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.
Classification of ACE inhibitors
The classification of ACE inhibitors is based on the pharmacokinetic principle: a group of active drugs (captoprit and lisino-pril) and proleksrev (the remaining ACE inhibitors) are distinguished, from which active metabolites are formed in the liver, giving a therapeutic effect (Table 16.5) .
Clinical pharmacology and pharmacotherapy
Chapter 16
Table 16.5. Classification of ACE inhibitors according to Opie (1999)
|
Lipophilic drugs: captopril, alacepril, fentiapril |
|
|
Lipophilic prodrugs |
|
|
PA class |
Drugs whose active metabolites are excreted primarily through the kidneys: enalapril, benazepril, perindopril, celazapril |
|
Class IV |
Drugs whose active metabolites have two main elimination routes: moexipril, ramipril. trandolapril, fosine opril |
|
Hydrophilic drugs: lisinopril |
Pharmacokinetics of ACE inhibitors
The pharmacokinetic features of the most commonly used ACE inhibitors are presented in table. 16.6.
Clinical use of ACE inhibitors
Main indications for the use of ACE inhibitors:
arterial hypertension of any etiology (as monotherapy and in combination with diuretics and antihypertensive drugs of other groups);
relief of hypertensive crises;
chronic heart failure;
systolic and diastolic dysfunction of the left ventricle;
IHD (to reduce the infarction area, to dilate coronary vessels and reduce dysfunction during reperfusion, to reduce the risk of recurrent myocardial infarction);
diabetic angiopathy (in particular, to slow the progression of diabetic nephropathy);
diagnosis of renovascular hypertension and primary aldosteronism (single dose of captopril).
Monitoring the effectiveness and safety of the use of ACE inhibitors.
The effectiveness of treatment with ACE inhibitors for arterial hypertension is determined by the dynamics of blood pressure.
To monitor the safety of therapy, it is also necessary to measure blood pressure to exclude possible hypotension. Hypotension develops more often in patients with chronic heart failure, renal failure, renal artery stenosis, and therefore the first dose of the drug must be taken while sitting or lying down. The development of hypotension requires a reduction in the dose of the drug, followed by titration under the control of blood pressure levels.
To exclude the growth of urate stones in patients with urolithiasis, it is necessary to determine the urate content in the urine, and to exclude hypoglycemia in patients with diabetes, monitor blood glucose levels.
ACE inhibitors remain one of the safest antihypertensive drugs. Men tolerate long-term drug therapy better than women.
Arterial hypertension< 213
Table 16.6. Pharmacokinetic features of ACE inhibitors
|
Peak them |
Prodrugsgva |
|||||||
|
enala-pri.1 |
fwna tell ril |
faux-adj |
tsila ia-nril | |||||
|
Time to achieve the "effect" | ||||||||
|
Duration >ffek1a. h | ||||||||
|
G>iolost\nn“hch. | ||||||||
|
Effect of food on absorption | ||||||||
|
Protein binding. % | ||||||||
|
Biotransformations |
11.00. gastrointestinal | |||||||
|
)kskrsnia |
T%, |
1 № |
11 points 50*. gastrointestinal tract 504 |
but-gut- |
||||
|
The influence of non-functional liver |
Decline biodos-tunno- |
Increasing the time to achieve the effect |
Increase in child life |
Increasing the time of men achieved the effect |
||||
|
In the treatment of chronic renal failure (creatinine ktirens. ml min) | ||||||||
|
Active metabolites | ||||||||
The most common ADR (from 1 to 48% during treatment with various ACE inhibitors) is a dry cough, which in some cases requires discontinuation of the drug. The mechanism of its occurrence is associated with an increase in the concentration of bradykinin in bronchial tissue. As a rule, cough is not dependent on the dose of the medicine.
The second most common (from less than 1% to 10-15% in heart failure) ADR of ACE inhibitors is the development of orthostatic hypotension. the so-called first vine effect, which occurs in patients with high RAAS activity. The development of a hypotensive reaction can also be caused by the simultaneous use of diuretics and other antihypertensive drugs.
214 # Clinical pharmacology and pharmaceuticals Granin * Chapter 16
In patients with cardiac failure (less commonly with AS), LIF inhibitors can worsen glomerular filtration and kidney function, and the incidence of severe ADRs increases with prolonged therapy. More often this happens with hidden kidney pathology and/or in patients. receiving diuretics and NSAIDs.
Clinically significant hyperkalemia (more than 5.5 µmol/l) is observed mainly in patients with kidney pathology. In renal failure, its frequency ranges from 5 to 50%,
In 0.1 0.5% of cases per<роне лечения ингибиторами АПФ развивается аши-онсвротический отек (агск Квинке), причем у женщин в 2 раза чаше, чем у мужчин.
In some cases, ACE inhibitors can cause pyEopenia (usually leukopenia, less often thrombo- and panitopenia). NK“..the schism of this NLR is connected with that. that the main substrate for ACE is the peptide N-appetyl-seryl-aspargyl-lysyl-iroline circulating in the blood - a negative regulator of temopo:) for. When the enzyme is blocked, the amount of peptide in the blood may increase. During therapy with ACE inhibitors moivi There are also such non-specific side effects. such as dizziness, headache, fatigue, weakness. dyspepsia (nausea, diarrhea), taste disturbances, skin rashes, etc.
The use of ACE inhibitors in the 11th and 3rd trimesters of pregnancy leads to the development of hypogenia. cranial typoplasia, anuria, reversible and irreversible renal failure and fetal death. In addition, a decrease in amniotic fluid, the development of joint contractures, cranial lip deformities and hypoplasia of the lungs are possible.
Contraindications to the use of LPF inhibitors
Absolute: drug intolerance: allergic reactions; pregnancy and lacgapia; bilateral sgenosis of the renal arteries (the possibility of sudden hypogenzia increases). severe chronic renal failure (serum creatine and n above 300 µmol/l), severe (above 5.5 µmol/l) hyperkalemia; hypertrophic cardomyopathy with obstruction of the outflow tract of the left ventricle: 1emodynamically significant stenosis of the aortic or mitral valve; constrictive pericarditis; transplantation of internal organs.
Otshyu/tetmye: hypotension; moderate chronic renal failure; moderate (5.0-5.5 µmol/l) hyperkatemia, gouty kidney (having a uricosuric effect, ACE inhibitors can accelerate the growth of urticaria): cirrhosis of the liver; chronic active hepatitis; obliterating agerosk-lero! arteries of the lower extremities; severe obstructive pulmonary diseases.
Reaction of LPF inhibitors with othersJIC(tide 16.7)
The pharmacokinetic interaction of ACE inhibitors is most significant with antacids. containing aluminum and/or magnesium hydroxide. "These antapids interfere with the absorption of captonril and (rosinopride) from the gastrointestinal tract.
Arterial hypertension ♦ 215
For clinical practice, the pharmacodynamic interaction of ACE inhibitors with other groups of drugs that differ from them in their mechanism of action is more important.
Table 16.7. Pharmacodynamic interaction of ACE inhibitors with drugs of other groups
|
Interaction |
Note" |
|
|
Antidiabetes drugs IHHCY.THH.ProTP- aqueous ulpho-nylureas) |
Strengthening the sugar-lowering effect | |
|
Diuretics (except imvvyharf-tatoshnkh) |
Increased risk of g and gene shn |
It is advisable to cancel the drugs 2-3 days before na shacheshtya ish iontors LPF. If the effectiveness of LPF inhibitors is insufficient, diuretics are given additionally. but not less than 2 hours before prescribing LPF inhibitors, [if preliminary withdrawal of diuretics is impossible. then I prescribe LPF inhibitors! first in minimal jo-te |
|
Potassium-storing diuretics |
Increase rijeka rašngnya gnperka-lnemia. especially > patients with chronic renal disease |
Undesirable combination, requires repeated monitoring of potassium levels in the blood |
|
Potassium preparations |
Increased risk of rltnitka gshterka-shemin. especially in patients with chronic renal failure |
Undesirable combination |
|
Lithium preparations |
A decrease in renal tissue volume and, as a result, an increase in its capacity |
Undesirable combination |
|
|3 - L. tre nob.tokat o-ry |
Strengthening of the protective and hypotensive effect |
A useful combination in the treatment of chronic heart failure |
|
Locators SCH?ajpeiiepi11CH1CH1M1 renepures |
Strengthening the potential of action |
An appropriate antihypertensive combination; blood pressure control is required when selecting a dosage agent" |
|
Jurassic block of chalk-.tennych calcium channels |
Strengthening the spogenic effect |
An appropriate genetic combination; better tolerated. than each component separately |
|
Locators prescription ORT for angiotensin |
Increasing tittoten-zshshho. har.sho- and retshrotektivshch about tffektov |
A suitable combination for high RALS activity |
|
Peyrodeschics and grshshk.shskie actilsprsssants |
Strengthening ihjioich-tivet tffekg, the possibility of pos-gu-ratnoy typotension |
Undesirable combination. Copgrol blood pressure if it is possible to cancel LPF inhibitors |
216 -о* Clinical pharmacology And pharmacotherapy ♦ Chapter 16
Table 16.7. Ending
Characteristics of basic drugsCaptopril. Captopril weakly binds to ACE , which determines the prescription of large doses. The effect of captopril has the shortest duration in the group of ACE inhibitors (6-8 hours compared to 24 hours for other drugs), but the earliest onset of effect, which allows its use sublingually for emergency treatment of hypertensive conditions. When taking captopril sublingually, the antihypertensive effect develops within 5-15 minutes. What distinguishes captopril from other ACE inhibitors is SH-rpynna, which determines its main side effects - nephrotoxicity and associated proteinuria (at a dose of more than 150 mg per day), cholestasis, neutropenia (usually in patients with diffuse connective tissue diseases and impaired renal function with long-term use). At the same time, the SH group promotes the antioxidant effect of captopril, increases coronary blood flow and increases tissue sensitivity to insulin.
The use of captopril in patients with acute myocardial infarction leads to a significant reduction in mortality. Long-term use of the drug (more than 3 years) reduces the risk of recurrent myocardial infarction by 25%, and the risk of death from it by 32%.
The captopril test is used in radionuclide diagnosis of renovascular hypertension and biochemical diagnosis of primary hyperaldosteronism (Conn's disease).
Enalapril in the liver it is converted into enaprilat (40-60% of the dose taken orally), which binds well to ACE.
When prescribing enalapril for the treatment of hypertension, it is necessary to discontinue diuretics for 2-3 days; if this is not possible, reduce the initial dose by 2 times.
Arterial hypertension ♦ 217
dose of the drug (5 mi). The first doses of enalapril should be minimal in patients With initially high activity of the RAAS. The effectiveness of the prescribed dose is determined every 2 weeks. The drug is prescribed 1-2 times V day.
Lyunnoprnl is an active metabolite of eialapril. LD decreases 1 hour after taking the drug. When lisinopril is prescribed once a day, its stable concentration in the blood is achieved after 3 days. The drug is excreted unchanged by the kidneys; in case of point failure, it exhibits pronounced cumulation (the half-life increases to 50 hours). In elderly patients, its concentration in the blood is 2 times higher than in young patients. When administered intravenously, the antihypertensive effect of lisinopril begins within 15-30 minutes, which allows it to be used to relieve hypertensive crises,
Perindopril is a prodrug and is converted in the liver into the active metabolite perindoprilat (20% of the administered dose of perindoprid). which binds well to ACE. The drug weakens hypertrophy of the vascular wall and myocardium. When taken, the amount of subendocardial collagen in the heart decreases.
Rnmnnril in the liver it is converted to ramiprilat. which binds well to ACE. Two pharmacokinetic features of ramipril are of great clinical importance - slow elimination from the body and double elimination pathway (up to 40% of the drug is excreted in the bile). However, in case of severe renal failure (glomerular filtration rate 5-55 ml/min), it is recommended to reduce its dose by half.
The main indication for the use of ramipril is arterial hypertension.
Trandoloprnl its effect on tissue ACE is 6-10 times greater than that of ena-dapril. Although trandoloprnl is considered a prodrug, it has pharmacological activity in its own right, but trandodoprilat is 7 times more active than grandolopril. The hypotensive effect of the drug with a single use lasts up to 48 hours.
Moexipril becomes active after biotrapsformapia in the liver in mo-zheinridate. Unlike most ACE inhibitors, up to 50% of mozsipril is excreted in bile, which makes it safer in patients with renal failure.
Moexipril is used primarily for the treatment of arterial hypertension; its antihypertensive effect lasts up to 24 hours.
Phosniopride refers to prodrugs. turning into the active substance fosinoprilat in the liver. The drug has a dual route of elimination - equally through the kidneys and the liver. In case of renal failure, the excretion of fosinopride through the liver increases, and in case of hepatic failure, through the kidneys, which makes it possible not to adjust the dose of the drug for these diseases in patients.
The drug is prescribed 1 time per day.
Fosinopril rarely causes a dry cough; therefore, if such a complication occurs during therapy with any ACE inhibitors, it is recommended to switch to fosinopril.
218 -fr Clinical pharmacology and pharmacotherapy ♦ Chapter 16
| " |
The widespread prevalence of arterial hypertension (AH) among the population and its role in the development of cardiovascular complications determine the relevance of timely and adequate antihypertensive therapy. Numerous controlled studies have shown the high effectiveness of drug methods of secondary prevention of hypertension in reducing the incidence of strokes, heart and kidney failure, including in mild hypertension.
Angiotensin-converting enzyme inhibitors (ACEIs) have widely entered clinical practice for the treatment of hypertension since the 70s of the last century, becoming first-line antihypertensive drugs in the treatment of hypertension.
The originality of drugs of this class lies in the fact that for the first time they provided the doctor with the opportunity to actively intervene in the enzymatic processes occurring in the renin-angiotensin-aldosterone system (RAAS).
Acting through the blockade of angiotensin II (AII) formation, ACE inhibitors influence the blood pressure (BP) regulation system and ultimately lead to a decrease in the negative aspects associated with the activation of AII receptors of the 1st subtype: they eliminate pathological vasoconstriction, suppress cell growth and proliferation of the myocardium and vascular smooth muscle cells, weaken sympathetic activation, reduce sodium and water retention.
In addition to influencing the pressor systems of blood pressure regulation, ACE inhibitors also act on the depressor systems, increasing their activity by slowing down the degradation of vasodepressor peptides - bradykinin and prostaglandin E2, which cause relaxation of vascular smooth muscles and promote the production of vasodilating prostanoids and the release of endothelium-relaxing factor.
These pathophysiological mechanisms provide the main pharmacotherapeutic effects of ACE inhibitors: antihypertensive and organoprotective action, no significant effect on carbohydrate, lipid and purine metabolism, decreased production of aldosterone by the adrenal cortex, decreased production of adrenaline and norepinephrine, suppression of ACE activity, decreased AII content and increased content of bradykinin and prostaglandins. in blood plasma.
Currently, 3rd generation ACEIs have been introduced into clinical practice. Drugs from the ACE inhibitor group differ from each other:
- by chemical structure (presence or absence of a sulfhydryl group);
- pharmacokinetic properties (presence of active metabolite, elimination from the body, duration of action, tissue specificity).
Depending on the presence of a structure in the ACE inhibitor molecule that interacts with the active center of ACE, they are distinguished:
- containing a sulfhydryl group (captopril, pivalopril, zofenopril);
- containing a carboxyl group (enalapril, lisinopril, cilazapril, ramipril, perindopril, benazepril, moexipril);
- containing a phosphinyl/phosphoryl group (fosinopril).
The presence of a sulfhydryl group in the chemical formula of an ACE inhibitor can determine the degree of its binding to the active site of ACE. At the same time, the development of some undesirable side effects, such as taste disturbances and skin rashes, is associated with the sulfhydryl group. This same sulfhydryl group, due to easy oxidation, may be responsible for the shorter duration of action of the drug.
Depending on the characteristics of metabolism and elimination pathways, ACE inhibitors are divided into three classes (Opie L., 1992):
Class I- lipophilic drugs, the inactive metabolites of which are eliminated through the liver (captopril).
Class II— lipophilic prodrugs:
- Subclass IIA - drugs whose active metabolites are excreted primarily through the kidneys (quinapril, enalapril, perindopril, etc.).
- Subclass IIB - drugs whose active metabolites have hepatic and renal elimination pathways (fosinopril, moexipril, ramipril, trandolapril).
Class III- hydrophilic drugs that are not metabolized in the body and are excreted unchanged by the kidneys (lisinopril).
Most ACE inhibitors (with the exception of captopril and lisinopril) are prodrugs, the biotransformation of which into active metabolites occurs mainly in the liver, and to a lesser extent in the mucous membrane of the gastrointestinal tract and extravascular tissues. In this regard, in patients with liver failure, the formation of active forms of ACE inhibitors from prodrugs can be significantly reduced. ACE inhibitors in the form of prodrugs differ from non-esterified drugs by a slightly more delayed onset of action and an increase in the duration of the effect.
According to the duration of the clinical effect, ACE inhibitors are divided into drugs:
- short-acting, which must be prescribed 2-3 times a day (captopril);
- medium duration of action, which must be taken 2 times a day (enalapril, spirapril, benazepril);
- long-acting, which in most cases can be taken once a day (quinapril, lisinopril, perindopril, ramipril, trandolapril, fosinopril, etc.).
Hemodynamic effects of ACE inhibitors are associated with an effect on vascular tone and consist of peripheral vasodilation (reducing pre- and afterload on the myocardium), reducing total peripheral vascular resistance and systemic blood pressure, and improving regional blood flow. Short-term effects of ACE inhibitors are associated with a weakening of the effect of AII on systemic and intrarenal hemodynamics.
Long-term effects are due to a weakening of the stimulating effects of AII on growth, cell proliferation in blood vessels, glomeruli, tubules and interstitial tissue of the kidneys, while simultaneously enhancing antiproliferative effects.
An important property of ACE inhibitors is their ability to provide organoprotective effects , caused by the elimination of the trophic effect of AII and a decrease in the sympathetic influence on target organs, namely:
- cardioprotective effect: regression of the left ventricular myocardium, slowing down the processes of cardiac remodeling, anti-ischemic and antiarrhythmic effect;
- angioprotective effect: increased endothelium-dependent vasodilation, inhibition of arterial smooth muscle proliferation, cytoprotective effect, anti-platelet effect;
- nephroprotective effect: increased natriuresis and decreased kaliuresis, decreased intraglomerular pressure, inhibition of proliferation and hypertrophy of mesangial cells, renal tubular epithelial cells and fibroblasts. ACE inhibitors are superior to other antihypertensive agents in their nephroprotective activity, which is, at least in part, independent of their antihypertensive effect.
The advantage of ACEIs over some other classes of antihypertensive drugs is their metabolic effects, which include improving glucose metabolism, increasing the sensitivity of peripheral tissues to insulin, antiatherogenic and anti-inflammatory properties.
Currently, data have been accumulated on the results of numerous controlled studies confirming the effectiveness, safety and the possibility of beneficial protective effects of long-term therapy with ACE inhibitors in patients with cardiovascular diseases in relation to target organs.
ACE inhibitors are characterized by a good spectrum of tolerability. When taking them, specific (dry cough, “first dose hypotension”, impaired renal function, hyperkalemia and angioedema) and nonspecific (taste disturbance, leukopenia, skin rash and dyspepsia) side effects may occur.
At the Department of Clinical Pharmacology and Pharmacotherapy of the Faculty of Postgraduate Professional Education of Doctors of the MMA named after. I.M. Sechenov has accumulated extensive experience in studying various ACE inhibitors in patients with hypertension, including when it is combined with other diseases of internal organs.
Long-acting ACE inhibitors lisinopril and fosinopril deserve special attention. The first of them is an active drug that does not undergo biotransformation and is excreted unchanged by the kidneys, which is important in patients with diseases of the gastrointestinal tract and liver. The second drug (fosinopril) has active lipophilic metabolites, allowing it to penetrate well into tissues, ensuring maximum organoprotective activity of the drug. The dual pathway (hepatic and renal) elimination of fosinopril metabolites is important in patients with renal and hepatic insufficiency. The results of numerous clinical studies have been accumulated, demonstrating effectiveness, good tolerability, safety and the possibility of improving the prognosis of the disease in patients with hypertension ( ).
Efficacy and tolerability of lisinopril in patients with hypertension
Lisinopril preparations available in the pharmacy network of the Russian Federation are presented in .
The antihypertensive efficacy and tolerability of the ACE inhibitor lisinopril at a daily dose of 10-20 mg was studied in 81 patients with stage I-II hypertension, including those in combination with chronic obstructive pulmonary diseases (COPD). Lisinopril was used in tablets of 10 and 20 mg. The initial dose was 10 mg once daily. If antihypertensive effectiveness was insufficient according to ambulatory blood pressure measurements, the dose of lisinopril was increased to 20 mg once a day; subsequently, if necessary, hydrochlorothiazide was additionally prescribed at 25 mg/day (once in the morning). Duration of treatment is up to 12 weeks.
All patients underwent 24-hour blood pressure monitoring (ABPM) using Schiller BR 102 oscillometric recorders according to the generally accepted method. Based on ABPM data, the averaged values of systolic blood pressure (SBP) and diastolic blood pressure (DBP) during the day and night hours, and heart rate (HR) were calculated. Blood pressure variability was assessed by the standard deviation of the varying value. To assess daily changes in blood pressure, the degree of night-time blood pressure reduction was calculated, equal to the percentage ratio of the difference between the average daily and average night blood pressure levels to the daily average. As indicators of pressure load, the percentage of hypertensive blood pressure values was assessed at different periods of the day (during wakefulness - more than 140/90 mm Hg, during sleep - more than 125/75 mm Hg).
The criteria for good antihypertensive effectiveness of lisinopril were: reduction in DBP to 89 mmHg. Art. or less and normalization of average daily DBP based on ABPM results; satisfactory - decrease in DBP by 10 mm Hg. Art. and more, but not up to 89 mm Hg. Art.; unsatisfactory - when DBP decreases by less than 10 mm Hg. Art.
According to the survey, examination, laboratory and instrumental (ECG, pulmonary function test - FVD) research methods, the individual tolerability and safety of lisinopril was assessed in all patients, the frequency of development and nature of adverse reactions, the time of their occurrence during long-term therapy were analyzed.
Tolerability of the drugs was assessed as good with no side effects; satisfactory - in the presence of side effects that do not require discontinuation of the drug; unsatisfactory - in the presence of side effects that required discontinuation of the drug.
Statistical processing of the results was carried out using the Excel program. The reliability of measurements was assessed using paired Student's t-test at p< 0,05.
During monotherapy with lisinopril at a daily dose of 10 mg, an antihypertensive effect was noted in 59.3% of patients. When the dose of lisinopril was increased to 20 mg/day, the effectiveness was 65.4%.
According to ABPM data, with long-term continuous therapy, a significant decrease in average daily blood pressure and hypertensive load indicators was observed. Reducing hypertensive load indicators is important, given the proven prognostic significance of these indicators in relation to target organ damage, including left ventricular myocardial hypertrophy. A comparison of the results obtained from ABPM after 4 and 12 weeks of therapy allows us to conclude that with long-term therapy with lisinopril there is no development of tolerance to the drug and a decrease in its antihypertensive effectiveness.
It is important that during therapy with lisinopril, the number of people with a normal daily blood pressure profile increased, and the number of patients with a non-dipper blood pressure profile significantly decreased. None of the patients had an excessive decrease in SBP or DBP at night.
Lisinopril therapy was generally well tolerated. The majority of patients felt better during treatment: headaches decreased, tolerance to physical activity increased, and mood improved, which indicates an increase in the quality of life of patients. Dry cough was noted in 11.1% of cases, dyspepsia - in 1.2%, transient moderate headaches - in 4.9%. Discontinuation of the drug due to poor tolerability was required in 2.4% of cases.
There were no clinically significant changes according to laboratory tests during therapy with lisinopril.
For patients with hypertension in combination with COPD, it is important that there is no negative effect of antihypertensive drugs on respiratory function indicators. No deterioration in respiratory function was observed, which indicates the absence of a negative effect of the drug on bronchial tone.
So, lisinopril in a daily dose of 10-20 mg is characterized by good tolerability, a low frequency of side effects, no effect on metabolic processes, and a beneficial effect on the daily blood pressure profile. The possibility of using lisinopril once a day increases patient adherence to therapy and reduces the cost of treatment.
Efficacy and tolerability of fosinopril in patients with hypertension
Trade names of fosinopril drugs available in the pharmacy chain of the Russian Federation are presented in .
The antihypertensive efficacy and tolerability of the ACE inhibitor fosinopril at a daily dose of 10-20 mg was studied in 26 patients with stage I-II hypertension. Fosinopril was used in tablets of 10 and 20 mg. The initial dose was 10 mg once a day, followed by an increase to 20 mg/day if antihypertensive effectiveness was insufficient according to ambulatory blood pressure measurements. Subsequently, if necessary, hydrochlorothiazide was additionally prescribed at a dose of 25 mg/day (once in the morning). The duration of treatment was 8 weeks.
Methods for assessing the effectiveness and tolerability of long-term treatment of patients with mild to moderate hypertension with fosinopril were comparable to the methods listed above in the lisinopril study.
ABPM was performed on patients using portable TONOPORT IV recorders that record blood pressure, either by auscultation or by oscillometric method before the start of treatment and after 8 weeks of fosinopril therapy according to the generally accepted method and with subsequent analysis of the results obtained.
During therapy with fosinopril after 2 weeks, an antihypertensive effect was noted in 15 (57.7%) patients: in 5 (19.2%) blood pressure normalized, in 10 (38.5%) DBP decreased by more than 10% from initial level. Insufficient effectiveness of antihypertensive therapy was observed in 11 patients (42.3%), which was the reason for increasing the initial dose of fosinopril. After 8 weeks of monotherapy with fosinopril, normalization of DBP was noted in 15 (57.7%) patients. Combination therapy with fosinopril and hydrochlorothiazide allowed sufficient control of blood pressure in another 8 (30.8%) patients. An unsatisfactory effect was noted in 3 (11.6%) patients. According to our data, the effectiveness of fosinopril monotherapy depended on the duration and degree of hypertension. Thus, in the group with low effectiveness of monotherapy, patients with a longer history of hypertension predominated.
According to ABPM data, therapy with fosinopril in patients with hypertension for 2 months led to a significant decrease in average daily SBP and DBP without changing heart rate. The pattern of 24-hour blood pressure curves did not change after treatment with fosinopril. Load indicators with “hypertensive” values during wakefulness decreased significantly: for SBP - by 39%, for DBP - by 25% (p< 0,01). В период сна данные показатели уменьшились на 27,24 и 23,13% соответственно (p < 0,01).
During treatment with fosinopril, the following side effects were registered in patients: heartburn when taking fosinopril at a dose of 10 mg on the 7th day of treatment - in one patient (3.9%); dizziness and weakness 1-2 hours after the first dose of 10 mg fosinopril - in one patient (3.9%); headache, weakness after increasing the dose of fosinopril to 20 mg - in one patient (3.9%); urticaria, itching of the skin, which developed on the 11th day of treatment with fosinopril at a dose of 10 mg - in one patient (3.9%). These side effects, with the exception of the last case, did not require discontinuation of fosinopril. Complaints of heartburn were noted in one patient who took 10 mg of fosinopril in the morning on an empty stomach. After changing the time of taking the drug (after breakfast), the patient did not suffer from heartburn.
Analysis of the safety of fosinopril therapy indicates the absence of clinically significant changes in renal and liver function during fosinopril therapy.
The results of our study are consistent with the data of numerous controlled studies of the effectiveness and tolerability of fosinopril therapy at a daily dose of 10-20 mg and in combination with hydrochlorothiazide in patients with hypertension.
The search for an individual approach to the treatment of hypertension remains a pressing problem in cardiology.
It is important for a practicing physician to be able to correctly use a particular drug in a given clinical situation. Long-acting ACE inhibitors are convenient for long-term treatment of patients with hypertension, since the possibility of taking the drug once a day significantly increases the patient’s adherence to the doctor’s prescriptions.
The results of numerous studies have shown that the combination of an ACE inhibitor with a diuretic (either hypothiazide or indapamide) can increase the effectiveness of antihypertensive therapy, especially in patients with moderate and severe hypertension, without compromising its tolerability, while it is possible to reduce the daily doses of both drugs.
The advantages of ACEIs are a gentle, gradual decrease in blood pressure without sharp fluctuations in the antihypertensive effect, combined with a wide range of organoprotective effects and a positive effect on the degree of cardiovascular risk.
For questions regarding literature, please contact the editor.
Zh. M. Sizova,
T. E. Morozova, Doctor of Medical Sciences, Professor
T. B. Andrushchishina
MMA im. I. M. Sechenova, Moscow
The main advantage of ACE inhibitors is that they do not cause changes in cholesterol, insulin and blood sugar levels, do not lead to a decrease in potassium levels and an increase in uric acid levels. Another advantage of these drugs is that they have few side effects.
Here are some of the possible side effects:
- The likelihood of a significant decrease in blood pressure if the patient has a reduced blood volume in the body (as, for example, after treatment with diuretics).
- In less than 20% of cases, patients taking these drugs have a dry cough, which causes significant discomfort.
- Skin rashes, loss of taste, and a decrease in the number of white blood cells are possible, but quite rare.
Such a deadly complication as angioedema (Quincke's edema) is extremely rare. The condition is characterized by severe swelling of the larynx and difficulty breathing. If symptoms of this complication appear, you should immediately stop taking the drug and consult a doctor immediately.
Among the adverse reactions, vascular edema of the face, lips, mucous membranes, tongue, pharynx, larynx, and extremities is often mentioned. The patient may develop not only a dry cough, but also a sore throat, and a decrease in appetite. These complications are associated with the accumulation of bradykinin and “substance P” (proinflammatory mediators) caused by ACE inhibitors. If cough occurs in mild cases, you can limit yourself to reducing the dose of the drug. If there is a threat of development of obstruction of the upper respiratory tract, a solution of adrenaline (1: 1000) is immediately injected subcutaneously, and the ACE inhibitor is stopped.
In patients with impaired renal function, neutropenia (a decrease in the number of neutrophils in the blood) was sometimes observed<1000/мм3). Такое случается в 3,7% случаев, обычно через 3 мес от начала лечения. Нейтропения исчезает через 2 недели после отмены каптоприла или его аналогов.
Excessive decrease in blood pressure due to ACE inhibitors
Nevertheless, among the adverse reactions caused by ACE inhibitors, the already mentioned arterial hypotension (excessive decrease in blood pressure), renal dysfunction and hyperkalemia are of leading importance. As for arterial hypotension, first of all it is necessary to mention the effect of the first dose, which is observed mainly in patients with heart failure. True, it is not expressed in all ACE inhibitors, especially weakly in. The risk of hypotension is minimal (<3%). С такой частотой она развивается преимущественно у больных с начинающейся застойной недостаточностью кровообращения, принимающих дополнительно диуретик.
In patients with hypertension with a more developed picture of congestive heart failure, with such combination therapy, a decrease in average hemodynamic pressure by more than 20% is already observed in half of the cases. In almost all of these patients, dangerous hypotension is preceded by diuretic-induced hyponatremia. A number of patients with hyponatremia and high plasma renin response activity react to the first dose of an ACE inhibitor with a sharp decrease in blood pressure.
More often, transient hypotension (hypotension) develops after several doses of captopril or related compounds. The maximum decrease in blood pressure occurs in the period from half an hour to 4 hours after the last dose of the drug. Approximately 30% of patients during a period of sharp decrease in pressure experience: dizziness, weakness, blurred vision (“everything blurs”). More persistent arterial hypotension (hypotension) can lead to renal failure or to the retention of sodium and water ions, i.e., a paradoxical effect, since ACE inhibitors usually increase the excretion (removal from the body) of sodium and water. Particularly dangerous hypotension develops in patients who have unilateral or, more often, bilateral narrowing of the renal arteries, i.e., with renovascular hypertension or with hypertension in combination with renovascular “supplement.”
Patients with a high risk of arterial hypotension should first of all reduce the dose of the diuretic, remove the ACE inhibitor from the diuretic for 24-72 hours, and also reduce the dose of the ACE inhibitor. In all of these cases, enalapril and lisinopril caused a more severe deterioration in renal function than short-acting captropril.
Renal failure during treatment with ACE inhibitors
The development of renal failure under the influence of ACE inhibitors depends mainly on the decrease in blood pressure and renal perfusion pressure (blood supply to the renal vessels).
If there is a risk of developing renal failure during treatment of hypertension with ACE inhibitors, three rules should be followed:
- Start treatment with small doses of drugs (2.5-5 mg enalapril or lisinopril), titrating the dose. Plasma creatinine levels may increase at the start of treatment. If the increase in creatinine concentration is no more than 30% of its initial level and it is combined with general clinical improvement, then this is considered a favorable fact.
- Reduce the dose of the diuretic and lengthen the intervals between its doses (we are, of course, talking about the treatment of patients with severe hypertension and (or) with weakened heart function, the development of congestion).
- Do not prescribe simultaneously with an ACE inhibitor or discontinue previously prescribed drugs that inhibit the synthesis of prostaglandins, for example: acetylsalicylic acid and other non-steroidal anti-inflammatory drugs, which may, for various reasons, be needed by a patient with hypertension. These drugs themselves cause a clear decrease in glomerular filtration rate. They also counteract the increase in renal plasma flow caused by ACE inhibitors. The activity of captopril can also be reduced by oral antidiabetic agents.
So, according to modern views, not only the blockade of angiotensin-2 synthesis itself, but to a greater extent the duration of such blockade during the day threatens renal dysfunction.
Side effect of ACE inhibitors is hyperkalemia
Another undesirable effect of ACE inhibitors is the occurrence of hyperkalemia (excessive increase in potassium concentration in the blood), mild hypoaldosteronism. These drugs not only increase the concentration of potassium ions in the plasma, but also counteract its excretion stimulated by diuretics. Excretion of magnesium ions in urine is also inhibited. ACE inhibitors do not have such a clear effect on the content of potassium ions in cells, although they can cause some degree of hypocaligistia. Substances of this class are not always compatible with veroshpiron (aldactone). They are contraindicated in hyperkalemia and acute renal failure.
If the doctor is able to systematically monitor the level of potassium and creatinine in plasma, then ACE inhibitors can be used in cases of severe hypokalemia temporarily along with potassium supplements (in moderate doses). In recent years, for the treatment of congestive heart failure, they have resorted to the combined administration of an ACE inhibitor and veroshpiron to the patient (in small doses - 25 mg/day).
An elderly body responds to treatment for hypertension with ACE inhibitors in the same way as a young one.
Compared to, and they do not lower blood pressure as much. If we compare these drugs with others in terms of negative consequences and deaths, ACE inhibitors are less harmless to the body compared to diuretics or beta-blockers, but more gentle than calcium antagonists.
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 ACE drugs from the latest generation (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 is rarely capable of causing 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.
