This is antihypertensive therapy. Treatment of hypertension. antihypertensive therapy

Permanent drug therapy is not required. It should be noted right away that in this article only drugs that have an antihypertensive effect are considered.

Indications for the appointment of drug antihypertensive therapy are the following clinical situations:

Labile or stable increase in SBP by 10-15 mm Hg. Art., and DBP - by 5-10 mmHg. Art. higher age norm or crisis course of the disease. A more objective picture is given by ABPM indicators;

Inadequate responses of blood pressure (especially DBP) and heart rate to a functional test with dosed physical activity;

Lack of effect from non-drug therapy for 6-12 months;

Presence of more than two risk factors for EAH
1) burdened heredity for hypertension;
2) obesity;
3) increased consumption of table salt and "salt sensitivity";
4) hypodynamia;
5) smoking or drinking alcohol;
6) traumatic brain injury in history;
7) prolonged psycho-emotional stress.

Drug therapy should be carried out against the background of non-drug treatment and measures to normalize lifestyle.

The goal of therapy in children and adolescents is to reduce blood pressure to less than the 95th percentile for the appropriate sex, age and height.

Drug treatment of AGP should be prescribed and supervised by the local pediatrician or the pediatrician of the residential institution. With insufficient clinical training in this matter, it is advisable to consult a specialist in a diagnostic center or a children's clinical hospital.

Of the drugs, first of all, drugs should be prescribed, the action of which is aimed at normalizing the activity of the central and autonomic nervous systems. In the absence of the effect of this therapy for 3 months and the preservation of the hyperkinetic type of blood circulation with a predominant increase in SBP in patients with both NCD and AH, beta-blockers are the drugs of choice.

Beta blockers. When prescribing, it must be borne in mind that 10% of patients with elevated blood pressure are resistant to drugs of this class, and 26% of patients have hypersensitivity to them. In this regard, before using beta-blockers, it is desirable to test for individual sensitivity to the drug. To do this, on an empty stomach, after a 10-minute state of rest and measuring blood pressure and heart rate in a sitting position, the patient is given 10-20 mg of anaprilin (obzidan) and after 30-45 minutes, blood pressure and heart rate are re-controlled. The test is considered positive if the heart rate decreases by 10-15, and blood pressure decreases by 20 mm Hg. Art.

Under the influence of beta-blockers, the tone of the sympathetic nervous system is normalized. In this regard, the use of these drugs is a pathogenetic method for the treatment of hyperkinetic NCD and essential hypertension with a hyperkinetic type of blood circulation. As a result of the blockade of R-adrenergic receptors of the heart, heart rate and stroke output decrease.

Until now, in the treatment of children and adolescents, beta-blockers of the 1st generation, propranolol (obzidan, anaprilin), have been widely used. This drug belongs to non-selective beta-blockers with a short duration of action. Treatment in children begins with a small dose of 0.5-1 mg / kg per day, divided into 3-4 doses. Upon reaching the effect, the dose can be reduced by 2-3 times, the drug is gradually canceled due to the danger sharp increase HELL. The course of treatment takes from 2 weeks to several months (on average 1-2 months), but sometimes propranolol is used for years.

With a more pronounced and stable increase in blood pressure, drugs with a longer duration of action are used. In pediatric practice, the most widely used selective beta-blocker atenolol. When taken orally, the duration of its action is 12-24 hours, so the drug is prescribed 1-2 times a day. The initial dose in children is 1 mg / kg per day and, if necessary, can be increased to 100 mg / kg per day. With insufficient effectiveness of beta-blockers in monotherapy, combined antihypertensive therapy is prescribed.

A stable antihypertensive effect is achieved only after 2-3 weeks of taking beta-blockers. An important property of drugs is the constancy of the effect, which does not depend on physical activity, body position, body temperature. It should be borne in mind that the magnitude of the antihypertensive effect does not depend on the dose of the drug and, as a consequence, on the concentration of the drug in the blood. The selection of the optimal dose of beta-blocker is carried out individually, guided by the clinical effect and hemodynamic parameters (heart rate and blood pressure).

Other long-acting beta-blockers are currently not widely used in the treatment of children in Russia.

In adolescents with persistently high blood pressure, metoprolol (Betaloc, Egiloc), which is a cardioselective lipophilic beta-blocker, can be used. The drug is prescribed in a daily dose of 50 mg in 1-2 doses. In case of impaired renal function, a change in the dose of the drug is not required.

The most common side effects that occur during treatment with beta-blockers are bradycardia, hypertension, increased left ventricular failure, exacerbation of broncho-obstructive syndrome, increased manifestations of Raynaud's syndrome and the appearance of intermittent claudication: when using high doses, impaired glucose tolerance and hyperlipidemia are possible. Due to the penetration of beta-blockers through the blood-brain barrier, drowsiness, dizziness, decreased reaction time, and weakness are sometimes observed. In children and adolescents, such phenomena are extremely important to recognize in a timely manner.

Diuretics are the second group of drugs with antihypertensive effect. The most widely used in the treatment of hypertension are thiazide and thiazide-like diuretics, the action of which is based on the blockade of the countertransport of sodium and chloride ions through the membrane of the initial segment of the distal tubules. As a result, the volume of blood plasma and extracellular fluid decreases, which leads to a decrease in cardiac output and mainly SBP. With long-term therapy, cardiac output returns to baseline with a parallel decrease in peripheral vascular resistance, which leads to a decrease in DBP. In Russia, the thiazide diuretic hydrochlorothiazide (hypothiazide) is more often used - a drug with moderate strength and duration of action. The diuretic effect occurs 1-2 hours after administration and lasts 6-12 hours. In children and adolescents, an intermittent regimen of taking the drug is more often used when it is prescribed in small doses (12.5-25 mg / day) 3-5 times a day. week. With more severe course hypothiazide is used daily at a dose of 12.5 mg or as part of combined preparations. At the same time, a diet rich in potassium and poor in sodium is indicated.

In recent years, the thiazide-like diuretic indapamide (arifon or arifon retard) has become widespread. The drug has not only natriuretic, but also vasodilating action. Apply at a dose of 1.25-2.5 mg 1 time per day. The persistent effect of diuretics in small doses develops after 4 weeks. Diuretics are advisable to use with a stable increase in blood pressure continuously, for many months. Side effects during treatment in small doses develop infrequently. Hypokalemia, impaired carbohydrate tolerance, weakness, dizziness, nausea are mainly noted. With the rational use of indapamide, side effects occur in exceptional cases.

Potassium-sparing diuretics are now rarely used - mainly to prevent hypokalemia during treatment with other diuretics and to enhance their effect. Amiloride is prescribed 2.5-5 mg per day 1 time, there are its combinations with hydrochlorothiazide. Spironolactone (veroshpiron) is not currently used in the treatment of essential hypertension, but is used only in the treatment of primary aldosteronism (Conn's disease). The most popular drug from this group in Russia is triamterene, which is more often used as part of the combination drug triampur (triamterene + hydrochlorothiazide). Treatment begins with 2 mg/kg, onset of action after 1-3 hours, duration 7-9 hours.

The loop diuretic furosemide is not used as a basic drug, but is prescribed only in urgent situations and with severe renal failure.

A test for predicting the effectiveness of diuretics is a test with furosemide. The test is considered positive if, after taking the drug at a daily dose of 1-2 mg / kg for 3 days, diuresis exceeds the amount of fluid drunk by 1.5-2 times and there is a decrease in SBP and DBP without a significant increase in heart rate (i.e., there is no reflex activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system).

Angiotensin-converting enzyme inhibitors (ACE inhibitors) are a class of drugs that have revolutionized modern cardiology. This group includes drugs that block the transition of the inactive angiotensin I peptide into a powerful hypertensive substance called angiotensin II. ACE inhibitors have little effect on cardiac output, heart rate, and glomerular filtration rate. They combine high efficiency and low frequency of side effects. These drugs inhibit the degradation of bradykinin, which is a powerful vasodilator. In addition, through their action, nitric oxide and prostaglandins, which are also strong vasodilators, are released from the endothelial cell. In addition, ACE inhibitors reduce the activity of the sympathetic nervous system.

In pediatrics with arterial hypertension, only two ACE inhibitors are actively used - captopril and enalapril. Captopril after oral administration begins to act after 15-60 minutes, the maximum effect develops after 60-90 minutes, the duration of action is 6-12 hours. To achieve the full clinical effect, several weeks of continuous administration are required. The recommended starting dose is 0.7 mc/kg divided into 2-3 doses. The maximum dose that can be used in children and adolescents is 6 mg/kg per day. Captopril can be used as a basic drug, as well as to quickly reduce blood pressure in crises. Enalapril is a drug with a longer period of action, so the duration of its action is 12-24 hours, it is prescribed 1-2 times a day at an initial dose of 0.15 mg / kg. It takes several weeks to develop a full therapeutic effect.

The most common complication encountered during treatment with ACE inhibitors is dry cough. Often, patients experience the effect of the "first dose", which is manifested by a sharp decrease in blood pressure at the beginning of treatment. Other complications are rare and the most dangerous of them is angioedema (Quincke's edema). ACE inhibitors are used to treat sick children and adolescents with stable arterial hypertension, when the increase in TPVR is the main reason for the increase in blood pressure.

Calcium antagonists - 4th class of AGP. This class combines various chemical compounds, the common property of which is their ability to block the entry of calcium ions into the cell and thereby reduce the ability of myocardial and vascular cells to contract. In the treatment of patients with calcium antagonists, pronounced vasodilation is noted, leading to a decrease in peripheral vascular resistance and, as a result, a decrease in SBP and DBP.

The entire class of calcium antagonists is divided into derivatives of dihydropyridine, papaverine and benzothiazepam. In Russia, drugs of the first two groups are mainly used.

Of the group of dihydropyridines in pediatric practice, nifedipine (corinfar, cordafen) is most often used. The drug acts mainly on the vessels, which leads to their dilatation and a decrease in blood pressure. At the same time, the heart rate slightly increases reflexively. The effect of the drug is dose-dependent, i.e., with an increase in the dose of nifedipine, its antihypertensive effect increases. The initial dose for children is 0.25 mg/kg divided into 3 doses. When administered orally, the clinical effect is observed after 30-60 minutes, the duration of action is 4-6 hours. In the case of taking the drug sublingually, the effect develops after 5-10 minutes. This allows the use of this drug for the relief of hypertensive crises. In children and adolescents with stage I hypertension, the use of nifedipine gives almost 100% effect. However, it is better to use a long-acting calcium antagonist - nifedipine retard (nifedipine SR, nifedipine SL). The drugs have the property of a two-phase or continuous release of the active substance from the dosage form, which allows you to maintain a uniform concentration of nifedipine in the blood and prevents significant fluctuations in blood pressure during the day. Assign prolonged forms of nifedipine 1-2 times a day.

Amlodipine is a 3rd generation dihydropyridine calcium antagonist. Assign 1 time per day, the peak concentration in the blood is reached within 6-12 hours, the heart rate increases slightly. Side effects are rare and mild.

Side effects of calcium antagonists of the dihydropyridine series are mainly associated with peripheral vasodilation: flushing of the skin, excessive decrease in blood pressure, headache. Often there are tachycardia and swelling of the legs, not associated with heart failure. Such side effects are much more common when using a simple form of nifedipine.

Verapamil is the main representative of non-dihydropyridine calcium antagonists. To a greater extent, its action is directed to the heart, and not to the vessels. In this regard, when using it, a decrease is noted not only in blood pressure, but also in heart rate. With poor tolerance to beta-blockers or contraindications to their use (especially in broncho-obstructive syndrome), verapamil may be an alternative drug in the treatment of patients with NCD according to hypertonic type or arterial hypertension with a hyperkinetic type of circulation. Usually the drug is prescribed at a dose of 120-160 mg per day, divided into 3-4 doses for a period of several weeks to several months, depending on the clinical situation. The most significant side effect of verapamil is considered to be conduction disturbance, therefore, before prescribing the drug, it is imperative to conduct an ECG analysis (special attention to the WPW phenomenon).

Unlike adults, in the treatment of children and adolescents, central adrenergic receptor agonists are still widely used today, which activate noradrenergic neurons of the nuclei of the hypothalamus and a,2-adrenergic receptors of the medulla oblongata, which limits sympathetic activation of peripheral resistive vessels, heart and kidneys. Clonidine (clofelge, hemiton) is effective in the treatment of grade I-II hypertension at very low doses. In children and adolescents, the initial dose is 0.0375 mg 2 times a day. With insufficient effectiveness, the dose of the drug is increased after 3-7 days to 0.075 mg 2 times a day or 0.15 mg 1 time in 2 days. Cancel the drug gradually. The most significant side effects include dry mouth, drowsiness, constipation, moderate sodium and water retention. For long-term treatment as a basic drug, it is better to refrain from using clonidine. It is most indicated when used for several days or for the relief of hypertensive crises. At present, a centrally acting drug that affects the imidozoline receptors of the central nervous system, moxonidine (physiotens, cint), has been successfully used. It is almost devoid of side effects characteristic of centrally acting drugs, it is prescribed in the usual doses for adult patients - 0.2 mg 1-2 times a day.

Rauwolfia preparations are used much less frequently in pediatric practice, due to a wide range of side effects when they are used (weakness, drowsiness, depression, bradycardia, nasal congestion, eye hyperemia, bronchospasm).
Alpha-blockers and angiotensin II receptor antagonists are not widely used in pediatric practice.

With stable high blood pressure, an almost continuous intake of antihistamines in a minimum effective doses against the background of non-drug methods of treatment and other rehabilitation measures. However, in most cases, with monotherapy, after a few months, counterregulatory mechanisms for maintaining elevated blood pressure are activated, leveling the antihypertensive effect of the drug used. In this regard, in most cases, it is necessary to add a second or third AGP to the treatment tactics. In recent years, with severe arterial hypertension, it is recommended to immediately use the regimen of combined antihypertensive therapy.

The most rational and effective combinations of AGP are currently recognized:

Thiazide (thiazide-like) diuretic + beta-blocker;

Thiazide (thiazide-like) diuretic + ACE inhibitor;

Beta-blocker + dihydropyridine calcium antagonist;

ACE inhibitor + calcium antagonist.

Different doctors may have their own treatment regimen. However, there are general concepts based on statistics and research.

At the initial stage

In uncomplicated cases, drug antihypertensive therapy is often started with the use of proven "conventional" drugs: beta-blockers and diuretics. In large-scale studies involving patients, it has been shown that the use of diuretics, beta-blockers reduces the risks of cerebral circulation, sudden death, myocardial infarction.

An alternative option is the use of captopril. According to new data, the incidence of heart attacks, strokes, deaths with conventional treatment or with captopril is almost the same. Moreover, in a special group of patients who have not previously been treated with antihypertensive drugs, captopril shows a clear advantage over conventional therapy, significantly reducing the relative risk of cardiovascular events by 46%.

Long-term use of fosinopril in patients with diabetes, as well as arterial hypertension, is also associated with a significant reduction in the risk of death, myocardial infarction, stroke, exacerbation of angina pectoris.

Therapy for left ventricular hypertrophy

As antihypertensive therapy many doctors practice the use of angiotensin-converting enzyme (ACE) inhibitors. These drugs have cardioprotective properties and lead to a decrease in the mass of the LV myocardium (left ventricle). When examining the degree of impact of various medicines on the LV myocardium, it was revealed that the reverse degree of development of its hypertrophy is most pronounced in ACE inhibitors, since antiotensin-2 controls the growth, hypertrophy of cardiomyocytes and their division. In addition to cardioprotective effects, ACE inhibitors have a nephroprotective effect. This is important, because despite all the successes of antihypertensive therapy, the number of patients who develop terminal renal failure is growing (4 times compared to the "eighties").

Therapy with calcium antagonists

Increasingly, calcium antagonists are being used as first-line drugs. For example, in isolated systemic arterial hypertension (AH), long-acting dihydropyridine blockers are effective. calcium channels. A four-year study of 5000 patients showed a significant effect of nitrendipine on the frequency cerebral stroke. In another study, the base drug was a long-acting calcium antagonist, felodipine. Patients were followed up for four years. As blood pressure (blood pressure) decreased, beneficial effects increased, there was a significant decrease in the risk of developing cardiovascular complications, and the frequency of sudden death did not increase. The SystEur study, which included 10 Russian centers, also showed a 42% reduction in the incidence of stroke with nisoldipine.

Calcium antagonists are also effective in pulmonary arterial hypertension (this is systemic hypertension that occurs in patients with obstructive pulmonary disease). Pulmonogenic hypertension develops several years after onset lung disease, and there is a clear connection between the exacerbation of the pulmonary process and pressure rises. An advantage of calcium antagonists in pulmonary hypertension is that they reduce calcium-mediated hypoxic vasoconstriction. The delivery of oxygen to tissues increases, hypoxia of the kidneys and vasomotor center decreases, blood pressure decreases, as well as afterload and myocardial oxygen demand. In addition, calcium antagonists reduce the synthesis of histamine, kinin, serotonin in tissues, swelling of the bronchial mucosa and bronchial obstruction. An additional advantage of calcium antagonists (in particular, isradipine) is their ability to change metabolic processes in patients with hypertension. By normalizing or lowering blood pressure, these drugs can prevent the development of dyslipidemia, glucose and insulin tolerance.

Calcium antagonists showed a clear relationship between dose, plasma concentration and pharmacological hypotensive effect. By increasing the dose of the drug, it is possible, as it were, to control the hypotensive effect, increasing or decreasing it. For long-term treatment of hypertension, long-acting drugs with a low absorption rate (amlodipine, a long-acting gastrointestinal form of nifedipine, or osmoadolat, a long-acting form of felodipine) are preferred. When using these drugs, smooth vasodilation occurs without reflex activation of the sympathetic-adrenal system, release of catecholamines, reflex tachycardia and increased myocardial oxygen demand.

Myotropic vasodilators, central alpha-2-adrenergic agonists, and peripheral adrenergic agonists are not recommended as first-choice drugs, taking into account tolerability.

Antihypertensive drugs: principles of therapy, groups, list of representatives

Antihypertensive drugs (antihypertensives) include wide range drugs designed to lower blood pressure. Since about the middle of the last century, they began to be produced in large volumes and massively used in patients with hypertension. Until that time, doctors had only recommended diet, lifestyle changes, and sedatives.

Arterial hypertension (AH) is the most frequently diagnosed disease of the cardiovascular system. According to statistics, approximately every second inhabitant of the planet of advanced age has signs of high blood pressure, which requires its timely and correct correction.

To prescribe drugs that reduce blood pressure (BP), you need to establish the very fact of the presence of hypertension, assess possible risks for the patient, contraindications to specific drugs and the appropriateness of treatment in principle. The priority of antihypertensive therapy is effective pressure reduction and prevention possible complications a dangerous disease such as stroke, myocardial infarction, kidney failure.

The use of antihypertensive drugs has reduced mortality from severe forms of hypertension over the past 20 years by almost half. Optimum level the pressure to be achieved with the treatment is considered to be a figure not exceeding 140/90 mm Hg. Art. Of course, in each case, the question of the need for therapy is decided individually, but with prolonged high blood pressure, the presence of damage to the heart, kidneys, retina, it should be started immediately.

According to the recommendation of the World Health Organization, an absolute indication for antihypertensive therapy is a diastolic pressure of 90 mm Hg or more. Art., especially if such a figure holds for several months or six months. Usually, drugs are prescribed for an indefinite period, for most patients - for life. This is due to the fact that when therapy is discontinued, three-quarters of patients again experience manifestations of hypertension.

Many patients are afraid of long-term or even lifelong medication, and often the latter are prescribed in combinations that include several items. Of course, the fears are understandable, because any medicine has side effects. Numerous studies have shown that there are no health risks with long-term use of antihypertensive drugs, side effects are minimal if the dose and regimen are correctly selected. In each case, the doctor individually determines the features of treatment, taking into account the form and course of hypertension, contraindications, comorbidities in the patient, however, possible consequences still need to be warned.

Principles of prescribing antihypertensive therapy

Thanks to many years of clinical studies involving thousands of patients, the main principles of drug treatment of arterial hypertension were formulated:

• Treatment begins with the smallest doses of the drug, using a drug with a minimum of side effects, that is, choosing the safest remedy.
• If the minimum dose is well tolerated, but the pressure level is still high, then the amount of the drug is gradually increased to the amount necessary to maintain normal blood pressure.
• To achieve the best effect, it is recommended to use combinations of drugs, prescribing each of them in the lowest possible dosages. Currently developed standard schemes combined treatment of hypertension.
• If the second prescribed drug does not give the desired result, or its administration is accompanied by side effects, then it is worth trying a remedy from another group without changing the dosage and regimen of the first drug.
• Long-acting drugs are preferred, which allow maintaining normal blood pressure throughout the day, without allowing fluctuations in which the risk of complications increases.

Antihypertensive drugs: groups, properties, features

Many drugs have antihypertensive properties, but not all of them can be used to treat patients with hypertension due to the need for long-term use and the possibility of side effects. Today, five main groups of antihypertensive drugs are used:

1. Angiotensin-converting enzyme inhibitors (ACE inhibitors).
2. Angiotensin II receptor blockers.
3. Diuretics.
4. calcium antagonists.
5. Beta blockers.

Drugs from these groups are effective in arterial hypertension, can be prescribed as initial treatment or maintenance therapy, alone or in various combinations. Choosing specific antihypertensive drugs, the specialist is based on the patient's pressure indicators, the characteristics of the course of the disease, the presence of lesions of target organs, comorbidities, especially those of the cardiovascular system. The overall likely side effect, the possibility of combining drugs from different groups, as well as the existing experience in the treatment of hypertension in a particular patient, is always evaluated.

Unfortunately, many effective drugs are not cheap, which makes them inaccessible to the general population. The cost of the drug may become one of the conditions under which the patient will be forced to abandon it in favor of another, cheaper analogue.

Angiotensin-converting enzyme inhibitors (ACE inhibitors)

ACE inhibitors are quite popular and are widely prescribed by the most different categories patients with high blood pressure. The list of ACE inhibitors includes such drugs as: captopril, enalapril, lisinopril, prestarium, etc.

As you know, the level of blood pressure is regulated by the kidneys, in particular, by the renin-angiotensin-aldosterone system, the correct operation of which determines the tone of the vascular walls and the final level of pressure. With an excess of angiotensin II, a spasm of the vessels of the arterial type of the systemic circulation occurs, which leads to an increase in the total peripheral vascular resistance. To ensure adequate blood flow during internal organs the heart begins to work with an excessive load, forcing blood into the vessels under high pressure.

In order to slow down the formation of angiotensin II from the precursor (angiotensin I), it was proposed to use drugs that block the enzyme involved in this stage of biochemical transformations. In addition, ACE inhibitors reduce the release of calcium, which is involved in the contraction of the vascular walls, thereby reducing their spasm.

mechanism of action of ACE inhibitors in CHF

The appointment of ACE inhibitors reduces the likelihood of cardiovascular complications (stroke, myocardial infarction, severe heart failure, etc.), the degree of damage to target organs, especially the heart and kidneys. If the patient already suffers from chronic heart failure, then the prognosis of the disease when taking funds from the ACE inhibitor group improves.

Based on the characteristics of the action, it is most rational to prescribe ACE inhibitors to patients with kidney pathology and chronic heart failure, with arrhythmias, after myocardial infarction heart, they are safe for use by the elderly and diabetics, and in some cases can be used even by pregnant women.

The disadvantage of ACE inhibitors is considered the most frequent adverse reactions in the form of dry cough associated with a change in the metabolism of bradykinin. In addition, in some cases, the formation of angiotensin II occurs without a special enzyme, outside the kidneys, so the effectiveness of ACE inhibitors is sharply reduced, and treatment involves choosing another drug.

Absolute contraindications to the appointment of ACE inhibitors are:

• Pregnancy;
• A significant increase in the level of potassium in the blood;
• Sharp stenosis of both renal arteries;
• Quincke's edema with the use of ACE inhibitors in the past.

Angiotensin II receptor blockers (ARBs)

The drugs from the ARB group are the most modern and effective. Like ACE inhibitors, they reduce the action of angiotensin II, but, unlike the latter, their point of application is not limited to a single enzyme. ARBs act more widely, providing a powerful antihypertensive effect by disrupting the binding of angiotensin to receptors on cells of various organs. Thanks to this targeted action, relaxation of the vascular walls is achieved, and the excretion of excess fluid and salt by the kidneys is also enhanced.

The most popular ARBs are losartan, valsartan, irbesartan, and others.

Like ACE inhibitors, agents from the group of angiotensin II receptor antagonists show high efficacy in the pathology of the kidneys and heart. In addition, they are practically devoid of adverse reactions and are well tolerated with long-term administration, which allows them to be widely used. Contraindications to ARBs are similar to those for ACE inhibitors - pregnancy, hyperkalemia, renal artery stenosis, allergic reactions.

Diuretics

Diuretics are not only the most extensive, but also the most long-used group of drugs. They help to remove excess fluid and salt from the body, thereby reducing the volume of circulating blood, the load on the heart and blood vessels, which eventually relax. The classification implies the allocation of groups of potassium-sparing, thiazide and loop diuretics.

Thiazide diuretics, among which are hypothiazide, indapamide, chlorthalidone, are not inferior in efficiency to ACE inhibitors, beta-blockers and other groups of antihypertensive drugs. High concentrations of them can lead to changes in electrolyte metabolism, lipid and carbohydrate metabolism, but low dosages of these drugs are considered safe even with long-term use.

Thiazide diuretics are used in combination therapy along with ACE inhibitors and angiotensin II receptor antagonists. It is possible to prescribe them to elderly patients, persons suffering from diabetes, various metabolic disorders. Absolute contraindication These medications are considered gout.

Potassium-sparing diuretics are milder than other diuretics. The mechanism of action is based on blocking the effects of aldosterone (an antidiuretic hormone that retains fluid). Pressure reduction is achieved by removing liquid and salt, but potassium, magnesium, calcium ions are not lost.

Potassium-sparing diuretics include spironolactone, amiloride, eplerenone, etc. They can be prescribed to patients with chronic heart failure, severe edema of cardiac origin. These drugs are effective in refractory hypertension, which is difficult to treat with other groups of drugs.

Due to their action on renal aldosterone receptors and the risk of hyperkalemia, these substances are contraindicated in acute and chronic renal failure.

Loop diuretics (lasix, edecrin) are the most aggressive, but at the same time, they can reduce blood pressure faster than others. For long-term use, they are not recommended, as the risk is high. metabolic disorders due to excretion along with fluid and electrolytes, but for the treatment of hypertensive crises, these drugs are successfully used.

calcium antagonists

The contraction of muscle fibers occurs with the participation of calcium. Vascular walls are no exception. Preparations of the group of calcium antagonists carry out their action by reducing the penetration of calcium ions into the smooth muscle cells of blood vessels. The sensitivity of vessels to vasopressor substances that cause vascular spasm (adrenaline, for example) also decreases.

The list of calcium antagonists includes drugs of three main groups:

1. Dihydropyridines (amlodipine, felodipine).
2. Benzothiazepine calcium antagonists (diltiazem).
3. Phenylalkylamines (verapamil).

The drugs of these groups differ in the nature of the effect on the walls of blood vessels, the myocardium, the conduction system of the heart. So, amlodipine, felodipine act mainly on the vessels, reducing their tone, while the work of the heart does not change. Verapamil, diltiazem, in addition to the hypotensive effect, affect the work of the heart, causing a decrease in heart rate and its normalization, therefore, they are successfully used for arrhythmias. By reducing the oxygen demand of the heart muscle, verapamil reduces pain syndrome with angina pectoris.

In the case of the appointment of non-dihydropyridine diuretics, it is necessary to take into account the possible bradycardia and other types of bradyarrhythmias. These drugs are contraindicated in severe heart failure, atrioventricular blockade, and simultaneously with intravenous administration of beta-blockers.

Calcium antagonists do not affect metabolic processes, reduce the degree of left ventricular hypertrophy in hypertension, and reduce the likelihood of stroke.

Beta blockers

Beta-blockers (atenolol, bisoprolol, nebivolol) have a hypotensive effect by reducing cardiac output and the formation of renin in the kidneys, causing vascular spasm. Due to their ability to regulate the heart rate and have an antianginal effect, beta-blockers are preferred for lowering blood pressure in patients suffering from coronary heart disease (angina pectoris, cardiosclerosis), as well as in chronic heart failure.

Beta-blockers change carbohydrate, fat metabolism, can provoke weight gain, so they are not recommended for diabetes and other metabolic disorders.

Substances with adrenoblocking properties cause bronchospasm and slow heart rate, and therefore they are contraindicated in asthmatics, with severe arrhythmias, in particular, atrioventricular block II-III degree.

Other antihypertensive drugs

In addition to the described groups of pharmacological agents for the treatment of arterial hypertension, additional drugs are also successfully used - imidazoline receptor agonists (moxonidine), direct renin inhibitors (aliskiren), alpha-blockers (prazosin, cardura).

Imidazoline receptor agonists act on nerve centers in the medulla oblongata, reducing the activity of sympathetic vascular stimulation. Unlike drugs of other groups, which at best do not affect carbohydrate and fat metabolism, moxonidine is able to improve metabolic processes, increase tissue sensitivity to insulin, and reduce triglycerides and fatty acids in the blood. Taking moxonidine in overweight patients promotes weight loss.

Direct renin inhibitors are represented by the drug aliskiren. Aliskiren helps to reduce the concentration of renin, angiotensin, angiotensin-converting enzyme in the blood serum, providing hypotensive, as well as cardioprotective and nephroprotective effects. Aliskiren can be combined with calcium antagonists, diuretics, beta-blockers, but the simultaneous use with ACE inhibitors and angiotensin receptor antagonists is fraught with impaired renal function due to the similarity of the pharmacological action.

Alpha-blockers are not considered drugs of choice, they are prescribed as part of combined treatment as a third or fourth additional antihypertensive agent. Medicines in this group improve fat and carbohydrate metabolism, increase blood flow in the kidneys, but are contraindicated in diabetic neuropathy.

The pharmaceutical industry does not stand still, scientists are constantly developing new and safe drugs to reduce pressure. Aliskiren (rasilez), olmesartan from the group of angiotensin II receptor antagonists can be considered drugs of the latest generation. Among diuretics, torasemide has proven itself well, which is suitable for long-term use, safe for elderly patients and patients with diabetes mellitus.

Combined preparations are also widely used, including representatives of different groups “in one tablet”, for example, the equator, combining amlodipine and lisinopril.

Folk antihypertensives?

The described drugs have a persistent hypotensive effect, but require long-term use and constant monitoring of the pressure level. Fearing side effects, many hypertensive patients, especially elderly people suffering from other diseases, prefer herbal remedies and traditional medicine to taking pills.

Hypotensive herbs have the right to exist, many really do good effect, and their action is associated mostly with sedative and vasodilating properties. So, the most popular are hawthorn, motherwort, peppermint, valerian and others.

There are ready-made fees that can be bought in the form of tea bags at a pharmacy. Tea Evalar Bio, containing lemon balm, mint, hawthorn and other herbal ingredients, Traviata is the most famous representatives of herbal antihypertensive drugs. Hypotensive monastic tea has also proven itself well. At the initial stage of the disease, it has a general strengthening and calming effect on patients.

Certainly, herbal preparations may be effective, especially in emotionally labile subjects, but it should be emphasized that self-treatment of hypertension is unacceptable. If the patient is elderly, suffers from heart disease, diabetes, atherosclerosis, then the effectiveness is only traditional medicine doubtful. In such cases, drug therapy is required.

In order for drug treatment to be more effective, and the dosage of drugs to be minimal, the doctor will advise patients with arterial hypertension to first change their lifestyle. Recommendations include quitting smoking, normalizing weight, and limiting salt, fluid, and alcohol intake. Importance have adequate physical activity and the fight against hypodynamia. Non-pharmacological measures to reduce pressure can reduce the need for drugs and increase their effectiveness.

Treatment of hypertension

A well-known main risk factor for the development of the most formidable vascular diseases (stroke and myocardial infarction) is hypertension. The main way to treat hypertension is antihypertensive therapy, i.e. lowering elevated blood pressure values ​​with the help of drugs without affecting the underlying cause of hypertension. Now there are many modern drugs that help lower blood pressure. All these drugs are divided into classes depending on the mechanism of their action.

Diuretics (diuretics) stimulate the excretory function of the kidneys, thereby helping the body get rid of excess fluid. These include arifon, hydrochlorothiazide, brinaldix, diuver, veroshpiron.

Adrenoblockers (alpha-blockers and beta-blockers) reduce the effect of adrenaline on nerve receptors, thereby reducing the effect of stress factors on blood vessels. Among them are prazosin, doxazosin (alpha-blockers) and atenolol, propranalol, nadolol, concor (beta-blockers).

The drugs prestarium, captopril, enalapril, losartan and valsartan, inhibit the action of angiotensin-converting enzyme, which causes an increase in pressure. Centrally acting drugs (clophelin, cint) and calcium antagonists (nifedipine, nimodipine, verapamil) can also lower blood pressure.

Unfortunately, all antihypertensive drugs have contraindications and side effects, therefore, in most cases, combination therapy is indicated using several drugs at once. It should be borne in mind that high blood pressure should be reduced gradually. A sharp drop in pressure can be no less dangerous than its increase. Often, an overdose of antihypertensive drugs can cause a very sharp decrease in pressure, which is dangerous in itself, especially for older people with altered blood vessels. Therefore, at stable increased values blood pressure should reach its target values ​​gradually, no faster than after a few weeks. In addition, in most cases, you should not stop antihypertensive therapy without consulting a doctor, even if you have reached your target “normal” pressure values ​​for you. Hypertension, as a rule, does not go away so easily: at any moment it can return and remind itself of its usual symptoms: headaches and heartaches, nausea, dizziness, after which, at best, everything will have to start over.

Cardiology Cheat Sheet: Antihypertensive Therapy

Antihypertensive therapy in patients with impaired liver function:

• first choice drugs: Verapamil, diltiazem; Nifedipine group;
• second choice drugs: Diuretics.

First choice drugs in patients with arterial hypertension:

• and rhythm disturbances (sinus tachycardia, supraventricular, ventricular arrhythmias):
  • Cardioselective beta-blockers;
  • Central antagonists;
  • Verapamil;
  • Diltiazem.
• and rhythm disturbances (sinus bradycardia, sick sinus syndrome, AV blockade):
  • Nifedipine-retard and other drugs of this group;
  • ACE inhibitors.
• • Diltiazem-retard;
  • Verapamil-retard;
  • Long-acting ACE inhibitors (enalapril).
• • ACE inhibitors;
  • Moderate diuretics (hypothiazid, indapamide, oxodoline).

Second choice drugs in patients with arterial hypertension:

• therapy, which should be carried out for a long time, in patients with a pronounced form of dyslipidemia:
  • Cardioselective beta-blockers.
• and systolic form of chronic heart failure (CHF):
  • Loop diuretics (furosemide, uregit);
  • Dihydroperidine calcium antagonists (nifedipine retard, amlodipine);
  • Metoprolol.
  • Drugs that have the most pronounced antihypertensive effect:
    • calcium antagonists;
  • Drugs that do not impair the quality of life and most effectively reduce blood pressure:
    • calcium antagonists;
    • ACE inhibitors;
    • Alpha1-adrenergic blockers
  • Drugs that do not negative influence on other risk factors for the development of cardiovascular complications and most effectively reduce blood pressure:
    • calcium antagonists;
    • ACE inhibitors;
    • Alpha1 - blockers;
    • Central agonists;
    • Arteriolar vasodilators (apressin, minoxidin).

    ATTENTION! There may be an inaccurate or incorrect answer. Please check information against other sources, such as lecture notes.

    Hypotensive action: what is it

    Hypotensive effect - what is it? This question is asked by women and men who first encountered the problem of high blood pressure or hypertension and have no idea what the hypotensive effect of the drugs prescribed by their doctor means. Hypotensive action is a decrease in blood pressure under the influence of a certain drug.

    Experienced professional therapists of the highest category of the therapy clinic of the Yusupov Hospital, who own advanced methods of treatment and diagnosis, will provide qualified assistance to patients with arterial hypertension, select an effective treatment regimen that excludes the development negative consequences.

    Antihypertensive therapy: general rules

    Both symptomatic hypertension and hypertension require correction with antihypertensive drugs. Antihypertensive therapy can be carried out with drugs that differ in the mechanism of action: antiadrenergic drugs, vasodilators, calcium antagonists, angiotensin antagonists, and diuretics.

    You can get information about what the hypotensive effect of the drug is, what medications to take with high blood pressure not only from your doctor, but also from a pharmacist.

    Arterial hypertension is a chronic disease that requires constant drug support, daily monitoring and regular intake of prescribed medications. Not only the state of health, but also the life of a person depends on compliance with these rules.

    Despite the general availability of the rules of therapy for reducing pressure, many patients have to be reminded of how the treatment regimen for hypertension should look like:

    • taking antihypertensive drugs should be regular, regardless of the patient's well-being and the level of blood pressure. This allows you to increase the effectiveness of blood pressure control, as well as prevent cardiovascular complications and damage to target organs;
    • it is necessary to strictly observe the dosage and apply the form of release of the drug, which was prescribed by the attending physician. Self-change of the recommended dose or replacement of the drug may distort the hypotensive effect;
    • even under the condition of constant intake of antihypertensive drugs, it is necessary to systematically measure blood pressure, which will allow to evaluate the effectiveness of therapy, timely identify certain changes and adjust treatment;
    • in the case of an increase in blood pressure against the background of constant antihypertensive treatment - the development of an uncomplicated hypertensive crisis, an additional dose of the previously taken long-acting drug is not recommended. It is possible to quickly lower blood pressure with the help of short-acting antihypertensive drugs.

    Antihypertensive therapy: drugs to reduce pressure

    In the course of antihypertensive therapy, several main groups of drugs that help lower blood pressure are currently used:

    • beta-blockers;
    • ACE inhibitors;
    • calcium antagonists;
    • diuretics;
    • angiotensin II receptor blockers.

    All of the above groups have comparable effectiveness and their own characteristics that determine their use in a given situation.

    Beta blockers

    The drugs of this group reduce the likelihood of developing coronary complications in patients with angina pectoris, prevent cardiovascular accidents in patients with myocardial infarction, tachyarrhythmia, and are used in patients with chronic heart failure. Beta-blockers are not recommended for patients with diabetes mellitus, lipid metabolism disorders and metabolic syndrome.

    ACE inhibitors

    Angiotensin-converting enzyme inhibitors have pronounced hypotensive properties, they have organoprotective effects: their use reduces the risk of complications of atherosclerosis, reduces left ventricular hypertrophy, and slows down the decline in kidney function. ACE inhibitors are well tolerated, with no negative effects on lipid metabolism and glucose levels.

    calcium antagonists

    In addition to antihypertensive properties, drugs of this group have antianginal and organ-protective effects, help reduce the risk of stroke, atherosclerotic lesions of the carotid arteries and left ventricular hypertrophy. Calcium antagonists may be used alone or in combination with other antihypertensive drugs.

    Diuretics

    Diuretic drugs are usually used while taking other antihypertensive drugs in order to enhance the therapeutic effect.

    Diuretics are also prescribed for people suffering from pathologies such as refractory hypertension and chronic heart failure. In order to avoid the development of side effects, with the constant intake of these drugs, minimal dosages are prescribed.

    Angiotensin II receptor blockers

    Drugs in this group, which have a neuro- and cardioprotective effect, are used to improve the control of blood glucose. They allow to increase the life expectancy of patients suffering from chronic heart failure. Antihypertensive therapy using angiotensin II receptor blockers can be prescribed to patients who have had a myocardial infarction, suffering from renal failure, gout, metabolic syndrome and diabetes mellitus.

    Antihypertensive therapy in hypertensive crisis

    Even despite constant antihypertensive therapy, a sudden increase in blood pressure to sufficiently high levels may periodically occur (there are no signs of target organ damage). The development of an uncomplicated hypertensive crisis may be due to unusual physical activity, emotional stress, drinking alcohol or salty, fatty foods. Such a condition is not life-threatening, but it threatens the development of negative consequences, therefore, it requires timely treatment.

    Too rapid a decrease in blood pressure is undesirable. Optimally, if in the first two hours after taking the drug, the pressure drops by no more than 25% of the initial values. Normal blood pressure values ​​are usually restored within a day.

    Quick-acting drugs help to restore blood pressure control, due to which an almost instantaneous hypotensive effect is provided. Each of the drugs for quickly lowering blood pressure has its own contraindications, so a doctor should select them.

    30 minutes after taking an antihypertensive drug, it is necessary to measure the level of blood pressure to assess the effectiveness of therapy. If necessary, in order to restore the normal level of blood pressure, after half an hour or an hour, you can take an additional tablet (orally or sublingually). If there is no improvement (less than 25% decrease in pressure or its previous excessively high rates), you should immediately seek the help of a doctor.

    In order for arterial hypertension not to turn into a chronic form, accompanied by rather serious complications, it is necessary to pay attention to the first signs of arterial hypertension in time. Do not self-medicate and randomly select drugs that reduce pressure. Despite their hypotensive effect, they can have a lot of contraindications and be accompanied by side effects that aggravate the patient's condition. The selection of drugs for antihypertensive therapy should be carried out by a qualified specialist familiar with the characteristics of the patient's body, his anamnesis.

    The Therapy Clinic of the Yusupov Hospital offers a comprehensive approach to addressing problems associated with high blood pressure.

    The clinic has the latest modern diagnostic and treatment equipment from the world's leading manufacturers of medical equipment, which makes it possible to identify the first manifestations of hypertension at the earliest diagnostic level and select the most effective methods of treating the disease. When drawing up a treatment regimen, the age, condition of the patient and other individual factors are taken into account.

    Conservative therapy in the Yusupov hospital involves the use of the latest generation of drugs with a minimum number of side effects. Consultations are carried out by highly qualified therapists with vast experience in treatment hypertension and its consequences, including stroke.

    You can sign up for a consultation with the leading specialists of the clinic by phone or on the website of the Yusupov hospital through the feedback form.

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    Antihypertensive therapy: what you need to know?

    Arterial hypertension is one of those chronic diseases that require constant drug support, daily monitoring and regular intake of prescribed drugs. Not only well-being, but also the life of a sick person directly depends on how carefully the rules of antihypertensive therapy are observed.

    Not only the attending physician, but the pharmacist who advises the visitor who has applied to the pharmacy can tell about how to properly treat arterial hypertension, what drugs are used and in what cases.

    General rules of therapy

    The rules of antihypertensive therapy are simple and well known, but many patients often neglect them, and therefore it will not be out of place to remind you once again what the treatment of hypertension should be.

    1. Antihypertensive drugs are taken constantly. Regardless of whether the person feels bad or well, the level of blood pressure (BP) is elevated or remains normal, drug therapy should be constant. Only with daily intake of antihypertensive drugs can effectively control the level of blood pressure, avoid damage to target organs and cardiovascular complications.
    2. Antihypertensive drugs are taken in the dosage and form of release in which they are prescribed by the doctor. You should not independently change the recommended dose or try to replace one drug with another, because. this may adversely affect the hypotensive effect.
    3. Even with constant intake of antihypertensive drugs, blood pressure should be measured regularly, at least 2 times a week. This is necessary to control the effectiveness of therapy, allows you to notice the changes taking place in the body in time and adjust the treatment.
    4. If, against the background of constant antihypertensive therapy, blood pressure suddenly rises, i.e. an uncomplicated hypertensive crisis develops, it is not recommended to take an additional dose of the drug familiar to the patient. For permanent reception are appointed for a long time active drugs, the effect of which develops gradually. To quickly reduce blood pressure, a hypertensive home medicine cabinet must have short-acting antihypertensive drugs.

    Features of different groups of drugs

    For the treatment of arterial hypertension, 5 main groups of antihypertensive drugs are currently used: ACE inhibitors, beta-blockers, diuretics, calcium antagonists and angiotensin II receptor blockers. All of them have comparable effectiveness, but each of the groups has its own characteristics that determine the use of these drugs in different situations.

    ACE inhibitors (enalapril, lisinopril, perindopril, captopril, etc.), in addition to a pronounced hypotensive effect, have organoprotective properties - they reduce the risk of atherosclerosis complications, reduce left ventricular hypertrophy, and slow down the decline in kidney function. The drugs of this group are well tolerated, do not have a negative effect on lipid metabolism and blood glucose levels, which allows them to be used in cases where arterial hypertension is combined with metabolic syndrome or diabetes mellitus, as well as in patients who have had myocardial infarction, in the case of chronic heart failure. insufficiency, arrhythmia, atherosclerosis and impaired renal function.

    Beta-blockers (atenolol, bisoprolol, metoprolol, carvedilol, nebivolol) reduce the risk of coronary complications in patients with angina pectoris and cardiovascular accidents in patients who have had myocardial infarction, as well as patients with chronic heart failure, can be used for tachyarrhythmia. The use of beta-blockers is undesirable in patients with metabolic syndrome, lipid metabolism disorders and diabetes mellitus.

    Diuretics (hydrochlorothiazide, chlorthalidone, indapamide, spironolactone) are most often used in combination with other antihypertensive drugs, such as ACE inhibitors, to more effectively control blood pressure. The drugs of this group have proven themselves in refractory hypertension and chronic heart failure. For continuous use, diuretics are prescribed in minimum doses- to reduce the risk of side effects.

    Calcium antagonists (nifedipine, amlodipine, verapamil, diltiazem), in addition to hypotensive, have antianginal and organ-protective effects, reduce the risk of stroke, prevent platelet aggregation, slow down atherosclerotic lesions of the carotid arteries and left ventricular hypertrophy. Calcium antagonists are used alone or in combination with other antihypertensive drugs(usually ACE inhibitors).

    Angiotensin II receptor blockers

    Angiotensin receptor blockers (losartan, candesartan, telmisartan, valsartan) have a cardio- and neuroprotective effect, improve blood glucose control, and have a positive effect on the life expectancy of patients with chronic heart failure. All drugs in this group can be used in the treatment of hypertension in patients with impaired renal function, myocardial infarction, metabolic syndrome, gout, diabetes mellitus.

    Hypertensive crisis - what to do?

    Even against the background of constant antihypertensive therapy, blood pressure can periodically rise suddenly to individually high numbers (without signs of target organ damage). This condition is called uncomplicated hypertensive crisis, most often it occurs after unusual physical activity, emotional stress, drinking alcoholic beverages or fatty salty foods.

    And although an uncomplicated form of a hypertensive crisis is not considered a life-threatening condition, it is impossible to leave it without treatment, because. even slight increase BP (by 10 mmHg) increases the risk of cardiovascular complications by 30%.2 And the sooner treatment is started, the better less likely unwanted consequences.

    Antihypertensive drugs for uncomplicated hypertensive crisis are often recommended to be taken sublingually, because. this method is convenient for the patient and at the same time provides a rapid development of the therapeutic effect. It is undesirable to reduce blood pressure too quickly - in the first 2 hours by no more than 25% of the baseline and to a normal level within 24 hours. To restore blood pressure control, short-acting drugs that provide a rapid hypotensive effect should be used: nifedipine, captopril, moxonidine, clonidine, propranolol. It is better if a doctor chooses a drug to quickly reduce pressure, since each of them has contraindications.

    Half an hour after taking 1 tablet of an antihypertensive drug, you should measure the level of blood pressure and evaluate the effectiveness of treatment. If necessary, to restore the normal level of blood pressure, after 30-60 minutes, you can additionally take another 1 tablet sublingually or orally. If after that the pressure has decreased by less than 25%, it is urgent to call a doctor.

    Therapy of comorbid conditions

    Arterial hypertension rarely develops as a separate disease, in most cases it is accompanied by background disorders that exacerbate target organ damage and increase the risk of cardiovascular complications. Therefore, in addition to antihypertensive drugs, patients with hypertension are often prescribed lipid-lowering therapy, agents for preventing thrombosis and correcting blood glucose levels in patients with metabolic syndrome and diabetes mellitus.

    A particularly important role in arterial hypertension is played by the use of statins (simvastatin, atorvastatin, rosuvastatin) - drugs that reduce the level total cholesterol, low density lipoproteins and triglycerides. Long-term use of statins can stop atherosclerotic vascular damage, suppress the inflammatory process in the plaque, improve endothelial function and thereby significantly reduce the risk of cardiovascular events (myocardial infarction and stroke). First of all, statins are prescribed to patients with coronary artery disease, as well as after myocardial infarction.

    Prophylactic antiplatelet therapy is also prescribed for patients at high cardiovascular risk, people with impaired renal function, as well as all those who have undergone vascular surgery (bypass surgery, stenting). Drugs in this group prevent the formation of blood clots and reduce the risk of arterial thrombosis. The most widely used today are acetylsalicylic acid, clopidogrel and dipyridamole, which are prescribed for long courses in minimal therapeutic doses.

    And, of course, all these drugs, as well as antihypertensive drugs, are prescribed only by the attending physician, because. any self-treatment for hypertension can be dangerous, which must be reminded to a pharmacy visitor.

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FSBI "Educational and Scientific Medical Center" of the Office of the President Russian Federation, Moscow

The literature review presents modern ideas on the relationship of cognitive dysfunction with major risk factors and adverse cardiovascular outcomes. The main approaches to antihypertensive therapy for primary and secondary prevention of stroke, as well as the prevention of vascular dementia, are analyzed. The effectiveness of the angiotensin receptor blocker olmesartan in the treatment of arterial hypertension is considered in detail. Evidence of its angioprotective and cerebroprotective properties is presented. They make it possible to recommend the drug primarily for the treatment of elderly patients with arterial hypertension, for whom the task of maintaining cognitive functions is one of the priorities.
Keywords Key words: olmesartan, arterial hypertension, cognitive functions, dementia, stroke.

Rational Antihypertensive Treatment as Basis for Cerebral Protection and Cognitive Decline Prevention

L.O. Minushkina

Educational and Science Medicine Center of RF President Administration Department for Property Management, Moscow

The review of literature presents modern concepts of the relationship between cognitive decline and major cardiovascular risk factors, adverse cardiovascular outcomes. Basic approaches to antihypertensive therapy for primary and secondary prevention of stroke and vascular dementia are described. The article details the effectiveness of angiotensin receptor blocker called olmesartan in the treatment of hypertension. The drug presents vascular and cerebral protective properties; so olmesartan should be used primarily in elderly patients with hypertension in order to maintain cognition.
keywords: olmesartan, hypertension, cognition, dementia, stroke.

Cognitive decline is a very significant risk factor for adverse outcomes. In a large study that included more than 30,000 patients followed up for about 5 years, it was shown that the presence of dementia is associated with the risk of stroke, heart failure, and cardiovascular mortality. Reductions in Mini Mental Status Assessment (MMSE) scores below 24 were similar to prior stroke in terms of effect on risk of recurrence. The association of cognitive dysfunction with other adverse outcomes is that dementia may be a marker of the severity of target organ damage. In addition, patients with dementia are characterized by low adherence to treatment. Patients with cognitive decline have lifestyle features associated with physical activity, the nature of nutrition, the frequent development of mental depression. All this contributes to the progression of vascular diseases. Arterial hypertension (AH) is one of the leading risk factors for the development of progressive forms of cerebrovascular pathology and the formation of cognitive impairment.

Antihypertensive therapy is the basis of stroke prevention

For most patients, a reduction in the risk of complications is achieved by lowering blood pressure (BP) to 140/90 mm Hg. Art. The same level of blood pressure is considered as a target for secondary prevention of strokes. Achieving lower BP levels does not improve prognosis in these patients. For elderly patients with hypertension, even a higher level of systolic blood pressure - 150 mm Hg is considered as a target. With a decrease in blood pressure in these groups of patients, it is especially important to consider the tolerability of treatment.

In a meta-analysis of the largest studies on secondary prevention of stroke in patients with ischemic, hemorrhagic stroke or transient ischemic attack, it turned out that the success of secondary prevention depends primarily on the level of systolic blood pressure achieved during treatment. The overall reduction in the risk of recurrent strokes was 24%. However, there were differences in the effectiveness different classes antihypertensive drugs. The use of thiazide diuretics, and especially the combination of the latter with ACE inhibitors, made it possible to more significantly reduce the risk of adverse outcomes than antihypertensive therapy with beta-blockers. One of the most well-known studies demonstrating the effectiveness of antihypertensive therapy in the secondary prevention of stroke was the PROGRESS study (Perindopril protection against recurrent stroke study), which showed a 28% reduction in the risk of recurrent stroke in the group active treatment(patients received perindopril as monotherapy and in combination with indapamide). In the group receiving only perindopril, blood pressure decreased by 5/3 mm Hg. st, and there was no significant reduction in the risk of stroke compared with the placebo group. In patients receiving combined therapy with perindopril and indapamide, the decrease in blood pressure was more significant - 12/5 mm Hg. Art., and the risk of stroke decreased by 46%, which was significant compared with placebo. The effectiveness of antihypertensive therapy in the secondary prevention of stroke was also shown in a number of other studies, such as PATS, ACCESS.

In the primary prevention of stroke in patients with arterial hypertension, the degree of reduction in blood pressure is also the most significant for the prognosis. Upon reaching the target values ​​of blood pressure, the reduction in the risk of stroke reaches 40%. In patients with a predominant increase in diastolic blood pressure, its decrease by 5-6 mm Hg. Art. leads to a 40% reduction in the risk of stroke. In patients with isolated systolic arterial hypertension, a decrease in systolic blood pressure reduces the risk of cerebrovascular accidents by 30%. Significant factors also include the use of statins, therapy with ACE inhibitors, endarterectomy in patients with hemodynamically significant stenoses. coronary arteries. The use of aspirin leads to a decrease in the risk of stroke in patients with high cardiovascular risk. In patients with low and moderate risk of complications, the use of aspirin did not lead to a decrease in the risk of stroke.

Until recently, the question of the effectiveness of antihypertensive therapy in patients of older age groups remained open. Specifically designed to evaluate the effectiveness of treatment in patients with arterial hypertension older than 80 years, the HYVET study showed that combination antihypertensive therapy reduced the risk of stroke by 39%.

There is evidence of possible cerebroprotective properties of angiotensin receptor blockers. Thus, in the SCOPE study, it was shown that in patients with arterial hypertension over the age of 70 years, therapy with the angiotensin receptor blocker candesartan significantly reduced the risk of non-fatal strokes. Particularly significant was the reduction in the risk of stroke in the treatment of angiotensin receptor blockers in patients with isolated systolic hypertension. This is confirmed by the results of the LIFE study, where losartan reduced the risk of stroke by 40% in patients with ISAH, and the SCOPE study, where a 42% reduction in the risk of stroke was achieved in this subgroup.

The mechanism by which angiotensin receptor blockers have cerebroprotective properties is associated with the effect of stimulation of type 2 angiotensin receptors. It is this type of receptor that is expressed in the central nervous system. Their stimulation leads to a significant increase in cerebral blood flow. When treated with selective angiotensin type 1 receptor blockers, there is an increase in the plasma level of angiotensin II, which, acting on type 2 receptors, creates conditions for cerebroprotection.

Prevention of vascular dementia

One of the most common manifestations of chronic cerebrovascular disease is vascular dementia. At the same time, data on the relationship between the progression of vascular dementia and the level of blood pressure and the effectiveness of antihypertensive therapy are contradictory. An increase in blood pressure is a factor contributing to the progression of atherosclerotic vascular lesions, causing prothrombotic shifts, and on the other hand, it is a compensatory reaction associated with impaired autoregulation of cerebral circulation. The relationship between the progression of vascular dementia and the level of blood pressure is non-linear. In addition, the severity of cognitive impairment is also affected by the presence of other concomitant diseases and conditions - dyslipidemia, diabetes mellitus. It should be noted that stroke itself is one of the most significant factors leading to the development of dementia. It is fixed in 10% of patients after the first stroke and in 30% of patients with repeated strokes. This raises the importance of stroke prevention as an opportunity to prevent the onset of severe cognitive impairment.

The effectiveness of antihypertensive therapy in relation to the prevention of cognitive impairment has been studied in several large randomized trials. In the Syst-Euro study, nitrendipine therapy was shown to reduce the incidence of vascular dementia by 50%. In the PROGRESS study, the incidence of vascular dementia in the group treated with perindopril (as monotherapy and in combination with indapamide) decreased by 19%. On the other hand, in studies such as SHEP, SCOPE, HYVET-COG, therapy did not affect the incidence of cognitive impairment.

Angiotensin receptor blockers help prevent the development of cognitive dysfunction. This was shown in a large meta-analysis that included data from the ONTARGET and TRANSDENT studies. Treatment with this group of drugs made it possible to achieve a 10% reduction in the risk of developing vascular dementia with long-term treatment.

It is interesting to note that, according to meta-analyzes, with a small decrease in blood pressure (by 4.6/2.7 mmHg), there is an improvement in short-term memory test scores. In studies that achieved more significant decrease BP (by 17/10 mm Hg), test scores worsened.

Tactics of lowering blood pressure for the prevention of cerebrovascular complications

It should be noted that the choice of a particular drug is most often not fundamentally important. In most patients, in order to achieve the target values ​​of blood pressure, one has to resort to the appointment of a combination therapy with two, three or more drugs from different groups. Monotherapy can be justified as a start in patients with grade 1 hypertension and a low or moderate risk of complications. In patients with grade 2–3 hypertension who have a high or very high additional risk of complications, treatment can be started immediately using combination therapy.

It should be noted that patients with cerebrovascular disease, elderly patients do not always tolerate such a decrease in blood pressure well. When selecting therapy, it is necessary to take into account individual tolerance and avoid episodes of hypotension. In this case, it is necessary to take into account age-related features, in particular, the optimal value of systolic blood pressure for the elderly is usually 135–150 mm Hg. Art., its further decrease leads to an aggravation of the clinical picture of cognitive dysfunction and an increased risk of ischemic stroke. Particular care should be taken to reduce blood pressure in patients with hemodynamically significant atherosclerosis of the carotid arteries. As one of the methods of control that facilitates the selection of therapy, daily monitoring of blood pressure can be used. This method allows you to control blood pressure at night, the rate and magnitude of the morning rise in blood pressure, the presence of episodes of excessive hypotension. When analyzing all the parameters of 24-hour BP monitoring, it turned out that the highest predictive value in relation to the risk of stroke is the level of systolic BP at night.

For the prevention of cerebrovascular events, the ability of drugs to influence the condition is also essential. vascular wall and affect central pressure. The significance of these effects was demonstrated in the CAFE study conducted by the ASCOT project. The combination of amlodipine and perindopril has been shown to reduce central aortic pressure to a greater extent than treatment with atenolol and bendroflumethiazide. As is known, central blood pressure is closely related to the stiffness/elasticity of the vascular wall and pulse wave velocity, which, in turn, can affect the occurrence of cardiovascular events, especially stroke.

The combination of a blocker of the renin-angiotensin system (ACE inhibitor or angiotensin receptor blocker) with a calcium antagonist or thiazide diuretic seems to be the most rational and pathogenetically justified today. The combination of two drugs in full doses does not normalize blood pressure in 10-20% of patients. If necessary, combine three antihypertensive agents, preferably a combination of a blocker of the renin-angiotensin system, a thiazide diuretic or a calcium antagonist.

In elderly patients, drugs from the group of angiotensin receptor blockers have certain advantages. This group of antihypertensive drugs is characterized by cerebroprotective properties, as well as very good tolerance, low risk of side effects, which leads to good adherence of patients to treatment. One of the drugs in this group is olmesartan (CardosalR, Berlin-Chemie/A.Menarini), which has shown good efficacy in elderly patients, angio- and cerebroprotective properties.

Efficacy of olmesartan in the elderly

Olmesartan medoxomil is rapidly absorbed from the gastrointestinal tract after oral administration. The bioavailability of the drug is 26-28%, 35-50% of the dose is excreted unchanged by the kidneys, the rest - with bile. The pharmacokinetics of olmesartan in elderly and young patients does not differ significantly. In the treatment of hypertension, the drug is prescribed at a dose of 10–40 mg per day in a single regimen.

A meta-analysis of randomized studies using angiotensin receptor blockers, which included 4892 patients treated with olmesartan, showed that the reduction in blood pressure during olmesartan therapy was more significant than during therapy with losartan and valsartan. At the same time, the tolerability of olmesartan is not worse than that of other sartans.

The efficacy of olmesaratan in elderly patients was evaluated in two similarly designed studies. A total of 1646 patients over 65 years of age participated in them. In one of the studies, the efficacy of olmesartan was evaluated in patients with isolated systolic hypertension, in the other - with systolic-diastolic hypertension. Olmesartan was prescribed at a dose of 20–40 mg/day. In patients with isolated systolic hypertension, after 12 weeks of therapy, systolic blood pressure decreased by 30 mm Hg. Art. with a slight change in diastolic blood pressure. After 24 weeks of therapy, blood pressure returned to normal in 62.5% of patients. The drug was well tolerated in patients aged 65-74 years, and in patients older than 75 years.

In a meta-analysis of 2 randomized trials comparing the efficacy of ramipril and olmesartan, data on the treatment of 1400 patients with grade 1 and 2 hypertension over the age of 65 years were analyzed. It turned out that olmesartan is more effective in reducing blood pressure. Therapy with olmesartan creates a more stable antihypertensive effect throughout the day, independent of the time of eating. Both drugs were well tolerated.

Two identically designed studies (European and Italian) compared the efficacy of ramipril and olmesartan in elderly patients. The dose of ramipril was titrated from 2.5 to 10 mg, olmesartan from 10 to 40 mg. A total of 1453 patients participated in the studies. In 715 of them, control over the effectiveness of therapy was carried out using daily monitoring of blood pressure. The decrease in blood pressure was more pronounced during olmesartan therapy - the difference in the achieved level of systolic blood pressure was 2.2 mm Hg. Art., diastolic blood pressure - 1.3 mm Hg. Art. Olmesartan created a significantly more pronounced decrease in blood pressure in the last 6 hours before taking the next dose. The smoothness index of BP reduction was also higher in the olmesartan group. Only in the treatment with this drug was there a significant decrease in the rate of the morning increase in blood pressure, in the ramipril group there was no such dynamics. Thus, olmesartan was more effective in the elderly. It has been shown that during long-term therapy in patients with hypertension, olmesartan not only leads to a persistent decrease in blood pressure, but also helps to reduce pressure variability and improves the state of autonomic regulation of vascular tone.

The 735 patients in this study had metabolic syndrome and were analyzed separately for drug efficacy. In general, in the group, normalization of blood pressure was achieved in 46% of patients in the olmesartan group and in 35.8% of patients in the ramipril group. The same regularities could be traced in groups of patients with both the presence and absence of the metabolic syndrome. Among elderly patients with metabolic syndrome during olmesartan therapy, the average daily systolic blood pressure decreased by 10.2 mm Hg. Art. and diastolic blood pressure - by 6.6 mm Hg. Art., and against the background of the appointment of ramipril - by 8.7 and 4.5 mm Hg. Art. respectively. The incidence of side effects was similar with both drugs.

Olmesartan is also effective in combination therapy. The Japanese study of olmesartan in the elderly (Miyazaki Olmesartan Therapy for Hypertension in the EldeRly - MOTHER) compared the efficacy of olmesartan in patients with hypertension in combination with a calcium antagonist and a thiazide diuretic. The combination with a calcium antagonist was somewhat more effective in patients with normal body weight, and the combination with a thiazide diuretic had little benefit in overweight patients. The blood creatinine level remained stable throughout the 6 months of treatment. In the group of patients with normal body weight, regardless of the type of treatment, there was a significant decrease in blood aldosterone activity, which was not found in patients with obesity.

Elderly patients showed good efficacy of the combination of olmesartan and hypothiazide. The antihypertensive efficacy of a combination of 40 mg of olmesartan and 25 mg of hypothiazide was studied in a group of 176 hypertensive patients over 65 years of age. 116 patients had grade 1 hypertension, 60 patients had grade 2 hypertension, 98 patients had isolated systolic hypertension. Titration of antihypertensive therapy was carried out according to the scheme of olmesartan 20 mg per day, then 40 mg per day, combination with hypothiazide 12.5 mg, then 25 mg. Combination therapy was required in 159 patients. Normalization of blood pressure during treatment was achieved in 88% of patients with grade 1 hypertension, in 56% of patients with grade 2 hypertension, and in 73% of patients with isolated systolic hypertension. Daily monitoring of blood pressure showed a sufficient duration of antihypertensive action when taking the combination once a day. The frequency of side effects associated with hypotension did not exceed 3%.

Angioprotective effects of olmesartan

Olmesartan is able to inhibit the progression of atherosclerotic vascular lesions, which was shown in a large randomized study MORE (The Multicentre Olmesartan atherosclerosis Regression Evaluation study). The study compared the effects of olmesartan and atenolol on carotid intima-media thickness and atherosclerotic plaque volume. Olmesartan was prescribed at a dose of 20–40 mg/day, atenolol – 50–100 mg/day. Examination of the carotid arteries using 2D and 3D ultrasound was performed at 28, 52 and 104 weeks of treatment. The thickness of the carotid intima-media complex decreased in both groups, there were no significant intergroup differences. The decrease in the volume of atherosclerotic plaques was more significant during olmesartan therapy, and in the group of patients with an initial lesion volume greater than the median of the group, differences in the effectiveness of the drugs were significant.

The angioprotective effect of olmesartan was also shown in a comparative study with the dihydropyridine calcium antagonist amlodipine. Patients with hypertension and diabetes received either 20 mg of olmesartan or 5 mg of amlodipine for a year. With the same antihypertensive effect, olmesartan also contributed to a significant decrease in the cardio-ankle index, which reflects the severity of arterial stiffness. The authors of the study attribute the angioprotective effect of olmesartan to its antioxidant properties.

A decrease in central pressure has also been shown during treatment with olmesartan. The combination of olmesartan with dihydropyridine calcium antagonists is especially effective. In a randomized trial compared the effect of two combinations on the level of central blood pressure. 486 patients were allocated to treatment with olmesartan and amlodipine 40/10 mg or perindopril and amlodipine 8/10 mg. Central systolic pressure while taking the first combination decreased by 14.5 mm Hg, and when using the second combination by 10.4 mm Hg. Art. Differences between groups were significant. In the olmesartan group, normalization of blood pressure was achieved in 75.4% of patients, in the treatment with perindopril - in 57.5%. .

In combination therapy, the combination of olmesartan with a dihydropyridine calcium antagonist is more effective in reducing central aortic pressure than the combination of olmesartan and a thiazide diuretic. The decrease in pressure on the brachial artery was the same.

The basis of the angioprotective action of olmesartan may be its effect on the processes of peroxidation, the function of the vascular endothelium, the level of inflammatory mediators, and some biomarkers. The antioxidant effect of olmesartan was shown in a small study where 20 patients with hypertension received olmesartan therapy at a dose of 20 mg / day for 6 months. The drug was effective and allowed to normalize blood pressure in all patients. At the same time, the level of markers of oxidative stress and oxidized lipoproteins, as well as markers of inflammation, significantly decreased.

In a comparative study on a group of 31 patients with hypertension compared the efficacy of olmesartan and amlodipine. Both drugs were equally effective in lowering blood pressure, but only with the use of olmesartan were signs of improvement in endothelial function revealed. Only treatment with olmesartan improved the degree of reactive hyperemia. In the same group, a decrease in the level of albuminuria, a decrease C-reactive protein. Increased urine antioxidant levels. The dynamics of the plasma level of superoxide disumutase was not revealed, however, there was a correlation between the level of this antioxidant defense enzyme and the degree of endothelium-dependent vasodilation.

In a group of 30 patients with hypertension, the effects of long-term (6 months) therapy with olmesartan at a dose of 20 mg/day were evaluated. Olmesartan effectively reduced blood pressure, contributed to a significant decrease in the cardio-ankle index, which reflects the stiffness of the arterial wall. The level of C-reactive protein and the protein that binds fatty acids of adipocytes significantly decreased.

All these angioprotective properties create the prerequisites for the effectiveness of olmesartan in the prevention of vascular dementia and cerebral stroke.

Cerebroprotective properties of olmesartan

The basis of the cerebroprotective effect of olmesartan may be its effect on the state of cerebral blood flow. This was shown in a study where a group of elderly hypertensive patients with no history of CNS involvement received olmesartan for 24 months. Initially, a decrease in regional blood flow in the frontal, parietal, temporal, and occipital lobes was shown by 11–20% compared with the control group, which included persons comparable in age but without AH. Initially, in the group of patients with hypertension, the mean blood pressure was 156/88 mm Hg. Art., and against the background of treatment with olmesartan - 136/78 mm Hg. Art. At the same time, at the end of treatment, the indices of regional cerebral blood flow did not differ from those in the control group.

In the group of patients who had a stroke, the efficacy of olmesartan therapy at a dose of 10–20 mg per day for 8 weeks was evaluated. During treatment, patients showed a significant improvement in the state of regional cerebral blood flow. The increase in cerebral blood flow in the affected area was 11.2%, in the contralateral zone - 8.9%. Improved autoregulation of tone cerebral vessels. As a result, this led to an improvement in the processes of rehabilitation of patients after a stroke and a decrease in neurological deficit. An improvement in the condition of patients according to the Bartels index and the MMSE scale was registered. When comparing the effectiveness of olmesartan and amlodipine therapy in patients after stroke, it turned out that with the same effect on peripheral blood pressure, only olmesartan therapy improved cerebral blood flow. Only in the group treated with olmesartan after a stroke, there was an increase in cerebral blood flow both from the side of the lesion and in the healthy hemisphere, as well as an increase in cerebrovascular reserve. The range of motion in the hand increased by 30%, the arm – by 40%, and the leg – by 100%. At the same time, the increase in movements in the arm and leg was significantly greater than during amlodipine therapy. The Bartels index and MMSE also increased.

Thus, olmesartan has not only good antihypertensive efficacy, the ability to reduce arterial stiffness, improve vascular endothelial function, but also has cerebroprotective properties. This allows us to recommend the drug primarily for the treatment of elderly patients with hypertension, for whom the task of maintaining cognitive functions is one of the priorities.

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For citation: Karpov Yu.A., Starostin I.V. Combined antihypertensive therapy: state of the art // BC. 2012. No. 25. S. 1283

An increase in blood pressure (BP) is the result of a complex interaction genetic factors and environmental factors leading to activation and/or suppression of blood pressure regulation systems. The complexity of the mechanisms that provide BP control, which was first mentioned by Irvine Page, significantly affects differences in individual sensitivity to antihypertensive therapy. A huge number of options for arterial hypertension (AH) makes it almost impossible, with few exceptions, to determine a specific option for increasing blood pressure in the daily practice of a doctor who decides on the choice of treatment.

Hypertension is a hemodynamic disorder by definition, and increased peripheral vascular resistance is the hallmark hemodynamic feature of elevated BP. Understanding this fact led to the discovery and development of a special class of vasodilators with a targeted mechanism of action, although many of the previously used antihypertensive agents also had a vasodilatory effect, for example, by blocking the activity of the sympathetic nervous system. The first non-specific vasodilator was hydralazine, followed by vasodilators that block calcium channels of vascular smooth muscle cells (calcium antagonists - AA), postsynaptic α-adrenergic receptors of peripheral neurons of the sympathetic nervous system (α-blockers) and blockers of the renin-angiotensin-aldosterone system (RAAS) ( angiotensin converting enzyme inhibitors (ACE inhibitors), angiotensin receptor blockers (ARBs), and finally direct renin inhibitors (RIRs).
The vasodilatory effect is also inherent in thiazide diuretics (TD), which, by reducing the sodium content in vascular smooth muscle cells, reduce their sensitivity to vasopressors - catecholamines, etc. When using antihypertensive drugs in a heterogeneous population of hypertensive patients, the selectivity of active substances and their other features lead to an unpredictable decrease in BP in each individual patient. For example, the appointment of an ACE inhibitor to a patient with hyperactivation of the RAAS due to stenosis renal artery will lead to a significant decrease in blood pressure and impaired renal function. In turn, the appointment of ACE inhibitors to older people and people of the Negroid race (who in most cases have a reduced level of RAAS activity) will only lead to a slight decrease in blood pressure. Most often, the "phenotype" of hypertension in a particular patient remains unspecified.
A recent meta-analysis of 354 placebo-controlled trials of various antihypertensive monotherapy regimens in specially selected hypertensive patients (n=56,000) showed a mean placebo-adjusted decrease in systolic BP of 9.1 mmHg. and diastolic blood pressure - by 5.5 mm Hg. . These average values ​​hide a wide range of individual reactions to antihypertensive therapy - from a decrease in SBP by 20-30 mm Hg. and until there is no effect, and sometimes even some increase in blood pressure.
The second factor that determines the individual response to antihypertensive monotherapy is the individual differences in BP counterregulation systems activated in response to a decrease in its level. In some cases, such a reaction can completely compensate for the decrease in blood pressure. Thus, the use of antihypertensive monotherapy does not always give a satisfactory result. What should be the next step in such a situation? Should I increase the dose, change the drug, or use a combination of antihypertensive agents?
Rationale for application
combined antihypertensive therapy
The rationale for using combination therapy for hypertension is clear enough. First, in contrast to blindly administered monotherapy, the combination of drugs acting on different systems regulation of blood pressure, significantly increases the likelihood of its effective reduction. Secondly, the appointment of a combination of drugs can be regarded as an attempt to block the activation of counterregulatory systems that counteract the decrease in blood pressure during the use of monotherapy (Fig. 1).
Thirdly, a significant part of the population of patients with hypertension suffers from the so-called moderate or severe hypertension (stage 2), this group includes patients with systolic blood pressure over 160 mm Hg. and / or diastolic blood pressure more than 100 mm Hg, which is about 15-20% of all patients with hypertension. These patients are at the highest risk of cardiovascular events. Increase in blood pressure for every 20 mm Hg. doubles the risk of such events.
The risk of hypertension increases with age, and the proportion of patients with stage 2 hypertension also increases. An increase in the proportion of patients with isolated systolic AH, which is the cause of loss of vascular elasticity and an increase in vascular resistance, is also associated with age.
Despite some differences in recommendations, in some of them combination treatment is considered first-line therapy, however, only under certain conditions. Such a place of combination therapy is natural in view of the risks of severe hypertension, the recognition of the inevitability of using dual (and sometimes triple) therapy to achieve target blood pressure values ​​of less than 140/90 mm Hg. and the need to quickly lower blood pressure to a more acceptable level to reduce the risks.
For systolic BP 20 mmHg above target and/or diastolic BP 10 mmHg above target, the US Joint National Committee on the Prevention, Diagnosis, and Treatment of High Blood Pressure (JNC-7) recommends start antihypertensive therapy with a combination of two drugs. Similar recommendations are contained in the latest Russian recommendations, and the recommendation for the use of combined first-line antihypertensive therapy also applies to patients with more low levels AD with multiple risk factors, target organ damage, diabetes mellitus, kidney disease, or associated cardiovascular disease.
There are concerns that the use of more than one antihypertensive drug at the start of treatment may, in some cases, provoke clinically significant hypotension and increase the risk of coronary events. An analysis of studies on the treatment of hypertension has provided some evidence for the existence of a J-shaped relationship between BP reduction and cardiovascular risk, however, apparently, this applies to high-risk patients, including those with known CAD, when a pronounced decrease in BP can lead to poor myocardial perfusion. Patients with uncomplicated hypertension tolerate low blood pressure satisfactorily, as, for example, in the Systolic hypertension in Elderly study (“Systolic hypertension in the elderly”), where in the active treatment group it was possible to reduce systolic blood pressure to 60 mmHg. . Ongoing studies designed to compare initiation of antihypertensive therapy with dual and sequential monotherapy will evaluate the safety of the new approach.
Fourth, compared with monotherapy, combination therapy can achieve a decrease in BP variability. Additional analysis of several randomized trials showed that visit-to-visit systolic BP variability is a strong and independent of mean BP predictor of myocardial infarction and stroke. It is noteworthy that AK and diuretics showed the greatest effectiveness in reducing such variability in blood pressure and the risk of stroke. β-blockers, on the contrary, increased systolic BP variability in a dose-dependent manner and showed the least effectiveness in preventing stroke. The addition of an AA or, to a lesser extent, a diuretic to a RAAS inhibitor reduces systolic BP variability, which is an additional argument in support of combination therapy.
Combinations of drugs
There are 7 classes of antihypertensive drugs, each of which includes several representatives, so there are a large number of combinations (Table 1). Below, combinations will be presented in accordance with their division into rational (preferred), possible (acceptable) and unacceptable or ineffective. Assigning a combination to one group or another depends on data on outcomes, antihypertensive efficacy, safety and tolerability.
Rational (preferred) combinations
RAAS inhibitors and diuretics. Currently, this combination is most often used in clinical practice. A significant number of factorial design studies have shown additional BP reduction with the combination of TD and ACE inhibitors, ARBs, or PIRs. Diuretics reduce the volume of intravascular fluid, activate the RAAS, which inhibits the excretion of salt and water, and counteracts vasodilation. The addition of a RAAS inhibitor to a diuretic weakens the effect of this counterregulatory mechanism. In addition, the use of a diuretic can cause hypokalemia and impaired glucose tolerance, and RAAS blockers can reduce this undesirable effect. It has been shown that chlorthalidone reduces blood pressure more effectively than hydrochlorothiazide, because. has a longer duration of action, so chlorthalidone should be preferred as the second component in combination with a RAAS inhibitor. Most RAAS inhibitors are available in fixed combination with hydrochlorothiazide.
The Hypertension in the Very Elderly (HYVET) study, which evaluated the efficacy of the thiazide-like diuretic indapamide, was recently completed. ACE inhibitor perindopril was added to this diuretic to enhance the antihypertensive effect in 75% of patients. A 30% reduction in stroke and a 64% reduction in heart failure was shown with this combination compared to placebo.

With the use of a combination of an ACE inhibitor and a diuretic, the EPIGRAPH project was implemented under the auspices of the All-Russian Scientific Society of Cardiology. This project consisted of two multicenter studies- EPIGRAPH-1 and EPIGRAPH-2. This project is valuable in that it contributed to the creation of a non-fixed combination of Enzix (Stada), containing two drugs in one blister - enalapril (ACE inhibitor) and indapamide (diuretic), which allows, if necessary, to change their dosages and correlate the time of administration with circadian rhythm BP, have 2 drugs in one package, rather than using two separate ones. The drug is available in three forms: Enziks - 10 mg of enalapril and 2.5 mg of indapamide; Enziks Duo - 10 mg of enalapril and 2.5 mg of indapamide + 10 mg of enalapril; Enziks Duo forte - 20 mg of enalapril and 2.5 mg of indapamide + 20 mg of enalapril. Various dosages make it possible to correct therapy depending on the severity and risk of hypertension, drug tolerance.
In a study conducted in Ukraine, we studied the effect of long-term therapy with a non-fixed combination of enalapril and indapamide in 1 blister (Enzix, Enziks Duo) on the daily blood pressure profile and LV remodeling parameters, its systolic and diastolic function, as well as the quality of life of patients with stable hypertension. The results of the study showed that in patients with AH long-term use a combination of enalapril and indapamide (Enzix, Enziks Duo) significantly improves the magnitude and speed of the morning rise in blood pressure and has a positive effect on blood pressure variability. Also, the obtained data indicated that long-term use of a non-fixed combination of enalapril and indapamide in 1 blister (Enzix, Enzix Duo) has a distinct antihypertensive effect, leads to a reversal of LV remodeling and improvement of its diastolic function, an increase in the quality of life along with a good safety profile and portability.

RAAS inhibitors and calcium antagonists. Combining AK with an ACE inhibitor, ARB or PIR allows you to achieve an additional reduction in blood pressure. Peripheral edema is a common dose-dependent adverse event observed with monotherapy with dihydropyridine AKs. The severity of this undesirable phenomenon can be weakened by adding a RAAS inhibitor to AK. According to a recent meta-analysis, ACE inhibitors are more effective than ARBs in this regard. According to the results of the ACCOMPLISH study (The Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension Trial, Study on the use of combination therapy to prevent cardiovascular events in patients with systolic hypertension), the fixed combination of ACE inhibitor benazepril with AK amlodipine is more effective in reducing morbidity and mortality than the fixed combination of an ACE inhibitor with hydrochlorothiazide. Overall, ACE inhibitors and ARBs showed similar reductions in endpoints, although it has been suggested that ACE inhibitors are slightly more cardioprotective and ARBs are better at protecting against strokes.
The international INVEST study compared two antihypertensive regimens: verapamil, to which trandolapril was added if necessary, and atenolol, to which hydrochlorothiazide was added, if necessary. The study included 22,576 patients with hypertension diagnosed with coronary artery disease, the observation was carried out for 2.7 years. The main composite endpoint, represented by cardiovascular events, was reached in both groups with the same frequency. Apparently, this can be explained by the fact that the disadvantages of the treatment regimen, which included a β-blocker in hypertension, were compensated by the advantages of β-blockers in CAD.
b-blockers and diuretics. Not all experts consider this combination to be rational. At the same time, it has been shown that the addition of diuretics to β-blockers causes an increase in the antihypertensive effect in populations with low-renin AH. Although both classes of drugs have similar side effects in terms of impaired glucose tolerance, development of diabetes mellitus and sexual dysfunction, however, the real clinical significance of "metabolic" side effects is greatly exaggerated, and endpoint studies have shown that the use of such a combination leads to a decrease in cardiovascular morbidity and mortality.
Possible (acceptable) combinations
Calcium channel blockers and diuretics. Most physicians do not always combine AKs with diuretics. However, in the VALUE (Valsartan Antihypertensive Long-term Use Evaluation Trial) study, hydrochlorothiazide was added to amlodipine, when it was not effective enough, and this combination was well tolerated by patients, although the risk of detecting diabetes mellitus and hyperkalemia increased compared with the valsartan group. However, in the amlodipine group, the reduction in morbidity and mortality was not less than in the valsartan group.
Calcium channel blockers and β-blockers. The combination of a β-blocker with dihydropyridine AK has additional effect to reduce blood pressure and is generally well tolerated. Conversely, β-blockers should not be combined with non-dihydropyridine AKs such as verapamil and diltiazem. The combination of the negative chronotropic effect of both classes of drugs can lead to the development of bradycardia or heart block, up to complete transverse, and death of the patient.
Double blockade of calcium channels. A recent meta-analysis showed that the combination of dihydropyridine AK with verapamil or diltiazem leads to an additional decrease in blood pressure without a significant increase in the frequency of adverse events. Such combination therapy can be used in patients with documented angioedema while taking RAAS inhibitors, as well as in patients with severe renal insufficiency, accompanied by a risk of hyperkalemia. However, data on long-term safety and outcomes against the background of such therapy are currently not available.
Double blockade of the RAAS. The use of this combination is based on an increase in blood pressure-lowering effect, which has been proven in a number of studies. However, the importance of this combination has diminished due to the lack of evidence of safety in long-term studies. In the ONTARGET study, patients receiving combination therapy with telmisartan and ramipril had more adverse events, and the number of cardiovascular events, despite some additional reduction in blood pressure, did not decrease compared with monotherapy. Thus, in such a combination in patients with a high risk of adverse events, there is little point. However, due to the fact that blockade of the RAAS by ACE inhibitors or ARBs increases plasma renin activity, it has been suggested that the addition of direct inhibitor renin. In a double-blind study of the combination of aliskiren and an ARB conducted in 1797 patients, a small but statistically significant decrease in blood pressure was found. Notably, in an open prospective cross-sectional study of patients with resistant hypertension, the aldosterone antagonist spironolactone was more effective in lowering blood pressure than double RAAS blockade. Use of a combination of PIR with an ACE inhibitor or ARB in the ALTITUDE (Aliskiren Trialin Type 2 Diabetes Using Cardiovascular and Renal Disease End points) study based on the results of the interim analysis in 2012 proved to be inappropriate due to the increased risk of adverse events, and the study was prematurely terminated. Apparently, it is advisable to transfer combinations of ACE inhibitors with ARBs to the group of non-recommended combinations.
Unacceptable and ineffective combinations
RAAS blockers and β-blockers. The combination of these classes of drugs is often used in patients who have had a myocardial infarction, as well as in patients with heart failure, because. they have been shown to reduce recurrent heart attacks and improve survival. However, this combination does not provide any additional reduction in blood pressure in comparison with monotherapy with these drugs. Thus, it is not reasonable to use a combination of a RAAS inhibitor and a β-blocker for the treatment of hypertension as such.
β-blockers and drugs with a central antiadrenergic effect. Combining β-blockers with centrally acting antiadrenergics such as clonidine provides little or no additional BP reduction. Moreover, when using such a combination, reactions with an excessive increase in blood pressure were even observed.
Other drug classes in combination therapy: α-blockers and spironolactone
α-adrenergic antagonists are widely used as adjunctive therapy to achieve BP targets. The emergence of extended-release dosage forms medicinal substance improved the tolerability profile of these drugs. Data from an observational analysis from the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) showed that doxazosin in the gastrointestinal therapeutic system dosage form, used as a third-line therapy, lowers blood pressure and causes a moderate decrease in serum lipids. In contrast to previous data from the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) study, doxazosin use in the ASCOT study did not show an association with an increase in heart failure.
Therapy consisting of 4 antihypertensive drugs is often required in patients with treatment-resistant drugs at maximum doses or triple antihypertensive therapy, including a RAAS blocker, AK and a thiazide diuretic, AH (failure to achieve target values<140/90 мм рт.ст.). Недавние сообщения свидетельствуют об эффективности добавления спиронолактона к тройной терапии, заключающейся в снижении АД в среднем на 22/9,5 мм рт.ст. Таким образом, спиронолактон может быть рекомендован в качестве компонента антигипертензивной терапии у больных с резистентной АГ.
Undesirable phenomena. There is evidence that the severity of edema associated with the use of dihydropyridine AKs can be reduced when RAAS blockers are added to the treatment, which can also reduce the incidence of hypokalemia caused by TD. On the other hand, the use of β-blockers is associated with an increase in the incidence of diabetes mellitus (DM), and when using a combination of TD with β-blockers, a more significant increase in the frequency of newly diagnosed DM is likely, however, paradoxically, this does not increase the frequency of cardiovascular events associated with such diabetes. -vascular endpoints, as shown in the ALLHAT study. The NICE guidelines provide data from a meta-analysis that found an increase in the incidence of newly diagnosed DM with the use of β-blockers and TD compared with more "newer" drugs.
The findings are based on the assumption that there are no differences in long-term morbidity and mortality between drugs within the same class. Among AKs, amlodipine has the largest evidence base. In studies on the study of ACE inhibitors and ARBs as part of combination therapy in patients with hypertension and other cardiovascular diseases, various representatives of these classes were studied, and no differences were found between them. There is an opinion that among thiazide and thiazide-like diuretics, chlorthalidone at medium doses (compared to other TDs at lower doses) has the greatest evidence base for long-term benefits. Unfortunately, further studies comparing drugs in this class seem unlikely.
The most commonly used β-blocker in studies was atenolol, and it has been repeatedly said that if other members of this class had been used in trials, the results would have been different. This seems unlikely, since Adverse events identified in the ASCOT study, which consisted of an effect on blood pressure variability and an increase in central intra-aortic pressure compared with amlodipine (both are associated with increased cardiovascular risk), most likely occur with most β-blockers. Studies investigating the effect of therapy with β-blockers with additional pharmacological properties (for example, β-1, β-2 and α-blocker carvedilol) on long-term outcomes in patients with hypertension have not been conducted.
Fixed combinations
and their advantages in influencing the prognosis
A recent review of the potential benefits of fixed-dose combinations (FDC) over the corresponding drugs taken alone found that FDC was associated with a significant improvement in adherence and a modest increase in the duration of dosing. The degree of adherence to treatment using FDA, according to a meta-analysis of 9 studies, is higher by 26% compared with taking the same drugs separately.
According to studies containing information on blood pressure values, the use of FDC is associated with a slight additional decrease in systolic and diastolic blood pressure (4.1 and 3.1 mm Hg, respectively). If maintained over a long period of time, these differences in blood pressure can translate into real benefits in cardiovascular outcomes.
Conclusion
Most patients with hypertension require therapy with two or more drugs from different classes of antihypertensive drugs to achieve target BP values. Combination antihypertensive therapy should be given to patients with BP greater than 20/10 mmHg above target. Rational (preferred) and possible (acceptable) drug combinations should be used. Fixed combinations increase adherence to therapy, which increases the frequency of achieving BP targets.

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Drug treatment of hypertension is indicated for all patients with blood pressure higher than 160/100 mm Hg. Art., and also when lifestyle modification measures have not led to the normalization of pressure indicators and it remains higher than 140/90 mm Hg. Art. There are many drugs that lower blood pressure. Depending on the composition and mechanism of action, they are divided into groups and even subgroups.

These drugs are called antihypertensive or antihypertensive drugs. We bring to your attention an overview of drugs for lowering blood pressure.

Principles of drug treatment of hypertension

Before considering each of the groups of drugs separately, let's briefly talk about the basic principles of drug treatment of essential hypertension, or hypertension.

1. Blood pressure lowering drugs must be taken by the patient continuously throughout life.
2. An antihypertensive agent should be prescribed exclusively by a doctor. Its choice depends on the individual characteristics of the course of the disease of a particular patient, on the presence or absence of insufficiency of the coronary vessels of the heart or arrhythmia, the type of hemodynamics, damage to target organs, the presence or absence of risk factors for heart and vascular diseases, concomitant pathology, and, finally, on the tolerability of this drug. drug to patients.
3. Treatment begins with the lowest possible dose of the drug, thus assessing the reaction of the patient's body to it and reducing the severity of possible side effects. If the drug is well tolerated, but there is no decrease in pressure to the desired figures, then the dose of the drug is increased, but not immediately to the maximum possible, but gradually.
4. It is unacceptable to quickly reduce blood pressure: this can lead to ischemic damage to vital organs. This point is especially relevant for elderly and senile patients.
5. Long-acting drugs are taken once a day. It is these drugs that should be preferred, since when taking them, daily fluctuations in blood pressure are less pronounced, plus it is easier for the patient to take 1 tablet in the morning and forget about it until tomorrow than to take 3 times a day, periodically skipping doses due to their own inattention.
6. If, when taking the minimum or average therapeutic dose of a drug containing only one active agent, the desired effect does not occur, the dose should not be increased to the maximum: it would be more correct (more effective) to add to the first drug a small dose of an antihypertensive agent of another group (with a different mechanism of action). Thus, not only a faster hypotensive effect will be ensured, but the side reactions of both drugs will be minimized.
7. There are drugs containing several active antihypertensive drugs from different groups at once. It is much more convenient for the patient to take such a drug than 2 or 3 separate tablets.
8. If the effect of the treatment is absent at all or if it is poorly tolerated by the patient (side effects are pronounced and cause inconvenience to the patient), this drug should not be combined with another or, moreover, its dose should be increased: it would be more correct to cancel this drug and proceed to drug treatment. means of another group. Fortunately, the choice of antihypertensive drugs is quite large, and, by trial and error, each individual patient will still be able to choose an adequate, effective antihypertensive therapy.

Classification of antihypertensive drugs

Drugs used to lower blood pressure can be divided into 2 large groups:
I. First line drugs. They are the drugs of choice in the treatment of hypertension. The vast majority of hypertensive patients are recommended to prescribe them. This group includes 5 more groups of medicines:

• angiotensin-converting enzyme inhibitors (abbreviated as ACE inhibitors);
• diuretics, or diuretics;
• angiotensin II receptor inhibitors;
• β-blockers, or β-blockers;
• calcium antagonists.

II. Second line drugs. For long-term treatment of essential hypertension, they are used only in certain classes of patients, for example, in women, or in people with low incomes who, for financial reasons, cannot afford the purchase of first-line drugs. These drugs include:

• α-blockers;
• rauwolfia alkaloids;
• α2-agonists of the central action;
• direct acting vasodilators.

Let's consider each of these groups separately.

Angiotensin-converting enzyme inhibitors, or ACE inhibitors

Group of the most effective antihypertensive drugs. The decrease in blood pressure when taking these drugs occurs due to vasodilation: their total peripheral resistance decreases, and consequently, the pressure also decreases. ACE inhibitors practically do not affect the magnitude of cardiac output and heart rate, therefore they are widely used in concomitant chronic heart failure.

Already after taking the first dose of the drug in this group, the patient notes a decrease in blood pressure. When used for several weeks, the hypotensive effect is enhanced and, having reached a maximum, stabilizes.

Adverse reactions to ACE inhibitors are observed quite rarely and are manifested mainly by an obsessive dry cough, taste disturbance and signs of hyperkalemia (increased levels of potassium in the blood). Hypersensitivity reactions to ACE inhibitors in the form of angioedema are rarely noted.

Since ACE inhibitors are excreted mainly by the kidneys, in severe patients, the dose of these drugs should be reduced. Drugs of this group are contraindicated during pregnancy, in case of bilateral stenosis of the renal arteries, as well as in case of hyperkalemia.

The main representatives of the class of ACE inhibitors are:

• enalapril (Enap, Berlipril, Renitek) - the daily dose of the drug ranges from 5-40 mg in 1-2 doses;
• captopril - taken at a dose of 25-100 mg per day for 2-3 doses;
• quinapril (Accupro) - the daily dose is 10-80 mg in 1-2 doses;
• lisinopril (Lopril, Diroton, Vitopril) - it is recommended to take 10-40 mg per day, the frequency of administration is 1-2 times;
• moexipril (Moex) - 7.5-30 mg daily dose, frequency of administration - 1-2 times; it is worth noting that this drug is one of the ACE inhibitors recommended for use by people with severe chronic renal failure;
• perindopril (Prenesa, Prestarium) - the daily dose is 5-10 mg in 1 dose;
• ramipril (Tritace, Ampril, Hartil) - a daily dose of 2.5-20 mg in 1-2 doses;
• spirapril (Quadropril) - taken at a dose of 6 mg 1 time per day;
• trandolapril (Gopten) - taken at a dose of 1-4 mg 1 time per day;
• Fosinopril (Fozicard) - take 10-20 mg 1-2 times a day.

Diuretics, or diuretics

Like ACE inhibitors, they are widely used in the treatment of hypertension. These drugs increase urine output, resulting in a decrease in circulating blood and extracellular fluid, a decrease in cardiac output, and vasodilation, all of which result in a decrease in blood pressure. It is worth noting that against the background of taking diuretics, development is possible.

Diuretic drugs are often used as part of combination therapy for hypertension: they remove excess water from the body, which is retained when taking many other antihypertensive drugs. They are contraindicated at.

Diuretics can also be divided into several groups.
1. Thiazide diuretics. Most often used with precisely hypotensive purpose. Generally, low dosages are recommended. They are ineffective in severe renal failure, which is also a contraindication to their use. The most commonly used thiazide diuretic is hydrochlorothiazide (Hypothiazide). The daily dose of this drug is 12.5-50 mg, the frequency of administration is 1-2 times a day.
2. Thiazide-like diuretics. The most prominent representative of this group of drugs is indapamide (Indap, Arifon, Ravel-SR). Take it, as a rule, 1.25-2.5-5 mg 1 time per day.
3. Loop diuretics. The drugs of this group do not play a significant role in the treatment of hypertension, however, in the case of concomitant or renal insufficiency in hypertensive patients, they are the drugs of choice. Often used in acute conditions. The main loop diuretics are:

• furosemide (Lasix) - the daily dose of this drug is from 20 to 480 mg, depending on the severity of the disease, the frequency of administration is 4-6 times a day;
• torasemide (Trifas, Torsid) - taken at a dose of 5-20 mg twice a day;
• ethacrynic acid (Uregit) - the daily dose ranges from 25-100 mg in two divided doses.

4. Potassium-sparing diuretics. They have a weak hypotensive effect, and also remove a small amount of sodium from the body, while retaining potassium. Alone for the treatment of hypertension are rarely used, more often in combination with drugs from other groups. Not applicable for . The most prominent representatives of this class are the following potassium-sparing diuretics:

• spironolactone (Veroshpiron) - the daily dose of the drug is 25-100 mg, the frequency of administration is 3-4 times a day;
• triamterene - take 25-75 mg 2 times a day.

Angiotensin II receptor inhibitors

The second name of the drugs in this group is sartans. This is a relatively new class of antihypertensive drugs that are highly effective. Provide effective 24-hour control of blood pressure when taking the drug 1 time per day. Sartans do not have the most common side effect of ACE inhibitors - dry, hacking cough, therefore, if ACE inhibitors are not tolerated, they are usually replaced with sartans. Preparations of this group are contraindicated during pregnancy, bilateral stenosis of the renal arteries, and also with hyperkalemia.

The main representatives of the sartans are:

• irbesartan (Irbetan, Converium, Aprovel) - it is recommended to take 150-300 mg 1 time per day;
• candesartan (Kandesar, Kasark) - taken at a dose of 8-32 g 1 time per day;
• losartan (Lozap, Lorista) - a daily dose of the drug 50-100 mg in 1 dose;
• telmisartan (Pritor, Micardis) - the recommended daily dose is 20-80 mg, in 1 dose;
• valsartan (Vazar, Diovan, Valsakor) - taken at a dose of 80-320 mg per day for 1 dose.

β-blockers

They reduce blood pressure due to the blocking effect on β-adrenergic receptors: cardiac output and renin activity in the blood plasma decrease. Especially indicated for arterial hypertension, combined with angina pectoris and some types. Because one of the effects of β-blockers is to decrease heart rate, these drugs are contraindicated in bradycardia.
Drugs in this class are divided into cardioselective and non-cardioselective.

Cardioselective β-blockers act exclusively on the receptors of the heart and blood vessels, and do not affect other organs and systems.
The drugs in this class include:

• atenolol (Atenol, Tenolol, Tenobene) - the daily dose of this drug is 25-100 mg, the frequency of administration is twice a day;
• betaxolol (Betak, Betacor, Lokren) - taken at a dose of 5-40 mg once a day;
• bisoprolol (Concor, Coronal, Biprol, Bicard) - taken at a dose of 2.5-20 mg per day at a time;
• metoprolol (Betaloc, Corvitol, Egilok) - the recommended daily dose of the drug is 50-200 mg in 1-3 doses;
• nebivolol (Nebilet, Nebilong, Nebival) - take 5-10 mg once a day;
• celiprolol (Celiprol) - take 200-400 mg once a day.

Cardioselective β-blockers affect the receptors not only of the heart, but also of other internal organs, therefore they are contraindicated in a number of pathological conditions, such as chronic obstructive pulmonary disease, intermittent claudication.

The most commonly used representatives of this class of drugs are:

• propranolol (Anaprilin) ​​- taken at 40-240 mg per day in 1-3 doses;
• carvedilol (Coriol, Medocardil) - the daily dose of the drug is 12.5-50 mg, the frequency of administration is 1-2 times a day;
• labetalol (Abetol, Labetol) - it is recommended to take 200-1200 mg per day, dividing the dose into 2 doses.

calcium antagonists

They reduce blood pressure well, but due to the mechanisms of their action, they can have very serious side effects.

1. Phenylalkylamine derivatives. Verapamil (Finoptin, Isoptin, Veratard) - it is recommended to take at a dose of 120-480 mg per day in 1-2 doses; can cause bradycardia and atrioventricular block.
2. Benzothiazepine derivatives. Diltiazem (Aldizem, Diacordin) - its daily dose is equal to that of verapamil and is 120-480 mg in 1-2 doses; causes bradycardia and AV block.
3. Derivatives of dihydropyridine. They have a pronounced vasodilating effect. Can cause, acceleration of the heart rate,. The main representatives of this class of calcium antagonists are as follows:

• amlodipine (Azomeks, Amlo, Agen, Norvask) - the daily dose of the drug is 2.5-10 mg in one dose;
• lacidipine (Lacipil) - take 2-4 mg per day at a time;
• lercanidipine (Zanidip, Lerkamen) - take 10-20 mg once a day;
• nifedipine (retard - long-acting - forms: Corinfar retard, Nifecard-XL, Nicardia) - take 20-120 mg per day at a time;
• felodipine (Felodipine) - the daily dose of the drug is 2.5-10 mg in one dose.

Combined drugs

Often, first-line antihypertensive drugs are part of combined preparations. As a rule, it contains 2, less often - 3 active substances belonging to different classes, which means that they reduce blood pressure in different ways.

Here are some examples of such drugs:

• Triampur - hydrochlorothiazide + triamterene;
• Tonorma - atenolol + chlorthalidone + nifedipine;
• Captopress - captopril + hydrochlorothiazide;
• Enap-N - enalapril + hydrochlorothiazide;
• Liprazide - lisinopril + hydrochlorothiazide;
• Vazar-N - valsartan + hydrochlorothiazide;
• Ziak - bisoprolol + hydrochlorothiazide;
• Bi-Prestarium - amlodipine + perindopril.

α-blockers

Currently, they are used relatively rarely, as a rule, in combination with 1st line drugs. The main very serious drawback of drugs in this group is that their long-term use increases the risk of developing heart failure, acute cerebrovascular accidents (strokes) and sudden death. However, α-blockers also have a positive property that distinguishes them from other drugs: they improve carbohydrate and lipid metabolism, which is why they are the drugs of choice for the treatment of hypertension in people with concomitant diabetes mellitus and dyslipidemia.

The main representatives of this class of drugs are:

• prazosin - take it 1-20 mg 2-4 times a day; this drug is characterized by the effect of the 1st dose: a sharp decrease in blood pressure after the first dose;
• doxazosin (Kardura, Zoxon) - the recommended dose is 1-16 mg 1 time per day;
• terazosin (Kornam, Alfater) - 1-20 mg per day for 1 dose;
• phentolamine - 5-20 mg per day.

Rauwolfia preparations

They have a good hypotensive effect (develops after about 1 week of regular drug intake), but they have many side effects, such as drowsiness, depression, nightmares, insomnia, dry mouth, anxiety, bradycardia, bronchospasm, weakening of potency in men, vomiting , allergic reactions, . Of course, these drugs are cheap, so many elderly hypertensive patients continue to take them. However, among the first-line drugs, there are also financially affordable options for most patients: they should be taken if possible, and rauwolfia drugs should be gradually abandoned. These drugs are contraindicated in severe, epilepsy, parkinsonism, depression, bradycardia and severe heart failure.
Representatives of rauwolfia preparations are:

• reserpine - it is recommended to take 0.05-0.1-0.5 mg 2-3 times a day;
• raunatin - taken according to the scheme, starting with 1 tablet (2 mg) per day at night, increasing the dose by 1 tablet every day, bringing up to 4-6 tablets per day.

Combinations of these drugs are most often used:

• Adelfan (reserpine + hydralazine + hydrochlorothiazide);
• Sinepres (reserpine + hydralazine + hydrochlorothiazide + potassium chloride);
• Neokristepin (reserpine + dihydroergocristine + chlorthalidone).

Central α2 receptor agonists

Drugs in this group reduce blood pressure by acting on the central nervous system, reducing sympathetic hyperactivity. They can cause quite serious side effects, but in certain clinical situations they are indispensable, for example, methyldopa for hypertension in pregnant women. Side effects of central α2 receptor agonists are due to their effect on the central nervous system - this is drowsiness, decreased attention and reaction speed, lethargy, depression, weakness, fatigue, headache.
The main representatives of this group of drugs are:

• Clonidine (Clonidine) - used at 0.75-1.5 mg 2-4 times a day;
• Methyldopa (Dopegit) - a single dose is 250-3000 mg, the frequency of administration is 2-3 times a day; the drug of choice for the treatment of arterial hypertension in pregnant women.

Direct acting vasodilators

They have a mild hypotensive effect due to moderate vasodilation. More effective in the form of injections than when taken orally. The main disadvantage of these drugs is that they cause the "steal" syndrome - roughly speaking, they disrupt the blood supply to the brain. This limits their intake in people suffering from atherosclerosis, and this is the bulk of patients with high blood pressure.
Representatives of this group of drugs are:

• bendazol (Dibazol) - inside is used at 0.02-0.05 g 2-3 times a day; more often used intramuscularly and intravenously to quickly lower blood pressure - 2-4 ml of a 1% solution 2-4 times a day;
• hydralazine (Apressin) - the initial dose is 10-25 mg 2-4 times a day, the average therapeutic dose is 25-50 g per day in 4 divided doses.

Medicines for the treatment of hypertensive crises

In order to treat uncomplicated, it is recommended to reduce the pressure not immediately, but gradually, over 1-2 days. Based on this, the drugs are prescribed in the form of tablets.

• Nifedipine - used orally or under the tongue (this method of administration is equated to intravenous efficiency) 5-20 mg; when taken orally, the effect occurs after 15-20 minutes, while sublingual - after 5-10 minutes; possible side effects such as headache, severe hypotension, tachycardia, redness of the skin of the face, symptoms of angina pectoris;
• Captopril - used at 6.25-50 mg under the tongue; begins to act in 20-60 minutes;
• Clonidine (Clonidine) - taken orally at 0.075-0.3 mg; the effect is observed after half an hour or an hour; side effects include the effect of sedation, dry mouth; care should be taken when using this drug in patients with;
• Nitroglycerin - the recommended dose is 0.8-2.4 mg sublingually (under the tongue); the hypotensive effect occurs quickly - after 5-10 minutes.

In the treatment of complicated hypertensive crises, the patient is prescribed intravenous infusions (infusions) of drugs. At the same time, blood pressure is constantly monitored. Most of the drugs used for this purpose begin to act within a few minutes after administration. As a rule, use the following drugs:

• Esmolol - injected intravenously; the onset of action is noted within 1-2 minutes after the start of the infusion, the duration of action is 10-20 minutes; is the drug of choice for dissecting aortic aneurysm;
• Sodium nitroprusside - used intravenously; the effect is noted immediately after the start of the infusion, lasts - 1-2 minutes; against the background of the administration of the drug, nausea, vomiting, as well as a sharp decrease in blood pressure may occur; caution should be exercised when using sodium nitroprusside in individuals with azotemia or high intracranial pressure;
• Enalaprilat - administered intravenously at 1.25-5 mg; the hypotensive effect begins 13-30 minutes after the injection and lasts for 6-12 hours; this drug is especially effective in acute insufficiency of the left ventricle;
• Nitroglycerin - administered intravenously; the effect develops 1-2 minutes after the infusion, the duration of action is 3-5 minutes; against the background of infusion often there is an intense headache, nausea; direct indications for the use of this drug are signs of ischemia of the heart muscle;
• Propranolol - administered intravenously by drip, the effect develops after 10-20 minutes and lasts for 2-4 hours; this drug is especially effective in acute coronary syndrome, as well as in the case of a dissecting aortic aneurysm;
• Labetalol - administered intravenously in a stream of 20-80 mg every 5-10 minutes or intravenously drip; a decrease in blood pressure is noted after 5-10 minutes, the duration of the effect is 3-6 hours; against the background of taking the drug, a sharp decrease in pressure, nausea, bronchospasm is possible; it is contraindicated in case of acute heart failure;
• Phentolamine - injected intravenously at 5-15 mg, the effect is noted after 1-2 minutes and lasts for 3-10 minutes; tachycardia, headache, and redness of the face may occur; this drug is especially indicated for a hypertensive crisis against the background of a tumor of the adrenal glands - pheochromocytoma;
• Clonidine - intravenously injected at 0.075-0.3 mg, the effect develops after 10 minutes; side effects include nausea and headache; possible development of tolerance (insensitivity) to the drug.

Since complicated hypertensive crises are often accompanied by fluid retention in the body, their treatment should begin with an intravenous jet injection of a diuretic - furosemide or torasemide at a dose of 20-120 mg. If the crisis is accompanied by increased urination or severe vomiting, diuretics are not indicated.
In Ukraine and Russia, with a hypertensive crisis, drugs such as magnesium sulfate (popularly Magnesia), papaverine, dibazol, aminofillin and the like are often administered. Most of them do not have the desired effect, lowering blood pressure to certain numbers, but, on the contrary, lead to rebound hypertension: an increase in pressure.

Which doctor to contact

To prescribe antihypertensive therapy, you must consult a therapist. If the disease is discovered for the first time or it is difficult to treat, the therapist may refer the patient to a cardiologist. In addition, all patients with hypertension are examined by a neurologist and an ophthalmologist to exclude damage to these organs, and ultrasound of the kidneys is also performed to exclude renovascular or renal secondary hypertension.