APF therapy. The best ACE inhibitors. Indications for angiotensin-converting enzyme inhibitors

And arterial hypertension is considered a risk factor for the development of a whole group of dangerous pathological processes and emergency conditions: from classic hemorrhagic or ischemic stroke to heart attack, acute renal failure or its chronic form with rapid progression.

The most effective therapy for this condition is in the early stages, when the tonometer readings do not reach consistently high values.

Effective treatment involves the use of a whole group of medications of different pharmaceutical types. They affect the triggers for rising blood pressure, but in different ways. Therefore, the likelihood of side effects, their severity, and overall effectiveness are not the same.

ACE inhibitors are powerful, but at the same time milder in terms of side effects, drugs for the treatment of arterial hypertension, which block the biochemical component of vasoconstriction, due to which they are considered one of the most effective drugs existing today.

They are used in long courses, in some cases requiring lifelong use.

Prescribed for the treatment of arterial hypertension and the prevention of emergency conditions in patients at risk (see Indications).

The essence of the pharmaceutical effect lies not in one, but in a group of positive phenomena.

The kidneys constantly produce the prehormone renin. Under the influence of a special substance during the reaction, it is converted into angiotensin, which contributes to the narrowing of the lumen of all blood vessels in the body and a stable increase in blood pressure.

When its concentration increases, persistent hypertension develops, which is difficult to correct by other means.

The substance that promotes the chemical reaction is angiotensin converting enzyme (ACE). The term inhibits means slows down or reduces the rate of synthesis to acceptable levels. Therefore, blood pressure returns to normal.

Inhibitor drugs act on a fundamental biochemical factor, which is why they are considered one of the most effective.

Activation of bradykinin production. Another specific substance. Acts as a natural cytological protector.

Prevents damage to tissues and cells of the kidneys, heart (myocardium). Reduces the risks of emergency conditions by 20-30% on average.

Therefore, ACE inhibitor of any generation is used as part of the prevention of heart attack and renal failure.

Slowing down the synthesis of adrenal hormones. By reducing the rate of production of renin and angiotensin.

For this reason, the filtering function of the kidneys remains at the proper level; fluid is not retained in the body.

Indirectly, this leads to a drop in blood pressure and reduces the load on the kidneys and heart.

This is especially important in patients with arterial hypertension, diabetes mellitus, and endocrine diseases.

Also, medications of the group that inhibit angiotensin converting enzyme prevent the adhesion of formed blood cells, prevent the formation of blood clots, and reduce the concentration of cholesterol.

The mechanism of action of ACE inhibitors (pharmacokinetics) is based on inhibition of some biochemical reactions and acceleration of others.

The effect is complex, which makes medications perhaps the most important in the matter of therapy at any stage of the pathological process.

Classification and differences

ACE inhibitors are classified by generation. Each includes a group of names of funds.

Accordingly, the next generation is considered more effective and safe than the previous one.

What is said is not always the absolute truth. Many early group remedies are highly effective, but also have significant risks, because they affect the body too harshly.

1st generation

Created in the mid-70s of the last century. Historically, the first products of this pharmaceutical group.

They are distinguished by high pharmacological activity and effectiveness, but they provoke many side effects and are extremely demanding in choosing the dosage (like other medications, but in this case we are talking about critical dependence).

If used incorrectly, a sharp drop in blood pressure occurs, which can lead to emergency conditions. Therefore, medications are absolutely not suitable for self-administration.

There are three key types with a sulfhydryl group on the market today:

Captopril. It has several trade names: Katopil, Capoten, Blockordil, Angiopril. It is considered the main medication for urgent, emergency lowering of blood pressure.

It is used in small dosages, because the result is achieved in a matter of minutes.

Historically, it was synthesized first in 1975. It is used in the practice of cardiologists as a means of emergency care for patients with hypertensive crisis. Also in the treatment of persistent hypertension (stable increase in blood pressure).

A milder ACE inhibitor with overall high pharmaceutical activity. Used to correct moderate stage arterial hypertension. Another indication is congestive heart failure.

(Zocardis). The mildest drug of the first generation. Causes minimal side effects. But the effect is not so pronounced. However, this makes the drug suitable for the treatment of the initial stages of arterial hypertension.

Key features of “early” ACE inhibitors:

Short duration of action, since the drugs are unstable and the main substances in the body are quickly oxidized.
High bioavailability. Which contributes to the rapid onset of a positive effect. The advantage of this point is the ability to use drugs for emergency assistance in hypertensive crisis and emergency conditions.
Excretion occurs mainly by the kidneys.

2nd generation

It is most actively used today in the practice of cardiologists in Russia and the countries of the former Soviet Union. It has a good combination of effectiveness and safety.

At the same time, the likelihood of side effects and their severity is still high.

List of names with carboxyl group:

Enalapril (Vazolapril, Enalacor, Enam, Renipril, Renitek, Enap, Invoril, Corandil, Berlipril, Bagopril, Miopril).

Used to treat pathological increases in blood pressure as a means for complex use.

Mainly in patients of the older age group, because it has pronounced activity in preventing the formation of blood clots and removing cholesterol, although it cannot compete in this regard with specialized medications.

Perindopril. It has many trading options: Perineva, Prestarium, Perinpress, Parnavel, Hypernik, Stopress, Arentopresi.

Used as a means of complex treatment of hypertension, as part of the prevention of heart attack and stroke.

It can also be used in solving the problem of monotherapy for hypertension in the early stages, symptomatic growth of tonometer readings.

It is considered the most effective and safe of the second generation ACE inhibitors.

Lisinopril. Among the names are Diroton, Irumed, Diropress, Liten, Sinopril, Dapril, Lysigamma, Prinivil and others.

It is used relatively often in patients without kidney pathologies with predominant damage to cardiac structures. Because it is completely excreted in the urine.

List of drugs: Dilaprel, Vazolong, Pyramil, Corpril, Ramepress, Hartil, Tritace, Amprilan.

Prescribed to patients as a treatment for arterial hypertension in the early stages.

More pronounced phases with a persistent increase in indicators require the use of other drugs.

Features of the second generation ACE inhibitors:

They are excreted in various ways: kidneys, liver, several at once (depending on the specific name).
High bioavailability. But it is less than that of the first generation products. Therefore, the effect does not occur immediately, but after 20-30 minutes, possibly more.
Duration of action is longer. If drugs like Captopril last about 1-1.5 hours, in this case it’s 5-8.

Medicines can be used as permanent treatments.

3rd generation

Despite the fact that they were created relatively late, and this is the last generation, their advantages are not as obvious as they might seem.

Factors of effectiveness (mild effect), number of side effects (occur infrequently, those that exist are relatively easily tolerated by patients) are noted.

However, what makes these medications controversial is their relatively low bioavailability (the result occurs in almost 30-60 minutes) and elimination via several routes at once: the liver and kidneys, which increases the number of contraindications and increases the risk of side effects due to dysfunction.

List of latest generation ACE inhibitor drugs with a phosphinyl group:

Fosinopril. Monopril, Fosinap, Fosicard, Fozinotec.
Ceronapril.

Attention:

In emergency situations, they are absolutely not suitable due to the long period before the onset of action.

At the same time, the clinical effect persists for many hours, which qualitatively distinguishes third-generation products from similar ones.

The list of specific brand options is incomplete, but these are the medications most commonly prescribed.

All generations considered have their own sphere of primary use; it is impossible to say which drugs are better or worse. Depends on the situation and the specific case, the patient.

ACE inhibitors can also be classified based on the frequency of administration:

Short duration of action: Captopril. Take 2-3 times a day.
Medium in duration. Enalapril. 2 times a day.
Prolonged. Perindopril, Lisinopril. 1 per day.

Indications

The reasons for using ACE inhibitors are varied. The main thing, of course, is arterial hypertension of any origin.

The effect will not be the same, because the cause of the narrowing of the vessel may be different, the biochemical component with the production of angiotensin from renin is always present, but the role in all situations is different.

In addition, the following indications for use can be mentioned:

. The drugs help reduce the rate of destruction of cardiac tissue, which reduces the total area and extent of damage to heart structures. The effect has already been described above.

, transferred in the recent past. That is, the condition after a heart attack. The essence is the same, ACE inhibitors reduce the risk of relapse.

Ischemic stroke. Death of brain tissue and cerebral structures without compromising the integrity of blood vessels.

ACE inhibitors are used to normalize blood pressure, which almost always increases during an emergency.

But doctors are closely monitoring the vital sign. Because instability of blood pressure levels is possible.

. Cardiac failure in any phase. To prevent heart attack.

Chronic renal dysfunction.

Attention:

An important condition is that the drug should not be excreted only by paired organs. Otherwise the condition will worsen.

Diabetes mellitus involving peripheral vessels in the pathological process (extremities suffer), as well as the excretory system. An increase in cholesterol concentration due to the course of endocrine disease.
Decrease in myocardial contractile function. .

Obliterating atherosclerosis of the arms or legs (without deposition of cholesterol plaques).
Nephropathy against the background of current diabetes mellitus. Its essence lies in kidney damage and a progressive decrease in filtering function.

These indications mostly require complex therapy; ACE inhibitors alone are not enough. Not counting mild and moderate forms of arterial hypertension as a diagnosis or symptomatic point.

It is not always advisable to use the specified pharmaceutical group if we are talking only about atherosclerosis, hypercholesterolemia without an increase in tonometer readings. There are more suitable means.

Attention:

In any case, medications should only be used on the recommendation of a doctor. These are not harmless vitamins (by the way, they can have negative effects if used incorrectly).

When taken systematically, ACE inhibitors almost halve the likelihood of stroke or heart attack, protect cardiac structures and blood vessels, and kidneys from destruction. Indirectly normalize myocardial contractility.

Contraindications

The described drugs cannot be used in all cases. In what situations is it better to abstain:

Increase in potassium concentration. Excessive amount of it (level over 5.5).
Consistently low blood pressure or a tendency for the tonometer readings to rise rapidly.
Severe renal failure.
Narrowing of the arteries of the same paired organ.
Individual hypersensitivity to the drug can only be detected experimentally.
Polyvalent allergic reaction to medications. Rarely seen. But it requires a careful approach. Relative contraindication.
Pregnancy, regardless of phase.
Lactation, breastfeeding.

If there is at least one reason described above, the harm may be disproportionately greater than the benefit. Without the appointment of a specialist, there is no talk of any appointment.

Side effects

Among the most common adverse reactions:

A sharp drop in blood pressure. Especially if a large dose is taken or the treatment regimen is inadequate. Usually the body adapts on its own after a few days, maximum a week after taking it and restores vascular tone.
Allergic reaction to the components of the drug. It manifests itself as skin itching, an attack of bronchial asthma, Quincke's edema, and in extreme cases, anaphylactic shock.
Dry non-productive cough for a long time.
Nausea, vomiting, heartburn, belching, diarrhea, alternating bowel movements (either weak or constipated).
Dyspeptic phenomena. Also in the early stages of treatment, before getting used to the effects of the drug.
Cholestasis. Pain in the right hypochondrium. Liver problems.
Perversion of gastronomic preferences. Rarely.
Acute renal failure. In the presence of cardiac dysfunction, failure of the paired organ is possible. A side effect occurs in seriously ill people, more often the elderly.
An increase in the number of neutrophils and eosinophils during a general blood test. This is a variant of the clinical norm, but doctors should be warned about taking the drugs so as not to draw a false conclusion.
Changes in biochemical parameters of the body, electrolytic imbalance.

These side effects of ACE inhibitors require additional consultation with the treating cardiologist, because they can pose a danger to health and life or significantly reduce the quality of the latter.

Otherwise, the medication is well tolerated; there is no reason to cancel or revise the course.

Finally

ACE inhibitors are effective drugs for complex treatment, and in some cases monotherapy, of arterial hypertension.

Complex mechanisms of influence on the body also make it possible to prescribe drugs of this group in combined cases when there are pathologies of the heart, kidneys, and blood vessels.

However, these are far from harmless medications, so there is no talk of independent uncontrolled use. Dangerous to life and health.

It is necessary to consult a cardiologist and undergo a full examination. Only then can we talk about therapy.

Angiotensin II is an important hormone that regulates the activity of the cardiovascular system. The advent of angiotensin-converting enzyme (ACE) inhibitors—medicines that reduce its levels in the blood—has become a significant breakthrough in the treatment of arterial hypertension (AH). Nowadays, drugs that suppress the activity of the renin-angiotensin system occupy a leading place in the fight against the main cause of mortality - cardiovascular pathology. The first ACE blocker, captopril, was synthesized in 1977. Today, many representatives of this class have been developed, which, according to their chemical structure, are divided into three large groups.

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 to 1000 times less active than their active metabolites but have greater oral bioavailability.

Representatives of this pharmaceutical group differ according to three criteria:

activity;
parent form: precursor of the active compound (prodrug) or 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 angiotensinI, have similar indications, contraindications and side effects. However, these drugs differ significantly in the nature of their distribution in tissues. However, it is not yet known whether this will provide any new benefits.

With the exception of fosinopril and spirapril, which are equally eliminated by the liver and kidneys, angiotensin-converting enzyme blockers are primarily excreted in the urine. Therefore, renal dysfunction reduces the elimination of most of these drugs and their dosage should be reduced in such patients.

List of trade names of ACE inhibitors

Captopril: Angiopril®, Blockordil, Capoten®, Katopil, etc.
Enalapril: Bagopril®, Berlipril®, Vazolapril, Invoril®, Corandil, Miopril, Renipril®, Renitek, Ednit®, Enalacor, Enam®, Enap®, Enarenal®, Enapharm, Envipril, etc.
Lisinopril: Dapril®, Diropress®, Diroton®, Zonixem®, Irumed®, Lizacard, Lysigamma®, Lisinoton®, Liziprex®, Lizonorm, Listril®, Liten®, Prinivil, Rileys-Sanovel, Sinopril, etc.
Perindopril: Arentopres, Hypernik, Parnavel, Perineva®, Perinpress, Prestarium®, Stopress, etc.
Ramipril: Amprilan®, Vazolong, Dilaprel®, Korpril®, Pyramil®, Ramepress®, Ramigamma, Ramicardia, Tritace®, Hartil®, etc.
Quinapril: Accupro®.
Zofenopril: Zocardis®.
Moexipril: Moex®.
Spirapril: Quadropril®.
Trandolapril: Hopten®.
Cilazapril: Inhibase®, Prilazide.
Fosinopril: Monopril®, Fosicard®, Fosinap, Fozinotec, 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 reduce blood pressure in all forms of hypertension, with the exception of primary hyperaldosteronism. Monotherapy with ACE inhibitors normalizes blood pressure in approximately 50% of patients with mild to moderate hypertension.

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

Angiotensin-converting enzyme blockers are the drugs of choice for hypertension associated with diabetes mellitus (they inhibit the progression of diabetic nephropathy) and left ventricular hypertrophy. They are also recommended for the combination of hypertension and coronary heart 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 small doses, since these patients may experience a sharp drop in blood pressure, especially against the background of a decrease in circulating blood mass. In addition, they reduce dilation (widening) of the left ventricle and, to some extent, restore the normal ellipsoidal shape of the heart.

Myocardial infarction

ACE inhibitors reduce mortality when administered early in myocardial infarction. They are especially effective when combined with hypertension and diabetes. 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 systems of the blood towards the latter. Scientific studies have proven that they significantly reduce the incidence of heart attack, stroke, and mortality in patients with vascular pathology, diabetes mellitus and other risk factors for cerebrovascular accidents.

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 in other renal pathologies, including severe ones.

Side effect

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

Arterial hypotension. The first dose 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 combination antihypertensive therapy;
with heart failure.

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

Cough. About 5-20% of patients taking drugs from this pharmaceutical group complain of a persistent dry cough. This side effect is usually independent of dose and occurs more often in women, usually between 1 week and 6 months from the start of use. After stopping the ACE blocker, the cough goes away on average within 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 supplements, beta-blockers or nonsteroidal anti-inflammatory drugs (NSAIDs).
Acute renal failure (ARF). They can lead to acute renal failure due to narrowing of the renal arteries on both sides, narrowing of the artery of a single kidney, heart failure, or a decrease in circulating blood mass caused by 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, kidney function is completely normalized in almost all patients.
Effect on the fetus. They do not affect the fetus during the period of organogenesis (first trimester), but their use in the second and third trimesters can lead to oligohydramnios, underdevelopment of the skull and lungs, intrauterine growth retardation, and death of the fetus and newborn. 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 discontinued. If this is done in the first trimester, the risk of a negative effect on the fetus is reduced to zero.
Rash. Members of this group sometimes cause a maculopapular rash, which may be accompanied by itching. It disappears on its own or after reducing the dose of the ACE blocker or a short course of antihistamines (diphenhydramine, suprastin, tavegil, etc.).
Proteinuria (excretion of protein in the urine). Patients taking drugs from this pharmaceutical group sometimes develop proteinuria (more than 1 g/day), but it is quite difficult to prove its connection with taking ACE inhibitors. It is believed that proteinuria is not a contraindication to their use; on the contrary, these medications 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 not dose dependent and usually occurs within a few hours of 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 within a few hours; during this time, measures are taken to maintain airway patency; if necessary, adrenaline, antihistamines and glucocorticosteroids (dexamethasone, hydrocortisone, prednisolone) are administered. Blacks are 4.5 times more likely to develop angioedema when taking ACE inhibitors than whites.
Taste disturbances. Patients taking drugs from this pharmaceutical group sometimes note a decrease or loss of taste. This side effect is reversible and is more common when taking captopril.
Neutropenia. This is a rare but serious side effect of ACE blockers. It is observed mainly when hypertension is combined with collagenosis or parenchymal kidney diseases. If the serum creatinine concentration is 2 mg or higher, the dose of the drug should be reduced.
A very rare and reversible side effect of ACE inhibitors is glucosuria (sugar in the urine) in the absence of hyperglycemia (high blood sugar). The mechanism is unknown.
Hepatotoxic effect. This is also an extremely rare, reversible complication. It usually manifests itself as cholestasis (stagnation of bile). The mechanism is unknown.

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. Representatives of this pharmaceutical group increase serum levels of digoxin and lithium and increase the allergic reaction to allopurinol (an anti-gout drug).

Angiotensin-converting enzyme (ACE) inhibitors are a group of hypertension medications that affect the activity of the renin-angiotensin-aldosterone system. ACE is an angiotensin-converting enzyme that converts a hormone called angiotensin-I into angiotensin-II. And angiotensin-II increases the patient’s blood pressure. This happens in two ways: angiotensin II causes a direct constriction of blood vessels, and also causes the adrenal glands to release aldosterone. Salt and liquid are retained in the body under the influence of aldosterone.

ACE inhibitors block the angiotensin-converting enzyme, as a result of which angiotensin-II is not produced. They can enhance the effects by reducing the body's ability to produce aldosterone when salt and water levels are reduced.

Efficacy of ACE inhibitors for the treatment of hypertension

ACE inhibitors have been successfully used to treat hypertension for more than 30 years. A 1999 study assessed the effect of the ACE inhibitor captopril on reducing blood pressure in patients with hypertension compared with diuretics and beta blockers. There were no differences between these drugs in terms of reducing cardiovascular morbidity and mortality, but captopril was significantly more effective in preventing the development of complications in patients with diabetes.

Read about the treatment of diseases associated with hypertension:

Also watch a video about the treatment of coronary artery disease and angina pectoris.

The results of the STOP-Hypertension-2 study (2000) also showed that ACE inhibitors are not inferior to diuretics, beta blockers, etc. in preventing complications from the cardiovascular system in patients with hypertension.

ACE inhibitors significantly reduce patients' mortality, risk of stroke, heart attack, all cardiovascular complications and heart failure as a cause of hospitalization or death. This was also confirmed by the results of a 2003 European study, which showed the advantage of ACE inhibitors in combination with calcium antagonists compared with the combination of a beta blocker in the prevention of cardiac and cerebral events. The positive effect of ACE inhibitors on patients exceeded the expected effect of lowering blood pressure alone.

ACE inhibitors, along with angiotensin II receptor blockers, are also the most effective drugs in reducing the risk of developing diabetes.

Classification of ACE inhibitors

ACE inhibitors, according to their chemical structure, are divided into drugs containing a sulfhydryl, carboxyl and phosphinyl group. They have different half-lives, different ways of being eliminated from the body, dissolve differently in fats and accumulate in tissues.

ACE inhibitor - name	Half-life from the body, hours	Renal excretion, %	Standard doses, mg	Dose for renal failure (creatine clearance 10-30 ml/min), mg
ACE inhibitors with a sulfhydryl group
Benazepril	11	85	2.5-20, 2 times a day	2.5-10, 2 times a day
Captopril	2	95	25-100, 3 times a day	6.25-12.5, 3 times a day
Zofenopril	4,5	60	7.5-30, 2 times a day	7.5-30, 2 times a day
ACE inhibitors with a carboxyl group
Cilazapril	10	80	1.25, 1 time per day	0.5-2.5, 1 time per day
Enalapril	11	88	2.5-20, 2 times a day	2.5-20, 2 times a day
Lisinopril	12	70	2.5-10, 1 time per day	2.5-5, 1 time per day
Perindopril	>24	75	5-10, 1 time per day	2, 1 time per day
Quinapril	2-4	75	10-40, once a day	2.5-5, 1 time per day
Ramipril	8-14	85	2.5-10, 1 time per day	1.25-5, 1 time per day
Spirapril	30-40	50	3-6, 1 time per day	3-6, 1 time per day
Trandolapril	16-24	15	1-4, 1 time per day	0.5-1, 1 time per day
ACE inhibitors with a phosphinyl group
Fosinopril	12	50	10-40, once a day	10-40, once a day

The main target of ACE inhibitors is the angiotensin-converting enzyme in blood plasma and tissues. Moreover, plasma ACE is involved in the regulation of short-term reactions, primarily in the increase in blood pressure in response to certain changes in the external situation (for example, stress). Tissue ACE is essential in the formation of long-term reactions, regulation of a number of physiological functions (regulation of circulating blood volume, sodium, potassium balance, etc.). Therefore, an important characteristic of an ACE inhibitor is its ability to influence not only plasma ACE, but also tissue ACE (in blood vessels, kidneys, heart). This ability depends on the degree of lipophilicity of the drug, i.e. how well it dissolves in fats and penetrates into tissues.

Although hypertensive patients with high plasma renin activity experience a more dramatic reduction in blood pressure with long-term treatment with ACE inhibitors, the correlation between these factors is not very significant. Therefore, ACE inhibitors are used in patients with hypertension without first measuring plasma renin activity.

ACE inhibitors have advantages in the following cases:

concomitant heart failure;
asymptomatic left ventricular dysfunction;
renoparenchymal hypertension;
diabetes;
left ventricular hypertrophy;
previous myocardial infarction;
increased activity of the renin-angiotensin system (including unilateral renal artery stenosis);
non-diabetic nephropathy;
atherosclerosis of the carotid arteries;
proteinuria/microalbuminuria
atrial fibrillation;
metabolic syndrome.

The advantage of ACE inhibitors lies not so much in their special activity in lowering blood pressure, but in the unique features of protecting the patient’s internal organs: beneficial effects on the myocardium, walls of resistive vessels of the brain and kidneys, etc. We now turn to the characterization of these effects.

How ACE inhibitors protect the heart

Hypertrophy of the myocardium and blood vessel walls is a manifestation of the structural adaptation of the heart and blood vessels to high blood pressure. Hypertrophy of the left ventricle of the heart, as has been repeatedly emphasized, is the most important consequence of hypertension. It contributes to the occurrence of diastolic and then systolic dysfunction of the left ventricle, the development of dangerous arrhythmias, the progression of coronary atherosclerosis and congestive heart failure. Based on 1 mm Hg. Art. decreased blood pressure ACE inhibitors reduce left ventricular muscle mass 2 times more intensely compared to other drugs from hypertension. When treating hypertension with these drugs, there is an improvement in the diastolic function of the left ventricle, a decrease in the degree of its hypertrophy and an increase in coronary blood flow.

The hormone angiotensin II enhances cell growth. By suppressing this process, ACE inhibitors help prevent or inhibit the remodeling and development of myocardial and vascular muscle hypertrophy. In implementing the anti-ischemic effect of ACE inhibitors, it is also important to reduce the myocardial oxygen demand, reduce the volume of the heart cavities, and improve the diastolic function of the left ventricle of the heart.

Watch also the video.

How ACE inhibitors protect the kidneys

The most important question, the answer to which determines the doctor’s decision whether to use ACE inhibitors in a patient with hypertension, is their effect on renal function. So, it can be argued that Among blood pressure medications, ACE inhibitors provide the best kidney protection. On the one hand, about 18% of patients with hypertension die from kidney failure, which develops as a result of increased blood pressure. On the other hand, a significant number of patients with chronic kidney disease develop symptomatic hypertension. It is believed that in both cases there is an increase in the activity of the local renin-angiotensin system. This leads to kidney damage and their gradual destruction.

The US Joint National Committee on Hypertension (2003) and the European Society of Hypertension and Cardiology (2007) recommend prescribing ACE inhibitors to patients with hypertension and chronic kidney disease to slow the progression of renal failure and lower blood pressure. A number of studies have demonstrated the high effectiveness of ACE inhibitors in reducing the incidence of complications in patients with hypertension in combination with diabetic nephrosclerosis.

ACE inhibitors best protect the kidneys in patients with significant protein excretion in the urine (proteinuria more than 3 g/day). It is currently believed that the main mechanism of the renoprotective effect of ACE inhibitors is their effect on renal tissue growth factors activated by angiotensin II.

It has been established that long-term treatment with these drugs improves renal function in a number of patients with signs of chronic renal failure, if there is no sharp decrease in blood pressure. At the same time, a reversible deterioration in renal function can occasionally be observed during treatment with ACE inhibitors: an increase in plasma creatinine concentration, depending on the elimination of the effect of angiotensin-2 on the efferent renal arterioles, which maintain high filtration pressure. It is appropriate to point out here that with unilateral renal artery stenosis, ACE inhibitors can deepen disorders on the affected side, but this is not accompanied by an increase in plasma creatinine or urea levels as long as the second kidney functions normally.

For renovascular hypertension (i.e., a disease caused by damage to the renal vessels), ACE inhibitors in combination with a diuretic are quite effective in controlling blood pressure in most patients. True, isolated cases of the development of severe renal failure in patients who had one kidney have been described. Other vasodilators (vasodilators) can also cause the same effect.

The use of ACE inhibitors as part of combination drug therapy for hypertension

It is useful for doctors and patients to have information about the possibilities of combination therapy for hypertension with ACE inhibitors and other blood pressure medications. Combination of an ACE inhibitor with a diuretic In most cases ensures rapid achievement of blood pressure levels close to normal. It should be taken into account that diuretics, by lowering the volume of circulating blood plasma and blood pressure, shift pressure regulation from the so-called Na-volume dependence to the vasoconstrictor renin-angiotensin mechanism, which is affected by ACE inhibitors. This sometimes leads to an excessive decrease in systemic blood pressure and renal perfusion pressure (renal blood supply) with deterioration of kidney function. In patients who already have such disorders, diuretics together with ACE inhibitors should be used with caution.

A clear synergistic effect, comparable to the effect of diuretics, is provided by calcium antagonists prescribed together with ACE inhibitors. Calcium antagonists can therefore be prescribed instead of diuretics if the latter are contraindicated. Like ACE inhibitors, calcium antagonists increase the distensibility of large arteries, which is especially important for elderly patients with hypertension.

Therapy with ACE inhibitors as the only treatment for hypertension gives good results in 40-50% of patients, perhaps even in 64% of patients with mild to moderate forms of the disease (diastolic pressure from 95 to 114 mm Hg). This indicator is worse than when treating the same patients with calcium antagonists or diuretics. It should be borne in mind that patients with the hyporenin form of hypertension and the elderly are less sensitive to ACE inhibitors. Such individuals, as well as patients in stage III of the disease with severe hypertension, sometimes becoming malignant, should be recommended combined treatment with ACE inhibitors with a diuretic, calcium antagonist or beta blocker.

The combination of captopril and a diuretic, prescribed at regular intervals, is often extremely effective, i.e., blood pressure is reduced to almost normal levels. With this combination of drugs it is often possible to achieve complete control of blood pressure in very sick patients. When combining ACE inhibitors with a diuretic or calcium antagonist, normalization of blood pressure is achieved in more than 80% of patients with advanced hypertension.

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

S. Yu. Shtrygol, Dr. honey. sciences, prof.
National Pharmaceutical University, Kharkov

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

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 through 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 the maximum coefficient of the 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

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.
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.
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. 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.

Angiotensin-converting enzyme (ACE) inhibitors appeared in 1975, when captopril was synthesized. Currently, all ACE inhibitors, depending on the chemical group associated in their molecule with the zinc ion in the active centers of the angiotensin I-converting enzyme, are divided into groups:

drugs with a sulfhydryl group (captopril, methiopril);
drugs with a carboxyalkyl group (enalapril, perindopril, ramipriril);
drugs with a phosphinyl group (fosinopril, ceronapril).

Only captopril and lisinopril have biological activity; all other ACE inhibitors are inactive substances and are converted into active diacid metabolites only as a result of hydrolysis after absorption in the gastrointestinal tract.

Mechanism of action

The antihypertensive effect of ACE inhibitors is based on their ability to suppress the activity of kininase II, while simultaneously influencing the functional activity of the renin-angiontensin and kallikrein-kinin systems. ACE inhibitors block the production of angiotensin II, which has a strong vasoconstrictor effect. Thus, by suppressing the production of angiotensin II, ACE inhibitors not only have a therapeutic effect in chronic heart failure, but also prevent it.

Pharmacologists highlight plasma And tissue ACE system - the first determines the regulation of blood pressure, the second has a long-term modulating effect in tissues.

Suppression of ACE in plasma:

prestarium - 80-95%
quinapril - 80%
trandolapril - 70-85%
ramipril - 60-80%

Affinity for tissue ACE:

prestarium - 6
quinapril - 5.8
ramipril - 5.2
enalapril - 3.6

Suppression of tissue ACE is the prevention of cardiac hypertrophy, hypertrophy of the muscular layer of arterioles, hypertrophy of the glomeruli of the kidneys with their subsequent death.

Ramipril and perindopril, which have the most pronounced cardioprotective effect, have high fat solubility.

According to the duration of the antihypertensive effect, ACE inhibitors are divided into 3 groups:

short-acting drugs (captopril, methiopril) - taken 2-3 times a day;
drugs with an average duration of action (enalapril) - 2 times a day;
long-acting drugs (quinapril, lisinopril, perindopril, ramipril, spirapril, trandolapril, fosinopril) - 1 time per day.

Dosage of ACE inhibitors in the treatment of hypertension, mg (recommended daily dose/initial dose/number of doses per day):

captopril (capoten) - 12.5-100/12.5/2-3
enalapril (Renitec) - 5-40/5/1
lisinopril (vinyl) - 5-40/5/1
cilazapril (inhibase) - 2.5-5/1/1
ramipril (tritace) - 1.25-7.5/1.25/1
perindopril (Prestarium A) - 2.5-10/1/1
fosinopril (monopril) - 10-20/5/1-2
benazepril (cibacen) - 10-40/2.5/1
moexipril (moex) - 7.5-15/3.75/1
trandolapril (hopten) - 1-4/0.5/1

Indications for the use of ACE inhibitors:

arterial hypertension;
heart failure (left ventricular dysfunction);
acute myocardial infraction (high risk of developing MI and heart failure after MI);
diabetes mellitus (diabetic nephropathy);
proteinuria;
left ventricular hypertrophy;
paroxysmal atrial fibrillation;
metabolic syndrome;
cardiovascular protection in atherosclerosis of the carotid arteries and cerebral arteries.

Contraindications to the use of ACE inhibitors:

stenosis of the artery of the only functioning kidney; bilateral renal artery stenoses;
severe renal failure (creatinine above 300 µmol/l);
hyperkalemia more than 5.5 mmol/l;
severe arterial hypotension (systolic blood pressure less than 90 mm Hg);
aortic stenosis;
pregnancy;
lactation;
childhood;
individual intolerance to ACE inhibitors.

Side effects of ACE inhibitors

In most cases, ACE inhibitors are well tolerated by patients, and side effects are rare. The most common side effects when taking ACE inhibitors: arterial hypotension, hyperkalemia, dry cough, impaired renal function, which is manifested by an increased concentration of creatinine in the serum, angioedema.

The risk of developing hyperkalemia is reduced when ACE inhibitors are used together with loop and thiazide diuretics.

Nonspecific side effects include impaired taste, leukopenia, skin rashes, dyspeptic disorders, and the development of anemia.

Drug interactions

The simultaneous use of ACE inhibitors with thiazide or loop diuretics enhances the hypotensive effect and reduces the risk of hypokalemia.

Treatment with acetylsalicylic acid in combination with ramipril is associated with a smaller reduction in cardiovascular mortality than treatment with an ACE inhibitor alone.

Risk factors for the development of hyperkalemia (along with renal failure) in patients receiving ACE inhibitors are the simultaneous use of potassium salts, potassium-sparing diuretics and non-steroidal anti-inflammatory drugs.

ACE inhibitors increase tissue sensitivity to insulin, which increases the glucose-lowering effect of insulin drugs.

Due to the worsening myelotoxic effect, the prescription of ACE inhibitors to patients receiving allopurinol, cytostatics, and immunosuppressants may increase the risk of developing leukopenia.

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