration below 80 ml/min - 5-10 mg/day, when glomerular filtration drops to 30-10 ml/min - a dose of 2.5-5 mg/day.

For heart failure, it is recommended to take 2.5 mg of the drug for 3 days, followed by increasing the dose to 5 mg/day (in two doses). In the second week, the dose of the drug can be increased to 10 mg/day, increasing in the absence of a severe hypotensive reaction to 20 mg/day.

For elderly patients, the initial dose is 1.25-2.5 mg per day with a gradual increase to 5-10 mg/day. When using the first dose, it is necessary to monitor blood pressure every 8 hours to avoid a hypotensive reaction.

Contraindications and side effects are similar to other ACE inhibitors.

Biodbstnos”№ - 25-50%, food intake does not affect the absorption of the drug. After a single dose, the concentration in the blood reaches a maximum after 6-8 hours and coincides with the maximum hypotensive effect. It is excreted unchanged in the urine. In elderly people, the concentration of the drug in the blood is 2 times higher than in young people.

LISINOPRIL. At a dose of 10 mg in patients with arterial hypertension, it blocks plasma ACE activity by 80% in the first 4 hours with a gradual decrease to 20% by the end of the day. In patients with heart failure, blockade of RAAS activity is provided in doses of 1.25-10 mg/day for 24 hours.

For heart failure, doses range from 5 to 20 mg/day. To avoid an excessive hypotensive reaction, it is preferable to start with a dose of 2.5 mg, gradually increasing it to the maximum. For chronic renal failure and glomerular filtration 30-10 ml/min - 2.5-5 mg, and for clearance less than 10 ml/min - 2.5 mg. Studies show that using lisinopril 24 hours after the onset of myocardial infarction for 6 weeks reduced mortality by 12%. The combination of lisinopril with nitroglycerin administered intravenously reduces mortality by 17%. In patients receiving lisinopril, hypotension developed in 20% of cases, and in the control group - in 36%.

Indications: arterial hypertension, heart failure. Contraindications and side effects similar to other ACE inhibitors.

RAMIPRIL is a predrug and is converted in the body into the active diacide ramiprilat. Suppression of the tissue RAAS system when taking equivalent doses of captopril and ramipril is 2 times higher in the latter.

Absorption when taken orally is 60%; in the liver it is converted into the active metabolite ramiprilat, which, with normal renal function, is excreted in the urine. After taking 5 mg of the drug, the peak concentration is observed after 1.2 hours and is 18 ng/ml, and for ramiprilat - 3.2 hours and 5 ng/ml, respectively. The half-life of ramipril is 5 hours, and the half-life of the active metabolite is 13-17 hours. Tissue kinetics indicate a longer elimination of the drug - up to 110 hours. About 60% of ramipril and its metabolites are excreted in urine, and 40% in feces. The maximum effect is observed within 4-6.5 hours and lasts more than 24 hours. Ramiprilat is 6 times more potent at blocking ACE than ramipril.

Indications: arterial hypertension, heart failure.

Treatment begins with a dose of 2.5 mg ramipril once or twice a day. For patients receiving diuretics, they should either be discontinued for 2-3 days or started with a dose of 1.25 mg. At a high risk of hypotension and in very severe heart failure, it is also recommended to start treatment with a dose of 1.25 mg.

In case of dehydration, decreased circulating blood volume, or hyponatremia, an isotonic sodium chloride solution is administered before using ramipril.

For patients with heart failure, a dose of ramipril 5 mg is equivalent to captopril 75 mg/day.

Senile age, the presence of renal and heart failure cause a decrease in the renal secretion of ramipril and its metabolites, leading to an increase in their concentration in the blood, which requires a reduction in the dose of the drug to 2.5 mg/day or every other day.

For chronic renal failure and glomerular filtration rate below 40 ml/min, the dose of the drug should be halved.

PERINDOPRIL (PRESTARIUM) is a long-acting ACE inhibitor. Does not contain a sulfhydryl group.

Metabolized in the liver, it turns into an active metabolite - perindoprilat. 75% The drug is excreted in the urine, 25% in feces. The effect in the body lasts for 24 hours. The onset of action is most often after 1-2 hours, the peak effect (in particular hypotensive) is after 4-8 hours. Simultaneous administration with food inhibits the conversion of perindopril to perindoprilat. Protein binding is 30%, which depends on the concentration of the drug. T1/2 of the drug is 1.5-3 hours, and its active metabolite is 25-30 hours.

In patients with heart failure, perindopril in a dose 7.-A mg/day leads to positive hemodynamic changes - a significant increase in cardiac output, a drop in peripheral vascular resistance, pressure in the pulmonary artery and pulmonary capillaries.

For heart failure, treatment begins with a dose of 2 mg/day.

For arterial hypertension, recommended doses 1-A mg/day taken in the morning. In case of insufficient effect, the dose can be increased to 6-8 mg/day or taken in combination with diuretics (for example, indapamide). In elderly patients, the daily dose of perindopril should not exceed 2-4 mg. The drug and its active metabolite accumulate in the body in patients with arterial hypertension and chronic renal failure with long-term use. Therefore, for such patients it is prescribed at a dose of 2 mg per day or every other day.

Contraindications and side effects are similar to other ACE inhibitors.

ACE INHIBITORS CAN BE USED:

* as monotherapy in the initial stages of heart failure;

* adding to therapy with diuretics and digoxin for severe heart failure;

* in combination with digoxin, diuretics and vasodilators for severe heart failure.

SIDE EFFECTS AND MAIN CONTRAINDICATIONS

Side effects common to all ACE inhibitors: cough, hypotension (especially common with renal artery stenosis, severe heart failure), changes in renal function, angioedema, renal failure (often with bilateral renal artery stenosis), hyperkalemia (with renal deficiency) or when using potassium-sparing diuretics, skin reactions.

Side effects described with high doses of captopril: proteinuria, loss of taste, damage to the oral mucosa, dry mouth.

Contraindications: renal - bilateral renal artery stenosis or similar changes, previous hypotension, severe aortic stenosis or obstructive cardiomyopathy, pregnancy.

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Angiotensin-converting enzyme (ACE) inhibitors

Drugs in this group are divided into two generations.

First generation:

• captopril (captopril-KMP, capoten)

Second generation:

• enalapril (Renitec, Enam)
• Quinapril (Accupro)
• lisinopril (diroton, lisopress, lisoril)
• ramipril (tritace)
• perindopril (Prestarium)
• moexipril (moex)
• fosinopril (monopril)
• cilazapril (inhibase)

There are also ready-made combinations of ACE inhibitors with thiazide diuretics - for example, captopril with hydrochlorothiazide (Capozide), 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 various properties were 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 are first data on the high effectiveness of these drugs in ischemic heart disease 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 reduction or cessation of the formation of angiotensin-II, its 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 is also reduced.

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

Of all the drugs, only captopril and lisinopril inhibit ACE directly, while the rest are “prodrugs,” i.e., they are converted in the liver into active metabolites that inhibit the enzyme.

All ACE inhibitors are well absorbed from the gastrointestinal tract and are taken orally, but injectable forms of lisinopril and enalapril (Vasotec) 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 promote autoimmunization and provoke a persistent dry cough. In addition, captopril has the lowest activity among all ACE inhibitors.

The remaining drugs (second generation) have the following advantages: greater activity, significant duration of action (can be prescribed once a day, regardless of meals); absence of sulfhydryl groups, good tolerability.

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

• absence of withdrawal syndrome, such as with clonidine;
• absence of depression of the central nervous system, inherent, for example, in clonidine, reserpine and drugs containing it;
• effective reduction of left ventricular hypertrophy, which eliminates the risk factor for the development of myocardial ischemia;
• no effect on carbohydrate metabolism, which makes it 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-induced hypoglycemia, thiazide diuretics cause hyperglycemia and impair carbohydrate tolerance);
• absence of disruption of cholesterol metabolism, while β-blockers and thiazide diuretics cause redistribution of cholesterol, increase its content in atherogenic fractions and can increase atherosclerotic vascular damage;
• absence or minimal severity of inhibition 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, to moexipril (Moex), which, along with a hypotensive effect, effectively increases bone density and 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 reduce collagen synthesis and sclerotic changes in the myocardium.

Features of prescribing ACE inhibitors. At the first dose, blood pressure should not decrease by more than 10/5 mmHg. 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. For 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 impaired.

Dosage regimen

For arterial hypertension:

• Captopril- initial dose 12.5 mg 3 times a day (2 hours before meals), if necessary, a single dose is increased to 50 mg, maximum daily dose - 300 mg
• Kaposid, Kaptopres-Darnitsa- combination drug; initial dose 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 action of the diuretic makes more frequent administration during the day irrational)
• Capozid-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 5 mg 1 time per day (with 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 drugs (in 1 tablet "Enap-N" - 10 mg enalapril maleate and 25 mg hydrochlorothiazide, in 1 tablet "Enap-HL" - 10 mg enalapril maleate and 12.5 mg hydrochlorothiazide), administered orally 1 time per day for 1 tablet (Enap-N) or 1–2 tablets (Enap-HL)
• Perindopril- initial dose 4 mg 1 time per day, if the effect is insufficient, increase to 8 mg.
• Quinapril- initial dose 5 mg 1 time per day, then 10–20 mg
• Ramipril- initial dose 1.25–2.5 mg 1 time per day, with insufficient effect up to 5–10 mg 1 time per day.
• Moexipril- initial dose 3.75–7.5 mg 1 time per day, if the effect is insufficient - 15 mg per day (maximum 30 mg).
• Cilazapril- initial dose 1 mg 1 time per day, then 2.5 mg, possibly increasing the dose to 5 mg per day.
• Fosinopril- initial dose 10 mg 1 time per day, then, if necessary, 20 mg (maximum 40 mg).

The dose of ACE inhibitors for arterial hypertension is increased gradually, usually over 3 weeks. The duration 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 on average 2 times lower than in uncomplicated arterial hypertension. This is important so that there is no decrease in blood pressure and an energetically and hemodynamically unfavorable reflex tachycardia does not occur. The duration of treatment is up to several months, it is recommended to visit a doctor 1–2 times a month, blood pressure, heart rate, and ECG are monitored.

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

Contraindications. Hyperkalemia (plasma potassium level more than 5.5 mmol/l), stenosis (thrombosis) of the renal arteries (including the solitary kidney), increasing azotemia, pregnancy (especially the second and third trimesters due to the risk of teratogenicity) and breastfeeding , leukopenia, thrombocytopenia (especially for captopril).

Interaction with other drugs

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

Irrational and dangerous combinations. You cannot 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 vasodilatory effect of ACE inhibitors; as a result, the effectiveness of ACE inhibitors is reduced.

Pharmacoeconomic aspects. Among ACE inhibitors, captopril and enalapril are the most widely used, which is associated with 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 use 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 In this case, the cost of a daily dose of Prestarium is approximately 15% lower than Renitec. And the total costs of all therapy in a group of 100 people per patient who reached the target dose turned out to be 37% lower for the more expensive Prestarium than for the cheaper Renitec.

To summarize, it should be noted that ACE inhibitors have significant advantages over many other antihypertensive drugs. These advantages are due to effectiveness and safety, metabolic inertia and beneficial effects on the blood supply to organs, the absence of replacement of one risk factor by 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 choice of drugs, it is advisable not to limit yourself to the usual and, as it seems only at first glance, relatively inexpensive drugs captopril and enalapril that are more economically beneficial for the patient. Thus, enalapril, which is excreted from the body primarily by the kidneys, is risky to prescribe in cases of impaired renal excretory function due to 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 in case of renal failure, it is excreted unchanged in the urine and can accumulate.

Moexipirl (moex), along with renal excretion, is excreted to a large extent in bile. Therefore, when used in patients with renal failure, the risk of accumulation is reduced. The drug can be considered especially indicated for concomitant osteoporosis, especially in elderly women.

Perindopril (Prestarium) and ramipril (Tritace) are excreted primarily by the liver. 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 a maximum coefficient of so-called end-peak action, which indicates the highest effectiveness of treating 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 its receptors (type 1) in the blood vessels, heart, kidneys and other organs. This eliminates the effects of angiotensin II. The main effect is hypotensive. These drugs are particularly effective in reducing total peripheral vascular resistance, reducing afterload on the myocardium and pressure in the pulmonary circulation. Angiotensin receptor blockers in modern conditions are of great importance in the treatment of arterial hypertension. They are also beginning to be used for chronic heart failure.

The first drug of this group was saralazine, created more than 30 years ago. Now it is not used because its effect is very short, 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 (as sometimes instead of blocking it causes stimulation of receptors) and is very allergic. Therefore, easy-to-use non-peptide angiotensin receptor inhibitors have been synthesized: losartan (cozaar, brozaar), created in 1988, and later valsartan, irbesartan, eprosartan.

The most common and well-proven drug in this group is losartan. It acts for a long time (about 24 hours), so it is prescribed once a 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 excretion of the drug and its metabolites through the liver (with bile), therefore, even in case of renal failure, it does not accumulate and can be prescribed in the usual dosage, but in case of liver pathology, the dose must be reduced. Metabolites of losartan reduce the level of uric acid in the blood, which is often increased by diuretics.

Angiotensin receptor blockers have the same pharmacotherapeutic advantages, which 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 to ACE inhibitors), renovascular arterial hypertension. Chronic heart failure.

Features of the destination. The initial dose of losartan for arterial hypertension is 0.05–0.1 g (50–100 mg) per day (regardless of food intake). If the patient receives dehydration therapy, the dose of losartan is reduced to 25 mg (1/2 tablet) per day. For heart failure, the initial dose is 12.5 mg (1/4 tablet) 1 time per day. The tablet can be divided into pieces and chewed. Angiotensin receptor blockers can be prescribed if ACE inhibitors are insufficiently effective after discontinuation of the latter. Blood pressure and ECG are monitored.

Side effects. They occur relatively rarely. Dizziness and headache are possible. Sometimes sensitive patients develop orthostatic hypotension and tachycardia (these effects depend on the dose). Hyperkalemia may develop and transaminase activity may increase. Dry cough is very rare, since bradykinin metabolism is not disrupted.

Contraindications. Individual hypersensitivity. Pregnancy (teratogenic properties, fetal death may occur) and lactation, childhood. In case of liver diseases with impaired liver 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. Combination with potassium-sparing diuretics is also not recommended (risk of hyperkalemia). When combined with diuretics, especially those prescribed in high doses, caution is required, since the hypotensive effect of angiotensin receptor blockers is significantly enhanced.

Literature

1. Gaevy M. D. Galenko-Yaroshevsky P. A. Petrov V. I. et al. Pharmacotherapy with the basics of clinical pharmacology / Ed. V. I. Petrova. - Volgograd, 1998. - 451 p.
2. Gorokhova S.G. Vorobyov P.A. Avksentyeva M.V. Markov modeling when calculating the cost/effectiveness ratio for some ACE inhibitors // Problems of standardization in healthcare: Scientific and practical peer-reviewed journal. - M: Newdiamed, 2001.- No. 4.- P. 103.
3. Drogovoz S. M. Pharmacology on the palms. - Kharkov, 2002. - 120 p.
4. Mikhailov I. B. Clinical pharmacology. - St. Petersburg. Folio, 1998.- 496 p.
5. Olbinskaya L. I. Andrushchishina T. B. Rational pharmacotherapy of arterial hypertension // Russian Medical Journal. - 2001. - T. 9, No. 15. - P. 615–621.
6. Solyanik E.V. Belyaeva L.A. Geltser B.I. Pharmacoeconomic effectiveness of Moex in combination with osteopenic syndrome // Problems of standardization in healthcare: Scientific and practical peer-reviewed journal. - M: Newdiamed, 2001. - No. 4. - P. 129.

In the article we will consider a list of ACE inhibitor drugs.

Hypertension is a common disease of the cardiac system. Often, an increase in blood pressure can be provoked by the influence of inactive angiotensin I. In order to prevent its influence, drugs that inhibit the effect of this hormone are included in the treatment regimen. These medications are inhibitors. The following is a list of the latest generation ACE inhibitors.

What kind of drugs are these?

ACE inhibitors belong to a group of synthetic and natural chemical compounds, whose use has helped achieve success in the treatment of patients with vascular and cardiac pathologies. ACEs have been used for more than forty years. The very first medicine was Captopril. Next, Lisinopril and Enalapril were synthesized. Then they were replaced by new generation inhibitors. In the field of cardiology, such drugs are used as the main agents that have a vasoconstrictor effect.

The benefit of the latest ACE inhibitors is the long-term blocking of a special hormone, which is angiotensin II. This hormone is the main factor influencing the increase in a person’s blood pressure. In addition, angiotensin-converting enzyme drugs can prevent the breakdown of bradykinin, helping to reduce the resistance of efferent arterioles, they also release nitric oxide and increase the concentration of vasodilatory prostaglandin.

New generation

In the pharmacological group of ACE inhibitors, drugs that must be taken repeatedly (for example, Enalapril) are considered obsolete, since they cannot provide the required effect. True, Enalapril still remains a popular drug that demonstrates excellent effectiveness in the treatment of hypertension. In addition, there is no confirmed evidence that the latest generation of ACE drugs (for example, drugs such as Perindopril, Fosinopril, Ramipril, Zofenopril and Lisinopril) have much more advantages over their analogues , released forty years ago.

The list of ACE inhibitor drugs is quite extensive.

Vasodilator drugs ACE

Vasodilator drugs ACEs in cardiology are often used to treat arterial hypertension. Here is a comparative description and list of ACE inhibitors that are the most popular among patients:

• The drug "Enalapril" is an indirect cardioprotector that quickly reduces blood pressure and reduces the load on the heart. This remedy acts on the body for up to six hours and is usually excreted by the kidneys. Rarely can cause decreased vision. The cost is 200 rubles.
• "Captopril" is a short-acting agent. This drug stabilizes blood pressure well, although this drug may require multiple doses. The dosage is determined by the doctor. The drug has antioxidant activity. In rare cases, it can provoke tachycardia. Its cost is 250 rubles.
• The medicine "Lisinopril" has a long duration of action. It works completely independently and does not need to be metabolized in the liver. This medicine is excreted by the kidneys. The drug is suitable for all patients, even those suffering from obesity. It can be used in patients with chronic kidney disease. This drug may cause headaches along with ataxia, drowsiness, and tremor. The cost is 200 rubles.
• The medication "Lotensin" helps lower blood pressure. This drug has vasodilating activity. It leads to a decrease in bradykinin. This product is contraindicated in nursing and pregnant women. The drug can rarely cause vomiting with nausea and diarrhea. The cost of the medicine is within 100 rubles.
• The drug "Monopril" slows down the metabolic processes of bradykinin. The effect of its use is usually achieved after three hours. This drug is not addictive. It should be prescribed with caution to patients with chronic kidney disease. The cost is 500 rubles.
• The drug "Ramipril" is a cardioprotector that produces ramiprilat. This medication reduces peripheral vascular resistance and is contraindicated in the presence of arterial stenosis. The cost is 350 rubles.
• The drug "Accupril" can help lower blood pressure. This medicine may relieve resistance in the pulmonary vessels. Quite rarely, this drug can cause vestibular impairment and loss of taste (side effects of ACE inhibitors). The average price is 200 rubles.
• The drug "Perindopril" helps the active metabolite to form in the human body. Its maximum effectiveness can be achieved within three hours after application. Rarely, it can cause diarrhea with nausea and dry mouth. The cost is 400 rubles. The list of latest generation ACE inhibitor drugs does not end there.
• The drug "Trandolapril" with long-term use reduces the severity of myocardial hypertrophy. An overdose of the drug can cause severe hypotension along with angioedema. The cost is 100 rubles.
• The drug "Quinapril" affects renin-angiotensin functions. This drug significantly reduces the load on the heart. It is very rarely capable of causing an allergic reaction and costs 360 rubles.

Not everyone knows what ACE inhibitor drugs are.

Classification

There are several inhibitory classifications. These drugs are classified depending on the method of removing them from the body and their activity. Modern medicine widely uses the chemical ACE classification of drugs, which includes the following groups:

• sulfhydryl group;
• carboxyl group (we are talking about dicarboxylate-containing drugs);
• phosphinyl group (phosphonate-containing medications);
• group of natural compounds.

Sulfhydryl group

ACE inhibitors of this group act as calcium antagonists.

Here is a list of the most famous medications from the sulfhydryl group:

• "Benazepril";
• "Captopril", along with "Epsitron", "Capoten", and "Alkadil";
• "Zofenopril" and "Zocardis".

Carboxyl group

This category of medications has a positive effect on the lives of patients with hypertension. These medications are used only once a day. They should not be taken if you have coronary heart disease, diabetes mellitus or renal failure. Here is a list of the most famous drugs from this group: “Perindopril” along with “Enalapril”, “Lisinopril”, “Diroton”, “Lisinoton”, “Ramipril”, “Spirapril”, “Quinapril” and so on. Mostly, such drugs are used to treat kidney failure and hypertension.

Phosphonate-containing inhibitors

These drugs have a high ability to penetrate the tissues of the human body; thanks to their use, the pressure is usually stabilized for a long period. The most popular drugs from this group are Fosinopril and Fosicard.

Your doctor will help you choose the best ACE inhibitors.

Natural inhibitors of the latest generation

Such means are original coordinators that limit the process of strong cell stretching. Blood pressure decreases while taking them due to a decrease in vascular peripheral resistance. Natural inhibitors that enter the body with dairy products are called cazokinins and lactokinins. They are found in small quantities in garlic, whey and hibiscus.

Indications for use

The latest generation products presented above are used today even in plastic surgery. True, they are more often prescribed to patients to lower blood pressure and to patients with disturbances in the functioning of the heart and blood vessels for the treatment of arterial hypertension. It is not recommended to use these medications on your own, as they have many contraindications and side effects. The main indications for the use of these drugs are the following pathologies:

• the patient has diabetic nephropathy;
• with dysfunction of the left ventricle of the heart;
• against the background of the development of atherosclerosis of the carotid arteries;
• against the background of myocardial infarction;
• in the presence of diabetes mellitus;
• against the background of obstructive bronchial disease;
• in the presence of atrial fibrillation;
• against the background of metabolic syndrome.

The latest generation of ACE inhibitors are used very often today.

Use for hypertension

These drugs effectively block angiotensin-converting enzymes. These modern medicines have a positive effect on human health and protect the kidneys and heart. Among other things, inhibitors have found wide use in diabetes mellitus. These medications increase cellular sensitivity to insulin, improving glucose uptake. As a rule, all new medications for hypertension are taken once a day. Here is a list of modern inhibitors that are widely used for hypertension: “Moexzhril” along with “Lozhopril”, “Ramipril”, “Talinolol”, “Fisinopril” and “Cilazapril”.

The list of latest generation ACE inhibitors goes on.

Inhibitors for heart failure

Often, treatment of chronic heart failure involves the use of inhibitors. This category of cardioprotectors in blood plasma prevents the transformation of inactive angiotensin I into active angiotensin II. Thanks to this, its adverse effects on the kidneys, heart and peripheral vascular bed are prevented. Here is a list of cardioprotective drugs approved for heart failure: Enalapril along with Captopril, Verapamil, Lisinopril and Trandolapril.

Mechanism of action of inhibitors

The mechanism of action of inhibitors is to reduce the activity of angiotensin-converting enzymes, which accelerate the transition of inactive angiotensin to active. These drugs inhibit the breakdown of bradykinin, which is considered a powerful vasodilator. These medications reduce blood flow to the heart, reducing strain and protecting the kidneys from the effects of diabetes and hypertension.

Taking modern inhibitors

Many patients with hypertension are often interested in how to properly take new generation ACE inhibitors? Answering this question, it must be said that the use of any drugs in this group must necessarily be agreed with a doctor. Typically, inhibitors are taken an hour before meals, that is, on an empty stomach. Dosage, frequency of use and interval between doses are determined by a specialist. During therapy with inhibitors, it is necessary to avoid anti-inflammatory non-steroidal medications and foods rich in potassium.

Inhibitors and contraindications to their use

The list of relative contraindications for the use of inhibitors is as follows:

• the patient has moderate arterial hypotension;
• presence of chronic severe renal failure;
• in childhood;
• in the presence of severe anemia.

Absolute contraindications include hypersensitivity, lactation, bilateral renal artery stenosis, severe hypotension, pregnancy and hyperkalemia.

People may experience side effects from ACE inhibitors in the form of itching, allergic rash, weakness, hepatotoxicity, decreased libido, stomatitis, fever, rapid heartbeat, swelling of the legs and so on.

Side effect

Long-term use of these drugs can lead to inhibition of hematopoiesis. As a result, the content of red blood cells, leukocytes and platelets in the blood decreases. Therefore, during the treatment period, regular repetition of a general blood test is required.

Allergic reactions and intolerances may also develop. This usually manifests itself as itching, redness of the skin, urticaria, and photosensitivity.

In addition, the function of the digestive system may be impaired, which will lead to distortion of taste, nausea and vomiting, and discomfort in the stomach. Sometimes people suffer from diarrhea or constipation, and the liver stops working normally. In some cases, ulcers (aphthae) occur in the mouth.

The tone of the parasympathetic nervous system can be enhanced by drugs, and the synthesis of prostaglandins can also be activated. A dry cough occurs and the voice changes. Symptoms can be alleviated by taking non-steroidal anti-inflammatory drugs, but not by using antitussives. If patients have a pronounced increase in blood pressure, a paradoxical increase in blood pressure cannot be ruled out. Hyperkalemia occurs in some cases, and fractures of limb bones due to falls occur more often.

The article reviewed the latest generation of ACE inhibitors.

The use of ACE inhibitors for therapeutic purposes has been going on for 30 years.

The spread of this type of medication began in the 1990s and they almost immediately began to displace other antihypertensive drugs from their leading positions.

Their main purpose is to counteract arterial hypertension, and their main advantage is their high efficiency. While taking ACE inhibitors, the negative consequences of cardiovascular complications are reduced.

Letters from our readers

Subject: Grandma's blood pressure has returned to normal!

From: Christina ( [email protected])

To: Site Administration

Christina
Moscow

My grandmother's hypertension is hereditary - most likely, I will have the same problems as I grow older.

This is the name given to complex chemical substances that can inhibit the activity of angiotensin-converting enzymes (circulating in the extracellular space). These components are found in a number of antihypertensive medications that reduce high blood pressure.

They are prescribed to people suffering. Also used in patients with heart disease who are recovering from a heart attack, or with diabetes.

Angiotensin enzyme blockers help maintain blood pressure, allowing nutrient-rich, oxygenated blood to circulate freely throughout the body.

Indications for use

ACE inhibitors are prescribed to treat any form of arterial hypertension. Also very effective for associated ailments, such as:

• decompensated myocardial dysfunction;
• hyperglycemia;
• obstructive pulmonary diseases;
• increased dyslipidemia;
• obliterating vascular disorders.

In addition, the advisability of use is determined by the presence of the following diseases:

• hypertrophic cardiomyopathy;
• heart failure syndrome;
• atrial fibrillation;
• renoparenchymal hypertension;
• diabetes mellitus;
• insulin resistance syndrome.

Also, ACEI drugs are prescribed in cases of coronary artery disease, including post-infarction cardiosclerosis. In addition, taking angiotensive blockers is advisable within 2 days after a heart attack.

Classification

Taking into account pharmacokinetic differences (i.e. absorption, distribution, material metabolism, excretion from the body), drugs that inhibit the effects of angiotensin-converting enzyme can be classified into 4 groups:

1. Thiol.
2. Carboxyl.
3. Phosphinyl.
4. Natural.

Thiol (sulfhydryl) group inhibitors

Due to their specific chemical reactivity, enzymes of this group help reduce various enzymatic activities. Drugs of this type include calcium channel blockers (). The most common medications belonging to the sulfhydryl group:

• Sibacen;
• Lotensin;
• Kapoten;

Carboxyl group

Drugs of this type are contraindicated for persons suffering from coronary artery disease, diabetes mellitus, and impaired renal function. The most famous medications containing dicarboxylate include:

• Coverex;
• Dapril;
• Sinopril;
• Amprilan;
• Quadropril;
• Kvinofar;
• Vitopril;
• Cilazapril.

Due to their monovalency, carboxyl group inhibitors demonstrate good results in hypertension. Often, medications containing dicarboxylate are taken only once a day.

Phosphine group drugs

Such drugs belong to a new generation of medications, the active substances of which penetrate well into tissues, stabilizing blood pressure for a long time. The list of phosphine group drugs includes:

• Fisonopril;
• Phosicard.

Phosphonates (esters of phosphonic acids) are capable of inhibiting the activity of zinc ion in angiotensin-converting enzyme.

In addition to hypertension, phosphonate-containing medications demonstrate high effectiveness in the treatment of renal dysfunction.

Natural group ACE inhibitors

A group of drugs that appeared thanks to the study of molecules with peptide bonds contained in the venom of the American spearhead snake. Medicines of this type can be called cell coordinators that prevent them from stretching.

The decrease in pressure occurs through the degression of peripheral vascular resistance. Natural ACE inhibitors include derivatives of the breakdown products of caseinogen and whey contained in dairy products (casokinins and lactokinins). Hibiscus also contains small amounts of them.

New generation drugs

The group of drugs that inhibit the action of angiotensin-converting enzyme includes both outdated drugs that began to be produced 20-30 years ago, and drugs of the latest generation that came into use less than 10 years ago.

The first include medications with multiple uses, for example Enalapril - this drug is effectively used in the fight against hypertension, which is why it is still popular today.

It is also worth noting that the latest generation of ACE blockers demonstrates higher effectiveness than inhibitors produced several decades ago.

Side effects

Despite its effectiveness in the treatment of cardiovascular diseases, taking ACE inhibitory drugs can also have negative consequences for the body, which should not be neglected.

First of all, it is worth considering adverse metabolic reactions, which are characterized by the following ailments:

• feeling dizzy;
• angioedema;
• presence of dry cough;
• increase in blood potassium.

Such symptoms completely disappear only after stopping the medication.

It is worth mentioning other side effects inherent in this type of medication:

• itchy skin rash;
• asthenic condition;
• hepatotoxicity;
• decreased sex drive.

Contraindications

ACEI drugs are contraindicated in combination with immunosuppressants and drugs that reduce cell growth - in order to avoid a critical deficiency of white blood cells.

• pregnancy and lactation period;
• some kidney diseases;
• symptomatic hypotension;
• high concentration of potassium in the blood;
• impaired renal function;
• autosomal dominant disease (hypertrophic cardiomyopathy);
• aortic stenosis.

Before taking ACEI drugs, it is necessary to take into account that their prescription, either alone or in combination with other drugs, should be carried out exclusively by a medical specialist, after undergoing a number of necessary examinations.

If risk factors are identified or negative consequences for the body occur, another course of treatment will be determined, more suitable for a particular case.

With severe hypertension, doctors can prescribe medications to their patients from various drug groups.

Very often, to reduce blood pressure, hypertensive patients have to take ACE inhibitors, the mechanism of action of which is aimed not only at having a hypotensive effect, but also at improving the functioning of the heart muscle.

To understand what these medications are, patients need to learn more about the mechanism of action and side effects of ACEs.

ACE inhibitors (this abbreviation stands for angiotensin-converting enzyme) are a group of medications that can block the formation of angiotensin, a hormone that accumulates in the blood plasma.

The mechanism of action of ACE inhibitors is that angiotensin constricts blood vessels, disrupts systemic blood flow and increases blood pressure. In addition, angiotensin stimulates the production of another hormone - aldesterone, which provokes the development of vascular spasms, fluid and sodium retention in the body, rapid heartbeat and some other symptoms that accompany arterial hypertension.

The mechanism of angiotensin formation is quite complex and is not always understandable to a person who has a superficial understanding of biology and chemistry. This substance arises as a result of many chemical reactions occurring in the human body.

Captopril tablets

Under the influence of adrenaline, the kidneys begin to produce the enzyme renin, which enters the systemic circulation and is converted there into angiotensinogen, which is also called angiotensin I. At the next stage, angiotensin I is converted into angiotensin II (angiotensin itself), this process is facilitated by a special angiotensin-converting enzyme, which inhibitor drugs act.

The first ACE inhibitors appeared more than 40 years ago. It was then that scientists managed to synthesize, which became one of the main drugs prescribed for high blood pressure. Captopril was replaced by Lisinopril and other new generation drugs.

– adrenergic blocker of beta receptors of the first and second groups. The drug is prescribed for diseases that are caused by instability of vascular tone.

– a reliable medicine widely used in cardiology. The drug reduces the manifestations of hypertension, coronary artery disease, and angina pectoris.

Therapeutic properties

If a person suffering from hypertensive syndrome does not consult a doctor in time or does not take medications prescribed by the doctor, the effects of angiotensin will negatively affect the condition of the walls of blood vessels and the heart muscle. In addition to high blood pressure, the patient will develop chronic heart failure and serious kidney diseases (renal failure, etc.).

Due to their action, ACE inhibitors have a whole range of therapeutic properties. Drugs belonging to this group:

• dilate blood vessels;
• prevent the occurrence of vascular spasms;
• restore damaged vessel walls;
• reduce the risks of heart attacks and strokes;
• normalize heart rhythms;
• reduce blood pressure;
• reduce the amount of protein in the urine;
• reduce left ventricular hypertrophy;
• prevent stretching of the walls of the heart chambers;
• improve blood supply and prevent the death of heart muscle cells that occurs during oxygen starvation;
• stimulate the production of bradykinin, a substance that stops pathological processes in the kidneys, heart and blood vessels;
• increase the concentration of potassium in the blood.

ACE inhibitors can be prescribed to a patient for pathologies such as:

• hypertensive syndrome;
• chronic heart failure;
• ischemia;
• suffered strokes and heart attacks;
• disorders of myocardial contractile functions;
• vascular pathologies;
• atherosclerotic syndrome;
• chronic renal failure;
• kidney damage that developed against the background of diabetes, etc.

Only the attending physician can choose a suitable inhibitor and select the daily dose of the drug for the patient; self-medication with drugs belonging to this group can provoke serious complications for the heart and blood vessels.

Species

ACE inhibitors can be divided into three types according to the main active ingredient included in their composition:

• sulfhydryl group(first generation drugs, act for a short time): Captopril, Zofenopril, Pivalopril;
• carboxyl group(second generation inhibitors, have an average duration of action): Enalapril, Lisinapril;
• phosphinyl group(third generation, long-acting): Fosinopril, Ceronapril.

Different inhibitors (even those belonging to the same class) have different times of absorption into the blood and elimination from the body. When prescribing a particular drug, the doctor must take into account the properties of the drug, and also pays attention to the patient’s condition and the severity of his disease.

Some of the most popular and frequently prescribed medications are those with the following trade names: Benzapril, Zocardis (first generation), Enalacor, Diroton, Enap (second generation), Monopril, Fosinap (third generation).

Side effects

Despite being well tolerated, in some cases ACE inhibitors can cause side effects, such as:

• a sharp decrease in pressure;
• cough syndrome;
• spasms in the bronchi;
• hyperkalemia;
• kidney dysfunction;
• increased swelling;
• change in taste sensations;
• stomach pain;
• disorders of digestive processes;
• vomiting and nausea;
• diarrhea;
• liver pathologies;
• disturbances in the outflow of bile;
• itching and rashes on the skin;
• anemia;
• convulsions;
• decreased libido;
• general weakness;
• sleep disorders, etc.

Most often, side effects of ACE inhibitors occur due to improper use or overdose of medications. Before starting treatment, the patient must make sure that there are no contraindications to the use of such medications. Patients often seek ACE inhibitors that do not cause coughing. According to statistics, in Europeans, when taking ACE inhibitors, side effects in the form of a dry cough occur in only 10% of patients.

It is not recommended to take medications for diseases and symptoms such as:

• hypotension;
• aortic stenosis;
• renal artery stenosis;
• severe form of renal failure;
• hypersensitivity (intolerance) to the components of the drug;
• leukopenia;
• porphyria;
• hyperkalemia.

ACE inhibitors should not be used by young children, nursing mothers, or pregnant women. Expectant mothers should understand that drugs in this group can reduce the amount of amniotic fluid and also negatively affect the fetus, causing growth retardation and the development of congenital anomalies.

Special instructions

To minimize the side effects of ACE inhibitors, patients must follow a number of rules when taking them:

• It is necessary to use antihypertensive medication only in the dosage prescribed by the doctor, and the patient should not exceed the duration of the prescribed treatment;
• before starting treatment, hypertensive patients are recommended to take a blood test to determine the level of potassium, iron and other indicators that may change under the influence of medications;
• during treatment, the patient is not recommended to use non-steroidal anti-inflammatory drugs, drugs that suppress the immune system and increase potassium levels;
• in the first weeks after starting treatment, a person needs to monitor his well-being and regularly measure his blood pressure; if the patient experiences any complications or adverse reactions while taking medications, they should be reported to the doctor immediately.

The optimal time for taking inhibitors is on an empty stomach, 60 minutes before meals (the attending physician should give the patient more accurate information about the time of taking the drug).

Video on the topic

This lecture presents the main pharmacological aspects of drugs acting on the renin-angiotensin-aldosterone system (ACE inhibitors, sartans and direct renin inhibitors):

ACE inhibitors are considered one of the most effective drugs that have a pronounced hypotensive effect. When used correctly and regularly, such medications will help lower blood pressure, restore kidney function, and normalize the condition of the heart and blood vessels. Like any other medications, ACE inhibitors cause side effects, so you need to take them carefully and not violate your doctor’s recommendations.