β-blockers block β-adrenergic receptors in various organs and tissues, which limits the effect of catecholamines, providing an organoprotective effect in cardiovascular diseases, making it possible to use them in ophthalmology and gastroenterology. On the other hand, the systemic effect on β-adrenergic receptors causes a number of side effects. To reduce undesirable side effects, selective β-blockers and β-blockers with additional vasodilating properties have been synthesized. The level of selectivity will determine the selectivity of the action. Lipophilicity determines their predominant cardioprotective effect. β-blockers are most widely used in the treatment of patients with coronary heart disease, arterial hypertension, and chronic heart failure.

Keywords:β-blockers, selectivity, vasodilating properties, cardioprotection.

TYPES AND LOCALIZATION OF β-ADRENORESCEPTORS

β-blockers, the action of which is due to blocking effects on β-adrenergic receptors of organs and tissues, have been used in clinical practice since the early 1960s and have hypotensive, antiaginal, anti-ischemic, antiarrhythmic and organoprotective effects.

There are 2 types of β-adrenergic receptors - and β 2 -adrenoreceptors; their ratio is different in different organs and tissues. The effects of stimulation of different types of β-adrenergic receptors are presented in table. 5.1.

PHARMACODYNAMIC EFFECTS OF β-ADRENORESCEPTOR BLOCKade

Pharmacodynamic effects of preferential β blockade l-adrenergic receptors are:

Decrease in heart rate (negative chronotropic, bradycardic effect);

Reduced blood pressure (reduced afterload, hypotensive effect);

Slowing of atrioventricular (AV) conduction (negative dromotropic effect);

Reduced myocardial excitability (negative bathmotropic, antiarrhythmic effect);

Decreased myocardial contractility (negative inotropic, antiarrhythmic effect);

Table 5.1

Localization and ratio of β-adrenergic receptors in organs and tissues

decreased pressure in the portal vein system (due to a decrease in hepatic and mesenteric arterial blood flow);

Reducing the formation of intraocular fluid (reducing intraocular pressure);

Psychotropic effects for beta-blockers that penetrate the blood-brain barrier (weakness, drowsiness, depression, insomnia, nightmares, hallucinations, etc.);

Withdrawal syndrome in case of sudden cessation of taking short-acting beta-blockers (hypertensive reaction, exacerbation of coronary insufficiency, including the development of unstable angina, acute myocardial infarction or sudden death).

Pharmacodynamic effects of partial or complete β blockade 2 -adrenergic receptors are:

Increased tone of the smooth muscles of the bronchi, including the extreme degree of its severity - bronchospasm;

Impaired mobilization of glucose from the liver into the blood due to inhibition of glycogenolysis and gluconeogenesis, the potentiating hypoglycemic effect of insulin and other hypoglycemic drugs;

Increased arterial smooth muscle tone - arterial vasoconstriction, causing an increase in peripheral vascular resistance, coronary spasm, decreased renal blood flow, decreased blood circulation in the extremities, a hypertensive reaction to hypercatecholaminemia during hypoglycemia, pheochromocytoma, after withdrawal of clonidine, during surgery or in the postoperative period.

STRUCTURE OF β-ADRENORESCEPTORS AND EFFECTS OF β-ADRENOBLOCKade

The molecular structure of β-adrenergic receptors is characterized by a specific sequence of amino acids. Stimulation of β-adrenergic receptors promotes the cascade of activity of G-protein, the enzyme adenylate cyclase, the formation of cyclic AMP from ATP under the influence of adenylate cyclase, and protein kinase activity. Under the influence of protein kinase, there is an increase in phosphorylation of calcium channels with an increase in the flow of calcium into the cell during the period of voltage-induced depolarization, calcium-induced release of calcium from the sarcoplasmic reticulum with an increase in the level of cytosolic calcium, an increase in the frequency and efficiency of the impulse, the force of contraction and further relaxation.

The action of β-blockers limits β-adrenergic receptors from the influence of β-agonists, providing negative chrono-, dromo-, batmo- and inotropic effects.

SELECTIVITY PROPERTY

The defining pharmacological parameters of β-blockers are β l-selectivity (cardioselectivity) and degree of selectivity, intrinsic sympathomimetic activity (ISA), level of lipophilicity and membrane-stabilizing effect, additional vasodilating properties, duration of action of the drug.

To study cardioselectivity, the degree of drug inhibition of the effect of β-adrenergic receptor agonists on heart rate, finger tremor, blood pressure, and bronchial tone is assessed in comparison with the effects of propranolol.

The degree of selectivity reflects the intensity of the connection with the β-adrenergic receptor and determines the strength and duration of action of the β-blocker. Preferential β blockade l-adrenergic receptors determines the selectivity index of β-blockers, reducing the effects of β 2 -blockade, thereby reducing the likelihood of side effects (Table 5.2).

Long-term use of β-blockers increases the number of β-receptors, which determines a gradual increase in the effects of β-blockade and a much more pronounced sympathomimetic response to catecholamines circulating in the blood in case of sudden withdrawal, especially of short-acting β-blockers (withdrawal syndrome).

1st generation β-blockers, causing blockade and β to the same extent 2 -adrenergic receptors, belong to non-selective β-blockers - propranolol, nadolol. Non-selective β-blockers without BCA have a definite advantage.

The second generation includes selective β l-adrenergic blockers, called cardioselective - atenolol, bisoprolol, betaxolol, metoprolol, nebivolol, talinolol, oxprenolol, acebutolol, celiprolol. At low doses β l-selective drugs have little effect on physiological responses mediated by peripheral β 2 -adrenergic receptors - bronchodilation, insulin secretion, mobilization of glucose from the liver, vasodilation and contractile activity of the uterus during pregnancy, therefore they have advantages in the severity of the hypotensive effect, lower frequency of side effects, compared to non-selective ones.

High level of selectivity β lβ-adrenergic blockade makes it possible to use it in patients with broncho-obstructive diseases, in smokers, due to a less pronounced reaction to catecholamines, in patients with hyperlipidemia, diabetes mellitus type I and II, and peripheral circulatory disorders compared to non-selective and less selective β-blockers.

The level of selectivity of β-blockers determines the effect on total peripheral vascular resistance as one of the determining components of the hypotensive effect. Selective β l-adrenergic blockers do not have a significant effect on peripheral vascular resistance, non-selective β-blockers, due to blockade of β 2 -vascular receptors, can enhance the vasoconstrictor effect and increase

The state of selectivity is dose dependent. An increase in the dose of the drug is accompanied by a decrease in the selectivity of action, clinical manifestations of β blockade 2 -adrenergic receptors, in large doses β l-selective beta blockers lose β l-selectivity.

There are β-adrenergic blockers that have a vasodilating effect, having a combined mechanism of action: labetalol (non-selective blocker and α1-adrenergic receptors), car-

vedilol (non-selective β blocker 1 β 2- and a 1 -adrenergic receptors), dilevalol (non-selective β-adrenergic receptor blocker and partial β agonist 2 -adrenergic receptors), nebivolol (b 1 -adrenergic blocker with activation of endothelial nitric oxide). These drugs have different mechanisms of vasodilating action and belong to the third generation β-blockers.

Depending on the degree of selectivity and the presence of vasodilating properties of M.R. Bristow in 1998 proposed a classification of beta-blockers (Table 5.3).

Table 5.3

Classification of beta-blockers (M. R. Bristow, 1998)

Some β-blockers have the ability to partially activate adrenergic receptors, i.e. partial agonistic activity. These β-blockers are called drugs with intrinsic sympathomimetic activity - alprenolol, acebutalol, oxprenolol, penbutalol, pindolol, talinolol, practolol. Pindolol has the most pronounced sympathomimetic activity.

The intrinsic sympathomimetic activity of β-blockers limits the reduction in resting heart rate, which is useful in patients with a low baseline heart rate.

Non-selective (β 1- + β 2-) β-blockers without BCA: propranolol, nadolol, sotalol, timolol, and with BCA: alprenolol, bopindolol, oxprenolol, pindolol.

Drugs with a membrane-stabilizing effect - propranolol, betaxolol, bisoprolol, oxprenolol, pindolol, talinolol.

LIPOPHILICITY, HYDROPHILICITY, AMPHOPHILICITY

Differences in the duration of action of β-blockers with a low selectivity index depend on the characteristics of the chemical structure, lipophilicity and elimination routes. There are hydrophilic, lipophilic and amphophilic drugs.

Lipophilic drugs are typically metabolized in the liver and have a relatively short elimination half-life (T 1/2). Lipophilicity is combined with the hepatic elimination route. Lipophilic drugs are quickly and completely (more than 90%) absorbed in the gastrointestinal tract, their metabolism in the liver is 80-100%, the bioavailability of most lipophilic β-blockers (propranolol, metoprolol, alprenolol, etc.) due to the “first pass” effect » through the liver is slightly more than 10-40% (Table 5.4).

The state of hepatic blood flow affects the metabolic rate, the size of single doses and the frequency of drug administration. This must be taken into account when treating elderly patients, patients with heart failure, and cirrhosis of the liver. In severe liver failure, the rate of elimination decreases pro-

Table 5.4

Pharmacokinetic parameters of lipophilic β-blockers

proportional to the decrease in liver function. Lipophilic drugs with long-term use can themselves reduce hepatic blood flow, slow down their own metabolism and the metabolism of other lipophilic drugs. This explains the increase in the half-life and the possibility of reducing the single (daily) dose and frequency of taking lipophilic drugs, increasing the effect, and the threat of overdose.

The influence of the level of microsomal oxidation on the metabolism of lipophilic drugs is significant. Drugs that induce microsomal oxidation of lipophilic β-blockers (heavy smoking, alcohol, rifampicin, barbiturates, diphenin) significantly accelerate their elimination and reduce the severity of the effect. The opposite effect is exerted by drugs that slow down hepatic blood flow and reduce the rate of microsomal oxidation in hepatocytes (cimetidine, chlorpromazine).

Among the lipophilic beta-blockers, the use of betaxolol does not require dose adjustment in case of liver failure, however, when using betaxolol, dose adjustment of the drug is required in case of severe renal failure and dialysis. Dose adjustment of metoprolol is carried out in case of severe liver dysfunction.

The lipophilicity of β-blockers facilitates their penetration through the blood-brain and hystero-placental barriers into the chambers of the eye.

Hydrophilic drugs are excreted predominantly by the kidneys unchanged and have a longer duration. Hydrophilic drugs are not completely (30-70%) and unevenly (0-20%) absorbed in the gastrointestinal tract, excreted by the kidneys by 40-70% unchanged or in the form metabolites have a longer half-life (6-24 hours) than lipophilic β-blockers (Table 5.5).

A reduced glomerular filtration rate (in elderly patients, with chronic renal failure) reduces the rate of excretion of hydrophilic drugs, which requires a reduction in dose and frequency of administration. You can navigate by the serum creatinine concentration, the level of which increases when the glomerular filtration rate decreases below 50 ml/min. In this case, the frequency of administration of the hydrophilic β-blocker should be every other day. Of the hydrophilic β-blockers, penbutalol does not require

Table5.5

Pharmacokinetic parameters of hydrophilic β-blockers

Table5.6

Pharmacokinetic parameters of amphophilic β-blockers

dose adjustment for renal impairment. Nadolol does not reduce renal blood flow and glomerular filtration rate, having a vasodilating effect on the renal vessels.

The influence of the level of microsomal oxidation on the metabolism of hydrophilic β-blockers is insignificant.

Ultra-short-acting β-blockers are destroyed by blood esterases and are used exclusively for intravenous infusion. β-blockers, which are destroyed by blood esterases, have a very short half-life; their effect ceases 30 minutes after stopping the infusion. Such drugs are used to treat acute ischemia, control ventricular rhythm during paroxysm of supraventricular tachycardia during surgery or in the postoperative period. The short duration of action makes their use safer in patients with hypotension and heart failure, and the βl-selectivity of the drug (esmolol) makes it safer for bronchial obstruction.

Amphophilic β-blockers are soluble in fats and water (acebutolol, bisoprolol, pindolol, celiprolol) and have two elimination routes - hepatic metabolism and renal excretion (Table 5.6).

The balanced clearance of these drugs determines the safety of their use in patients with moderate renal and hepatic insufficiency and a low likelihood of interaction with other drugs. The rate of drug elimination decreases only in severe renal and hepatic impairment. In this case, daily doses of β-blockers with balanced clearance must be reduced by 1.5-2 times.

The amphophilic β-blocker pindol in chronic renal failure can increase renal blood flow.

Doses of β-blockers must be selected individually, focusing on the clinical effect, heart rate, and blood pressure levels. The initial dose of the β-blocker should be 1/8-1/4 of the average therapeutic single dose; if the effect is insufficient, the dose is increased every 3-7 days to the average therapeutic single dose. Heart rate at rest in an upright position should be in the range of 55-60 per minute, systolic blood pressure - not lower than 100 mm Hg. The maximum severity of the β-blocker effect is observed after 4-6 weeks of regular use of the β-blocker; lipophilic β-blockers, which can

able to slow down their own metabolism. The frequency of dosing depends on the frequency of anginal attacks and the duration of action of the β-blocker.

It should be taken into account that the duration of the bradycardic and hypotensive effects of β-blockers significantly exceeds their half-life periods, and the duration of the antianginal effect is less than the duration of the negative chronotropic effect.

MECHANISMS OF ANTIANGINAL AND ANTIISCHEMIC ACTION OF β-ADRENOBLOCKERS IN THE TREATMENT OF ANGINA PARDIA

Improving the balance between myocardial oxygen demand and its delivery through the coronary arteries can be achieved by increasing coronary blood flow and by reducing myocardial oxygen demand.

The antianginal and anti-ischemic action of β-blockers is based on their ability to influence hemodynamic parameters - to reduce myocardial oxygen consumption by reducing heart rate, myocardial contractility and systemic blood pressure. β-blockers, by reducing heart rate, increase the duration of diastole. Oxygen delivery to the myocardium of the left ventricle is carried out mainly in diastole, since in systole the coronary arteries are compressed by the surrounding myocardium and the duration of diastole determines the level of coronary blood flow. A decrease in myocardial contractility, along with an extension of the time of distolic relaxation with a decrease in heart rate, contributes to an extension of the period of diastolic perfusion of the myocardium. A decrease in diastolic pressure in the left ventricle due to a decrease in myocardial contractility with a decrease in systemic blood pressure contributes to an increase in the pressure gradient (the difference between dastolic pressure in the aorta and diastolic pressure in the left ventricular cavity), providing coronary perfusion in diastole.

A decrease in systemic blood pressure is determined by a decrease in myocardial contractility with a decrease in cardiac output by

15-20%, inhibition of central adrenergic effects (for drugs that penetrate the blood-brain barrier) and antirenin (up to 60%) action of β-blockers, which causes a decrease in systolic and then diastolic pressure.

A decrease in heart rate and a decrease in myocardial contractility as a result of blockade of β-adrenergic receptors of the heart leads to an increase in volume and end-diastolic pressure in the left ventricle, which is corrected by a combination of β-blockers with drugs that reduce venous return of blood to the left ventricle (nirovasodilators).

Lipophilic beta-adrenergic receptor blockers, which do not have intrinsic sympathomimetic activity, regardless of selectivity, have a greater cardioprotective effect in patients who have suffered acute myocardial infarction with long-term use, reducing the risk of recurrent myocardial infarction, sudden death and overall mortality in this group of patients. Such properties were noted in metoprolol, propranolol (BHAT study, 3837 patients), timolol (Norwegian MSG, 1884 patients). Lipophilic drugs with intrinsic sympathomimetic activity have less prophylactic antianginal effectiveness. The effects of carvedilol and bisoprolol in terms of cardioprotective properties are comparable to the effects of the retardated form of metoprolol. Hydrophilic β-blockers - atenolol, sotalol did not affect overall mortality and the incidence of sudden death in patients with coronary heart disease. Data from a meta-analysis of 25 controlled studies are presented in Table. 5.8.

For secondary prevention, β-blockers are indicated in all patients who have had a Q-wave myocardial infarction for at least 3 years in the absence of absolute contraindications to the use of drugs of this class, especially in patients over 50 years of age with an infarction of the anterior wall of the left ventricle, early post-infarction angina, high heart rate, ventricular arrhythmias, symptoms of stable heart failure.

Table 5.7

β-blockers in the treatment of angina pectoris

Note,- selective drug; # - currently the original drug is not registered in Russia; the original drug is highlighted in bold;

* - single dose.

Table 5.8

Cardioprotective efficacy of β-blockers in patients who have suffered myocardial infarction

EFFECTS OF β-ADRENOBLOCKERS IN CHF

The therapeutic effect of β-blockers in CHF is associated with a direct antiarrhythmic effect, a positive effect on the function of the left ventricle, a decrease in chronic ischemia of the dilated ventricle even in the absence of coronary artery disease, and suppression of the processes of apoptosis of myocardiocytes activated under conditions of βl-adrenergic stimulation.

In CHF, there is an increase in the level of basal norepinephrine in the blood plasma, associated with its increased production by the endings of adrenergic nerves, the rate of entry into the blood plasma and a decrease in the clearance of norepinephrine from the blood plasma, accompanied by an increase in dopamine and often adrenaline. The concentration of basal plasma norepinephrine level is an independent predictor of death in CHF. The initial increase in the activity of the sympathetic-adrenal system in CHF is compensatory in nature and contributes to an increase in cardiac output, redistribution of regional blood flow towards the heart and skeletal muscles; renal vasoconstriction helps improve perfusion of vital organs. Subsequently, an increase in the activity of the sympathetic-adrenal

ovary system leads to increased oxygen demand by the myocardium, increased ischemia, cardiac arrhythmia, and a direct effect on cardiomyocytes - remodeling, hypertrophy, apoptosis and necrosis.

With prolonged elevated levels of catecholamines, myocardial β-adrenergic receptors enter a state of reduced sensitivity to neurotransmitters (desinitization state) due to a decrease in the number of receptors on the plasma membrane and disruption of the coupling of receptors with adenylate cyclase. The density of myocardial β-adrenergic receptors is reduced by half, the degree of receptor reduction is proportional to the severity of CHF, myocardial contractility and ejection fraction. The ratio and β change 2 -adrenergic receptors in the direction of increasing β 2 -adrenoreceptors. Disruption of the coupling of β-adrenergic receptors with adenylate cyclase leads to direct cardiotoxic effects of catecholamines, overload of cardiomyocyte mitochondria with calcium ions, disruption of ADP rephosphorylation processes, depletion of creatine phosphate and ATP reserves. Activation of phospholipases and proteases contributes to the destruction of the cell membrane and the death of cardiomyocytes.

A decrease in the density of adrenergic receptors in the myocardium is combined with depletion of local reserves of norepinephrine, disruption of adequate load of adrenergic support of the myocardium, and progression of the disease.

The positive effects of β-blockers in CHF are: a decrease in sympathetic activity, a decrease in heart rate, an antiarrhythmic effect, an improvement in diastolic function, a decrease in myocardial hypoxia and regression of hypertrophy, a decrease in necrosis and apoptosis of cardiomyocytes, a decrease in the severity of congestion due to blockade of the renin-angiotensin-aldosterone system.

Based on research data from the USCP - American program for carvedilol, CIBIS II with bisoprolol and MERIT HF with metoprolol succinate with sustained release of the drug, COPERNICUS, CAPRICORN about a significant reduction in overall, cardiovascular, sudden death, a reduction in the frequency of hospitalizations, a reduction in the risk of death by 35 % in the severe category of patients with CHF, the above β-blockers occupy one of the leading positions in the pharmacotherapy of patients with CHF of all functional classes. β-blockers along with ACE inhibitors

are the main means in the treatment of CHF. Their ability to slow the progression of the disease, the number of hospitalizations and improve the prognosis of decompensated patients is beyond doubt (evidence level A). β-blockers should be used in all patients with CHF who do not have the usual contraindications for this group of drugs. The severity of decompensation, gender, age, initial pressure level (SBP not less than 85 mm Hg) and initial heart rate do not play an independent role in determining contraindications to the use of β-blockers. Prescription of β-blockers begins with 1 /8 therapeutic dose for patients with achieved stabilization of CHF. β-blockers in the treatment of CHF are not “emergency medicine” and cannot relieve patients from a state of decompensation and overhydration. Possible appointment β l-selective β-blocker bisoprolol as an initial treatment drug in patients over 65 years of age with NYHA class II - III CHF, left ventricular ejection fraction<35% с последующим присоединением ингибитора АПФ (степень доказанности В). Начальная терапия βl A -selective β-blocker may be justified in clinical situations where severe tachycardia predominates at low blood pressure, followed by the addition of an ACE inhibitor.

The tactics for prescribing β-blockers in patients with CHF are presented in Table. 5.9.

In the first 2-3 months, the use of even small doses of β-blockers causes an increase in peripheral vascular resistance and a decrease in myocardial systolic function, which requires titration of the dose of the β-blocker prescribed to a patient with CHF and dynamic monitoring of the clinical course of the disease. In these cases, it is recommended to increase the doses of diuretics, ACE inhibitors, the use of positive inotropic drugs (small doses of cardiac glycosides or calcium sensitizers - levosimendan), and a slower titration of the dose of the beta-blocker.

Contraindications to the use of β-blockers for heart failure are:

Bronchial asthma or severe bronchial pathology, accompanied by an increase in symptoms of bronchial obstruction when a beta-blocker is prescribed;

Symptomatic bradycadia (<50 уд/мин);

Symptomatic hypotension (<85 мм рт.ст.);

Table 5.9

Initial, target doses and dosing schedules of beta-blockers in heart failure based on large-scale placebo-controlled studies

research

A-V blockade of the second degree and higher;

Severe obliterating endarteritis.

The administration of β-blockers to patients with CHF and type 2 diabetes is absolutely indicated. All the positive properties of drugs of this class are completely preserved in the presence of diabetes mellitus. Use of non-cardioselective and adrenoblocker with additional properties 0 4 The β-blocker carvedilol may be the drug of choice in such patients by improving the sensitivity of peripheral tissues to insulin (evidence level A).

Results of the SENIORS study using β l-selective β-blocker nebivolol, which demonstrated a small but significant overall reduction in the frequency of hospitalizations and deaths in patients with CHF over 75 years of age, allowed us to recommend nebivolol for the treatment of patients with CHF over 70 years of age.

Doses of β-arenoblockers for the treatment of patients with CHF, established by the National Recommendations of GFCI and OSHF, are presented in Table 5.10.

Table 5.10

Doses of beta-blockers for the treatment of patients with CHF

left ventricle<35%, была выявлена одинаковая эффективность и переносимость бетаксолола и карведилола.

The use of the non-selective β-blocker bucindolol, which has moderate intrinsic sympathomimetic activity and additional vasodilating properties (BEST study), did not significantly reduce overall mortality and the frequency of hospitalizations due to CHF; there was a worsening prognosis and an increase in the risk of death by 17% in the group of black patients.

Further clarification of the effectiveness of drugs in this group in certain demographic groups of patients, in elderly patients, and in patients with atrial fibrillation is required.

MAIN MECHANISMS OF HYPOTENSIVE ACTION OF β-ADRENOB LOCATORS

β-blockers are initial therapy drugs in the treatment of arterial hypertension. β-blockers are first-line drugs in the treatment of hypertension in patients after myocardial infarction, suffering from stable angina, heart failure, in people intolerant to ACE inhibitors and/or ATII receptor blockers, in women of childbearing age planning pregnancy.

As a result of blockade of β-adrenergic receptors of the heart, the heart rate and myocardial contractility decrease, and cardiac output decreases. Blockade of β-adrenergic receptors in the cells of the juxtaglomerular apparatus of the kidneys leads to a decrease in the secretion of renin, a decrease in the formation of angiotensin, and a decrease in peripheral vascular resistance. Reducing aldosterone production helps reduce fluid retention. The sensitivity of the baroreceptors of the aortic arch and carotid sinus changes, and the release of norepinephrine from the endings of postganglionic sympathetic nerve fibers is inhibited. Central adrenergic effects are inhibited (for β-blockers that penetrate the blood-brain barrier).

The use of β-adrenor blockers helps reduce systolic and diastolic blood pressure, control blood pressure in the early morning hours, and normalize

daily blood pressure profile. Left ventricular hypertrophy is today considered one of the most significant risk factors for the development of cardiovascular complications.

β-blockers, as a result of reducing the activity of the sympathetic and renin-angiothesin system, are the optimal class of drugs for the prevention and reversal of left ventricular hypertrophy. Indirect reduction of aldosterone levels limits the simulation of myocardial fibrosis, improving left ventricular diastolic function.

The level of selectivity of β-blockers determines the effect on total peripheral vascular resistance as one of the determining components of the hypotensive effect. Selective β l-adrenergic blockers do not have a significant effect on peripheral vascular resistance, non-selective, due to β blockade 2 -vascular receptors, can enhance the vasoconstrictor effect and increase peripheral vascular resistance.

β-blockers in combination with vasodilators or labetolol are the drugs of choice when there is a threat of aortic aneurysm dissection due to increased blood pressure. This is the only clinical situation of high blood pressure that requires a rapid decrease in blood pressure within 5-10 minutes. The administration of a beta-blocker should precede the administration of a vasodilator to prevent increases in cardiac output that may aggravate the situation.

Labetolol is the drug of choice in the treatment of hypertensive crisis complicated by acute coronary insufficiency; parenteral administration of a non-selective β-blocker is indicated for the development of tachycardia or rhythm disturbances.

Labetolol and esmolol are the drugs of choice for the management of patients with traumatic brain injuries complicated by hypertensive crises.

Labetolol and oxprenalol are the drugs of choice for controlling blood pressure in pregnant women in case of intolerance to methyldopa. The effectiveness of pindolol is comparable to oxprenolol and labetolol. With long-term use of atenolol, a decrease in the weight of the newborn and the placenta was found, which is associated with a decrease in feto-placental blood flow.

In table Table 5.11 presents the main doses and frequency of administration of β-blockers for the treatment of hypertension.

Table 5.11

Daily doses and frequency of use of β-blockers for the treatment of hypertension

MONITORING THE EFFECTIVENESS OF THERAPY WITH β-ADRENOBLOCKERS

The effective heart rate at the maximum expected effect of the next dose of beta-blocker (usually 2 hours after administration) is 55-60 beats per minute. A stable hypotensive effect occurs after 3-4 weeks of regular use of the drug. Given the possibility of slowing atrioventricular conduction, electrocardiographic monitoring is necessary, especially in cases of a more significant decrease in heart rate. Patients with symptoms of latent circulatory failure require attention; such patients require a longer titration of the dose of the β-blocker due to the threat of the development of decompensation phenomena (the appearance of fatigue, weight gain, shortness of breath, wheezing in the lungs).

Age-related features of the pharmacodynamics of β-adrenergic blockers are due to changes in the interaction between β-adrenergic receptors and stimulation of alanine aminotransferase production and binding of the receptor to adenylate cyclase. The sensitivity of β-adrenergic receptors to β-blockers changes and becomes distorted. This determines the multidirectional and difficult to predict nature of the pharmacodynamic response to the drug.

Pharmacokinetic parameters also change: the protein capacity of the blood, water and muscle mass of the body decrease, the volume of adipose tissue increases, and tissue perfusion changes. The volume and speed of hepatic blood flow decreases by 35-45%. The number of hepatocytes and the level of their enzymatic activity decreases - liver weight decreases by 18-25%. The number of functioning glomeruli of the kidneys, the rate of glomerular filtration (by 35-50%) and tubular secretion decrease.

SELECTED β-ADRENOBLOCKER DRUGS

Non-selectiveβ - adrenergic blockers

Propranolol- a non-selective beta-blocker without its own sympathomimetic activity with a short-term effect. The bioavailability of propranolol after oral administration is less than 30%, T 1/2 - 2-3 hours. Due to the high rate of metabolism of the drug during the first passage through the liver, its concentrations in the blood plasma after taking the same dose can vary from person to person by 7-20 times. 90% of the dose taken is eliminated in the urine in the form of metabolites. The distribution of propranolol and, apparently, other β-blockers in the body is influenced by a number of drugs. At the same time, beta-blockers themselves can alter the metabolism and pharmacokinetics of other drugs. Propranolol is prescribed orally, starting with small doses - 10-20 mg, gradually (especially in older people and in cases of suspected heart failure) over 2-3 weeks, bringing the daily dose to an effective dose (160-180-240 mg). Given the short half-life of the drug, to achieve a constant therapeutic concentration it is necessary to take propranolol 3-4 times a day. Treatment can be lengthy. It should be remembered that high

Doses of propranolol may result in increased side effects. To select the optimal dose, regular measurement of heart rate and blood pressure is necessary. It is recommended to discontinue the drug gradually, especially after long-term use or after using large doses (reduce the dose by 50% within one week), since abrupt cessation of its use can cause withdrawal syndrome: increased frequency of angina attacks, development of gastric tachycardia or myocardial infarction, and AH - a sharp rise in blood pressure.

Nadolol- a non-selective β-blocker without internal sympathomimetic and membrane-stabilizing activity. It differs from other drugs in this group in its long-lasting action and ability to improve kidney function. Nadolol has antianginal activity. Has less cardiodepressive effect, possibly due to the lack of membrane-stabilizing activity. When taken orally, about 30% of the drug is absorbed. Only 18-21% binds to plasma proteins. Peak concentration in the blood after oral administration is reached after 3-4 hours, T 1/2

From 14 to 24 hours, which allows the drug to be prescribed once a day in the treatment of patients with both angina and hypertension. Nadolol is not metabolized in the body and is excreted unchanged by the kidneys and intestines. Complete release is achieved only 4 days after a single dose. Nadolol is prescribed 40-160 mg once a day. A stable level of its concentration in the blood is achieved after 6-9 days of administration.

Pindolol is a non-selective β-adrenergic receptor blocker with sympathomimetic activity. It is well absorbed when taken orally. Features high bioavailability, T 1/2

3-6 hours, the beta-blocking effect lasts for 8 hours. About 57% of the dose taken is combined with protein. 80% of the drug is excreted in the urine (40% unchanged). Its metabolites are presented in the form of glucuronides and sulfates. CRF does not significantly change the elimination constant and half-life. The rate of drug elimination is reduced only in severe renal and hepatic impairment The drug penetrates the blood-brain barrier and the placenta. Compatible with diuretics, antiadrenergic drugs, methyldopa, reserpine, barbiturates, digitalis. In terms of β-adrenergic blocking action, 2 mg of pindolol is equivalent to 40 mg of propranolol. Pindolol is used 5 mg 3-4 times a day, and in severe cases - 10 mg 3 times a day.

If necessary, the drug can be administered intravenously in a dose of 0.4 mg; the maximum dose for intravenous administration is 1-2 mg. The drug causes a less pronounced negative inotropic effect at rest than propranolol. It has a weaker effect on β than other non-selective β-blockers. 2 -adrenergic receptors and therefore in normal doses is safer for bronchospasm and diabetes mellitus. In hypertension, the hypotensive effect of pindolol develops more slowly than that of propranolol: the onset of action is after a week, and the maximum effect is after 4-6 weeks.

Selectiveβ - adrenergic blockers

Nebivolol- highly selective third-generation β-blocker. The active substance of nebivolol is a racemate, consisting of two enantiomers. D-nebivolol is a competitive and highly selective β l-blocker. L-nebivolol has a mild vasodilating effect by modulating the release of relaxing factor (NO) from the vascular endothelium, which maintains normal basal vascular tone. After oral administration, it is quickly absorbed. Highly lipophilic drug. Nebivolol is actively metabolized, partially with the formation of active hydroxymetabolites. The time to reach a stable equilibrium concentration in individuals with rapid metabolism is achieved within 24 hours, for hydroxymetabolites - after several days.

The level of the hypothetical effect and the number of patients responding to therapy increases in proportion to the 2.5-5 mg daily dose of the drug, therefore the average effective dose of nebivolol is taken to be 5 mg per day; in case of renal failure, as well as in persons over 65 years of age, the initial dose should not exceed 2.5 mg.

The hypotensive effect of nebivolol develops after the first week of treatment, increases by the 4th week of regular use, and with long-term treatment up to 12 months, the effect is stably maintained. After discontinuation of nebivolol, blood pressure slowly returns to its original level over 1 month; withdrawal syndrome in the form of exacerbation of hypertension is not observed.

Due to the presence of vasodilating properties, nebivolol does not affect renal hemodynamic parameters (renal artery resistance, renal blood flow, glomerular filtration,

filtration fraction) both in patients with normal and impaired renal function against the background of arterial hypertension.

Despite its high lipophilicity, nebivolol is practically free of side effects from the central nervous system: it did not cause sleep disturbances or nightmares, which are characteristic of lipophilic β-blockers. The only neurological disorder is paresthesia - their frequency is 2-6%. Sexual dysfunction occurred at a rate not different from placebo (less than 2%).

Carvedilol has β- and a 1 -adrenergic blocking as well as antioxidant properties. It reduces the effects of stress on the heart through arteriolar vasodilation and inhibits neurohumoral vasoconstrictor activation of blood vessels and the heart. Carvedilol has a prolonged antihypertensive effect. It has an antianginal effect. It does not have its own sympathomimetic activity. Carvedilol inhibits the proliferation and migration of smooth muscle cells, apparently acting on specific mitogenic receptors. Carvedilol has lipophilic properties. T 1/2 is 6 hours. During the first passage through the liver, it is metabolized. In blood plasma, carvedilol is 95% protein bound. The drug is excreted through the liver. Used for hypertension - 25-20 mg once a day; for angina pectoris and chronic heart failure - 25-50 mg twice a day.

Bisoprolol- a highly selective, long-acting β-blocker without internal sympathomimetic activity and does not have a membrane-stabilizing effect. It has amphophilic properties. Due to its prolonged action, it can be prescribed once a day. The peak effect of bisoprolol occurs 2-4 hours after administration, the antihypertensive effect lasts 24 hours. Bioavailability is 65-75% for bisoprolol hydrochloride and 80% for bisoprolol fumarate. The bioavailability of the drug increases in the elderly. Food intake does not affect the bioavailability of bisoprolol. Low binding to plasma proteins (30%) ensures safety when used together with most drugs. 20% of bisoprolol is metabolized into 3 inactive metabolites. There is a linear dependence of the pharmacokinetics of the drug on the dose within the range of 2.5-20 mg. T s is 7-15 hours for bisoprolol fumarate and 4-10 hours for bisoprolol hydrochloride. Bisoprolol fumarate binds to blood proteins by 30%,

bisoprolol hydrochloride - by 40-68%. Accumulation of bisoprolol in the blood is possible in case of impaired liver and kidney function. Excreted equally by the liver and kidneys. The rate of drug elimination decreases only in cases of severe renal and hepatic insufficiency, which is why bisoprolol can accumulate in the blood if liver and kidney function are impaired.

Penetrates the blood-brain barrier. Used for arterial hypertension, angina pectoris, heart failure. The initial dose for hypertension is 5-10 mg per day, it is possible to increase the dose to 20 mg per day; in case of insufficiency of liver and kidney function, the daily dose should not exceed 10 mg. Bisoprolol does not affect the level of glucose in the blood in patients with diabetes and the level of thyroid hormones, and has virtually no effect on potency in men.

Betaxolol- a cardioselective β-blocker without its own sympathomimetic activity and with weakly expressed membrane-stabilizing properties. The potency of β-adrenergic receptor blockade is 4 times greater than the effects of propranolol. It has high lipophilicity. Well (more than 95%) absorbed from the gastrointestinal tract. After a single dose, it reaches maximum concentrations in the blood plasma after 2-4 hours. Food intake does not affect the degree and rate of absorption. Unlike other lipophilic drugs, the bioavailability of betaxolol when taken orally is 80-89%, which is explained by the absence of a “first pass” effect through the liver. Individual metabolic features do not affect the variability of drug concentrations in the blood serum, which allows us to expect a more stable response to the action of the drug when used. The degree of heart rate reduction is proportional to the dose of betaxolol. There is a correlation of the antihypertensive effect with the peak concentration of betaxolol in the blood 3-4 hours after administration and then for 24 hours, the effect is dose dependent. With regular use of betaxolol, the antihypertensive effect reaches its maximum after 1-2 weeks. Betaxolol is metabolized in the liver by microsomal oxidation, however, cimetidine does not change the concentration of the drug when used together and does not lead to a prolongation of T1/2. T1/2 is 14-22 hours, which allows you to take the drug once a day. In older people, T1/2 increases to 27 hours.

Binds to plasma proteins by 50-55%, of which to albumin by 42%. Liver and kidney disease does not affect the degree of protein binding; it does not change when taking digoxin, aspirin, or diuretics at the same time. Betaxolol and its metabolites are excreted in the urine. The rate of drug elimination decreases only in severe renal and hepatic insufficiency. The pharmacokinetics of betaxolol do not require changes in the dosage regimen for severe hepatic and moderate renal failure. Dose adjustment of the drug is necessary only in cases of severe renal failure and in patients on dialysis. For patients with significant renal impairment requiring hemodialysis, the initial dose of betaxolol is 5 mg per day, the dose can be increased by 5 mg every 14 days, the maximum dose is 20 mg. The initial dose for hypertension and angina pectoris is 10 mg once a day; if necessary, the dose can be doubled after 7-14 days. To enhance the effect, betaxalol can be combined with thiazide diuretics, vasodilators, imdazoline receptor agonists, and o 1 -blockers. The advantage over other selective β 1 -adrenergic receptors is the absence of a decrease in HDL concentration. Betaxolol does not affect the process of glucose metabolism and compensatory mechanisms during hypoglycemia. In terms of the degree of reduction in heart rate, blood pressure, and increase in exercise tolerance in patients with angina pectoris, the effects of betaxolol did not differ from those of nadolol.

Metoprolol- selective blocker of β 1-adrenergic receptors. The bioavailability of metoprolol is 50%, TS is 3-4 hours for the regular release dosage form. About 12% of the drug is bound to blood proteins. Metoprolol quickly dissolves in tissues, penetrates the blood-brain barrier, and is found in breast milk in higher concentrations than in plasma. The drug undergoes intensive hepatic metabolism in the cytochrome P4502D6 system and has two active metabolites - α-hydroxymetoprolol and o-dimethylmetoprolol. Age does not affect the concentration of metoprolol; cirrhosis increases bioavailability to 84% and half-life to 7.2 hours. In chronic renal failure, the drug does not accumulate in the body. In patients with hyperthyroidism, the level of maximum concentration achieved and the area under the kinetic curve are reduced. The drug exists in the form of metoprolol tartrate (regular and delayed release forms).

nia), metoprolol succinate with prolonged controlled release. Sustained release forms have a maximum peak concentration of the active substance 2.5 times lower than regular release forms, which is advantageous in patients with circulatory insufficiency. Pharmacokinetic parameters for metoprolol of various releases at a dose of 100 mg are presented in table. 5.12.

Table 5.12

Pharmacokinetics of dosage forms of metoprolol

Metoprolol succinate in controlled release form has a constant rate of release of the active substance, absorption in the stomach does not depend on food intake.

For hypertension and angina pectoris, metoprolol is prescribed 2 times a day, 50-100-200 mg. The hypotensive effect occurs quickly, systolic blood pressure decreases after 15 minutes, maximum after 2 hours. Diastolic pressure decreases after several weeks of regular use. Sustained release forms are the drugs of choice in the treatment of circulatory failure. The clinical effectiveness of ACE inhibitors in heart failure increases significantly with the addition of a β-blocker (ATLAS, MERIT HF, PRECISE, MOCHA studies).

Atenolol- selective β l- an adrenergic blocker that does not have its own sympathomimetic and membrane-stabilizing activity. Absorbed from the gastrointestinal tract by approximately 50%. The peak plasma concentration occurs after 2-4 hours. It is almost not metabolized in the liver and is eliminated mainly by the kidneys. About 6-16% binds to plasma proteins. T 1/2 is 6-7 hours for both single and long-term

destination. After oral administration, a decrease in cardiac output occurs within an hour, the maximum effect is between 2 and 4 hours and lasts at least 24 hours. The hypotensive effect, like all β-blockers, does not correlate with plasma levels and increases after continuous use for several weeks For hypertension, the initial dose is 25-50 mg; if there is no effect within 2-3 weeks, the dose is increased to 100-200 mg, divided into 2 doses. In elderly patients with chronic renal failure, dose adjustment is recommended when glomerular filtration rate is below 35 ml/min.

DRUG INTERACTIONS WITH β-ADRENOBLOCKERS

Table 5.13

Drug interactions

SIDE EFFECTS AND CONTRAINDICATIONS TO THE USE OF β-ADRENOBLOCKERS

Side effects of β-blockers are determined by their predominant blocking effect on one or another type of receptor; the level of lipophilicity determines the presence of side effects from the central nervous system (Table 5.14).

The main side effects of β-blockers are: sinus bradycardia, development or increase in the degree of atrioventricular block, manifestation of latent congestive heart failure, exacerbation of bronchial asthma or other obstructive pulmonary diseases, hypoglycemia, impaired

Table 5.14

Characteristics of side effects of β-blockers

function in men, various manifestations of vasospasm, general weakness, drowsiness, depression, dizziness, decreased reaction speed, the possibility of developing withdrawal syndrome (mainly for drugs with a short duration of action).

Contraindications to the use of β-blockers. The drugs should not be used for severe bradycardia (less than 48 beats/min), arterial hypotension (systolic blood pressure below 100 mm Hg), bronchial asthma, sick sinus syndrome, and high-grade atrioventricular conduction disorders. Relative contraindications are diabetes mellitus in the stage of decompensation, severe peripheral circulatory disorders, severe circulatory failure in a state of decompensation, pregnancy (for β-blockers that do not have a vasodilating effect).

PLACE OF β-ADRENOBLOCKERS

IN COMBINED THERAPY

Monotherapy with β-blockers is effective for the prevention of anginal attacks in angina pectoris of functional class I-III and in 30-50% of patients with mild and moderate hypertension to maintain target blood pressure values.

According to the HOT study, to achieve a target diastolic blood pressure below 85-80 mmHg. 68-74% of patients require combination antihypertensive therapy. Combination therapy to achieve target blood pressure values ​​is indicated for the vast majority of patients with diabetes and chronic renal failure.

The undeniable advantages of rational combinations are the potentiation of the hypotensive effect due to the impact on various parts of the pathogenesis of arterial hypertension, improving drug tolerability, reducing the number of side effects, limiting counter-regulatory mechanisms (bradycardia, increased total peripheral resistance, arteriospasm, excessive decrease in myocardial contractility and others), including at the initial stages of prescribing antihypertensive drugs (Table 5.15). Combined antihypertensive therapy is indicated for patients with moderate arterial hypertension, in the presence of proteinuria, diabetes mellitus, and renal failure.

An effective combination is the combined use of a β-blocker and a diuretic. The diuretic and vasodilating effect of the diuretic limits sodium retention and increased peripheral vascular tone characteristic of beta-blockers. β-blockers, in turn, suppress the activity of the sympathoadrenal and renin-angiotensin systems, characteristic of a diuretic. It is possible to inhibit the development of diuretic hypokalemia with a β-blocker. The low cost of such combinations is attractive.

There are combined dosage forms: tenoretic (50-100 mg atenolol and 25 mg chlorthalidone), lopressor HGT (50-100 mg metoprolol and 25-50 mg hydrochlorothiazide), corzoid (40-80 mg nadolol and 5 mg bendroflumetazide), viscaldix (10 mg pindolol and 5 mg clopamide), Ziac (2.5-5-10 mg bisoprolol and 6.25 mg gyrochlorothiazide).

When combined with dihydropyridine antagonists of slow calcium channels, β-blockers have an additive effect, counteracting the development of tachycardia and activation of the sympathetic nervous system, characteristic of initial therapy with dihydropyridines. This combination therapy is indicated for patients with hypertension and coronary artery disease, patients with severe refractory arterial hypertension. Logimax is a fixed combination with a long-term release system of active components of 50-100 mg of metoprolol and 5-10 mg of felodipine, which selectively acts on precapillary resistive vessels. 50 mg of atenolol and 5 mg of amlodipine are included in the drug tenochek.

The combination of β-blockers and calcium antagonists - verapamil or diltiazem - is dangerous in terms of significant slowdown of atrioventricular conduction.

The combination of β-blockers and a1-adrenergic receptor blockers is beneficial. β-blockers inhibit the development of tachycardia, which is typical when α-blockers are prescribed. Blockers of a 1 -adrenergic receptors reduce the effects of β-blockers, such as increased peripheral vascular resistance and effects on lipid and carbohydrate metabolism.

Drugs beta-blockers and ACE inhibitors, by reducing the activity of the renin-angiotensin system, can have a synergistic hypotensive effect. The administration of an ACEI does not completely suppress the formation of angiotensin II, since there are alternative pathways for its formation. Hyperreninemia resulting from ACE inhibitor inhibition can be reduced by the direct suppressive effect of β-blockers on renin secretion by the juxtaglomerular apparatus of the kidneys. Suppression of renin secretion will reduce the production of angiotensin I and, indirectly, angiotensin II. The vasodilating properties of ACEIs may reduce the vasoconstrictor effects of β-blockers. The organoprotective effect of this combination has been proven in patients with congestive heart failure.

The combination of a β-blocker and an imidazoline receptor agonist (a centrally acting drug) may be rational in the combination therapy of arterial hypertension to achieve target blood pressure values ​​in patients with metabolic disorders (up to 80% of patients with arterial hypertension suffer from metabolic disorders). Additive

the hypotensive effect is combined with the correction of insulin resistance, impaired glucose tolerance, and dyslipidemia, characteristic of the class of β-blockers.

Table 5.15

Combined antihypertensive therapy with β-blockers

In this article we will look at beta blockers.

A very important role in the regulation of the functions of the human body is played by catecholamines, which are adrenaline and norepinephrine. They are released into the blood and act on particularly sensitive nerve endings called adrenergic receptors. 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 beta-blockers for short, are a group of drugs that bind beta-adrenergic receptors and prevent the effects of catecholamines on them. Such drugs are especially widely used in cardiology.

In the case of activation of β1-adrenergic receptors, the frequency and strength of heart contractions increases, and in addition, the coronary arteries dilate, the level of conductivity and automaticity of the heart increases. Among other things, the breakdown of glycogen in the liver increases and energy is produced.

In case of stimulation of β2-adrenergic receptors, the walls of blood vessels and bronchial muscles relax, uterine tone decreases during pregnancy, and the release of insulin 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.

Mechanism of action of drugs

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

There is an extension of diastole - a period of rest and general relaxation of the heart, during which the vessels are filled with blood. A decrease in diastolic intracardiac pressure also contributes to improvement of coronary perfusion. There is a process of redistribution of blood flow from normally blood-supplied 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, prevent the accumulation of calcium ions in heart cells, which worsen energy metabolism in the myocardial region.

The list of beta-blocker drugs is very extensive.

Classification of drugs in this group

The substances presented are a fairly large group of drugs. They are classified according to many characteristics. 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 adrenergic blockers, the less danger there is in their use for concomitant pathologies of the respiratory canals and peripheral vessels, and in addition, for diabetes mellitus. But selectivity is a relative concept. If the drug is prescribed in excessive doses, the degree of selectivity decreases.

Some beta-blockers are characterized by the presence of intrinsic sympathomimetic activity. It lies in the ability to cause stimulation of beta-adrenergic receptors to some extent. Compared to conventional beta-blockers, such drugs slow down heart rate and contraction force much less, and are less likely to lead to withdrawal syndrome. 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 vasodilating properties. This mechanism is usually realized through internal pronounced sympathomimetic activity.

The duration of exposure most often directly depends on the characteristics of the chemical structure of selective and non-selective beta-blockers. Lipophilic agents can act for several hours and are quickly eliminated from the body. Hydrophilic drugs, for example Atenolol, are effective for a longer time and can 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 action, only up to thirty minutes; an example is the drug Esmolol.

Non-cardioselective drugs

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

• Propranolol-based products, for example “Anaprilin” and “Obzidan”.
• Drugs based on nadolol, for example Korgard.
• Medicines based on sotalol: Sotahexal along with Tenzol.
• Products based on timolol, for example "Blocarden".

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

• Medicines based on oxprenolol, for example Trazicor.
• Products based on pindolol, for example "Whisken".
• Preparations based on alprenolol, for example "Aptin".
• Medicines based on penbutolol, for example Betapressin along with Levatol.
• Products based on bopindolol, for example Sandorm.

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

The list of beta-blocker drugs does not end there.

Cardioselective drugs

The following medications that do not have internal sympathomimetic activity are classified as cardioselective:

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

The following cardioselective drugs have sympathomimetic activity: Acekor, along with Sectral, Kordanum and Vazacor.

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

Medicines with vasodilating properties

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

The drugs Carvedilol, Nebivolol and Celiprolol are considered cardioselective.

How do beta blockers act differently?

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

Use against the background of angina pectoris

In many cases, such medications are among the leading ones for treating angina pectoris and preventing attacks. Unlike nitrates, such drugs do not cause drug resistance during long-term use. Beta-blocker drugs can accumulate in the body, which makes it possible to reduce the dosage of the drug after some time. These medications protect the heart muscle, improving the prognosis by reducing the risk of another heart attack. The antianginal activity of these drugs is the same. They should be selected depending on the duration of the effect and adverse reactions.

Begin therapy with a small dosage, which is gradually increased until it is effective. The dose is selected so that the resting heart rate is at least fifty per minute, and the systolic pressure level is at least one hundred millimeters of mercury. Once the therapeutic effect is achieved, angina attacks stop and 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 medications with other groups of medications. Such drugs should not be abruptly discontinued, as withdrawal syndrome may occur. Beta blockers are especially indicated if angina is combined with sinus tachycardia, glaucoma, arterial hypertension or constipation.

The newest beta blockers are effective for myocardial infarction.

Treatment for heart attack

Early use of beta blockers against the background of a heart attack helps 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 occurs with drugs without sympathomimetic activity; it is preferable to use cardioselective drugs. They are especially useful when a heart attack is combined with such ailments as arterial hypertension, sinus tachycardia, post-infarction angina and tachysystolic atrial fibrillation.

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

Use of beta blockers for chronic heart failure

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

Use for 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 for heart rhythm disturbances

BABs are 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, although the effectiveness in this case will be less pronounced. Beta blockers in combination with potassium preparations are used to treat arrhythmias caused by

What are the possible side effects on the heart?

BBs can inhibit the ability of the sinus node to produce 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 beta blockers with sympathomimetic activity.

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

Adverse reactions from the respiratory system

BBs can cause bronchospasms. This side effect is less pronounced among cardioselective drugs. However, their dosages that are effective against angina are often quite high. The use of high dosages of these drugs can provoke apnea along with temporary cessation of breathing. BAs can worsen the course of an allergic reaction to insect bites, as well as to medications and food allergens.

Nervous system response

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

Treatment with beta blockers is sometimes accompanied by disturbances in nerve conduction. This leads to muscle weakness, rapid fatigue and decreased endurance.

Metabolic reaction

Non-selective beta blockers can suppress insulin production. 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 leads to a significant increase in pressure. Therefore, if it is necessary to prescribe a beta blocker to a patient with concomitant diabetes, it is better to give preference to cardioselective drugs or change them to calcium antagonists.

Many blockers, especially non-selective ones, reduce the level 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, do not have this drawback.

What other possible side effects are there?

Treatment with beta blockers 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, beta-blockers can cause skin changes, which usually manifest themselves 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 inhibition of hematopoiesis with the occurrence of thrombocytopenic purpura and agranulocytosis.

Contraindications to the use of beta blockers

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 the peripheral arteries, which is accompanied by the occurrence of intermittent claudication.

So, we have looked at the list of beta blockers. We hope that the information presented was useful to you.

Today adrenergic blockers are actively used in various fields of pharmacology and medicine. Pharmacies sell a variety of medications based on these substances. However, for your own safety, it is important to know their mechanism of action, classification and side effects.

What are adrenergic receptors

The body is a well-coordinated mechanism. Communication between the brain and peripheral organs and tissues is ensured through special signals. The transmission of such signals is based on special receptors. When a receptor binds to its ligand (some substance that recognizes that particular receptor), it provides further signal transmission, during which specific enzymes are activated.

An example of such a pair (receptor-ligand) is adrenoreceptors-catecholamines. The latter include adrenaline, norepinephrine, and dopamine (their precursor). There are several types of adrenergic receptors, each of which triggers its own signaling cascade, as a result of which fundamental changes occur in our body.

Alpha adrenergic receptors include alpha1 and alpha2 adrenergic receptors:

1. Alpha1 adrenergic receptor is located in arterioles, ensures their spasm, increases pressure, and reduces vascular permeability.
2. Alpha 2 adrenergic receptor lowers blood pressure.

Beta adrenergic receptors include beta1, beta2, beta3 adrenergic receptors:

1. The beta1 adrenergic receptor increases heart contractions (both their frequency and strength) and increases blood pressure.
2. Beta2 adrenergic receptor increases the amount of glucose entering the blood.
3. The beta3 adrenergic receptor is located in adipose tissue. When activated, it provides energy production and increased heat production.

Alpha1 and beta1 adrenergic receptors bind norepinephrine. Alpha2 and beta2 receptors bind both norepinephrine and adrenaline (beta2 adrenergic receptors absorb adrenaline better).

Mechanisms of pharmaceutical action on adrenergic receptors

There are two groups of fundamentally different drugs:

• stimulants (aka adrenomimetics, agonists);
• blockers (antagonists, adrenolytics, adrenoblockers).

The action of alpha 1 adrenergic agonists is based on stimulation of adrenergic receptors, as a result of which changes occur in the body.

List of drugs:

• oxymetazoline;
• ibopamine;
• cocaine;
• sydnofen.

The action of adrenolytics is based on the inhibition of adrenergic receptors. In this case, diametrically opposite changes are triggered by adrenergic receptors.

List of drugs:

• yohimbine;
• pindolol;
• esmolol.

Thus, adrenolytics and adrenomimetics are antagonistic substances.

Classification of adrenergic blockers

The taxonomy of adrenolytics is based on the type of adrenergic receptor that the blocker inhibits. Accordingly, they distinguish:

1. Alpha blockers, which include alpha1 blockers and alpha2 blockers.
2. Beta blockers, which include beta1 blockers and beta2 blockers.

Adrenergic blockers can inhibit one receptor or several. For example, the substance pindodol blocks beta1 and beta2 adrenergic receptors - such adrenergic blockers are called non-selective; the substance esmolod acts only on the beta-1 adrenergic receptor - such an adrenolytic is called selective.

A number of beta-blockers (acetobutolol, oxprenolol and others) have a stimulating effect on beta-adrenergic receptors and are often prescribed to people with bradycardia.

This ability is called internal sympathomic activity (ISA). Hence another classification of drugs - with BCA, without BCA. This terminology is mainly used by doctors.

Mechanisms of action of adrenergic blockers

The key effect of alpha adrenergic blockers is their ability to interact with adrenergic receptors of the heart and blood vessels, “turning off” them.

Adrenergic blockers bind to receptors instead of their ligands (adrenaline and norepinephrine), as a result of this competitive interaction they cause the completely opposite effect:

• the diameter of the lumen of blood vessels decreases;
• blood pressure rises;
• more glucose enters the blood.

Today, there are various drugs based on alpha adrenoblockers, which have both pharmacological properties common to this line of drugs and highly specific ones.

It is obvious that different groups of blockers have different effects on the body. There are also several mechanisms for their operation.

Alpha blockers against alpha1 and alpha2 receptors are primarily used as vasodilators. An increase in the lumen of blood vessels leads to improved blood supply to the organ (usually drugs in this group are intended to help the kidneys and intestines), and blood pressure is normalized. The amount of venous blood in the superior and inferior vena cava decreases (this indicator is called venous return), which reduces the load on the heart.

Alpha adrenergic blocking drugs have become widely used for the treatment of sedentary and obese patients. Alpha blockers prevent the development of reflex heartbeat.

Here are some key effects:

• unloading of the heart muscle;
• normalization of blood circulation;
• decreased shortness of breath;
• accelerated absorption of insulin;
• in the pulmonary circulation the pressure decreases.

Non-selective beta blockers are primarily intended to combat coronary heart disease. These drugs reduce the likelihood of developing a myocardial infarction. The ability to reduce the amount of renin in the blood is due to the use of alpha adenoblockers for hypertension.

Selective beta blockers support heart muscle function:

1. Normalize heart rate.
2. Promotes antiarrhythmic effect.
3. They have an antihypoxic effect.
4. Isolate the area of ​​necrosis during infarction.

Beta blockers are often prescribed to individuals whose activities involve physical and mental stress.

Indications for the use of alpha-blockers

There are a number of basic symptoms and pathologies for which the patient is prescribed alpha-blockers:

1. With Raynaud's disease (spasms occur in the fingertips, over time the fingers become swollen and cyanide-colored; ulcers may develop).
2. For acute headaches and migraines.
3. When a hormonally active tumor occurs in the kidneys (in chromaffin cells).
4. For the treatment of hypertension.
5. When diagnosing arterial hypertension.

There are also a number of diseases whose treatment is based on adrenergic blockers.

Key areas where adrenergic blockers are used: urology and cardiology.

Adrenergic blockers in cardiology

Note! The concepts of hypertension and hypertension are often confused. Hypertension is a disease that often becomes chronic. If you have hypertension, you are diagnosed with an increase in blood pressure (blood pressure) and general tone. An increase in blood pressure is arterial hypertension. Thus, hypertension is a symptom of a disease, such as hypertension. With a constant hypertensive state, a person’s risk of stroke and heart attack increases.

The use of alpha adenoblockers for hypertension has long been included in medical practice. Terazosin, an alpha1 adrenergic blocker, is used to treat arterial hypertension. A selective adrenergic blocker is used, since under its influence the heart rate increases to a lesser extent.

The main element of the antihypertensive effect of alpha-blockers is the blockade of vasoconstrictor nerve impulses. Due to this, the lumen in the blood vessels increases, and blood pressure normalizes.

Important! When using antihypertensive therapy, remember that the treatment of hypertension has its pitfalls: in the presence of alpha-blockers, blood pressure decreases unevenly. The hypotonic effect prevails in an upright position, therefore, when changing position, the patient may lose consciousness.

Adrenergic blockers are also used for hypertensive crisis and hypertensive heart disease. However, in this case they have a concomitant effect. A doctor's consultation is required.

Important! Alpha-blockers alone will not cope with hypertension, because they primarily act on small blood vessels (therefore, they are more often used to treat diseases of the cerebral and peripheral circulation). The antihypertensive effect is more characteristic of beta-blockers.

Adrenergic blockers in urology

Adrenolytics are actively used in the treatment of the most common urological pathology - prostatitis.

The use of adrenergic blockers for prostatitis is due to their ability to block alpha-adrenergic receptors in the smooth muscles of the prostate gland and bladder. Drugs such as tamsulosin and alfuzosin are used to treat chronic prostatitis and prostate adenoma.

The effect of blockers is not limited to the fight against prostatitis. The drugs stabilize the outflow of urine, due to which metabolic products and pathogenic bacteria are removed from the body. To achieve the full effect of the drug, a two-week course is required.

Contraindications

There are a number of contraindications to the use of adrenergic blockers. First of all, this is the patient’s individual predisposition to these medications. For sinus block or sinus node syndrome.

If you have lung diseases (bronchial asthma, obstructive pulmonary disease), treatment with adrenergic blockers is also contraindicated. For severe liver diseases, ulcers, type I diabetes.

This group of drugs is also contraindicated for women during pregnancy and breastfeeding.

Adrenergic blockers can cause a number of common side effects:

• nausea;
• fainting;
• problems with stool;
• dizziness;
• hypertension (when changing position).

The following side effects (individual) are typical for alpha-1 adrenergic blocker:

• decrease in blood pressure;
• increase in heart rate;
• blurred vision;
• swelling of the limbs;
• thirst;
• painful erection or, conversely, decreased arousal and libido;
• pain in the back and in the area behind the sternum.

Alpha-2 receptor blockers lead to:

• the emergence of feelings of anxiety;
• decreased frequency of urination.

Alpha1 and alpha2 receptor blockers additionally cause:

• hyperreactivity, which leads to insomnia;
• pain in the lower extremities and heart;
• poor appetite.

High blood pressure is a disease in the fight against which various means are used, ranging from traditional medicine to drugs that have a beneficial effect on the body as a whole.

Alpha blockers can be divided into 3 types of blockers. Their difference is determined depending on the content of adrenergic receptors:

• Alpha-beta blockers have the properties to successfully combat high blood pressure, reduce the load on the heart, and increase the resistance of the vascular system. When using such drugs, the heart muscle is strengthened and mortality gradually decreases.
• Beta-blockers have not received much use in prescription to patients, since they do not carry certain pharmacological properties.
• Alpha-blockers in professional language are called selective. The effect occurs on nerve endings. Due to the internal composition, ion channels are activated. By using them, the patient has the opportunity to reduce the risk of heart attack; oxygen activity in the body increases.

The prescription of any of the listed blockers is made depending on the indications. All drugs are divided into separate groups and have a strong effect on receptors.

Classification

Vessels filled with blood have 4 types of adrenergic receptors. The entire composition is divided into alpha - 1.2 and beta - 1.2. In addition, they are divided into selective and non-selective; they are prescribed to the patient only when a diagnosis is made based on the presence of a number of indications.

Non-selective ones can be prescribed for the treatment of benign tumors, migraines, circulatory disorders, etc. Specialists note a special effect if the prescription is made to a patient with withdrawal symptoms. The drugs also help well with alcoholism and binge drinking.

Prescriptions for a long time are not made, since they cannot keep the body normal for a long time. Types of such drugs:

• Yohimbine – alpha-2;
• Phentolamine, Digodroerotoxin - alpha 1,2;
• Atenolol, Bisoprolol – beta 1;
• Tamsulosin, Terazosin – alpha-1;
• , proxodolol – alpha-beta adrenergic blockers;
• Metypranolol, Sotacol – beta 1,2.

Classification is also made according to BCA indicators. It is immediately worth noting that the classification is auxiliary and for patients it is not important, but it helps doctors decide on the choice of necessary medications for various diseases to treat the patient.

Indications for use

The list of drugs is simply huge. The appointment occurs in case of emergency assistance in a number of diseases that are not related to each other. The receptors are particularly sensitive to adrenaline, which is found in almost all muscles.

Alpha receptor blockers are prescribed for the following health problems:

• After the diagnosis, a diagnosis of hypertension is made, but it develops against the background of;
• adenoma or other diseases of the male reproductive system;
• heart failure, diseases of the cardiovascular system.

Alpha 1,2 receptors are prescribed when the patient receives one of the diagnoses listed below:

• thrombosis, aortoarteritis;
• disorders associated with diseases;
• spasms, subsequently causing dizziness;
• acute and chronic circulatory disorders;
• changes in the functioning of the optic nerve.

Independent selection and use of drugs is prohibited. Use is possible only with the permission of the attending physician. By correctly administering drug therapy, you can record a long-term effect of stable pressure.

The active components of the medication are removed from the body along with urine.

How do they affect blood pressure?

With regular use of any of the listed remedies, patients and medical staff note a positive effect on the functioning of blood vessels. Prazosin, Doxazosin, Terazosin are often prescribed. They allow you to delay vasoconstrictor impulses entering the arteries and also block the calcium channel.

Alpha blockers help dilate blood vessels, lower blood pressure and prevent it from rising.

Positive properties of this group of drugs:

• The patient has the opportunity to exercise, go to work, since none of the listed remedies causes drowsiness.
• Reduce heart rate. As a result, a drop in blood pressure occurs (Talinolol, Atenolol, Bisoprolol).
• At the same time, you can fight angina pectoris. Medicines will help with chest pain and prevent blockage of blood vessels.

Medicines are not prescribed if the patient has a decrease in heart rate or is diagnosed with heart failure. If you start using drugs, you can only worsen the patient’s situation. Medicines help keep muscle tone under control and increase the amount of calcium. As a result, the muscles of the arteries relax and the pressure drops sharply.

Alpha blocker 1 Prazosin is often prescribed when hypertension is diagnosed. Thanks to its components, the tone of the vascular walls decreases, but Prazosin does not have a direct effect on the kidneys and other internal organs.

Please note: prescribing one drug will not help the patient; it is also necessary to use additional medications, most often diuretics.

List of alpha blockers

When blockers appeared in medicine, it was found that there are adrenergic receptors, which belong to a new class of therapeutic agents. Scientific research has revealed that they can be divided into alpha and beta. In turn, each of the groups is divided into two subgroups.

• vascular smooth muscle fibers – alpha-1;
• alpha 2 - receptors responsible for vasomotor receptors;
• the use of non-selective adrenolytics helps protect blood vessels.

They reduce arterial tone and cause a decrease in blood pressure, without a drop in glucose levels or an increase in heart rate.

Let's look at a number of drugs and determine their type of effect:

• Terazosin is aimed at combating high blood pressure. The composition contains substances that promote the rapid expansion of blood vessels.
• Prazosin - helps the body obtain the necessary amount of oxygen, which reduces the risk of myocardial infarction;
• Doxazosin – has vasodilating properties and antispasmodic effects.

Depending on the disease, as well as how often the blood pressure rises, a specialist may prescribe any drug.

Side effects

All of these drugs are similar in their components, but when used they cause various side effects:

• Alpha-blockers 1 and 2 forms cause headaches when used. If the patient suddenly stands up or sits down, there is an immediate decrease in blood pressure. There may be nausea, vomiting, fatigue, nervousness, swelling, shortness of breath, dry mouth. In patients suffering from an allergic reaction, the condition may worsen.
• Alpha-blockers 2 can cause: anxiety, increased blood pressure, agitation, tachycardia.
• Beta-blockers - cause headaches and dizziness, memory loss (short-term), confusion about where a person is. It is also possible to experience tinnitus, convulsions, nightmares during sleep, palpitations, arrhythmia, abdominal pain, and flatulence.

If there are one or more symptoms that cause a side effect, you must inform your doctor about this, and he, in turn, will replace the drug.

Contraindications

When prescribing a drug, the doctor is guided by the presence of contraindications. Drugs are not prescribed in cases.

Content

Adrenergic blockers refer to a large group of drugs that have the same pharmacological properties. They neutralize adrenaline-dependent receptors in blood vessels and the heart that respond to norepinephrine or adrenaline. The action of adrenergic blockers is exactly the opposite of these substances.

What are adrenergic blockers

There are alpha and beta adrenergic blockers. All of them act on adrenergic receptors located in the walls of blood vessels and the heart, blocking them. In a free state, such receptors are influenced by impulses of adrenaline and norepinephrine. The first leads to vasoconstrictor, hypertensive, antiallergic, hyperglycemic, bronchodilator effects.

Adrenolytics are antagonists of adrenaline, increase the lumen of blood vessels, reduce pressure, reduce the lumen of the bronchi and blood sugar levels. Based on the type of action on receptors, such drugs are divided into:

• beta blockers 1,2 – non-selective Metipranolol, Sotalol;
• beta1-blockers (cardioselective) - Betaxolol, Esmolol;
• alpha-beta blockers – Carvedilol, Proxodolol;
• α-blockers type 1 – Alfuzosin, Tamsulosin;
• alpha-blockers type 2 - Yohimbine.

The actions of each blocker are different, as is their purpose in medicine. Effects of drugs:

1. Alpha-1-blockers and non-selective alpha-1,2-blockers– have a similar effect, but differ in side effects (1,2-drugs have more of them). Medicines in this group dilate the blood vessels of organs, especially the skin, intestines, mucous membranes, and kidneys. Due to this, peripheral vascular resistance decreases, tissue blood circulation improves, blood pressure and the degree of development of tumors and migraines decrease. This leads to a decrease in the amount of circulating blood, the load on the heart and making it easier to work with. They are used for chronic heart failure with moderate symptoms of shortness of breath and hypotensive pressure surges. The drugs increase the concentration of high-density lipoproteins and the sensitivity of cells to insulin. Alpha-blockers do not lead to the development of reflex heartbeat and reduce the severity of symptoms of obstructive and inflammatory processes in the genitourinary organs against the background of prostate hyperplasia. Short-term use of tablets can cure withdrawal symptoms and hypertension.
2. Alpha-2 blockers– have a slight effect on the blood vessels of internal organs, therefore they are used in the treatment of diseases of the vascular system of the genital organs. They are limited to a narrow scope of application - they treat impotence in men caused by prostate adenoma.
3. Beta-1,2-blockers– non-selective drugs of this group are characterized by a decrease in heart rate, a decrease in blood pressure, a reduction in myocardial contractility, a decrease in the heart’s need for oxygen, and an increase in its resistance to ischemia. Due to the action of the drugs, the activity of the foci of excitation is reduced, arrhythmia is prevented, and the production of renin by the kidneys is reduced. The drugs prevent platelet aggregation, increase myometrial contraction, increase the tone of the esophageal sphincter and bronchi, and relax the bladder detrusor. With the help of medications, the formation of thyroid hormones is slowed down, intraocular pressure decreases in glaucoma.
4. Beta1 blockers– selective (cardioselective) are used in the treatment of heart diseases. Additionally, they reduce the heart rate, the automaticity of the pacemaker of the sinus node, inhibit the conduction of impulses through the atrioventricular node, and suppress the contractility and excitability of the heart.
5. Alpha-beta blockers– reduce blood pressure and peripheral vascular resistance. They normalize lipid profiles, reduce cholesterol and triglyceride levels, and afterload on the heart.

Alpha-1 blockers

In medicine, alpha blockers for prostate adenoma from the group of alpha1-adrenergic blockers are used for hypertension, chronic heart failure, and benign prostatic hyperplasia. Side effects include:

• hypotension, tachycardia;
• swelling, arrhythmia, shortness of breath;
• irritability;
• cerebrovascular accidents;
• blurred vision;
• rhinitis;
• urinary incontinence;
• abdominal discomfort, dry mouth;
• pain in the chest, back;
• decreased libido, priapism;
• allergic reactions - rash, itching, urticaria.

Contraindications to alpha1-blockers include stenosis of the aortic or mitral heart valves, orthostatic hypotension, cardiac or renal failure, and heart defects. It is forbidden to take drugs during pregnancy, lactation, hypersensitivity, severe liver damage. Group representatives:

Alpha-2 blockers

Alpha adrenergic receptor blockers from group 2 are prescribed exclusively for the treatment of male impotence. Their side effects include tremor, anxiety, agitation, irritability, priapism, anxiety, tachycardia, urinary disturbances, abdominal pain, and increased motor activity.

Contraindications to the use of alpha-2 blockers are:

• arterial hypotension, bradycardia;
• severe atherosclerosis of peripheral vessels;
• angina pectoris and other organic heart disorders;
• myocardial infarction less than 3 months ago;
• hypersensitivity to components;
• acute bleeding;
• lactation, childbearing.

Alpha 1,2 blockers

The mechanism of action of alpha adrenergic blockers from group 1,2 is based on the expansion of blood vessels and normalization of pressure. Drugs in this group are indicated for circulatory disorders, migraines, Raynaud's disease, endarteritis, and urinary disorders. They are used for dementia, vertigo, diabetic angiopathy, dystrophic diseases of the cornea, optic neuropathy, prostate hypertrophy. Side effects of the drugs:

• allergies, redness of the body skin, itching, erythema, urticaria;
• insomnia, agitation;
• cold extremities;
• angina attacks;
• loss of appetite, abdominal pain;
• sweating;
• ejaculation disorder;
• pain in arms and legs.

Contraindications to the use of drugs include individual intolerance, surges in blood pressure, impaired renal function, liver dysfunction, uncontrolled hypotension or hypertension. The drugs of the group differ in the active substance:

Alpha adrenergic blockers in urology

For prostatitis, doctors prescribe alpha-1 blockers to patients, which contain alfuzosin, tamsulosin, doxazosin and terazosin. These substances improve the process of urination. Indications for their use are low pressure inside the urethra, weakened tone of the neck and body of the bladder, and prostate muscles. Due to their use, the outflow of urine is normalized and the elimination of decay products is accelerated. The drugs have an anti-inflammatory effect, which develops after 2 weeks from the start of treatment.

In cardiology

Alpha1-blockers and alpha-beta blockers are used to treat cardiac problems. The latter are indicated for arterial hypertension, stable angina, arrhythmia or hypertensive crisis. Alpha1-blockers contain doxazosin, urapidil, prazosin, terazosin. They can be used in long-term treatment of hypertension, reducing blood pressure and maintaining it at a normal level. Drugs in this group are optimal for hypertension without concomitant heart failure.

Alpha-2-blockers have a hypotensive effect. They contain phentolamine, butyroxane, prazosin hydrochloride, pyrroxane and nicergoline. The drugs affect the heart, therefore they are used in the treatment of heart disease and arterial hypertension combined with coronary artery disease, angina pectoris and myocardial infarction. Alpha-1,2-blockers are used to treat circulatory disorders. In theory, they can be used to lower blood pressure, but this will not be effective.

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