Beta-blockers - a description of the drugs and their use. Beta-blockers (bab) Effects of blockers

Before the first trials of β-blockers, no one expected that they would have an antihypertensive effect. However, it turned out that pronetalol (this drug has not found clinical use) reduces blood pressure in patients with angina pectoris and arterial hypertension (AH). Subsequently, the hypotensive effect was found in propranolol and other β-blockers.

Mechanism of action

The hypotensive effect of drugs in this group is determined precisely by their β-blocking action. Blockade of β-adrenergic receptors affects blood circulation through many mechanisms, including through a direct effect on the heart: a decrease in myocardial contractility and cardiac output. And on healthy people at restβ-blockers, as a rule, do not have a hypotensive effect, but reduce blood pressure in patients with hypertension, as well as during exercise or stress. In addition, against the background of blockade of β-adrenergic receptors, renin secretion decreases, and hence the formation of angiotensin II, a hormone that has multiple effects on hemodynamics and stimulates the formation of aldosterone, i.e., the activity of the renin-angiotensin-aldosterone system decreases.

Pharmacological properties

Beta-blockers differ in fat solubility, selectivity (selectivity) with respect to β 1 -adrenergic receptors, the presence of internal sympathomimetic activity (ICA, the ability of a β-blocker to partially excite β-adrenergic receptors that it suppresses, which reduces undesirable effects) and quinidine-like (membrane-stabilizing, local anesthetic) actions, but have the same hypotensive effect. Almost all β-blockers reduce renal blood flow rather quickly, but kidney function is rarely affected even with long-term use.

Application

Beta-blockers are effective in hypertension of any severity. They differ significantly in pharmacokinetics, but the hypotensive effect of all these drugs is long enough that they can be taken twice a day. Beta-blockers are less effective in the elderly and dark-skinned, although there are exceptions. Usually, these drugs do not cause salt and water retention, and therefore there is no need to prescribe diuretics to prevent the development of edema. However, diuretics and β-blockers enhance the hypotensive effect of each other.

Side effects

Beta-blockers should not be prescribed for bronchial asthma, weakness syndrome sinus node or violations of atrioventricular conduction, as well as during pregnancy and before childbirth.

They are not first-line drugs in the combination of hypertension with heart failure, as they reduce myocardial contractility and at the same time increase the total peripheral vascular resistance. Beta-blockers should also not be prescribed to patients with insulin-dependent diabetes mellitus.

Beta-blockers without ICA increase the concentration of triglycerides in plasma, and high-density lipoprotein cholesterol - reduce, but do not affect total cholesterol. Preparations with ICA almost do not change the lipid profile or even increase the level of high-density lipoprotein cholesterol. The long-term effects of these effects are not known.

After the abrupt cancellation of some β-blockers, rebound syndrome occurs, manifested by tachycardia, heart rhythm disturbances, increased blood pressure, exacerbation of angina pectoris, the development of myocardial infarction, and sometimes even sudden lethal outcome. Thus, β-blockers should be discontinued only under close supervision, gradually reducing the dose over 10-14 days until completely cancelled.

Non-steroidal anti-inflammatory drugs, for example, indomethacin, can weaken the hypotensive effect of β-blockers.

A paradoxical increase in blood pressure in response to taking β-blockers is observed with hypoglycemia and pheochromocytoma, as well as after the abolition of clonidine or against the background of the administration of adrenaline.

I generation - non-selective β-blockers (blockers of β 1 - and β 2 -adrenergic receptors)

Non-selective β-adrenergic blockers have a large number of β 2 -adrenergic receptors due to blockade side effects: narrowing of the bronchi and increased cough, increased tone of the smooth muscles of the uterus, hypoglycemia, hypothermia of the extremities, etc.

Propranolol (Anaprilin, Obzidan®)

Kind of the standard against which other β-blockers are compared. It does not have an ICA and does not react with α-adrenergic receptors. Fat-soluble, therefore, it quickly penetrates the central nervous system, providing a calming effect. The duration of action is 6-8 hours. Rebound syndrome is characteristic. Possible individual hypersensitivity to the drug with a rapid and significant drop in blood pressure, so you should start taking propranolol with a low dose (5-10 mg) under medical supervision. The dosage regimen is individual, from 40 to 320 mg / day. in 2-3 doses for hypertension.

Pindolol (Whisken®)

It has BCA, moderate fat solubility, and also a weak membrane-stabilizing effect, which has no clinical significance. The dosage regimen is set individually from 5 to 15 mg / day. in two steps.

Timolol

A powerful β-adrenergic blocker that does not have an ICA and membrane stabilizing action. Dosage regimen - 10-40 mg / day in 2 divided doses. More widely used in ophthalmology for the treatment of glaucoma (in the form of eye drops), but even instillation of timolol into conjunctival sac can cause a pronounced systemic effect - up to asthma attacks and decompensation of heart failure.

Nadolol (Korgard™)

Prolonged β-blocker (half-life - 20-24 hours), without quinidine-like action and ICA. Approximately equally blocks β 1 - and β 2 -adrenergic receptors. The dosage regimen is individual, from 40 to 320 mg per day once.

II generation - selective (cardioselective) β 1 -blockers

Selective β-blockers rarely cause complications, but it should be noted that in high doses, even they can partially block β 2 -adrenergic receptors, i.e., their cardioselectivity is relative.

Atenolol (Betacard®)

It used to be very popular. It is water-soluble, so it does not penetrate the blood-brain barrier well. Does not have an ICA. Cardioselectivity index - 1:35. Rebound syndrome is characteristic. The dosage regimen for hypertension is 25-200 mg / day. in 1-2 doses.

metoprolol

Metoprolol is a fat-soluble β-blocker, and therefore is used in the form of salts: tartrate and succinate, which improves its solubility and delivery rate to the vascular bed. The type of salt and production technology determine the duration of the therapeutic effect of metoprolol.

• Metoprolol tartrate is the standard form of metoprolol, the duration of the clinical effect of which is 12 hours. It is represented by the following trade names: Betaloc®, Corvitol®, Metocard®, Egilok®, etc. The dosage regimen for hypertension is 50-200 mg / day. in 2 doses. There are prolonged forms of metoprolol tartrate: Egilok® Retard tablets of 50 and 100 mg, dosing regimen - 50-200 mg / day. once.

• Metoprolol succinate is represented by retard dosage form delayed release active substance, due to which the therapeutic effect of metoprolol lasts more than 24 hours. It is produced under the trade names: Betalok® ZOK, Egilok® S. Dosage regimen - 50-200 mg / day. once.

Bisoprolol (Concor®, Aritel®, Bidop®, Biol®, Bisogamma®, Cordinorm, Coronal, Niperten, etc.)

Perhaps the most common β-blocker today. It does not have BCA and membrane stabilizing effect. Cardioselectivity index - 1:75. It is allowed to take bisoprolol with diabetes(with caution in the decompensation phase). Less pronounced rebound syndrome. The dosage regimen is individual - 2.5-10 mg / day. in one go.

Betaxolol (Lokren®)

It has a weak membrane-stabilizing effect. Does not have a VSA. Cardioselectivity index -1:35. Works for a long time. Dosing regimen - 5-20 mg / day. once.

III generation - β-blockers with vasodilating (vasodilating) properties

The most clinically important members of this group are carvedilol and nebivolol.

Carvedilol (Vedicardol®, Acridilol®)

Non-selective β-blocker without ICA. Expands peripheral vessels (due to the blockade of α 1 -adrenergic receptors) and has antioxidant properties. Dosing regimen for hypertension - 12.5-50 mg / day. in 1-2 doses.

In this article, we will consider drugs beta-blockers.

A very important role in the regulation of functions human body play catecholamines, which are adrenaline with norepinephrine. They are released into the blood and act on especially sensitive nerve endings called adrenoreceptors. They are divided into two large groups. The first is alpha-adrenergic receptors, and the second is found in many human organs and tissues.

Detailed description of this group of drugs

Beta-blockers, or BABs for short, are a group of medicinal substances, which bind beta-adrenergic receptors and prevent the effects of catecholamines on them. Such preparations are particularly useful in cardiology.

In the case of activation of β1-adrenergic receptors, an increase in the frequency and strength of heart contractions occurs, and in addition, coronary arteries, increases the level of conduction and automatism of the heart. Among other things, the breakdown of glycogen in the liver is enhanced and energy is produced.

In the case of excitation of β2-adrenergic receptors, the walls of blood vessels and bronchial muscles relax, uterine tone decreases during pregnancy, insulin secretion increases along with the breakdown of fat. Thus, the process of stimulation of beta-adrenergic receptors through catecholamines leads to the mobilization of all forces, which contributes to active life.

A list of new generation beta-blockers will be presented below.

The mechanism of action of drugs

These drugs are able to reduce the frequency along with the force of heart contractions, thereby lowering blood pressure. As a result, oxygen consumption by the heart muscle decreases.

There is an elongation of diastole - a period of rest and general relaxation of the heart, during which the vessels are filled with blood. The improvement of coronary perfusion is also facilitated by a decrease in diastolic intracardiac pressure. There is a process of redistribution of blood flow from normally vascularized areas to ischemic areas, as a result of which a person's tolerance to physical activity increases.

Beta-blockers have antiarrhythmic effects. They are able to suppress the cardiotoxic and arrhythmogenic effects of catecholamines, and in addition, they prevent the accumulation of calcium ions in the heart cells, which impair energy metabolism in the myocardial region.

The list of beta-blockers is very extensive.

Classification of drugs in this group

Substances presented are quite a large group of medicines. They are classified according to many criteria. Cardioselectivity is the ability of a drug to block only β1-adrenergic receptors, without affecting β2-adrenergic receptors located in the vascular and bronchial walls. The greater the selectivity of beta-1-blockers, the less danger in their use in concomitant pathologies of the respiratory canals and peripheral vessels, and in addition, in diabetes mellitus. But selectivity is a relative concept. In the case of prescribing the drug in excessive doses, the degree of selectivity decreases.

Some beta-blockers are characterized by the presence of internal sympathomimetic activity. It lies in the ability to some extent cause stimulation of beta-adrenergic receptors. Compared to conventional beta-blockers, such drugs slow down heart rate and contraction much less, less often lead to withdrawal symptoms. In addition, they do not have such a negative effect on lipid metabolism.

Some selective beta-blockers can additionally dilate blood vessels, that is, they are endowed with vasodilatory properties. This mechanism is usually realized through internal pronounced sympathomimetic activity.

The duration of exposure most often directly depends on the characteristics chemical structure selective and non-selective beta-blockers. Lipophilic agents can act for several hours and are quickly excreted from the body. Hydrophilic drugs, such as Atenolol, are effective for a longer time and may be prescribed less frequently. To date, long-acting lipophilic drugs have also been developed, for example, Metoprolol Retard. In addition, there are beta-blockers with a very short duration of exposure, only up to thirty minutes, as an example, the drug "Esmolol" can be mentioned.

Non-cardioselective drugs

The group of non-cardioselective beta-blockers includes drugs that do not have intrinsic sympathomimetic activity. These are the following:

• Means based on propranolol, for example, Anaprilin and Obzidan.
• Preparations based on nadolol, for example, Korgard.
• Medicines based on sotalol: "Sotahexal" along with "Tenzol".
• Funds based on timolol, for example "Blocarden".

The list of beta-blockers with sympathomimetic activity includes the following drugs:

• Medicines based on oxprenolol, for example Trazikor.
• Pindolol-based products, such as Wisken.
• Preparations based on alprenolol, for example Aptin.
• Medications based on penbutolol, for example, Betapressin along with Levatol.
• Funds based on bopindolol, for example, "Sandorm".

Among other things, Bucindolol has sympathomimetic activity along with Dilevalol, Karteolol and Labetalol.

The list of beta-blockers does not end here.

Cardioselective drugs

Cardioselective drugs include the following drugs that do not have intrinsic sympathomimetic activity:

• Medicines based on metoprolol, for example Betaloc along with Corvitol, Metozok, Metocard, Metokor, Serdol and Egilok.
• Preparations based on atenolol, for example "Betacard" along with "Stenormin".
• Betaxolol-based products, such as Betak, Kerlon and Lokren.
• Esmolol-based medicines, such as Breviblok.
• Preparations based on bisoprolol, for example, "Aritel", "Bidop", "Biol", "Biprol", "Bisogamma", "Bisomor", "Concor", "Corbis", "Cordinorm", "Coronal", "Niperten" and Tirez.
• Medications based on carvedilol, for example, Acridilol, along with Bagodilol, Vedicardol, Dilatrend, Carvedigamma, Karvenal, Coriol, Recardium and Talliton.
• Preparations based on nebivolol, such as Binelol along with Nebivator, Nebikor, Nebilan, Nebilet, Nebilong and Nevotenz.

The following cardioselective drugs have sympathomimetic activity: Acecor along with Sektral, Kordanum and Vasakor.

Let's continue the list of new generation beta-blockers.

Medications with vasodilatory properties

Non-cardioselective drugs in this category include drugs such as Amozulalol along with Bucindolol, Dilevalol, Labetolol, Medroxalol, Nipradilol and Pindolol.

Carvedilol, Nebivolol and Celiprolol are equated to cardioselective drugs.

How does the action of beta-blockers differ?

Long-term exposure agents include Bopindolol along with Nadolol, Penbutolol and Sotalol. And among the beta-blockers with ultra-short action, it is worth mentioning Esmolol.

Use against the background of angina pectoris

In many cases, such drugs serve as one of the leading drugs for the treatment of angina pectoris and the prevention of attacks. Unlike nitrates, these agents do not cause drug resistance over long-term use. Beta-blockers are able to accumulate in the body, which makes it possible to reduce the dosage of the drug after a while. These medicines serve to protect the heart muscle, improving the prognosis by reducing the risk of a second heart attack. The antianginal activity of such drugs is the same. They need to be selected depending on the duration of the effect and side reactions.

Start therapy with a small dosage, which is gradually increased to an effective one. The dose is selected in such a way that the heart rate at rest is not less than fifty per minute, and the level of systolic pressure is not less than one hundred millimeters of mercury. Upon reaching the therapeutic effect, angina attacks stop, exercise tolerance improves. Against the background of progress, the dosage should be reduced to the minimum effective.

Long-term use of high doses of such drugs is considered inappropriate, as this increases the risk of adverse reactions. In case of insufficient effectiveness, it is better to combine these drugs with other groups of drugs. Such funds should not be abruptly canceled, as a withdrawal syndrome may appear. Beta-blockers are especially indicated if angina pectoris is combined with sinus tachycardia, glaucoma, arterial hypertension, or constipation.

The newest beta-blockers are effective in myocardial infarction.

Treatment for a heart attack

Early use of BAB against the background of a heart attack helps to limit necrosis of the heart muscle. This significantly reduces mortality and the risk of recurrent heart attack. In addition, the risk of cardiac arrest is reduced.

A similar effect turns out to be drugs without sympathomimetic activity, it is preferable to use cardioselective drugs. In particular, they are useful in the combination of a heart attack with such ailments as arterial hypertension, sinus tachycardia, post-infarction angina and tachysystolic form of atrial fibrillation.

These drugs can be prescribed to patients immediately upon admission to the hospital, provided that there are no contraindications. In the absence of side effects, treatment should continue for at least a year after a heart attack.

The use of BAB in chronic heart failure

The use of beta-blockers in heart failure is currently being studied. It is believed that they should be used in the combination of heart failure with angina pectoris. Pathologies in the form of rhythm disturbances, arterial hypertension are also grounds for prescribing this group of drugs to patients.

Use in hypertension

BAB is prescribed for the treatment of hypertension, which is complicated by ventricular hypertrophy. They are also widely used among young patients who lead an active lifestyle. This category of drugs is prescribed in the case of a combination of arterial hypertension with cardiac arrhythmias, and in addition, after a heart attack.

How else can you use the new generation beta-blockers from the list?

Use in cardiac arrhythmias

BAB is widely used for atrial fibrillation and flutter, and in addition, against the background of poorly tolerated sinus tachycardia. They can also be prescribed in the presence of ventricular arrhythmias, however, the effectiveness in this case will be less pronounced. BAB in combination with potassium preparations is used to treat arrhythmias caused by

What are the possible side effects from the work of the heart?

BAB can inhibit the ability of the sinus node to generate impulses that cause heart contractions. These drugs can slow the heart rate to less than fifty per minute. This side effect is less pronounced in BABs with sympathomimetic activity.

Drugs in this category can cause varying degrees of atrioventricular block. They reduce strength heart contraction. In addition, BABs lower blood pressure. Medicines of this group cause spasms of peripheral vessels. Patients may experience cold extremities. New generation beta-blockers reduce renal blood flow. Due to the deterioration of blood circulation during treatment with these drugs, sometimes patients experience severe weakness.

Adverse reactions from the respiratory system

BABs can cause bronchospasm. This side effect less pronounced among cardioselective drugs. However, their dosages, which are effective against angina pectoris, are often quite high. The use of high doses of these drugs can provoke sleep apnea along with temporary respiratory arrest. BABs can worsen the course of an allergic reaction to insect stings, as well as to drugs and food allergens.

The reaction of the nervous system

"Propranolol" along with "Metoprolol" and other lipophilic BAB can penetrate into brain cells through the blood-brain barrier. In this regard, they can cause headaches, sleep disturbance, dizziness, memory impairment, and depression. In severe cases, hallucinations, seizures or coma may occur. These side reactions are much less pronounced in hydrophilic drugs, in particular, Atenolol.

Treatment of BAB is sometimes accompanied by impaired nerve conduction. This leads to weakness in the muscles, fatigue and reduced stamina.

Metabolic reaction

Non-selective β-blockers are able to suppress the production of insulin. Also, these drugs significantly inhibit the processes of glucose mobilization from the liver, which contributes to the development of prolonged hypoglycemia in patients with diabetes. Hypoglycemia, as a rule, promotes the release of adrenaline into the blood, which acts on alpha-adrenergic receptors. This results in a significant rise in pressure. Therefore, if it is necessary to prescribe a BAB to a patient with concomitant diabetes, it is better to give preference to cardioselective drugs or change them to calcium antagonists.

Many BABs, especially non-selective ones, reduce the content of normal cholesterol in the blood and, accordingly, increase the level of bad cholesterol. True, such drugs as "Carvedilol" along with "Labetolol", "Pindolol", "Dilevalol" and "Celiprolol" are deprived of this drawback.

What other side effects are possible?

Treatment of BAB in some cases may be accompanied by sexual dysfunction, and in addition, erectile dysfunction and loss of sexual desire. To date, the mechanism of this effect is unclear. Among other things, BAB can cause skin changes, which, as a rule, manifests itself in the form of erythema, rash, and symptoms of psoriasis. In rare cases, hair loss occurs along with stomatitis. The most serious side effect is the inhibition of hematopoiesis with the occurrence of thrombocytopenic purpura and agranulocytosis.

Contraindications to the use of BAB

Beta-blockers have many different contraindications and are considered completely prohibited in the following situations:

A relative contraindication to the prescription of drugs in this category is Raynaud's syndrome, along with atherosclerosis of peripheral arteries, which is accompanied by the occurrence of intermittent claudication.

So, we have reviewed the list of beta-blockers. We hope that the information provided was useful to you.

Why is modern cardiology unthinkable without this group of drugs?

Savely Barger (MOSCOW),

cardiologist, candidate of medical sciences. In the 1980s, he was one of the first scientists in the USSR to develop a technique for diagnostic transesophageal pacing. Author of manuals on cardiology and electrocardiography. He is the author of several popular books on various problems of modern medicine.

It is safe to say that beta-blockers are first-line drugs for the treatment of many diseases of the cardiovascular system.

Here are some clinical examples.

Patient B., 60 years old, 4 years ago suffered an acute myocardial infarction. Currently, the characteristic squeezing pains behind the sternum with little physical exertion are disturbing (at a slow pace of walking, it is possible to walk no more than 1000 meters without pain). Along with other drugs, he receives bisoprolol 5 mg in the morning and evening.

Patient R., 35 years old. At the reception complains of constant headaches in the occipital region. Blood pressure 180/105 mm Hg. Art. Bisoprolol therapy is carried out at a daily dosage of 5 mg.

Patient L., 42 years old, complained of interruptions in the work of the heart, a feeling of "fading" of the heart. 24-hour ECG recording revealed frequent ventricular extrasystoles, episodes of ventricular tachycardia "jogging". Treatment: sotalol at a dosage of 40 mg twice a day.

Patient S., 57 years old, worried about shortness of breath at rest, attacks of cardiac asthma, decreased performance, edema is noted on lower limbs, intensifying in the evening. At ultrasound examination heart revealed diastolic dysfunction of the left ventricle. Therapy: metoprolol 100 mg twice a day.

In such diverse patients: coronary heart disease, hypertension, paroxysmal ventricular tachycardia, heart failure - drug treatment carried out by drugs of one class - beta-blockers.

Beta-adrenergic receptors and mechanisms of action of beta-blockers

There are beta 1-adrenergic receptors, which are located mainly in the heart, intestines, kidney tissue, in adipose tissue, to a limited extent - in the bronchi. Beta 2-adrenergic receptors are found in the smooth muscles of blood vessels and bronchi, in the gastrointestinal tract, in the pancreas, and to a limited extent in the heart and coronary vessels. No tissue contains exclusively beta 1 or beta 2 adrenoreceptors. In the heart, the ratio of beta 1 - and beta 2 -adrenergic receptors is approximately 7:3.

Table 1. Main indications for the use of beta-blockers

The mechanism of action of beta-blockers is based on their structure, similar to catecholamines. Beta-blockers act as competitive antagonists of catecholamines (epinephrine and norepinephrine). The therapeutic effect depends on the ratio of the concentration of the drug and catecholamines in the blood.

Blockade of beta 1-adrenergic receptors leads to a decrease in heart rate, contractility and speed of contraction of the heart muscle, while reducing myocardial oxygen demand.

• Beta-blockers cause depression of the 4th phase of diastolic depolarization of the cells of the conduction system of the heart, which determines their antiarrhythmic effect. Beta-blockers reduce the flow of impulses through the atrioventricular node and reduce the speed of impulses.
• Beta-blockers reduce the activity of the renin-angiotensin system by reducing the release of renin from juxtaglomerular cells.
• Beta-blockers affect the sympathetic activity of vasoconstrictor nerves. The appointment of beta-blockers without internal sympathomimetic activity leads to a decrease in cardiac output, peripheral resistance increases, but returns to normal with prolonged use.
• Beta-blockers inhibit catecholamine-induced apoptosis of cardiomyocytes.
• Beta-blockers stimulate the endothelial arginine/nitroxide system in endothelial cells, i.e., they turn on the main biochemical mechanism for expanding vascular capillaries.
• Beta-blockers block part of the calcium channels of cells and reduce the calcium content in the cells of the heart muscle. This is probably associated with a decrease in the strength of heart contractions, a negative inotropic effect.

Non-cardiac indications for the use of beta-blockers

• anxiety states
• alcoholic delirium
• juxtaglomerular hyperplasia
• insulinoma
• glaucoma
• migraine (attack prevention)
• narcolepsy
• thyrotoxicosis (treatment of rhythm disturbances)
• portal hypertension

Table 2. Properties of beta-blockers: useful and side effects, contraindications

Clinical pharmacology

Treatment with beta-blockers should be carried out in effective therapeutic dosages, dose titration of the drug is carried out upon reaching the target heart rate in the range of 50–60 min -1.

For example, in the treatment hypertension beta-blocker maintains systolic blood pressure of 150-160 mm Hg. Art. If at the same time the heart rate does not decrease less than 70 min -1. , one should think not about the ineffectiveness of the beta-blocker and its replacement, but about increasing daily dose until the heart rate reaches 60 min -1. .

An increase in the duration of the PQ interval on the electrocardiogram, the development of 1st degree AV block when taking a beta-blocker cannot serve as a reason for its cancellation. However, the development of AV block II and III degree, especially in combination with the development of syncopal conditions (Morgagni-Adams-Stokes syndrome), serves as an unconditional basis for the abolition of beta-blockers.

The cardioprotective effect of beta-blockers is more typical for lipophilic drugs than for hydrophilic ones. The ability of lipophilic beta-blockers to accumulate in tissues and increase vagal activity is important. Lipophilic beta-blockers penetrate the blood-brain barrier better and may have greater CNS side effects.

In randomized clinical research cardioprotective doses of beta-blockers have been established, i.e. doses, the use of which statistically significantly reduces the risk of death from cardiac causes, reduces the incidence of cardiac complications (myocardial infarction, severe arrhythmias), and increases life expectancy. Cardioprotective doses may differ from dosages at which control of hypertension and angina pectoris is achieved. When possible, beta-blockers should be given at a cardioprotective dose that is higher than the average therapeutic dose.

It should also be taken into account that not all beta-blockers showed cardioprotective effects in randomized trials, only lipophilic metoprolol, propranolol, timolol and amphiphilic bisoprolol and carvediol are able to increase life expectancy.

Increasing the dose of beta-blockers above the cardioprotective dose is unjustified, because it does not lead to a positive result, increasing the risk of side effects.

Chronic obstructive pulmonary disease and bronchial asthma

While beta-blockers cause bronchospasm, beta-agonists (such as the beta2-agonist salbutamol) can cause angina. The use of selective beta-blockers helps: cardioselective beta 1-blockers bisoprolol and metoprolol in patients with coronary artery disease or hypertension in combination with chronic obstructive pulmonary disease (COPD) and bronchial asthma. In this case, it is necessary to take into account the function of external respiration (RF). In patients with mild impairment of respiratory function (forced expiratory volume more than 1.5 liters), the use of cardioselective beta-blockers is acceptable.

At moderate and severe course chronic bronchitis and bronchial asthma should refrain from prescribing beta-blockers, including cardioselective ones.

When choosing treatment tactics in patients with hypertension, angina pectoris or heart failure in combination with COPD, the priority is the treatment of cardiovascular pathology. In this case, it is necessary to individually assess whether it is possible to neglect the functional state of the bronchopulmonary system and, vice versa, stop bronchospasm with beta-agonists.

Diabetes

When treating diabetic patients taking beta-blockers, one should be prepared for the more frequent development of hypoglycemic conditions, while the clinical symptoms of hypoglycemia change. Beta-blockers largely eliminate the symptoms of hypoglycemia: tachycardia, tremor, hunger. Insulin-dependent diabetes with a tendency to hypoglycemia is a relative contraindication to the use of beta-blockers.

Peripheral vascular disease

If beta-blockers are used in peripheral vascular disease, then cardioselective atenolol and metoprolol are safer.

Atenolol does not worsen the course of peripheral vascular disease, while captopril increases the frequency of amputations.

Nevertheless, peripheral vascular diseases, including Raynaud's disease, are included in the relative contraindications for the appointment of beta-blockers.

Heart failure

Although beta-blockers are widely used in the treatment of heart failure, they should not be prescribed for class IV failure with decompensation. Severe cardiomegaly is a contraindication to beta-blockers. Beta-blockers are not recommended when the ejection fraction is less than 20%.

Blockades and arrhythmias of the heart

Bradycardia with heart rate less than 60 min -1 (initial heart rate before prescribing drugs), atrioventricular blockade, especially of the second or more degree, is a contraindication to the use of beta-blockers.

Personal experience

It is likely that each physician has his own pharmacotherapeutic reference book, reflecting his personal clinical experience with drugs, addictions and negative attitudes. The success of using the drug in one to three to ten first patients ensures that the doctor is addicted to it for many years, and literature data strengthen the opinion about its effectiveness. Here is a list of some modern beta-blockers for which I have my own clinical experience.

propranolol

The first of the beta-blockers that I began to use in my practice. It seems that in the mid-70s of the last century, propranolol was almost the only beta-blocker in the world and certainly the only one in the USSR. The drug is still one of the most commonly prescribed beta-blockers, has more indications for use compared to other beta-blockers. However, I cannot consider its current use justified, since other beta-blockers have much less pronounced side effects.

Propranolol can be recommended in the complex therapy of coronary heart disease, it is also effective in lowering blood pressure in hypertension. When prescribing propranolol, there is a risk of developing orthostatic collapse. Propranolol is prescribed with caution in heart failure, with an ejection fraction of less than 35%, the drug is contraindicated.

According to my observations, propranolol is effective in the treatment of prolapse mitral valve: Dosages of 20-40 mg per day are sufficient for the prolapse of the leaflets (usually anterior) to disappear or significantly decrease from the third or fourth degree to the first or zero.

bisoprolol

The cardioprotective effect of beta-blockers is achieved at a dosage that provides a heart rate of 50-60 per minute.

A highly selective beta 1 blocker that has been shown to reduce myocardial infarction mortality by 32%. A dose of 10 mg of bisoprolol is equivalent to 100 mg of atenolol, the drug is prescribed in a daily dosage of 5 to 20 mg. Bisoprolol can be confidently prescribed for a combination of hypertension (reduces arterial hypertension), coronary heart disease (reduces myocardial oxygen demand, reduces the frequency of angina attacks) and heart failure (reduces afterload).

metoprolol

The drug belongs to beta 1-cardioselective beta-blockers. In patients with COPD, metoprolol at a dose of up to 150 mg / day causes less pronounced bronchospasm compared with equivalent doses of non-selective beta-blockers. Bronchospasm when taking metoprolol is effectively stopped by beta2-agonists.

Metoprolol effectively reduces the frequency ventricular tachycardia at acute infarction myocardium and has a pronounced cardioprotective effect, reducing the death rate of cardiac patients in randomized trials by 36%.

Currently, beta-blockers should be considered as first-line drugs in the treatment of coronary heart disease, hypertension, heart failure. The excellent compatibility of beta-blockers with diuretics, calcium channel blockers, ACE inhibitors, of course, is an additional argument in their appointment.

Mechanism of action of beta-blockers

The effects of beta-blockers are realized by the blockade of β1 and β2-adrenergic receptors. There are two types of β-adrenergic receptors (β1- and β2-adrenergic receptors), which differ in structural and functional features and distribution in tissues. β1-adrenergic receptors dominate in the structures of the heart, islet tissue of the pancreas, juxtaglomerular apparatus of the kidneys, adipocytes.

Drugs, by binding to β1-adrenergic receptors of the heart, prevent the action of noradrenaline, adrenaline on them, reduce the activity of adenylate cyclase. A decrease in enzyme activity leads to a decrease in cAMP synthesis and inhibition of Ca2+ entry into cardiomyocytes. Thus, the main effects of β-blockers are realized:

• negative inotropic effect(the force of heart contractions decreases);
• negative chronotropic effect (decreased heart rate);
• negative dromotropic effect (conductivity is suppressed);
• negative bathmotropic effect (automatism decreases).

The antianginal effect of drugs is manifested by a decrease in the strength of heart contractions and heart rate, which reduces myocardial oxygen demand.

Due to the inhibition of conduction and automatism, the drugs have an antiarrhythmic effect.

A decrease in the Ca2+ content due to blockade of β1-adrenergic receptors in the cells of the juxtal merular apparatus (JGA) of the kidneys is accompanied by inhibition of renin secretion, and, accordingly, a decrease in the formation of angiotensin II, which leads to a decrease in blood pressure and determines the effectiveness of β-blockers as antihypertensive drugs.

Blockade β2-blockers contributes to the increase:

• bronchial smooth muscle tone;
• contractile activity of the pregnant uterus;
• contraction of smooth muscle cells gastrointestinal tract(manifested by abdominal pain, vomiting, nausea, diarrhea, much less often constipation).

In addition, narrowing of arterioles and venules causes an increase in peripheral vascular resistance and can impair blood supply to the extremities up to the development of Raynaud's syndrome.

β-blockers cause changes in lipid and carbohydrate metabolism. They inhibit lipolysis, prevent an increase in the content of free fatty acids in the blood plasma, while the content of TG increases, and the concentration of total cholesterol does not change, the content of HDL cholesterol decreases, LDL cholesterol increases, which leads to an increase in the atherogenic coefficient.

β-blockers cause activation of the synthesis of glycogen from glucose in the liver and inhibit glycogenolysis, which can lead to hypoglycemia, especially against the background of the use of hypoglycemic drugs in patients with diabetes mellitus. Due to the blockade of beta-blockers in the pancreas and the inhibition of physiological secretion of insulin, drugs can cause hyperglycemia, but in healthy people they usually do not affect the concentration of glucose in the blood.

According to their effect on receptors, beta-blockers are divided into non-selective (affecting β1- and β2-adrenergic receptors) and cardioselective (affecting β1-adrenergic receptors), in addition, some of them have internal sympathomimetic activity (ICA).

Beta-blockers with ICA (pindolol, Bopindolol, oxprenolol) reduce heart rate and myocardial contractility to a lesser extent, practically do not affect lipid metabolism, they have a less pronounced withdrawal syndrome.

The vasodilating effect of beta-blockers is due to one of the following mechanisms or a combination of them:

• pronounced ICA in relation to β-blockers of vessels (for example, pindolol, celiprolol);
• a combination of β- and α-adrenergic blocking activity (for example, carvedilol);
• release of nitric oxide from endothelial cells (nebivolol);
• direct vasodilatory effect.

Cardioselective beta-blockers in low doses, unlike non-selective ones, have little effect on bronchial and arterial tone, insulin secretion, glucose mobilization from the liver, contractile activity of the pregnant uterus, so they can be prescribed for concomitant chronic obstructive pulmonary diseases, diabetes mellitus, and peripheral circulatory disorders ( e.g. Raynaud's syndrome, pregnancy). They practically do not cause vasoconstriction of skeletal muscles, therefore, when using them, increased fatigue and muscle weakness are less likely to be noted.

Pharmacokinetics of beta-blockers

The pharmacokinetic action of various beta-blockers is determined by the degree of their solubility in fats and water. There are three groups of beta-blockers:

• fat-soluble (lipophilic),
• water-soluble (hydrophilic),
• fat and water soluble.

Lipophilic beta-blockers (metoprolol, alprenolol, oxprenolol, propranolol, timolol) are rapidly absorbed from the gastrointestinal tract, easily penetrate the BBB (often cause side effects such as insomnia, general weakness, drowsiness, depression, hallucinations, nightmares). Therefore, single doses and frequency of administration should be reduced in elderly patients, with diseases nervous system. Lipophilic beta-blockers can slow down the elimination from the blood of other drugs that are metabolized in the liver (for example, lidocaine, hydrolasine, theophylline). Lipophilic β-blockers should be prescribed at least 2-3 times a day.

Hydrophilic beta-blockers (atenolol, nadolol, sotalol) are not completely (30-70%) absorbed in the gastrointestinal tract and are slightly (0-20%) metabolized in the liver. Excreted mainly by the kidneys. They have a long half-life (6-24 years). T1 / 2 of hydrophilic drugs increases with a decrease in glomerular filtration rate (for example, with renal failure, in elderly patients). The frequency of application varies from 1 to 4 times a day.

There are beta-blockers that are soluble in fats and water (acebutolol, pindolol, celiprolol, bisoprolol). They have two routes of elimination - hepatic (40-60%) and renal. Fat and water-soluble drugs can be prescribed 1 time per day, with the exception of Pindolol: it is taken 2-3 times. T1 / 2 is 3-12 hours. Most drugs (bisoprolol, pindolol, celiprolol) practically do not interact with drugs that are metabolized in the liver, so they can be prescribed in patients with moderate hepatic or kidney failure(in severe violations of the functions of the liver and kidneys, the dose of the drug is recommended to be reduced by 1.5 times).

Pharmacokinetic parameters of beta-blockers:

					metabolites
Atenolol
Betaxolol
bisoprolol
Carvedilol
metoprolol
Pindolol
propranolol
Talinolol
Celiprolol
	250-500 mcg/kg

*Note: ? - no data found

Indications for the use of beta-blockers

• angina pectoris,
• acute coronary syndrome,
• Hypertension and primary prevention of stroke and coronary artery disease in hypertensive patients,
• prevention of ventricular and supraventricular arrhythmias,
• prevention of recurrent myocardial infarction,
• prevention sudden death in patients with long QT syndrome,
• chronic heart failure (carvedilol, metoprolol, bisoprolol, nebivolol),
• systemic diseases with increased influence of the sympathetic nervous system,
• thyrotoxicosis,
• essential tremor,
• alcohol withdrawal,
• dissecting aortic aneurysm,
• hypertrophic cardiomyopathy,
• digitalis intoxication,
• mitral stenosis (tachysystolic form),
• mitral valve prolapse,
• Fallot's tetrad.

Side effects and contraindications of beta-blockers

The main side effects and contraindications of beta-blockers are presented in the table.

Side effects of beta-blockers, contraindications to their use and conditions requiring special care when using beta-blockers:

Side effects	Absolute contraindications	Conditions requiring special care
Cardiac: severe sinus bradycardia, sinus arrest, complete atrioventricular block, decreased systolic function of the left ventricle. Neurological: depression, insomnia, nightmares. Gastrointestinal: nausea, vomit, flatulence, constipation, diarrhea. Bronchostriction (in persons with bronchial asthma, COPD). Weakness. Fatigue. Drowsiness. sexual dysfunction. Increased risk of developing insulin-induced hypoglycemia. Masking the symptoms of hypoglycemia. Coldness of extremities. Raynaud's syndrome. Severe hypotension. Hypertriglyceridemia, decreased high-density lipoprotein levels. Hepatotoxicity.	Individual hypersensitivity. Bronchial asthma. COPD with bronchial obstruction. Atrio-ventricular block I-II st. Clinical bradycardia. Sick sinus syndrome. Cardiac shock. Severe lesions of the peripheral arteries. Hypotension with clinical manifestations.	Diabetes. COPD without bronchial obstruction. Damage to the peripheral arteries. depression. Dyslipidemia. Asymptomatic sinus node dysfunction. Atrio-ventricular block I stage.

For β-blockers, withdrawal syndrome is characteristic.

Drug Interactions

Combination of beta-blockers with others medicines, exhibits a negative foreign and chronotropic effect, can lead to severe adverse reactions. With the combination of β-blockers with clonidine, a pronounced decrease in blood pressure and bradycardia develops, especially in the horizontal position of patients.

The combination of the appointment of beta-blockers with verapamil, amiodarone, cardiac glycosides can lead to severe bradycardia and AV conduction disturbances.

The combination of beta-blockers with nitrates or calcium channel blockers is justified, since the former reduce myocardial oxygen demand, while others, by reducing the tone of peripheral and coronary vessels, provide hemodynamic unloading of the myocardium and increase coronary blood flow.

Preparations of the group of beta-blockers are of great interest due to their amazing effectiveness. They are used for coronary heart disease, heart failure and certain disorders of the heart.

Doctors often prescribe them for pathological changes heart rhythm. Beta-blockers are drugs that block various types (β1-, β2-, β3-) of adrenoreceptors for a certain time period. The importance of these substances is difficult to overestimate. They are considered the only class of medicines in cardiology of their kind, for the development of which the Nobel Prize in Medicine was awarded.

Allocate beta-blockers selective and non-selective. From reference books, you can learn that selectivity is the ability to block only β1-adrenergic receptors. It is important to note that it does not affect β2-adrenergic receptors in any way. This article contains basic information about these substances. Here you can get acquainted with their detailed classification, as well as drugs and their effect on the body. So what are selective and non-selective beta-blockers?

The classification of beta-blockers is quite straightforward. As noted earlier, all drugs are divided into two main groups: non-selective and selective beta-blockers.

Non-selective blockers

Non-selective beta-blockers - drugs that non-selectively block β-adrenergic receptors. In addition, they have strong antianginal, hypotensive, antiarrhythmic and membrane stabilizing effects.

The group of non-selective blockers includes such drugs:

• Propranolol (medicines with a similar active substance: Inderal, Obzidan);
• Bopindolol (Sandinorm);
• Levobunolol (Vistagen);
• Nadolol (Corgard);
• Obunol;
• Oxprenolol (Coretal, Trazikor);
• Pindolol;
• Sotalol;
• Timozol (Arutimol).

The antianginal effect of this type of β-blockers is that they are able to normalize the heart rate. In addition, myocardial contractility decreases, which gradually leads to a decrease in its need for portions of oxygen. Thus, the blood supply to the heart is significantly improved.

This effect is due to a slowdown in sympathetic stimulation of peripheral vessels and inhibition of the activity of the renin-angiotensin system. At the same time, there is a minimization of total peripheral vascular resistance and a decrease in cardiac output.

Non-selective blocker Inderal

But the antiarrhythmic effect of these substances is explained by the removal of arrhythmogenic factors. Some categories of these drugs have what is known as intrinsic sympathomimetic activity. In other words, they have a powerful stimulating effect on beta-adrenergic receptors.

These medicines do not decrease or only slightly decrease resting heart rate. In addition, they do not allow the latter to be increased when executing exercise or under the influence of adrenomimetics.

Cardioselective drugs

There are the following cardioselective beta-blockers:

• Ormidol;
• Prinorm;
• Atenol;
• Betacard;
• Blockium;
• catenol;
• catenolol;
• Hypotene;
• Myocord;
• Normiten;
• Prenormin;
• Telvodin;
• Tenolol;
• Tenzikor;
• Velorin;
• Falitonsin.

As you know, in the structures of the tissues of the human body there are certain receptors that respond to the hormones adrenaline and norepinephrine. On the this moment distinguish α1-, α2-, β1-, β2-adrenergic receptors. Recently, β3-adrenergic receptors have been described.

The location and significance of adrenoreceptors can be represented as follows:

• α1- are located precisely in the vessels of the body (in arteries, veins and capillaries), active stimulation leads to their spasm and a sharp increase in the level blood pressure;
• α2- are considered a "negative feedback loop" for the system of regulating the performance of body tissues - this suggests that their stimulation can lead to an instant decrease in blood pressure;
• β1- located in the heart muscle, and their stimulation leads to an increase in heart rate, and also increases myocardial oxygen demand;
• β2- located in the kidneys, stimulation provokes the removal of bronchospasm.

Cardioselective β-blockers have activity against β1-adrenergic receptors. But as for non-selective ones, they equally block β1 and β2. In the heart, the ratio of the latter is 4:1.

In other words, stimulation of this organ of cardio-vascular system energy is conducted mainly through β1. With the rapid increase in the dosage of beta-blockers, their specificity is gradually minimized. Only after this, the selective drug blocks both receptors.

It is important to note that any beta-blocker, selective or non-selective, equally lowers blood pressure.

However, at the same time, it is cardioselective beta-blockers that have much fewer side effects. It is for this reason that they are much more appropriate to use for various concomitant ailments.

Thus, they are most likely to provoke the phenomena of bronchospasm. This is due to the fact that their activity will not affect the β2-adrenergic receptors located in an impressive part of the respiratory system - the lungs.

It is worth noting that selective blockers are much weaker than non-selective ones. In addition, they increase peripheral vascular resistance. It is due to this unique property that these drugs are prescribed to cardiologist patients with severe peripheral circulatory disorders. This mainly applies to patients with intermittent claudication.

Be sure to pay attention to the fact that a drug called Carvedilol does not belong to the category of cardioselective drugs.

Few people know, but infrequently prescribed to lower blood pressure and eliminate arrhythmias. It is generally used to treat heart failure.

Latest generation beta blockers

At the moment there are three main generations of such drugs. Naturally, it is desirable to use the medicines of the latest (new) generation. They are recommended to be consumed three times a day.

Drug Carvedilol 25 mg

In addition, we must not forget that they are directly related to only a minimal amount of unwanted side effects. Innovative drugs include Carvedilol and Celiprolol. As mentioned earlier, they are quite successfully used for the treatment various diseases heart muscle.

Non-selective long-acting drugs include the following:

• Bopindolol;
• Nadolol;
• Penbutolol;
• Sotalol.

But the selective long-acting drugs include the following:

• Atenolol;
• Betaxolol;
• Epanolol.

When observing the low effectiveness of the selected medication, it is important to reconsider the prescribed drug.

If necessary, you should contact your personal doctor so that he picks up a new medicine. The thing is that often the funds simply do not provide the right influence on the patient's body.

At the moment, more and more preference is given to those drugs that have precisely prolonged action. They contain in their composition active ingredients that are released gradually, over an impressive period of time, smoothly affecting the health of the cardiologist patient.

Medicines can be very effective, but this or that patient is simply not receptive to them. In this case, everything is very individual and depends on certain characteristics of the patient's health.

It is for this reason that treatment must be carried out with care and special scrupulousness. It is very important to pay attention to all the individual characteristics of the human body.

Contraindications for use

It is precisely for the reason that beta-blockers have the ability to somehow affect various bodies and systems (not always in a positive way), their use is undesirable and even contraindicated in some concomitant ailments of the body.

Various adverse effects and prohibitions for use are directly related to the presence of beta-adrenergic receptors in many organs and structures of the human body.

Contraindications for use medications, are:

• asthma;
• symptomatic decrease in blood pressure;
• decrease in heart rate (significant slowing of the patient's pulse);
• severe decompensated heart failure.

You should not independently select a drug from this category of drugs for the heart. It is important to remember that this can cause serious harm to the health of the patient.

Contraindications can be relative (when the significant benefit for the therapy process outweighs the harm and the likelihood of undesirable effects):

• various diseases of the cardiovascular system;
• obstructive respiratory disease of a chronic nature;
• in persons with heart failure and slowing of the pulse, the use is undesirable, but not prohibited;
• diabetes;
• transient lameness of the lower extremities.

Related videos

Which non-selective and selective beta-blockers (drugs from these groups) are used to treat and treat heart diseases:

In diseases where the use of beta-blockers is indicated, they should be used with extreme caution. This is especially true for women who are carrying a baby and breastfeeding. Another important point is the sudden cancellation of the selected medicinal product: in no case is it recommended to abruptly stop drinking this or that drug. Otherwise, an unexpected phenomenon called “withdrawal syndrome” awaits a person.