Sympathomimetic and sympatholytic agents. The use of sympathomimetic drugs for the treatment of bronchial asthma Ephedrine belongs to the group of sympathomimetics

Ephedrine is an alkaloid found in various types of ephedra (Ephedra L.). The chemical structure is similar to adrenaline, but unlike it does not contain hydroxyls in the aromatic ring (it is not a catecholamine).
a
CH-CH-N,H -HCI OH CHz "CH'
Ephedrine hydrochloride
Plant based ephedrine is the levorotatory isomer, while synthetic ephedrine is a racemic mixture of the levorotatory and dextrorotatory isomers and is less active. In medical practice, it is used in the form of ephedrine hydrochloride.
Ephedrine promotes the release of the norepinephrine mediator from varicose thickenings of sympathetic nerve fibers, and also directly stimulates adrenoreceptors, but this effect is not pronounced, so ephedrine is classified as an indirect adrenomimetic. The effectiveness of ephedrine depends on the stores of the mediator in the endings of sympathetic fibers.
Under the action of ephedrine, the same subtypes of a-and (3-adrenergic receptors) are excited as under the action of adrenaline (but to a lesser extent), therefore, ephedrine mainly causes pharmacological effects characteristic of adrenaline. It increases the strength and frequency of heart contractions and constricts blood vessels, as a result, it increases blood pressure.The vasoconstrictive effect of ephedrine is also manifested when it is applied topically - when applied to mucous membranes.Ephedrine expands the bronchi, reduces intestinal peristalsis, dilates the pupils (does not affect accommodation), increases blood glucose, increases the tone of skeletal muscles.
Ephedrine has a stimulating effect on the central nervous system: it increases the activity of the respiratory and vasomotor centers, has a moderate psychostimulant effect - reduces the feeling of fatigue, the need for sleep, and increases efficiency. According to the psychostimulating effect, ephedrine is inferior to amphetamine (which causes the release of norepinephrine and dopamine from the nerve endings).
Ephedrine is used as a bronchodilator. To stop attacks of bronchial asthma, the drug is administered subcutaneously, and for prevention - inside (it is part of the combined preparations "Teofedrin", "Solutan", "Bronholitin").
Sometimes ephedrine is used to increase blood pressure. Ephedrine is inferior to adrenaline in activity (to achieve the same pressor effect, the dose of ephedrine should be 50 or more times higher than the dose of adrenaline). The pressor effect of ephedrine is less pronounced than that of adrenaline, but lasts much longer (1-1.5 hours). With repeated injections of ephedrine at short intervals (10-30 minutes), its pressor effect decreases - addiction develops. This rapid development of addiction is called tachyphylaxis. This effect is due to the rapid depletion of norepinephrine reserves in the endings of sympathetic fibers.
In addition, the drug is effective in allergic diseases (hay fever, serum sickness), it can be applied topically with a cold (narrowing of the vessels of the nasal mucosa leads to a decrease in the inflammatory reaction), with atrioventricular block (atrioventricular conductivity increases). Due to the stimulating effect on the central nervous system, ephedrine can be used for narcolepsy (pathological drowsiness).
It is administered orally subcutaneously, intramuscularly. Inside is prescribed before meals. Ephedrine is quickly and completely absorbed from the gastrointestinal tract into the blood, while it is practically not metabolized by MAO (resistant to its action). The elimination half-life is 3-6 hours. It is excreted by the kidneys. Ephedrine is used only on prescription, as it causes a number of serious side effects: nervous excitement, insomnia, circulatory disorders, trembling limbs, loss of appetite, urinary retention. The drug is contraindicated in insomnia, hypertension, atherosclerosis, hyperthyroidism. Ephedrine refers to doping drugs and is prohibited for use by athletes.
Interaction of adrenomimetics with other drugs

Adrenomimetics, sympathomimetics	Other medicines (groups of medicines)	Result interactions
epinephrine (adrenalin), norepinephrine (norepinephrine)	Halogen-containing drugs for inhalation anesthesia MAO inhibitors	Risk of developing cardiac arrhythmias due to increased sensitivity of the myocardium to catecholamines Cardiac arrhythmias
dobutamine	Tricyclic antidepressants	hypertension
	cardiac glycosides	Risk of developing cardiac arrhythmias
Nafazoline	Tricyclic antidepressants MAO inhibitors	Strengthening the vasoconstrictor effect of naphazoline. Hypertensive effect
Ephedrine	Halogen-containing means for inhalation anesthesia	Risk of developing cardiac arrhythmias
	(3 - adre nob locators	Inhibition of the action of ephedrine on the heart

142 ^ PHARMACOLOGY ^ Private pharmacology
Basic drugs

International non-proprietary name	Proprietary (trade) names	Release form	Information for the patient
1	2	3	4
Epinephrine hydrochloride (Epinephrini hydrochloridum)	Adrenaline hydrochloride	Vials of 10 ml of 0.1% solution. Ampoules of 1 ml of 0.1% solution	Injectable solutions are used only as directed by a doctor. To stop bleeding, you can use swabs moistened with a solution of the drug.
Epinephrine hydrotartrate (Epinephrini bitartras)	Adrenaline hydrotartrate	Vials of 10 ml of a 0.18% solution. Ampoules of 1 ml of 0.18% solution
Norepinephrine hydrotartrate (Norepinephrini hydrotartras)	Norepinephrine hydrotartrate	Ampoules of 1 ml of 0.2% solution
Phenylephrine hydrochloride (Phenylephrini hydrochloridum)	Mezaton	Ampoules of 1 ml of 1% solution	Injectable solutions are used only as directed by a doctor.
Naphazoline nitrate (Naphazolini nitras)	Naphthyzin Sanorin	Vials of 10 ml of 0.05% and 0.1% solution	With prolonged use, the effect of the drug decreases, so after 5-7 days of use, you should take a break for a few days
Fenoterol (Phenotelum)	Berotek	Aerosol cans 10 ml (200 mcg per dose, 200 doses), inhalation solution (vials with dropper) 0.1%, 20 ml	If after the first inhalation the bronchodilatory effect did not occur, then the second inhalation is carried out only after 5 minutes. Subsequent inhalations are carried out after 5 hours
	Partusisten	Tablets and suppositories of 0.005 g. Ampoules of 10 ml of a 0.005% solution	To reduce the tone of the uterus, tablets are taken 30-40 minutes before meals. To prevent hypotension, it is necessary to take the drug lying down
Salmeterol (Salmeterolum)	Serevent	Aerosol for inhalation (vials), 25 mcg per dose, 60 and 120 doses; powder for inhalation, 50 mcg in a dose of 4 doses (rotadisk), 60 doses (multidisc)	The drug is intended for the prevention of asthma attacks. Do not use for the relief of bronchospasm. Use with caution in pregnant women and the elderly
dobutamine (Dobutaminum)	Dobutrex	Ampoules of 20 ml of 1.25% solution and 5 ml of 5% solution	The drug is administered intravenously under medical supervision. Self-administration of the drug by patients is excluded

End of table

Sympathomimetics are substances that increase the release of norepinephrine from the endings of adrenergic fibers.

Sympathomimetics include ephedrine, amphetamine, tyramine.

Ephedrine(Ephedrine) - ephedra alkaloid (Kuzmicheva grass). In terms of chemical structure and pharmacological effects, ephedrine is similar to adrenaline, but differs significantly from it in terms of the mechanism of action.

Ephedrine enhances the release of norepinephrine from the endings of adrenergic nerve fibers and only slightly directly stimulates adrenergic receptors. Thus, the effectiveness of ephedrine depends on the stores of the neurotransmitter in the endings of adrenergic fibers. With the depletion of mediator reserves in the case of frequent injections of ephedrine or against the background of the action of sympatholytics, the effect of ephedrine is weakened.

In experiments with vascular denervation, ephedrine has only a weak vasoconstrictor effect, and adrenaline acts more strongly than usual due to an increase in the number of adrenoreceptors during sympathetic denervation (Fig. 31).

Ephedrine differs from epinephrine in that it is less active, more stable (effective when administered orally), and has a longer duration of action.

Ephedrine constricts blood vessels and stimulates the heart. In this regard, ephedrine increases blood pressure; duration of action - 1-1.5 hours.

With very frequent administration of ephedrine, its effect quickly decreases. This phenomenon is referred to as "tachyphylaxis" (rapid addiction).

The vasoconstrictor effect of ephedrine is also manifested when applied topically - when its solutions are applied to the mucous membranes. In the case of inflammation of the mucous membranes, the narrowing of the blood vessels leads to a decrease in the effects of inflammation.

Ephedrine relaxes the muscles of the bronchi.

Ephedrine stimulates the central nervous system, in particular the vital centers - respiratory and vasomotor. It has moderate psychoactive properties.

Rice. 31. The effect of ephedrine and adrenaline on the tone of blood vessels. E- ephedrine; adr- adrenaline. With preserved vascular innervation, ephedrine and adrenaline can cause the same increase in vascular tone. With denervation of blood vessels, the effect of ephedrine is significantly weakened, and the effect of adrenaline is enhanced.

Indications for the use of ephedrine:

1) bronchial asthma(to stop attacks, the drug is injected under the skin, to prevent them, it is prescribed orally);

2) allergic diseases(hay fever, serum sickness, etc.);

3) rhinitis(in the form of drops in the nose);

4) arterial hypotension during surgical operations (in particular, with spinal anesthesia), with injuries; possible intramuscular or intravenous administration;

5) CNS depression(in particular, narcolepsy);

6) enuresis(stimulation of the central nervous system facilitates waking up with the urge to urinate);

7) myasthenia gravis.

Ephedrine is prescribed orally, and also injected under the skin, intramuscularly or intravenously. Side effects of ephedrine:

- nervous excitement;

- hand tremor, insomnia;

- heartbeat;

- increased blood pressure;

- urinary retention;

- loss of appetite.

Ephedrine is contraindicated in arterial hypertension, atherosclerosis, severe organic heart disease, and sleep disorders. Ephedrine can be addictive.

Amphetamine(Amphetamine; phenamine) is similar in properties to ephedrine. However, to a much greater extent it has a stimulating effect on higher nervous activity, showing a pronounced psychostimulating effect. When using phenamine as a psychostimulant, the sympathomimetic effect of the drug manifests itself in the form of tachycardia, increased blood pressure.

It has a sympathomimetic effect tyramine, which is found in many foods (cheese, wine, beer, smoked meats). Under normal conditions, tyramine is inactivated by MAO mainly in the intestinal wall. However, when using these products against the background of the action of MAO inhibitors, the sympathomimetic effect of tyramine is manifested - a significant increase in blood pressure is possible.

Drugs that block adrenergic synapses

Adrenoblockers

Adrenoblockers are substances that block adrenoreceptors. In accordance with different types of adrenergic receptors, this group of substances is divided into:

1) α-blockers;

2) β-blockers;

3) α-, β-blockers.

α-blockers

α 1 -Adrenergic blockers

α 1 -blockers include prazosin(Prazosin; minipress, polpressin), terazosin(Terazosin; Cornam) doxazosin(Doxazosin; tonocardin, cardura). These drugs dilate arterial and venous vessels; reduce blood pressure. Relax the smooth muscles of the bladder neck, prostate and prostatic urethra. Prazosin acts 6 hours, terazosin and doxazosin - 18-24 hours.

These drugs are used for arterial hypertension. In addition, they are effective in urinary retention associated with benign prostatic hyperplasia.

Side effects of α 1 -blockers:

- moderate reflex tachycardia;

- orthostatic hypotension;

- nasal congestion (expansion of the vessels of the nasal mucosa);

- peripheral edema;

- frequent urination.

Tamsulosin(Tamsulosin; omnic) blocks mainly α 1A -adrenergic receptors and therefore selectively relaxes the smooth muscles of the bladder neck, prostate and prostatic urethra; blood pressure does not change significantly. Tamsulosin is used orally for urinary retention in patients with benign prostatic hyperplasia.

Alfuzosin(Alfuzosin; dalfaz) - α 1 -blocker. It has a pronounced relaxing effect on the smooth muscles of the triangle of the bladder, urethra, prostate. The drug is prescribed orally 1-2 times a day for benign prostatic hyperplasia.

α 2 -Adrenergic blockers

Yohimbine(Yohimbine) is an alkaloid from the bark of a tree native to West Africa (Corynanthe yohimbe). In connection with the blockade of presynaptic α 2 -adrenergic receptors in the central nervous system, yohimbine has a central stimulating effect, in particular, increases sexual desire. Due to the blockade of peripheral α 2 -adrenergic receptors, it dilates blood vessels, increases the blood supply to the cavernous bodies and improves erection.

Yohimbine has an antidiuretic effect (possibly stimulates the secretion of antidiuretic hormone).

Yohimbine is used as a remedy for impotence. Assign inside 1-3 times a day.

Side effects of yohimbine:

- increased excitability;

- tremor;

- some decrease in blood pressure;

- tachycardia;

- dizziness;

- headache;

- diarrhea.

α 1 -, α 2 -Adrenergic blockers

Phentolamine(Phentolamine) blocks postsynaptic α 1 -adrenergic receptors and extrasynaptic α 2 -adrenergic receptors. Therefore, phentolamine reduces the stimulating effect of sympathetic innervation and adrenaline and noradrenaline circulating in the blood on blood vessels and causes them to dilate.

At the same time, phentolamine blocks presynaptic α 2 -adrenergic receptors of noradrenergic endings and increases the release of norepinephrine. This limits the vasodilating effect of phentolamine (Fig. 32).

Rice. 32. Influence of phentolamine on adrenergic innervation of blood vessels. Phentolamine blocks presynaptic α 2 -adrenergic receptors and increases the release of norepinephrine. Phentolamine blocks postsynaptic α 1 -adrenergic receptors and interferes with the action of norepinephrine.

Phentolamine dilates arterial and venous vessels, lowers blood pressure, causes severe tachycardia. Tachycardia occurs reflexively, and also due to increased release of the mediator - norepinephrine - in the heart (associated with the blockade of presynaptic α 2 -adrenergic receptors) (Fig. 33).

Rice. 33. Influence of phentolamine on the release of norepinephrine in the heart. Phentolamine blocks presynaptic α 2 -adrenergic receptors and increases the release of norepinephrine, which stimulates β 1 -adrenergic receptors of sinoatrial node cells and increases the heart rate.

Phentolamine has a pronounced hypotensive effect in pheochromocytoma (a tumor of the adrenal medulla that releases excessive amounts of adrenaline into the blood). Against the background of blockade of α 1 - and α 2 -adrenergic receptors, adrenaline secreted by the tumor further reduces blood pressure by stimulating β 2 -adrenergic receptors of vessels (Fig. 34).

Pheochromocytoma is usually removed surgically. Phentolamine is used to prevent hypertensive crises before surgery, during surgery, and in cases where surgery is not possible.

In addition, phentolamine is used for spasms of peripheral vessels (Raynaud's syndrome, obliterating endarteritis).

Rice. 34. Comparison of the hypotensive effect of phentolamine in essential hypertension and pheochromocytoma. With pheochromocytoma, against the background of blockade of α 1 - and α 2 -adrenergic receptors, it stimulates β 2 -adrenergic receptors and further reduces blood pressure.

Side effects of phentolamine:

Severe tachycardia;

Dizziness;

Nasal congestion (swelling of the nasal mucosa due to vasodilation);

orthostatic hypotension;

Increased secretion of the salivary glands and glands of the stomach;

Ejaculation disorder.

In pheochromocytoma, β-blockers are used to reduce tachycardia after the administration of phentolamine. It is impossible to prescribe β-blockers before phentolamine, since β-blockers contribute to an increase in blood pressure in pheochromocytoma.

Proroxan(Proroxan) blocks central and peripheral postsynaptic α 1 -adrenergic receptors and presynaptic α 2 -adrenergic receptors. It has antihypertensive and sedative effects. Reduces abstinence in dependence on opioids, alcohol. Proroxan is administered under the skin or intramuscularly in case of hypertensive crises. Inside is prescribed for the prevention of hypertensive crises, with motion sickness.

β-blockers

β-Adrenergic blockers are first-line agents in the treatment of:

1) tachyarrhythmias and extrasystoles;

2) angina pectoris;

3) arterial hypertension.

At the same time, they are contraindicated in chronic obstructive pulmonary diseases, obliterating vascular diseases, atrioventricular block. These substances reduce physical activity, cause dyslipidemia. β-blockers are divided into:

1) β 1 -, β 2 -blockers;

2) β 1 -blockers;

3) β-blockers with internal sympathomimetic activity.

β 1 -, β 2 -blockers

β 1 -, β 2 -blockers (non-selective β-blockers) include propranolol, nadolol, penbutolol, timolol.

propranolol(Propranolol; anaprilin, obzidan, inderal) due to with blockade of β 1 -adrenergic receptors:

1) inhibits the activity of the heart:

a) weakens the contractions of the heart;

b) slows down contractions of the heart (reduces the automatism of the sinus node);

c) reduces the automatism of the atrioventricular node and Purkinje fibers (in the ventricles of the heart);

d) hinders atrioventricular conduction;

2) reduces the secretion of renin by juxtaglomerular cells of the kidneys.

Due with blockade of β 2 -adrenergic receptors:

1) narrows blood vessels (including coronary);

2) increases the tone of the smooth muscles of the bronchi;

3) increases the contractile activity of the myometrium;

4) reduces the hyperglycemic effect of adrenaline.

Propranolol is lipophilic, easily penetrates into the central nervous system. The duration of action of propranolol is about 6 hours. The drug is administered orally 3 times a day; retard capsules - 1 time per day. In emergency cases, propranolol is administered slowly intravenously.

Indications for the use of propranolol:

1) angina pectoris; due to the weakening and slowing of the contractions of the heart, propranolol reduces the oxygen consumption of the heart in vasospastic angina pectoris, propranolol is contraindicated.

2) Prevention of myocardial infarction. After the acute phase of myocardial infarction, with a stable condition of the patient, the use of propranolol prevents recurrent heart attacks and reduces the mortality of patients (apparently, the decrease in the heart's need for oxygen, the redistribution of coronary blood flow in favor of the ischemic area of ​​the myocardium; antiarrhythmic effect) is important.

3) cardiac arrhythmias. Propranolol reduces the automaticity of the sinus node, the automaticity and conductivity of the atrioventricular node, the automaticity of the Purkinje fibers. Effective for supraventricular tachyarrhythmias: sinus tachycardia, paroxysmal atrial tachycardia, atrial fibrillation and flutter (to normalize the rhythm of ventricular contractions). It can be used for ventricular extrasystoles associated with an increase in automatism.

4) Arterial hypertension. Propranolol reduces cardiac output (weakens and slows down the contraction of the heart) and in isolated systolic hypertension can lower blood pressure at the first use. However, most often with a single use of propranolol, blood pressure decreases slightly, since, by blocking β 2 -adrenergic receptors of blood vessels, propranolol causes vasoconstriction and an increase in total peripheral vascular resistance.

With the systematic appointment of propranolol for 1-2 weeks, vasoconstriction is replaced by their expansion; blood pressure drops significantly. Vasodilation is explained by:

1) restoration of the baroreceptor depressor reflex (weakened in patients with hypertension);

2) inhibition of central sympathetic influences on the heart and blood vessels;

3) the inhibitory effect of propranolol on the secretion of renin (block β 1 -adrenergic receptors);

4) blockade of presynaptic β 2 -adrenergic receptors (the release of norepinephrine by sympathetic fibers decreases).

Propranolol is also used:

With hypertrophic cardiomyopathy;

With thyrotoxicosis (symptomatic therapy);

With essential (family) tremor (block β 2 -adrenergic receptors of skeletal muscles);

For the prevention of migraine (prevents the expansion and pulsation of cerebral vessels);

To ease withdrawal symptoms after drinking alcohol;

With anxiety, tension (reduces tachycardia).

In the treatment of pheochromocytoma with α-blockers, propranolol is used after lowering blood pressure to eliminate tachycardia caused by α-blockers. Propranolol should not be used before α-blockers, since propranolol increases blood pressure in pheochromocytoma (by blocking β 2 -adrenergic receptors of vessels, it eliminates the vasodilating effect of adrenaline).

Side effects of propranolol:

Excessive weakening of the contractions of the heart (possible heart failure);

Weakness during physical exertion, increased fatigue;

bradycardia;

Difficulty atrioventricular conduction (contraindicated in atrioventricular block II-III degrees);

Dry eyes (decrease in the production of tear fluid), xerophthalmia;

Feeling cold extremities (constriction of peripheral vessels);

Increased bronchial tone (bronchospasm may develop in patients with bronchial asthma);

Increased tone and contractile activity of the myometrium;

Decreased glucose tolerance, hypoglycemia (elimination of the hyperglycemic action of adrenaline associated with the activation of β 2 -adrenergic receptors); propranolol enhances the effect of hypoglycemic agents.

In addition, nausea, vomiting, diarrhea, cramping abdominal pain, drowsiness, nightmares, depression, attacks of disorientation, hallucinations, impotence, alopecia, skin rashes are possible. Propranolol increases the level of VLDL in the blood plasma and reduces the level of HDL.

The use of propranolol is characterized by pronounced withdrawal syndrome: with a sharp discontinuation of the drug, an exacerbation of coronary insufficiency, arterial hypertension is possible.

Propranolol is contraindicated in heart failure, sick sinus syndrome, severe bradycardia, atrioventricular block II-III degrees, vasospastic angina (Prinzmetal's angina), spasms of peripheral vessels, bronchial asthma and chronic obstructive pulmonary disease (COPD), pheochromocytoma (with pheochromocytoma, propranolol increases blood pressure). pressure; used only against the background of α-blockers), pregnancy. Propranolol enhances the effect of hypoglycemic agents used in diabetes mellitus.

Nadolol(Nadolol; Korgard) differs from propranolol in its long-term effect - up to 24 hours. It is prescribed orally 1 time per day for the systematic treatment of hypertension, angina pectoris.

Timolol(Timolol) is used for arterial hypertension, angina pectoris, for the prevention of migraine. The drug is administered orally 2 times a day.

Timolol maleate(Timolol maleate) is used for open-angle glaucoma in the form of eye drops 1-2 times a day (timolol, unlike propranolol, does not have a local anesthetic effect).

The decrease in intraocular pressure under the action of timolol is associated with a decrease in the production of intraocular fluid. The intraocular fluid is formed due to secretion by the cells of the epithelium of the ciliary (ciliary) body and filtration of blood plasma through the endothelium of blood vessels. Timolol:

1) blocks β 2 -adrenergic receptors of the epithelium of the ciliary body and reduces the secretion of intraocular fluid;

2) in connection with the blockade of β 2 -adrenergic receptors of blood vessels, it causes their narrowing and reduces filtration (Table 6).

After instillation of a solution of timolol into the conjunctival sac, intraocular pressure begins to decrease after 20 minutes, the maximum effect is achieved after 2 hours; duration of action - about 24 hours.

Table 6. Drugs used in glaucoma

1 Dorzolamide (Dorsolamide; Trusopt) inhibits carbonic anhydrase involved in the formation of intraocular fluid. Assign in the form of eye drops 1 drop 3 times a day.

2 Latanoprost (Latanoprost; xalatan) - prostaglandin F 2α drug; increases the outflow of intraocular fluid through the choroid of the eyeball (uveoscleral outflow). Assign in the form of eye drops, 1 drop at night.

β 1 -Adrenoblockers

β 1 -Adrenoblockers (cardioselective β-blockers) - metoprolol, atenolol, talinolol, betaxolol, bisoprolol, esmolol, nebivolol - block predominantly β 1 -adrenergic receptors and, to a lesser extent, β 2 -adrenergic receptors.

Since β1-blockers do not have absolute specificity for β 1 -adrenergic receptors, their side effects are generally similar to those of propranolol. However, compared with non-selective (non-selective) β-blockers, drugs in this group:

To a lesser extent, they increase the tone of the bronchi (with bronchial asthma, they are still contraindicated);

Less increase the tone of peripheral vessels;

To a lesser extent, they affect blood sugar levels.

In connection with the blockade of β 1 -adrenergic receptors, these substances weaken and slow down the contractions of the heart, reduce the secretion of renin.

Apply β 1 -blockers for angina pectoris, cardiac arrhythmias, arterial hypertension.

For short-term treatment can be applied metoprolol(Metoprolol; betaloc), talinolol(Talinolol; cordanum), which act for 6-8 hours and are prescribed 3 times a day (they produce metoprolol tablets with a delayed release of the drug - retard tablets, which are prescribed 1 time per day).

For systematic long-term treatment, it is recommended to use atenolol, betaxolol, bisoprolol, nebivolol. These drugs are prescribed 1 time per day.

Atenolol(Atenolol; tenormin), unlike propranolol, is a hydrophilic compound, poorly penetrates the blood-brain barrier and, therefore, has less effect on the central nervous system. Valid for 24 hours. Used for arterial hypertension, angina pectoris, myocardial infarction, supraventricular tachyarrhythmias.

Betaxolol(Betaxolol; lokren) acts for about 36 hours. It is used for arterial hypertension.

In the form of eye drops (1 drop 2 times a day), betaxolol (Betoptik drug) is used for open-angle glaucoma. After instillation of a solution of betaxolol into the conjunctival sac, intraocular pressure begins to decrease after 30 minutes, the maximum effect is achieved after 2 hours; duration of action - about 12 hours.

bisoprolol(Bisoprolol; Concor) is used for arterial hypertension, angina pectoris, supraventricular arrhythmias, chronic heart failure (together with ACE inhibitors).

Nebivolol(Nebivolol; nebilet) is a cardioselective β-blocker with vasodilating properties. The drug is a racemate: the D-isomer has a β 1 ​​-adrenergic blocking effect, and the L-isomer is a vasodilator (promotes the release of NO from the endothelium). Reduces the strength and frequency of contractions of the heart, total peripheral vascular resistance, blood pressure. It has antiplatelet, antioxidant, anti-atherosclerotic properties. Virtually no effect on bronchial tone, lipid and carbohydrate metabolism; no withdrawal syndrome. Nebivolol is prescribed orally 1 time per day for arterial hypertension (the effect develops within 2-5 days) and angina pectoris.

Esmolol(Esmolol; breviblok) - short-acting β 1 -blocker ( t 1/2 - 9 min). After intravenous administration, the action appears after 2 minutes and stops after 15-20 minutes. The short duration of action is associated with the rapid hydrolysis of esmolol by esterases of the erythrocyte cytosol. Esmolol solution is administered intravenously as a bolus or drip for supraventricular tachyarrhythmias (atrial fibrillation, atrial flutter), including when flicker (fibrillation) or atrial flutter occurs during or after surgical operations (to normalize the rhythm of ventricular contractions).

β-blockers with intrinsic sympathomimetic activity

β-blockers with intrinsic sympathomimetic activity, in particular pindolol(Pindolol; whisken), - do not, in fact, belong to β-blockers. These substances weakly stimulate β 1 - and β 2 -adrenergic receptors, that is, they are partial agonists of these receptors. Since partial agonists interfere with the action of full agonists, these substances weaken the action of full agonists - norepinephrine and epinephrine on β-adrenergic receptors. In this case, the same effects occur as with the action of true β-blockers. The stronger the influence of sympathetic innervation, the more pronounced the blocking effect of these drugs. On the contrary, with a low tone of sympathetic innervation, these substances are not very effective.

Of practical importance is the fact that β-blockers with internal sympathomimetic activity do not cause excessive bradycardia, to a lesser extent than non-selective β-blockers, increase bronchial tone, peripheral vascular tone and less enhance the effect of hypoglycemic agents.

Apply β-blockers with internal sympathomimetic activity in arterial hypertension and angina pectoris.

β 1 -blockers with intrinsic sympathomimetic activity include acebutolol and celiprolol.

Acebutolol(Acebutolol) - β 1 -blocker with internal sympathomimetic activity. At rest, it has little effect on the strength and frequency of heart contractions. When sympathetic influences are activated (physical or emotional stress), it reduces the strength and frequency of heart contractions, reduces myocardial oxygen demand. In medium doses, acebutolol does not significantly affect the tone of the bronchi and peripheral vessels. The drug is prescribed orally 1-2 times a day for arterial hypertension, exertional angina pectoris, tachyarrhythmias and extrasystole.

Celiprolol(Celiprolol) - β 1 -blocker with internal sympathomimetic and weak α 1 -blocking activity. Assign inside 1 time per day for arterial hypertension.

α-, β-blockers

Carvedilol(Carvedilol; dilatrend) blocks β 1 -, β 2 - adrenoreceptors and, to a lesser extent, α-adrenergic receptors.

In connection with the blockade of agadrenoreceptors, it quickly reduces blood pressure, and due to the blockade of β-adrenergic receptors, it does not cause tachycardia.

Has antioxidant properties.

Carvedilol is prescribed orally 1-2 times a day for arterial hypertension, stable angina pectoris, and also for moderate chronic heart failure.

Side effects of carvedilol:

- bradycardia;

- orthostatic hypotension;

- dizziness;

- urination disorder;

- diarrhea.

In addition to carvedilol, this group of drugs includes labetalol (Labetalol).

Sympatholytics

Sympatholytics are substances that block sympathetic innervation at the level of noradrenergic fiber endings. The mechanisms of blockade of the endings of noradrenergic fibers in different sympatholytics are different, but the end result of their action is the same: sympatholytics reduce the release of the mediator - norepinephrine - from noradrenergic nerve endings.

Unlike adrenoblockers, sympatholytics do not affect adrenoreceptors and do not weaken the action of adrenomimetics. On the contrary, against the background of sympatholytics, adrenomimetics act more strongly than usual, since with a decrease in the release of the mediator, the number of adrenoreceptors increases.

By blocking noradrenergic nerve endings, sympatholytics eliminate the stimulating effect of sympathetic innervation on the heart and blood vessels. As a result, there is a weakening and slowing of the contractions of the heart, the expansion of blood vessels - blood pressure decreases.

With the blockade of sympathetic innervation by sympatholytics, the influences of parasympathetic innervation become predominant. This can be manifested by bradycardia, stimulation of peristalsis of the gastrointestinal tract, increased secretion of the gastric glands.

Sympatholytics include guanethidine and reserpine.

Guanethidine(Guanethidine; octadin, ismelin) is an effective long-acting antihypertensive drug. The drug is administered orally 1 time per day. In this case, the hypotensive effect develops gradually, reaches a maximum on the seventh to eighth day of treatment and after discontinuation of the drug lasts up to two weeks.

The mechanism of sympatholytic action of guanethidine is associated with its ability to be captured by the endings of noradrenergic fibers. Guanethidine penetrates the vesicles and displaces norepinephrine from them. Accumulating in vesicles, guanethidine prevents the synthesis of norepinephrine. The action of guanethidine on vesicles is irreversible. Thus, guanethidine causes a significant depletion of norepinephrine stores in noradrenergic nerve endings, which leads to a weakening of the effects of sympathetic innervation.

The action of guanethidine with systematic use develops within a few days, since in order to disrupt noradrenergic transmission, it is necessary to reduce the reserves of norepinephrine in the endings of adrenergic fibers by more than half. After stopping the drug, the effect lasts up to two weeks (the time required for the formation of new vesicles).

Guanethidine reduces intraocular pressure.

Guanethidine does not affect the level of catecholamines in the adrenal glands, since they do not have a neuronal reuptake mechanism. Guanethidine does not affect the central nervous system, as it does not penetrate the blood-brain barrier.

Despite the high efficiency of guanethidine, its use is limited by side effects:

- severe orthostatic hypotension;

- bradycardia;

- nasal congestion;

- an increase in the secretion of HCl;

- diarrhea;

- violation of ejaculation.

With pheochromocytoma, guanethidine does not reduce, but increases blood pressure.

Tricyclic antidepressants interfere with the action of guanethidine by interfering with the uptake of guanethidine by noradrenergic endings.

Guanethidine is used only in severe forms of arterial hypertension.

Guanethidine eye drops are used in primary open-angle glaucoma.

Reserpine(Reserpine) is a rauwolfia alkaloid (a plant native to India).

Reserpine has the ability to accumulate in the membranes of vesicles at the endings of noradrenergic fibers. Wherein:

1) the entry of dopamine into the vesicles is disrupted, and, consequently, the synthesis of norepinephrine is reduced;

2) the reuptake of norepinephrine by vesicles is hindered.

As a result, the content of norepinephrine in the endings of noradrenergic fibers decreases, as a result of which the transmission of excitation in noradrenergic synapses is disrupted - the effects of sympathetic innervation decrease (Fig. 35).

Rice. 35. The mechanism of action of reserpine. Reserpine is deposited in vesicle membranes and prevents dopamine (DA) entry and norepinephrine (NA) reuptake by vesicles.

The action of reserpine on vesicles is irreversible, and after discontinuation of the drug, its effect persists for up to two weeks (the time required for the formation of new vesicles).

In connection with the suppression of the influences of sympathetic innervation, the influences of parasympathetic innervation functionally predominate. This is manifested by symptoms such as miosis, bradycardia, increased secretion of the gastric glands, increased gastrointestinal motility.

Unlike guanethidine, reserpine reduces the content of catecholamines (adrenaline and norepinephrine) in the adrenal glands.

Unlike guanethidine, reserpine penetrates the blood-brain barrier and reduces the content of norepinephrine, dopamine and serotonin (5-hydroxytryptamine) in the central nervous system.

Due to the decrease in the level of norepinephrine in the central nervous system, reserpine has a sedative effect.

A decrease in dopamine levels is manifested by a weak antipsychotic effect, parkinsonism, an increase in prolactin secretion and an associated decrease in the secretion of gonadotropic hormones.

A decrease in serotonin and norepinephrine levels can lead to the development of depression.

According to the ability to reduce blood pressure, reserpine is inferior to guanethidine, but it corresponds to the duration of action. The drug is used in mild forms of arterial hypertension.

Reserpine is generally well tolerated by most patients. Unlike guanethidine, it practically does not cause orthostatic hypotension. The drug can be prescribed for a long time (addiction to reserpine does not develop).

However, with the systematic appointment of reserpine, some patients may have side effects:

Subjectively unpleasant sedative effect (absent-mindedness, inability to concentrate);

Drowsiness;

Depression;

The phenomena of parkinsonism;

Gynecomastia;

Impotence;

Ovarian cycle disorders;

Nasal congestion;

dry mouth;

Increased secretion of the glands of the stomach (contraindicated in peptic ulcer disease);

If signs of depression appear, the drug should be discontinued. To reduce the symptoms of reserpine depression, MAO inhibitors are used.

At the same time, against the background of the action of MAO inhibitors, reserpine should not be used. Reserpine prevents the uptake of norepinephrine by vesicles. Therefore, when MAO is inhibited, norepinephrine accumulates in the cytoplasm of noradrenergic endings, is released from the endings, and has a stimulating effect on postsynaptic adrenoreceptors. In this regard, against the background of MAO inhibitors, reserpine acts paradoxically: it does not reduce, but increases blood pressure, it has not a sedative, but an exciting effect.