Alpha 1 adrenergic blocking drugs. Adrenergic blockers. General characteristics of these drugs

To block nerve impulses in the body, adrenergic blockers are prescribed. This pharmacological group can be divided into alpha-blockers and beta-blockers. The drugs are widely used in cardiology and urology. They have vasodilating properties and are indispensable for health in hypertension.

Adrenergic blockers (or adrenolytics) are a pharmacological group of drugs that block nerve impulses that respond to adrenaline and norepinephrine. Drugs from this category have a calming effect on the central nervous system.

The medications included in the group “interrupt” the action of adrenergic receptors located in the heart and walls of blood vessels. They can be divided into alpha and beta blockers. Each species has several more subspecies, differing in the mechanism of action on the body.

Mechanism of action:

1. Vasodilating property. The drugs have a peripheral effect; after taking the medication, redness of the skin and mucous membranes is noticed. Microcirculation of the blood of internal organs is restored, which reduces blood pressure (BP), but does not increase heart rate.
2. Reduced cardiac workload. Medicines are indicated for hypertension; they have the property of dilating blood vessels without causing tachycardia. At the same time, the load on the heart muscle is reduced. Thanks to this advantage, medications can be used in old age.
3. Influence on metabolic processes. Taking medications reduces the level of bad cholesterol and triglycerides, and increases high-density lipoprotein levels. Drug treatment is indicated even for hypertension complicated by atherosclerosis.
4. Effect on carbohydrate metabolism. Treatment improves the absorption of glucose by the body, and there is an increase in sensitivity to insulin at the cellular level. Medicines are indicated for use by diabetics with type 1 and type 2 diabetes mellitus.
5. Anti-inflammatory effect. This is an additional property of drug therapy. Medicines effectively cope with inflammatory processes, eliminating the symptoms of diseases of the genitourinary system. Most often, drugs are prescribed for benign prostatic hyperplasia and problems with urination.

Alpha-2 adrenaline receptor blockers have the opposite effect: they constrict blood vessels and increase blood pressure. Therefore, they are not used in cardiological practice. But they successfully treat.

Classification of alpha-blockers

The pharmacological group can be divided into selective and non-selective types. Each of them has a separate effect, despite belonging to the same category of drugs. The former act on alpha-1 adrenergic receptors, and the latter act on both alpha1- and alpha2-adrenergic receptors.

Selective

The selective species has an effect on the receptors of the first group (alpha-1). Medicines block the effect on arteriolar receptors without disrupting feedback mechanisms or interfering with the release of catecholamines.

Indications for use of the selective type:

• hypertension (high blood pressure), complicated by diabetes mellitus, metabolic diseases;
• cardiovascular pathologies;
• inflammatory diseases of the prostate gland, prostate adenoma and problems with urination.

Unlike the non-selective subgroup of drugs, selective drugs have the ability to lower blood pressure without changes in heart rate and glucose spikes. Taking the drugs is accompanied by the body's self-defense from excessive activation of the sympathoadrenal system - this is a decrease in the release of norepinephrine in the nerve endings.

Non-selective

A non-selective type of medicine is usually used to relieve symptoms and not to treat hypertension. They are not indicated for long-term therapy. Taking non-selective drugs is accompanied by blocking of adrenergic receptors, but with an increase in heart rate.

Such medications often cause side effects and have more contraindications, but are highly effective and quickly act on the problem. The most common negative effects of treatment are nausea and vomiting.

Indications for the use of drugs from the non-selective group:

• diseases of the central nervous system (atherosclerosis, stroke);
• pathologies associated with impaired peripheral circulation;
• Raynaud's disease;
• headache;
• obliterating endarteritis;
• benign neoplasms (some types).

Also on the list of indications for treatment with non-selective types are withdrawal syndrome and pheochromocytomas. The duration of action is short compared to the selective subgroup. Among the drugs, the most famous are: Nicergoline, Butyroxane, Phentolamine, Pyrroxane and Tropodifene.

Indications for use

Despite the general effect - blocking adrenaline in nerve endings, the drugs differ in instructions for use. The list of indications includes cardiac, urological diseases and metabolic disorders.

General indications for use:

• high blood pressure (hypertension);
• , prostate adenoma;
• chronic heart failure with myocardial hypertrophy;
• acrocyanosis, Raynaud's disease, diabetes mellitus and peripheral microcirculation disorders;
• bedsores, frostbite, thrombophlebitis and atherosclerosis, which are accompanied by impaired metabolic processes in tissues;
• headache, migraine;
• some diseases of the central nervous system;
• rehabilitation after stroke;
• elimination of manifestations of a neurogenic bladder;
• age-related mental development disorders (senile dementia);
• vascular disorders of the vestibular apparatus;
• optic neuropathy;
• corneal dystrophy;
• urological disorders ().

The non-selective type of drugs has a stimulating effect, so alpha-2 blockers are often prescribed for the treatment of erectile dysfunction. The medicine helps fill the penis with blood and returns sexual activity to the man.

How to take medications

Instructions for use of medications differ depending on the specific medication and the active substance in the composition. In most cases, tablets or capsules are intended for single use.

Carefully read the complete instructions before starting treatment, find out the permitted single dose and the maximum daily concentration. The treatment course lasts on average from 4 to 10 weeks. The drug is started with a reduced dosage, gradually increasing the concentration of the active substance in the blood.

In urology

Medicines from this pharmacological group are able to eliminate the symptomatic manifestations of inflammatory diseases and fight the cause of the disease. Pathological cell proliferation disrupts the process of urination; other diseases often occur against the background of prostatitis or hyperplasia.

Indications for medications in urological practice:

• low speed when urinating;
• high pressure when closing the urinary canal;
• insufficient dilatation of the bladder neck.

Drug treatment helps eliminate pain when urinating, since drugs have vasodilating properties. The drugs produce an effect only with long-term drug therapy.

Medicines are prescribed for acute or chronic prostatitis, benign prostatic hyperplasia. The therapeutic effect can be noticed after 2 weeks of continuous use. There is a decrease in smooth muscle tone, and the outflow of urine is normalized.

Drugs used in urology, their brief characteristics:

1. Terazosin. Indicated to eliminate urinary problems. Helps relax smooth muscles, which reduces pain when going to the toilet and helps increase the rate of urine flow.
2. Doxazosin. One of the most popular and effective remedies that has a positive effect on the functionality of the prostate. Drug therapy has a positive effect on overall urodynamics.
3. Alfuzosin. Reduces pressure in the urethra and is prescribed to relieve dysuria. The drug produces a cumulative effect, the effect of the active substance can be noticed after 1.5-2 weeks of taking the medicine.

The treatment regimen and specific drug are prescribed only by the attending physician. The duration of therapy depends on the diagnosis and the patient’s history of aggravating diseases. Alpha blockers are the most effective drugs for the treatment of urological pathologies.

In cardiology

In cardiological practice, drugs also help with a hypertensive attack. Testing is recommended before regular appointments are made. It is necessary to start the course with small dosages of the active substance.

1. Gradual increase in dose. This measure is necessary to avoid reactions of individual intolerance to the active ingredient and to select the most suitable drug for treatment.
2. Taking the first pill. After taking the first therapeutic dose, the patient is recommended to remain motionless for 2-3 hours and observe the body’s reaction. Exceeding the dosage is permitted only with the approval of a physician.
3. Control of concomitant diseases. If you have diabetes, atherosclerosis or other diseases, you need to monitor your blood sugar levels and heart rate.

Remember to be careful. If used incorrectly or significantly exceeding the dosage, side effects may occur.

In the worst cases, medications can cause a stroke or myocardial infarction.

List of popular drugs and prices

Among the drugs from the group of alpha-blockers, there are drugs specifically intended for the treatment of prostatitis or, and there are blockers that reduce blood pressure. Let's take a look at the list of alpha-blocker drugs and brief instructions for use.

Tamsulosin

There are not many alpha-blockers available for the treatment of prostatitis, but these are the most effective drugs. Each of them has its own characteristics. Tamsulosin is a urodynamic corrector; it is a selective drug.

A brief description of:

1. Treatment scheme. The maximum permitted daily dosage is 400 mg of the active substance. The minimum course of treatment is 10 days.
2. Release form. On sale you can find tablet form and capsules.
3. Side effects. Undesirable reactions of the central nervous system may occur: general weakness, dizziness, decreased concentration, slowness of action. Blood pressure may decrease. However, all symptoms are observed in the first hour after administration and disappear quickly.
4. List of contraindications. Do not use if you have low blood pressure, impaired liver function, or individual intolerance.

Tamsulosin has the property of reducing sensitivity when urinating and eliminating pain. The medication acts specifically on the organs of the urinary system, promoting relaxation of smooth muscles. You can buy a package for a price starting from 400 rubles.

Pyrroxane

The drug has a sedative effect and has a positive effect on the cardiovascular system. The patient quickly calms down after taking the pills. The list of indications includes hypertensive and diencephalic crises, alcohol withdrawal and conditions that are accompanied by increased arousal.

Brief instructions for use:

1. Treatment scheme. The maximum daily dose is 180 mg. Exceeding the recommended dosage may cause side effects.
2. Release form. Sold as an injection solution (1%) and tablets.
3. Side effects. The medicine can provoke heart rhythm disturbances, increased heart rate (tachycardia) and hypotensive crisis.
4. List of contraindications. Use for heart failure, cerebrovascular accidents, and severe atherosclerosis is strictly prohibited.

Pyrroxane is a non-selective species that has a sedative effect on the central nervous system. The medication is also prescribed for mental illnesses that are accompanied by increased aggression or anxiety. The price per package (50 tablets) starts from 1,400 rubles.

Tropaphen

Drug therapy with Tropaphen helps block adrenaline and its derivatives. The drug has vasodilating properties and helps reduce blood pressure during a hypertensive crisis. Has a weak anticholinergic effect.

The drug is used for pathologies associated with impaired peripheral circulation. Due to its antispasmodic effect, use is advisable for urological problems. The main indication for use is hypertension.

Brief instructions for using the medicine:

1. Treatment regimen. The drug is indicated for intravenous or intramuscular administration of 0.5-1-2 ml of 1% or 2% solution 1-3 times a day. The duration of therapy is from 10-15 days or more.
2. Release form. Injection solution in ampoules (lyophilisate) with a dosage of the active substance of 1% and 2%.
3. Side effects. Negative reactions occur very rarely; a sharp decrease in blood pressure is possible. After the injection, the patient is advised to lie down for a long time. Sometimes tachycardia develops.
4. List of contraindications. The drug is not prescribed to children, pregnant and lactating women, as well as patients with severe cardiovascular diseases.

This drug is indicated for rapid action in emergency situations; the active substance is administered intramuscularly or intravenously. The effect occurs within 5-10 minutes. The medicine costs from 100 rubles.

Phentolamine

The drug is primarily intended to relieve vascular spasms. Taking the medication helps restore normal blood circulation in the tissues and reduce blood pressure. The list of indications is practically no different from the general use of alpha-blockers.

Brief instructions for Phentolamine:

1. Treatment regimen. It is recommended to take the drug after meals with plenty of water. The dosage is prescribed individually depending on the age of the patient. The maximum daily dose is 200 mg, duration of therapy is up to 5 weeks.
2. Release form. You can find tablets and injection solution on sale.
3. Side effects. The development of orthostatic collapse (a sharp drop in blood pressure), redness of the skin due to vasodilation, tachycardia, disruption of the digestive system with increased sensitivity to the components of the composition.
4. List of contraindications. Do not use the product if you have an individual intolerance to the active substance, severe cardiovascular disease, or hypotension.

The drug is approved for use even in childhood. Therapy can be prescribed to patients with diabetes, as the drug tends to increase the release of insulin into the blood.

Overdose symptoms or side effects are more likely to occur when the medication is used incorrectly. Follow your doctor's instructions strictly. After using tablets, capsules or injections, it is recommended to remain in a horizontal position for several hours. The average cost per package is 50 rubles.

Overdose

Overdose symptoms are different for each drug. Reactions from the central nervous system may be observed: dizziness, disorientation in space, headaches. Sometimes nausea, vomiting and other gastrointestinal disturbances occur.

Reduced blood pressure is treated with symptomatic therapy. In case of severe individual reactions, seek help from a doctor or call an ambulance.

Side effects

Side effects of the group are different, they depend on the active substance in the composition. But there are some common negative effects that can be experienced after taking the pills.

Side effects:

1. From the gastrointestinal tract: ischemic colitis, indigestion, nausea, vomiting, problems with bowel movements, diarrhea.
2. From the cardiovascular system: poor circulation in the arms and legs, heart failure, bradycardia, tachycardia and other heart rhythm disturbances.
3. From the urinary system: loss of sexual desire, deterioration of potency, decrease in renal blood flow.
4. From the endocrine system: hypoglycemia (applies to patients with diabetes), hyperglycemia.
5. From the central nervous system: dizziness, loss of orientation in space, sleep disturbances, insomnia, development of depression, deterioration of memory and concentration, hallucinations.

In case of individual intolerance reactions, allergic reactions may occur: skin rashes, bronchospasm, urticaria, Quincke's edema and anaphylactic shock. It is recommended to take antihistamines and carry out symptomatic treatment.

Contraindications

The drugs have a wide spectrum of action and help relieve many diseases. But it is not recommended to use alpha-blockers in pediatric practice.

In the list of contraindications:

• individual intolerance to the active component or additional substances in the composition;
• During pregnancy and breastfeeding;
• childhood;
• liver and kidney failure;
• hypotension (low blood pressure);
• heart failure and other diseases of the cardiovascular system in severe form.

Alpha blockers are medications that have the ability to quickly block adrenaline and its derivatives in nerve endings. This property helps relieve spasms, dilate blood vessels and eliminate unpleasant symptoms of urological and cardiac diseases.

Video

Find out even more about the pharmacological group from the video.

Classa-adrenergic blockers are represented by drugs, non-selective drugs acting on peripherala 1 - Anda2-adrenergic receptors (phentolamine) and selectivea1-blockers (prazosin, doxazosin, terazosin). There are uroselectivea1a- adrenergic blockers - alfuzosin, tamsulosin.

Pharmacodynamic effectsa1-blockers: antihypertensive, hypolipidemic, improvement of ureter.

As a result of the blockadea1-adrenergic receptors achieve dilatation of resistive (arterial) and capacitive (venous) vessels, a decrease in total peripheral vascular resistance and a decrease in blood pressure; a slight reflex stimulation of cardiac output and heart rate develops.a1-blockers do not change renal blood flow and excretion of electrolytes; lead to a decrease in microalbuminuria.a1-blockers can cause regression of LVH.

0 1 - blockers have a beneficial effect on lipid and carbohydrate profiles: they cause a small but significant decrease in the level of total cholesterol, LDL and TG, and increase the content of HDL. With long-term use, they lead to a decrease in insulin resistance and glycemic levels.

Additional effecta1-blockers is to relax the muscle tone of the urethra in the prostate gland, which helps improve urination and reduce prostatic hyperplasia.

Most significant side effecta1-adrenergic blockers - “first dose” hypotension.

Keywords: a1-adrenergic receptors,a1-blockers, hypotensive effect, hypolipidemic effect, improvement of ureter, pharmacodynamics, pharmacokinetics, side effects, drug interactions.

Among the drugs that affect the adrenergic regulation of vascular tone, there are, along with drugs with a central mechanism of action (central α-agonists, imidazoline receptor agonists), peripheral α-adrenergic receptor blockers.

Adrenergic receptors are widely distributed in different organs and tissues and perform various functions. In this regard, α- and β-adrenergic receptors are distinguished, for each of which 2 subtypes have been identified. They differ in the predominant amount in different organs, in functions, and in sensitivity to norepinephrine and adrenaline (Table 9.1).

α- and β-adrenergic receptors localized at the endings of vasoconstrictor nerves participate in the regulation of vascular tone. Their mediator is norepinephrine. In the synaptic cleft, norepinephrine, released from the presynaptic terminal, stimulates postsynaptic A 1-adrenergic receptors of the vascular wall, the number of which predominates on the postsynaptic membrane over β1-adrenergic receptors, which leads to vasoconstriction. Presynaptic and β2-adrenergic receptors regulate noradrenergic mediator feedback mechanisms. At the same time, stimulation 2 -adrenergic receptors is accompanied by an increase in the reverse deposition of the transmitter from the synaptic cleft into the vesicles of the presynaptic terminal and inhibition of the subsequent release of norepinephrine (negative feedback). β 2 -adrenergic receptors, on the contrary, increase the release of norepinephrine into the gap (positive “feedback”).

The class of α-adrenergic blockers is represented by drugs that non-selectively act on α1- and α2-adrenergic receptors (phentolamine) and selective α1-blockers (prazosin, doxazosin, etc.).

Non-selective blockade of α-adrenergic receptors, like phentolamine, causes a short-term decrease in blood pressure due to loss of control

Table 9.1

Localization and functionsa 1 - adrenergic receptors

Note:a1a -- uroselective receptors.

over a 2 -adrenergic receptors stimulates the release of norepinephrine and leads to loss of effect. This drug is unsuitable for long-term therapy (it is used only to relieve hypertensive crises).

Since 1980, selective a 1 - adrenergic blockers.

Currently, the group of selective α 1 -blockers includes several drugs. Conventionally, they are divided into 2 generations due to the duration of action: 1st generation (short-acting) - prazosin, 2nd generation (long-acting) - doxazosin, terazosin. There are uroselective a1a --adrenergic blockers - alfuzosin, tamsulosin, blocking a1a - adrenergic receptors localized in the smooth muscles of the urogenital tract.

Blockade a 1 - adrenergic receptors leads to a decrease in vascular tone and blood pressure. However, the sensitivity of α-adrenergic receptors to drugs is not the same: prazosin, terazosin and doxazosin have the greatest affinity for α1-adrenergic receptors, and clonidine - for α 2 -adrenoreceptors. In addition, terazosin and doxazosin have half the affinity for α1-adrenergic receptors as prazosin.

PHARMACODYNAMICSa 1 - ADRENO BLOCKERS

Pharmacodynamic effectsa 1 - blockers: antihypertensive, hypolipidemic, ureter improvement.

According to the mechanism of hypotensive action a 1 - blockers are “pure” vasodilators. As a result of the blockade a 1 - adrenoreceptors, dilation of both resistive (arterial) and capacitive (venous) vessels, a decrease in total peripheral vascular resistance (TPVR) and a decrease in blood pressure is achieved. Due to peripheral vasodilation of both arteries and veins, a slight reflex stimulation of cardiac output is observed due to modulation of the release of norepinephrine by unblocked a 1 -adrenoreceptors. These hemodynamic effects occur at rest and during exercise, which contrasts with β-blockers (Table 9.2). It should be considered that the most favorable physiological effect of an antihypertensive drug on hemodynamics is a drop in blood pressure due to a significant decrease in peripheral vascular resistance due to an approximately equal decrease in tone

arterioles and venules with preserved cardiovascular reflex mechanism and unchanged cardiac output.

There is evidence of central mechanisms of hypotensive action a 1 - blockers, due to a decrease in central sympathetic tone. Hypotensive effect a 1 - blockers are not accompanied by an increase in plasma renin activity.

Table 9.2

Comparison of hemodynamic effectsα- Andβ - adrenergic blockers

The most significant decrease in blood pressure is observed after taking the first dose, especially in a standing position. Equivalent doses of drugs that cause the same reduction in blood pressure are as follows: 2.4 mg prazosin, 4.5 mg doxazosin or 4.8 mg terazosin.

Hypotensive effect a 1 - blockers may be accompanied by the development of reflex tachycardia, since presynaptic a 2 - receptors remain unblocked; or due to antagonism to the central a 1 - adrenergic receptors that suppress reflex tachycardia. A significant increase in heart rate is observed after taking the first dose, especially in a standing position; with long-term use, heart rate does not change significantly.

The main disadvantage of the hypotensive effect a 1 - blockers is the rapid development of tolerance, but its clinical significance is unknown.

a 1 - blockers do not change renal blood flow and electrolyte excretion. At the same time, doxazosin leads to a decrease in microalbuminuria, which may indicate its nephroprotective properties in hypertension.

a 1 - blockers can cause regression of LVH during long-term monotherapy in patients with hypertension. However, according to a meta-analysis of clinical studies, they are inferior to calcium antagonists and ACE inhibitors; degree of reduction in myocardial mass a 1 - blockers averages no more than 10%.

and 1-blockers have a beneficial effect on lipid and carbohydrate metabolism. They cause a small but significant decrease in the level of total cholesterol, LDL and especially triglycerides (up to 30%), while simultaneously increasing the content of HDL. The mechanisms of these changes are associated with antagonism to a 1 -adrenergic receptors involved in the metabolism of cholesterol and triglycerides: a decrease in the activity of 3-hydroxy-3-methyl-glutaryl (HMG) CoA reductase, which is involved in the key reaction of cholesterol biosynthesis in the liver; an increase in the functional activity of receptors for LDL, ensuring their binding due to a decrease in cholesterol synthesis by almost 40%; decreased activity of endothelial lipoprotein lipase involved in triglyceride catabolism; stimulation of the synthesis of apolipoprotein A1 (the main component of HDL).

and 1-blockers with long-term use lead to a decrease in glycemia and insulin levels due to increased tissue sensitivity to glucose and insulin-dependent utilization of glucose by tissues. The mechanism of these phenomena may be a decrease in blood pressure, on the one hand, or an increase in blood flow through muscle tissue, on the other.

A comparison of the effects of different classes of antihypertensive drugs is given in Table. 9.3.

An additional effect of α1-blockers is the relaxation of the muscle tone of the urethra in the prostate gland, which is regulated a1s - adrenoreceptors. Decreased urethral muscle tone helps reduce resistance to urinary flow and improve urination in patients with benign prostatic hyperplasia. In addition, nonspecific blockade a1s - adrenergic receptors causes dose-dependent relaxation of the muscles of the prostate gland, which reduces its hyperplasia.

Table 9.3

Metabolic effects of antihypertensive drugs in patients with hypertension

PHARMACOKINETICSa 1 - ADRENO BLOCKERS

and 1-blockers are lipophilic drugs. Comparative pharmacokinetic data a 1 - adrenergic blockers are presented in table. 9.4.

a 1-blockers are well and completely absorbed after oral administration; bioavailability is 50-90%. The time to reach maximum concentration (Tmax) varies slightly - from 1 hour for prazosin to 3 hours for doxazosin, which affects the rate of development of the hypotensive effect and its tolerability. The level of maximum concentration (Cmax) is dose-dependent over a wide range of drug doses.

a 1 -blockers are highly bound to plasma proteins (98-99%), mainly with albumin and a 1 -acid glycoprotein and have a large volume of distribution.

and 1-blockers undergo active hepatic biotransformation with the help of microsomal enzymes (cytochrome P450). The active metabolite of prazosin has clinical significance in its antihypertensive effect. Prazosin has a high hepatic clearance (including presystemic), the hepatic clearance of doxazosin and terazosin does not correlate with the rate of hepatic blood flow and is significantly less than that of prazosin.

Excreted a 1 - blockers mainly with bile (more than 60%) in an inactive form; renal clearance is less important.

Important for the duration of the hypotensive effect 1 -blockers has T 1/2: long T 1/2 have terazosin and doxazosin.

In recent years, a controlled-release dosage form of dixazosin (doxazosin GITS) has been introduced into clinical practice. Features of the pharmacokinetics of this dosage form: increase in T max up to 8-9 hours (compared to 4 for the conventional dosage form), decrease in C max by 2-2.5 times, with a comparable level of C min, fluctuation in C max / C min - 50 -60% (versus 140-200% for the conventional dosage form).

Age and renal function do not affect the pharmacokinetics of α1-blockers.

Uroselective drugs have similar pharmacokinetics and long half-life 1/2 (alfuzosin - 9 hours, tamsulosin - 10-13 hours).

Table 9.4

Comparative pharmacokineticsa 1 - adrenergic blockers

* There is first-pass metabolism

INDICATIONS, CONTRAINDICATIONS AND SIDE EFFECTS

Indications: for hypertension (prazosin, terazosin, doxazosin) as second-line drugs, for benign prostatic hyperplasia (alfuzosin, tamsulosin).

Contraindications: hypersensitivity, hypotension, pregnancy (category C), breastfeeding, childhood.

Most side effects a 1 - adrenergic blockers is the result of their pharmacodynamic (hemodynamic) action and depends on the speed of its onset.

Most significant side effects a 1 - adrenergic blockers - hypotension and orthostatic collapse, observed more often after taking the first dose of prazosin than terazosin and doxazosin, because the latter act more slowly. This hemodynamic side effect is called the “first dose” phenomenon (or effect). The “first dose” phenomenon is dose-dependent and appears during the period of development of the maximum hypotensive effect (after 2-6 hours). When taking repeated doses a 1 - With adrenergic blockers, postural phenomena are no longer observed. However, they can also appear during long-term treatment if it is necessary to increase the doses of drugs; in this case, the first dose of the increased dose may manifest itself with the effects described above.

Orthostatic collapse is described in 2-10% of patients receiving o 1 -blockers, for uroselectin drugs - less than 5%. Collapse can be avoided if the first dose of prazosin is reduced to 0.5 mg and given at night. Other manifestations of postural effects are dizziness, headache, drowsiness, fatigue, which occur in almost 20% of patients. A sharp vasodilating effect can cause exacerbation of coronary artery disease and angina pectoris. Caution is required when using beta-blockers in elderly patients, as well as in patients receiving concomitant antihypertensive therapy (especially diuretics); in these groups the risk of postural phenomena may increase.

Doxazosin GITS has a lower risk of developing “first dose” hypotension due to slower pharmacokinetics.

Edema is less common in a 1 - blockers (about 4%), however, a characteristic manifestation of vasodilation caused a 1 - block-

tori, is swelling of the nasal mucosa (nasal congestion, rhinitis).

Palpitations when taking o 1 -blockers are rare (about 2%).

In 5-10% of patients, the development of withdrawal syndrome is described when stopping treatment with β-blockers.

DRUG INTERACTIONS

o 1-blockers may have pharmacodynamic interactions associated with changes in the severity of the hypotensive effect: other antihypertensive drugs and diuretics enhance the effect, NSAIDs, estrogens, sympathomimetics lead to a weakening of the effect.

CHARACTERISTICS OF INDIVIDUAL DRUGS

Prazosin- selective blocker of postsynaptic αι-adrenergic receptors. The hypotensive effect of prazosin is not accompanied by an increase in renin activity. Reflex tachycardia is expressed to a small extent, mainly only when taking the drug for the first time. Prazosin dilates the venous bed, reduces preload, and also lowers systemic vascular resistance, so it can be used in congestive heart failure. Prazosin does not significantly affect renal function and electrolyte metabolism, so it can be taken in cases of renal failure. The hypotensive effect of the drug increases in combination with thiazide diuretics. The drug has significant hypolipidemic properties.

Prazosin is absorbed differently in patients depending on food intake and other individual characteristics. Average bioavailability is about 60%. Its half-life is 3 hours, but the hypotensive effect, like many other antihypertensive drugs, is not related to plasma drug levels and lasts longer. Prazosin begins to act 0.5-3 hours after oral administration. The drug is actively metabolized; 90% of it is excreted in feces, 10% in urine and only 5% as unchanged

form. There is an active metabolite of prazosin, which has a hypotensive effect and the ability to accumulate in the body.

The drug is prescribed starting with small doses (0.5-1 mg) in order to avoid the development of side effects (tachycardia, hypotension) associated with the first dose. The dose is gradually increased to 3-20 mg per day in 2-3 doses. The full hypotensive effect is observed after 4-6 weeks. The average maintenance dose is 5-7.5 mg per day.

Side effects: postural hypotension, dizziness, weakness, fatigue, headache. Drowsiness, dry mouth, and impotence are mildly expressed. In general, the drug is well tolerated.

Doxazosin- refers to long-acting a 1 - adrenergic blockers. Vasodilation and decreased peripheral vascular resistance cause a decrease in blood pressure both at rest and during exercise. At the same time, there is no increase in heart rate and cardiac output. Norepinephrine levels do not change or increase slightly with doxazosin treatment, while the levels of epinephrine, renin, dopamine and serotonin remain the same.

Leads to a decrease in ureteral resistance. It has a hypolipidemic effect, due to this it is especially indicated for patients with hypertension in combination with hyperlipidemia, smoking, and type II diabetes mellitus. There is evidence of the beneficial effect of doxazosin on fibrinolysis and the presence of antiaggregation properties of the drug.

The bioavailability of doxazosin is 62-69%, peak concentration in the blood is observed 1.7-3.6 hours after oral administration. The drug undergoes O-demethylation and hydroxylation in the body; the metabolites are inactive (their significance in clinical effectiveness is unknown). The drug accumulates during long-term use, and therefore the final half-life 1/2 increases from 16 to 22 hours; age, renal function status and dose do not affect T 1/2.

Doxazosin is used in a dose of 1 to 16 mg once a day; Due to the development of the “first dose” effect, titration of the drug dose is required from the initial 0.5-1 mg. A controlled release dosage form of doxazosin has been created - doxazosin GITS, 4 and 8 mg. The advantages of this form are a slower development of the hypotensive effect with a comparable degree of reduction in SBP and DBP, which does not require dose titration and a decrease in the frequency of “first dose” hypotension and improved tolerability.

Side effects: dizziness, nausea, headache.

Terazosin also has a vasodilator, antidysuric and hypolipidemic effect. Terazosin dilates large resistive vessels and reduces peripheral vascular resistance, and also selectively blocks o 1 -adrenergic receptors of the smooth muscles of the celiac vessels, prostate gland and bladder neck. Normalizes plasma lipid profile.

After taking the drug orally, it is quickly and completely absorbed, bioavailability exceeds 90%, presystemic biotransformation is almost not observed. The maximum concentration in the blood is achieved within 1 hour. In plasma, the drug is 90-94% protein bound. A number of inactive metabolites are formed from terazosin in the liver. The half-life is about 12 hours, but the therapeutic effect lasts for at least 24 hours. 60% of the drug is excreted by the liver; in case of liver pathology, a decrease in the clearance of the drug and a prolongation of its therapeutic effect are observed.

Side effects: weakness, fatigue, drowsiness, anxiety, headache, dizziness, paresthesia, decreased libido, blurred vision, tinnitus, “first dose” effect, hypotension, tachycardia, arrhythmias, peripheral edema, cough, bronchitis, xerostomia, pharyngitis , nausea, vomiting, arthralgia, myalgia, allergic reactions.

Terazosin enhances the hypotensive activity of diuretics, adrenergic blockers, calcium antagonists, and ACE inhibitors. The drug is prescribed orally 1 mg once before bedtime in the supine position (to avoid orthostatic hypotension); if necessary, the dose is gradually increased to 10-20 mg 1 time per day.

Adrenergic receptors sensitive to catechol amines are located in different organs and differ from each other in their functionality and susceptibility. They also differ in the variability of reactions that occur when they are activated.

Medicines that affect the sensitivity of certain receptors include alpha-blockers. Subtypes of this class include non-selective agents. Since 1980, selective drugs have also been used for therapy.

What are alpha blockers?

The effect obtained from taking the drugs of this drug group is already clear from the name.

Alpha-blocker drugs are distinguished by their ability to “protect” adrenergic receptors, blocking their sensitivity to the effects of mediator substances. The latter include adrenaline, dopamine and norepinephrine.

Mechanism of action

The effect observed after administration depends on the type of alpha receptors blocked. They are usually divided into two groups: a1 and a2. It is more convenient to consider the body’s response to the effects of blockers within the framework of the table.

Table 1. Mechanism of action of alpha-blockers affecting a1 adrenergic receptors

Blocking type A2 receptors with alpha-blockers has a different result, namely it leads to:

• narrowing of the lumen of blood vessels;
• increased pressure;
• release of norepinephrine;
• increasing physical activity;
• increasing libido and normalizing sexual functions;
• stimulates the central nervous system, etc.

Mechanism of action of alpha-blockers

Classification

Several types of drugs are used for therapeutic purposes. They differ in their selective or non-selective effects on receptors.

Selective

These drugs act on receptors selectively, in particular, they affect type A1 adrenergic receptors. At the moment, the classification of selective alpha-blockers includes several subgroups that differ in the duration of their action. Medicines with a short-term effect include prazosin. Prolonged action was observed with terazosin and doxazosin. In addition, a separate group includes uroselective blockers that affect adrenergic receptors located in the muscles of the genitourinary tract.

Non-selective

Unlike previous drugs, these alpha blockers act nonselectively. They block peripheral alpha receptors type a1 and type a2. The non-selective effect of alpha-blockers leads to a short-term decrease in blood pressure due to the effect on α1. However, blocking alpha-2 adrenergic receptors stimulates the release of norepinephrine, which leads to the leveling of the hypotensive effect.

Non-selective therapeutic agents can only be used for emergency short-term treatment, but are not suitable for long-term use.

List of drugs

Adrenergic receptor blockers have a wide range of application features. Only a specialist can prescribe funds. Let's look at some of the tools from this class within the table.

Table 2. List of alpha-blocker drugs that affect a1 and a2 receptors

Indications

The wide range of action allows the use of drugs of the class for therapy for various diseases. Most often, the drugs are used in cardiological practice, as well as for the treatment of pathologies of the genitourinary system.

Benign prostatic hyperplasia

Previously, this disease, which is a benign formation in the prostate gland, was called prostate adenoma. On average, every second man who reaches the age of 40-45 years suffers from this pathology.

The use of alpha-blockers makes it possible to relieve the manifestations of obstruction and irritation caused by the adenoma.

Arterial hypertension

Regularly elevated blood pressure up to mm Hg. column or more is called arterial hypertension (hypertension). To reduce blood pressure, specialists in some cases prescribe a1 blockers. Alpha-blockers for selective hypertension help reduce blood pressure without increasing the number of heart contractions. Class drugs reduce pre- and post-load on the muscle tissue of the heart. The products have a long-lasting effect – up to 24 hours.

Other cardiovascular diseases

Alpha-a1 blockers also have other indications for use. In particular, the drugs are recommended for therapy in heart failure. The drugs provide a pronounced reversal effect in left ventricular hypertrophy. As for a2 receptor blockers, they are recommended for erectile dysfunction and impotence.

Contraindications

Before using drugs, you should familiarize yourself with the restrictions on their use.

Table 3. Contraindications to treatment with α1 alpha-blockers

A2 blockers are not recommended for bleeding disorders, bleeding, prostate hyperplasia, diabetes mellitus, depressed emotional state, pregnancy, etc. More detailed information can be found in the instructions for the specific drug.

Arterial hypertension as a factor in the development of stroke

Side effects from taking

The most obvious negative effects caused by taking A1 blockers include a decrease in blood pressure and orthostatic collapse. Typically, these side effects are observed after the first use of an alpha-blocker (the “first dose” phenomenon). Patients are also found to have:

• headache, dizziness;
• fatigue, drowsiness, decreased performance;
• exacerbation;
• increased risk of postural phenomena, etc.

Therapy with alpha-2 adrenergic blockers may lead to increased blood pressure, tremor, dyspeptic disorders, frequent urination, etc.

Instructions for use of some tablets

Annotation for medicinal products includes detailed information about the mechanism of action, dosage regimen and features of use. Some aspects outlined in the instructions for alpha-blockers are given below.

To prevent the “first dose” effect, it is recommended to prescribe the drug starting with a minimum amount of 0.5-1 mg. In addition, there is a special form of this alpha-blocker, which has a controlled release of the active substance.

Its use contributes to a gentler decrease in both systolic and diastolic pressure. In this case, a dose reduction is not required upon first use.

A drug based on doxazosin mesylate, produced in Germany. An alpha blocker leads to a significant decrease in blood pressure. Even with long-term therapy, patients were not found to develop tolerance to this drug. In addition to the hypotensive effect, it has a beneficial effect on erectile function.

Prazosin

It is recommended to start pharmacological therapy with a small amount - 0.5-1 mg, in order to avoid a pronounced decrease in blood pressure. The daily amount of alpha-blocker is gradually increased. The maximum daily dosage is 7.5 mg. As a rule, the drug is well tolerated.

It may cause decreased performance, headaches, blurred vision, tinnitus, changes in heart rate, dyspeptic disorders, etc. This alpha-blocker enhances the effect of calcium antagonists, ACE inhibitors, diuretics, etc.

Setegis is an alpha-blocker produced in Hungary. It is an analogue of the previous drug. The daily dose of Setegis is selected individually, based on the blood pressure of a particular patient. It is recommended to start taking it with a minimum amount and gradually increase mg.

Useful video

From the following video you can learn useful information about the role of alpha-blockers in the treatment of arterial hypertension:

conclusions

1. Alpha-blockers are effective medications used to normalize blood pressure, treat prostate adenoma, increase libido and combat impotence.
2. Drugs of this class should be taken with caution due to an impressive list of restrictions and possible side effects.
3. It is strictly forbidden to take alpha-blockers without a doctor's recommendation.

• Classification of alpha adrenergic blockers
• Treatment with alpha adrenergic blockers in urology
• Treatment with alpha adrenergic blockers in cardiology
• List of the most popular products in this group
• Contraindications and side effects
• Effect of the first dose

Alpha adrenergic blockers are part of a group of drugs whose action is aimed at slowing down nerve impulses passing through the adrenergic synapse. Their action is based on temporary blocking of α 1 - and α 2 -adrenergic receptors.

The drugs have found their use in a special system for the treatment of arterial hypertension, having proven themselves to be quite effective. In urology, alpha blockers help improve urination, which is especially important for prostate diseases.

Classification of alpha adrenergic blockers

Depending on the spectrum of action, alpha adrenergic blockers are divided into two types. Those of them that are capable of blocking exclusively α 1 -adrenergic receptors are called selective. Non-selective ones affect α 1 -adrenergic receptors and α 2 -adrenergic receptors. Effective as an antihypertensive agent and in the treatment of prostate adenoma.

Non-selective blockers are prescribed for the diagnosis of benign tumors, in the treatment of migraines, peripheral circulatory disorders, cerebral circulation, withdrawal syndrome (binge drinking) and hypertensive crisis. Their action is characterized by a short-lived effect, which excludes the possibility of use as permanent antihypertensive drugs.

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Treatment with alpha adrenergic blockers in urology

Urologists traditionally use only five drugs from the group of alpha adrenergic blockers, which help prevent acute urinary retention or provide a therapeutic effect for chronic prostatitis and prostate adenoma. First of all, the attention of a urologist is drawn to alfuzosin and tamsulosin due to their ability to block alpha adrenergic receptors of the smooth muscles of the bladder, prostate gland, and urethra many times more effectively than the smooth muscles of blood vessels. This property allows the drugs to have a slight effect on blood pressure.

In some cases, it is possible to prescribe terazosin and doxazosin, used in cardiology. Their use requires special caution. The first dose can cause orthostatic syncope. You must strictly follow the instructions of your doctor, and if there are none, then the instructions for use included in the package of the medicine.

In extremely rare cases, prazosin may be prescribed to restore urination.

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Treatment with alpha adrenergic blockers in cardiology

Cardiology values ​​these drugs for their ability to reduce the risk of atherosclerosis. The beneficial property is provided by changes in the lipid profile and cholesterol levels in the blood plasma. The drugs have the ability to lower blood pressure without increasing heart rate, and they do not affect potency or blood glucose levels. Also among the advantages is a modest number of side effects, the main of which is the reaction to the first dose. For patients with chronic heart failure, alpha blockers may be prescribed in combination with beta blockers.

Based on studies conducted by KIPPAG, it was found that taking prazosin as the main drug in an antihypertensive course gives a positive result in 50% of patients. In most cases, stable results can be achieved after six months of treatment. In some - within a month. Experts note a decrease in the effectiveness of the drug on the 5th day of use without increasing the dosage. It has been noted that taking alpha adrenergic blockers in some cases causes fluid retention in the body; in this case, diuretics are prescribed in parallel.

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List of the most popular products in this group

Dihydroergotamine and dihydroergotoxin are in a better position than ergot alkaloids due to successful experiments to reduce toxicity. They allow you to achieve a decrease in blood pressure by inhibiting the vasomotor center and blocking vascular adrenergic receptors. The frequency of administration is 2-3 per day.

Prescribing phentolamine is advisable if necessary to lower blood pressure, restore blood supply to muscles or skin, and relieve spasm of peripheral vessels. High effectiveness was achieved for patients suffering from bedsores, trophic ulcers of the extremities, endarteritis and Raynaud's disease.

Phentolamine is prescribed to lower blood pressure, restore blood supply to muscles or skin, and relieve spasm of peripheral vessels. The drug has proven itself well when taken by patients with Raynaud's disease, endarteritis, bedsores, and trophic ulcers of the extremities. The frequency of administration reaches 5 times a day.

Taking tropafen helps restore peripheral circulation and stop a hypertensive crisis. After its administration intramuscularly, subcutaneously or intravenously, blood pressure decreases and peripheral vessels dilate.

For patients with hypertensive crises associated with mental stress, suffering from seasickness or Meniere's syndrome, experts recommend taking pyrroxan. It affects peripheral and central adrenergic receptors, blocking which allows one to achieve a pronounced sedative effect.

Butyroxane shows good results in the treatment of alcoholism, allergic dermatosis and hypertension. The drug is available in two forms, allowing it to be taken orally or by injection. The frequency of administration is from 2 to 4 times a day, depending on the chosen form.

Acute or chronic disorders in the cerebral circulatory system and peripheral circulatory disorders are provoked by the administration of nicergoline. The drug, being a synthetic derivative of ergot alkaloids, has a myotropic effect on blood vessels. Frequency of administration: 3 times a day.

Among the methods of treating hypertension, prazosin hydrochloride shows an unexpectedly striking result. Experts recommend adding diuretics to the treatment course. The action of the drug is based on postsynaptic blocking of adrenergic receptors in a selective manner.

The use of alpha blockers for hypertension as an adjuvant helps to quickly dilate blood vessels and reduce blood pressure. Despite their effectiveness, the drugs have a number of contraindications.

Treatment of hypertension is based on the selection of a group of drugs that act on various parts of the pathogenesis of the disease. An integrated approach ensures good control over blood pressure (BP) levels. Thus, alpha blockers for hypertension are necessarily included in therapeutic regimens and have proven effectiveness.

Almost all muscle fibers of blood vessels contain alpha receptors that respond to the action of adrenaline and norepinephrine. Depending on their location relative to the synapse (the area where nerve endings connect to each other or to a responding cell), there are 2 types of receptors. Localized before the synapse (presynaptic) - α1, after - α2. When irritated, the intracellular composition of myocytes (the structural unit of muscles) changes, they contract and the lumen of the vessel narrows.

When arteries spasm, the overall vascular resistance increases, which the blood flow must overcome to bring oxygen to every cell of the body. As a result, the pressure increases.

It is in order to block this link in pathogenesis that alpha adrenergic blockers are prescribed for hypertension.

They prevent impulses that cause vasospasm from reaching the arteries. As a result, the pressure decreases.

Effect of drugs based on alpha-blockers

Medicines that contain α-blockers can be selective (act only on α1 receptors) and non-selective (block α1 and α2). For hypertension, such drugs are prescribed when the pressure rises above 140/90 mmHg. Art.

The main pharmacological effects of alpha blockers are the following:

• vasodilation;
• removing the tone of the sympathetic nervous system;
• increased lipolysis (fat breakdown);
• decreased insulin resistance (resistance to the action of insulin);
• increasing the influence of parasympathetic regulation.

The mechanism of the positive effect of this group of drugs on fat metabolism is not fully understood. But it has been proven that the use of adrenergic blockers for hypertension lowers the concentration of cholesterol and triglycerides in the blood. At the same time, the amount of low-density lipoproteins (“harmful”), which contribute to atherosclerosis, is reduced. And the concentration of “useful” high-density lipoproteins, on the contrary, increases.

The use of alpha 1 blockers helps to increase tissue sensitivity to insulin, a hormone that regulates carbohydrate metabolism. Thanks to this, its secretion by pancreatic cells is reduced and blood sugar levels are normalized.

List of alpha blockers

Drugs containing adrenaline receptor inhibitors are quite widely represented on the pharmacy market. Depending on the effect on certain types of alpha receptors, these drugs belong to different groups of drugs.

List of drugs containing α1-blockers:

• alfuzosin (Alfuprost, Dalfaz, Alfuzosin) – tablets used for prostatitis;
• prazosin (Prazosin, Prazosinbene) - prescribed for the treatment of arterial hypertension;
• urapidil (Takhiben, Urapidil carino, Ebrantil) - capsules and intravenous solution can be used to relieve a hypertensive crisis;
• silodosin (Urorek) – a drug that improves urination in case of prostate disease;
• doxazosin (Artesin, Doxazosin, Kamiren, Zoxon, Urocard, Cardura, Tonocardin) - tablets for the treatment of hypertension and prostate pathologies;
• tamsulosin (Hyperprost, Omnic) – used for prostate adenoma;
• Terazosin (Cornam, Setegis, Terazosin) - tablets prescribed for arterial hypertension of any origin and benign prostate growth.

Preparations that contain alpha-2 adrenergic blockers - Yohimbine and Yohimbine hydrochloride. They are used for erectile dysfunction, decreased libido and male menopause. Contraindicated in arterial hypertension.

Medicines containing alpha-1,2-blockers are represented by the following list:

• nicergoline (Sermion, Nicergoline) - a drug used for any circulatory disorder in the brain, for pressure, for vasoconstriction of the extremities, Raynaud's syndrome;
• Proroxan is prescribed for hypotholamic crisis, which is accompanied by an increase in blood pressure;
• phentolamine (Regitin, Dibasin) – tablets for the treatment of hypertensive crisis in pheochromocytoma.
• dihydroergotamine (Ditamine, Clavigrenin) – the drug is indicated for migraines;
• dihydroergotoxin (Redergin, Vasolax) – used for transient hypertension;
• Dihydroergocristine (Brinerdin, Normotens) - tablets for blood pressure and cerebral blood flow disorders.

Arterial hypertension of any origin is a direct indication for the use of α1-blockers.

How do α-blockers work for hypertension?

Although these drugs are not included in the group of first-line drugs for the treatment of hypertension, their prescription in cardiological practice is very common and justified. Thanks to the block of receptors that are sensitive to adrenaline, vasodilation occurs. The antispasmodic effect is especially pronounced in the periphery, since the concentration of adrenergic receptors is higher there. This is due to the positive effect of alpha blockers on microcirculation.

The dilation of arterioles reduces peripheral vascular resistance, which entails a decrease in pressure. At the same time, the minute stroke volume of the heart does not increase, since venous return does not increase due to the dilation of the veins.

Dilation of the coronary vessels improves the nutrition of the heart, reduces the need for oxygen and reduces the symptoms of its chronic failure. An increase in the lumen of the arteries of the pulmonary circulation causes a decrease in pulmonary hypertension.

The effect of alpha adrenergic blockers on fat metabolism, in particular the reduction of cholesterol, LDL and triglycerides, explains the prescription of these drugs for atherosclerosis or a tendency to it, as well as for obesity, which is combined with hypertension. The use of α1-blockers is especially necessary for metabolic syndrome.

Indications

Receptors for adrenaline are located in smooth muscles that are part of the structure of many organs. This may explain the wide range of indications for the use of drugs containing alpha-blockers.

Conditions that require the use of drugs that block α1 receptors:

• hypertension (especially caused by stress);
• prostate adenoma;
• chronic heart failure.

The prescription of α1,2 blockers is justified for the following pathologies:

• acute and chronic cerebrovascular accident;
• Raynaud's syndrome;
• impaired peripheral circulation (aortoarteritis obliterans, thrombosis of leg vessels);
• migraine;
• dementia, especially of vascular origin;
• vertigo (dizziness) caused by vasospasm;
• angiopathy in diabetes mellitus;
• corneal dystrophy;
• optic neuropathy.

With regular use, a long-lasting antihypertensive effect is noted. The metabolism of active substances occurs in the liver, and they are excreted in urine and feces.

Contraindications

When prescribing adrenergic blockers, the doctor must take into account the contraindications that are present in a particular patient. This will help avoid side effects and worsening concomitant pathologies.

Taking drugs from this group is contraindicated in the following conditions:

• congenital and acquired heart valve defects (aortic, mitral);
• acute bleeding;
• myocardial infarction (recent);
• severe bradycardia (decreased heartbeat);
• orthostatic hypotension (a drop in pressure when changing body position);
• severe liver disease;
• lactation period;
• intolerance to the components of the drug;
• simultaneous use of beta blockers;
• pregnancy;
• angina pectoris;
• children's age (up to 12 years).

All indications and contraindications must be carefully assessed by a physician. Unreasonable prescription of the drug, and even more so as a means of self-medication, is unacceptable.

Side effects

Adrenaline receptor blockers affect smooth muscles throughout the body, producing not only a positive effect, but also possible adverse effects.

Among the side effects of prescribing medications for hypertension that block alpha receptors are the following conditions:

• orthostatic hypotension;
• dizziness and short-term loss of consciousness;
• temporary redness of the face;
• fatigue or drowsiness;
• vomiting and nausea;
• difficulty falling asleep, insomnia;
• cold hands and feet;
• stomach ache;
• angina attack;
• allergic reactions.

Because of the possibility of fainting as a result of treatment with these blood pressure medications, the first dose should be administered or taken while lying down or sitting.

Alpha-blockers are effective drugs for the treatment of hypertension and relief of crises caused by increased blood pressure. When using such products, it is necessary to take into account indications and contraindications for use. If side effects occur, you should immediately inform your doctor.