“Adrenoblockers. Simpatholitics "

Drugs blocking adrenergic receptors

adrenoceptor blocking agents

Blocking α-adrenergic receptors

Tropafen (α1, α2) Phentolamine (α1, α2)

Dihydroergotoxin (α1, α2) Prazosin (α1)

Blocking the β-adrenergic receptors

Inderal (β1, β2) metoprolol, atenolol, talinolol (β1)

Blocking α- and β-adrenergic receptors

Labetalol (β1, β2, α1)

Means blocking adrenergic receptors (blockers)Adrenergic blockers blocking, inhibiting action to them mediator (norepinephrine), and adrenomimetic substances. The synthesis of

norepinephrine blockers do not affect.Means blocking the α-adrenergic receptors

(α-blockers)The presence of α-adrenoceptor blocking agents effect is easily detected by their ability to reduce the pressor effect of epinephrine or "pervert"

him. Last seen in the fact that on the background of α-blockers adrenaline does not increase blood pressure, and reduces it. This is due

to the fact that against the background of a block-adrenoceptor stimulating effect is the effect of adrenaline on the β-adrenergic

receptors vessels, accompanied by their extension (reduced smooth muscle tone). Synthetic drugs that block α1- and α2-adrenergic

receptors, and phentolamine are thropaphen.

Phentolamine (regitin) is a derivative of imidazoline. Character-ized by severe, but short-lived α-adrenoceptor blocking action (10-15 min after intravenous injection). Furthermore, tachycardia (partly due to block presynaptic α2-adrenoceptor), increases the motility of the gastrointestinal tract, increased secretion of gastric glands and miotropnoe exerts vasodilating action. Lowers blood pressure phentolamine, due to its α-adrenergic blocking miotropnym and antispasmodic action.

Phentolamine (regitin) is a derivative of imidazoline. Character-ized by severe, but short-lived α-adrenoceptor blocking action (10-15 min after intravenous injection). Furthermore, tachycardia (partly due to block presynaptic α2-adrenoceptor), increases the motility of the gastrointestinal tract, increased secretion of gastric glands and miotropnoe exerts vasodilating action. Lowers blood pressure phentolamine, due to its α-adrenergic blocking miotropnym and antispasmodic action.

For a semi-synthetic drugs include di-ergot alkaloids - dihydroergotoxin and dihydroergotamine.Dihydrogenated ergot alkaloids are characterized by a more pronounced natural α-adrenoceptor blocking effect, no stimulating effect on the myometrium (pregnant uterus) less vasoconstrictor activity and lower toxicity.

In medical practice, drugs that block the α1 and α2-adrenergic receptors, use relatively rare. The most important effect of α-blockers is to expand the peripheral vessels. Since it involves the use of these drugs for various violations of the peri-periph- eral circulation (endarteritis, Raynaud's disease, and others.), Including the shock (hemorrhagic, cardiogenic), in which the spasm of the arterioles - a fairly typical phenomenon. Logical assignment α-blockers in pheochromocytoma. Sometimes α-blockers are used in hypertensive crises.

Considered drugs block as post-and presynaptic α-adrenergic receptors (α1- and α2-). Keep in mind that block the presynaptic α2-adrenoceptor violates physiological autoregulation products neurotransmitter norepinephrine. As a result of violation of a negative feedback occurs excessive release of norepinephrine, the recovery of the adrenergic transmission. The latter explains the lack of resistance block postsynaptic α1-adrenoceptor antagonists using indiscriminate effects (blockers α1- and α2- adrenoreceptors). Marked tachycardia is also a result of increased release of norepinephrine. From this point of view to practical medicine more interesting blockers that block predominantly postsynaptic α1-adrenergic receptors. Thanks functioning presynaptic α2-adrenoceptor retained a negative feedback mechanism and, therefore, increased noradrenaline release does not occur. Thus, the block of postsynaptic α1-adrenoceptor sta¬novitsya more stable. Furthermore, there is no marked tachycardia.

The drugs have an advantageous effect on the postsynaptic α1-adrenergic receptors, is prazosin (pratsiol, minipress). By blocking the activity of phentolamine exceed about 10 times. The main effect of prazosin - lowering blood pressure. This effect is due to decreased arterial tone and to a lesser extent of venous vessels, venous return and decrease in heart function. Heart rate changes little (may be a slight tachycardia). There are data on the inhibitory effect of prazosin on phosphodiesterase.The drug is effective when administered orally. Its action comes in 30-60 minutes and lasts for 6-8 hours.Prazosin is used as an antihypertensive agent. Assign it usually on the inside (possibly parenteral administration).

Means blocking the β-adrenergic receptors (β-blockers)The most widely used β-blocker is a n a n Reelin (propranolol hydrochloride, Inderal, obzidan, stobetin). It blocks β1 and β2-adrenergic receptors (heart and blood vessels, bronchi, gastrointestinal tract, etc.).Blocking β1-adrenergic receptors of the heart, propranolol causes bradycardia and reduces the force of heart contractions, in connection with which cardiac output is reduced. Depresses atrioventricular conduction reduces automaticity.Blood pressure is reduced upon administration of propranolol, particularly during chronic administration. This is due to some extent to the decrease in cardiac output. Total peripheral resistance generally tends first to increase and then decrease. Against the background of the introduction of propranolol pressor effect of adrenaline becomes similar to that of norepinephrine, because it eliminates the final phase (lowering blood pressure) associated with β2-adrenergic stimulation vessels. The hypotensive effect of propranolol is also due to a decrease in production of renin.

Inderal increases the tone of the bronchi and may provoke bronchospasm (the result of β2-adrenergic receptors block the bronchi). An antagonist in relation to its adrenalin hyperglycemic and lipolytic action.Inderal is used in the treatment of angina pectoris (β1-adrenoceptor block leads to a reduction of the heart, which reduces its oxygen demand), hypertension (duration of treatment is accompanied by a gradual and sustained reduction in blood pressure). Inderal is shown at supraventricular, such as atrial fibrillation (as a result of the oppression of β1-adrenoceptor Inderal reduces the automatism and increases the duration of the excitation from the atria to the ventricles). Inderal is used to eliminate tachycardias different etiology (in mitral stenosis, thyrotoxicosis), and arrhythmias induced by agonists or digitalis glycosides. Using Inderal and glaucoma.

Possible side effects: heart failure, heartunit, increased tone of peripheral vessels, bronchospasm. With PICs-vanced prescribed Inderal diabetics, because it prolongs the drug hypoglycemia.By blockers β1 and β2-adrenergic receptors is also oxprenolol (trazikor, koretal) and a number of other drugs. Synthesized compounds blocking β1-adrenergic receptors primarily heart. One of them - metoprolol (betalok, seloken). Β2-adrenergic receptors on the bronchi, vessels had little effect. These drugs are usually referred to as cardioselective (β1) blockers.Metoprolol absorbed from the intestine well, but when passing through the liver, a significant part of it is destroyed. The maximum effect is approximately 1½ hours and lasts about 5-6 hours. Provided kidneys mainly as metabolites.Metoprolol is used orally for hypertension. The side effects observed headache, fatigue, sleep disturbance. In bronchial asthma may slightly increase the tone of the bronchi.

Means blocking the α- and β-adrenergic receptors (α, β-blockers)Drugs that block both types of adrenergic receptors is labetalol (trandat). He also inhibits the neuronal uptake of noradrenaline reverse. β-Adrenoceptors labetalol more sensitive than the α-adrenergic receptors. On ability to block β-adrenergic receptors inferior anaprilinu and oppression by α-adrenergic receptors - phentolamine. Reduces the total peripheral vascular resistance. Labetalol is well absorbed when given enterally. Much of it is destroyed by the first passage through the liver. Valid for 8- 10 hours. Provided kidneys (mainly as metabolites). Labetalol is used as an antihypertensive agent.

TOOLS presynaptic active agent, inhibits the transfer of excitation to adrenergic neurons (sympatholytic)Simpatolitiki violate the transfer of excitation at the level of varicose nodules adrenergic fibers, t. E. Pre-synaptic function. Adrenoretseptory not affect. Against the background of these substances agonists direct effect not only reduced, but even increased. Thus, sympatholytic and blockers have a blocking effect on the different stages of the adrenergic nerve impulse transmission.

By Simpatolitiki are oktadin, reserpine, ornid et al. Acting on varicose thickening of adrenergic nerve fibers, these substances reduce the amount of the neurotransmitter norepinephrine, released on nerve impulses. Indirect action agonists (tyramine, ephedrine, amphetamine) in their background are weaker than normal. Keep in mind that the mechanism of action of different simpatolitikov varies. Among active simpatolitikov refers guanidine derivatives - oktadin (guanethidine sulfate, ismelin, izobarin, sanotenzin, abapressin). Its ability to inhibit the transmission of excitation from adrenergic nerves in the effector for the following reasons.

Initially, when the content of norepinephrine in the varicose bulges are not reduced, this can be attributed to the blocking effect of the drug on presynaptic membrane and disrupting the release of neurotransmitter. Gradually, under the influence of oktadin noradrenaline in varicose thickening decreases. Attribute this to the fact that oktadin prevents norepinephrine reuptake varicose bulges, as he undergoes oktadin neuronal uptake due to the same transport systems, and norepinephrine. In intraneyronalnyh depot oktadin also replaces norepinephrine. There are also a depressing effect on the membrane vesicles oktadin and violation of the deposit process norepinephrine. All this leads to the fact that the located free in the cytoplasm norepinephrine largely inactivated by monoamine oxidase (intraneyronalno) and partially released from varicose thickenings unchanged.

As a result, on the background of accumulation in varicose thickening oktadin content of norepinephrine significantly reduced. Therefore, in response to the number of nerve impulses released neurotransmitter into the synaptic cleft decreases, resulting in a reduction reaction of the effector. Noted umenshe¬nie content of norepinephrine in the heart, blood vessels and other organs.Oktadin little effect on the level of catecholamines in the central nervous system (does not penetrate the blood-brain barrier) and the adrenal medulla.The main effect is gradually developing oktadin (for several days) sustained reduction in blood pressure. This is due to a decrease in cardiac output, the occurrence of bradycardia, inhibition of pressor reflexes. With prolonged use may decrease oktadin and total peripheral vascular resistance. Oktadin also provides short-term ganglion-blocking action and a stimulating effect on β2-adrenergic receptors vessels.

Hypotension can be preceded by a short (a few minutes to 1 hour or more) increase in blood pressure caused by the release of norepinephrine from adrenergic endings, which leads to an increase in cardiac output and vasoconstriction. Oktadin affects the eyes. It appears a small contraction of the pupil and the reduction of intraocular pressure. The latter is obviously the result of improvement of outflow from the anterior chamber of the eye and reduce production of intraocular fluid.In connection with the blocking effect on adrenergic innervation oktadin motility of the gastrointestinal tract increases. With the introduction of oktadin been a slight depression of neuromuscular transmission.Enter the oktadin inside. Thus 50% of absorbed substance. Through the blood-brain barrier drug penetrates poorly. Biotrans-formation occurs in the liver substance. Unchanged oktadin and its metabolites are excreted primarily by the kidneys.

Expressed sympatholytic properties has rezerpin- alkaloid plants of the genus Rauwolfia (Rauwolfia serpentina Benth. Et al.). Chemically an indole derivative.Reserpine disrupts the deposit of norepinephrine in the vesicles, which leads to a decrease in the content of norepinephrine in the varicose bulges. The main part of

accumulated within the cytoplasm of varicose thickenings free norepinephrine deaminated as reserpine (as well as oktadin) does not inhibit monoamine oxidase.

A small portion of norepinephrine released from the endings unchanged. In reverse the neuronal uptake of noradrenaline reserpine apparently not affected.

Reserpine reduces the amount of norepinephrine in the heart, blood vessels, adrenal medulla and other organs. Reduced levels of catecholamines (and

serotonin) also observed in the central nervous system. As a result, the central nervous system reserpine has a depressing effect. Reserpine has a calming

(sedative) and weak antipsychotic action, in connection with which it also refers to a group of neuroleptics. Promotes sleep. Suppresses interoceptive reflexes.

Enhances the effect of sleeping pills and anesthetic drugs. Several depresses respiration, body temperature lowers.

As neuroleptic reserpine now rarely used. The greatest practical importance is the hypotensive effect due to its peripheral (sympatholytic) effects.Arterial blood pressure when administered reserpine gradually decreases (the maximum effect is observed in a few days). Hypotension during chronic administration of reserpine associated with decreased cardiac output and a decrease in total peripheral resistance and inhibition of the pressor reflex. Ganglioblokiruyuschimi adrenoceptor blocking properties and reserpine does not possess. Effect of reserpine on vasomotor centers of most authors is denied, as in the experiment reserpine does not reduce the efferent impulses in pregan-glionarnyh fibers adrenergic (sympathetic) innervation.Inhibition of reserpine adrenergic innervation leads to transformations incense-cholinergic effects. This is manifested by bradycardia, increased secretory and motor activity of the gastrointestinal tract, myositis.

It is also Simpatolitiki monochetvertichnoe ammonium compound ornid (bretylium). It is different mechanism of action from oktadin and reserpine. Basically blocks presynaptic membrane, disrupting the release of neurotransmitter. Ornid inhibits monoamine oxidase. In addition, it inhibits the reuptake of norepinephrine. For short application Ornid noradrenaline in varicose thickening adrenergic fibers may not change, long-term use is reduced. The duration of action is considerably less than oktadin and reserpine (5-8 hr.).

Apply oktadin and reserpine mainly in the treatment of hyper-pertonicheskoy disease. Oktadin as a hypotensive agent is more effective than reserpine. Oktadin sometimes prescribed for glaucoma. Getting used to oktadin and reserpine develops very slowly, which is a great advantage of these drugs to others, as they are usually used for a long time. Ornid as antihypertensive agent is not used, because of the digestive tract it is poorly absorbed and it quickly develops addictive. In some cases ornid prescribed for heart arrhythmias.

Side effects when using oktadin and reserpine manifest increase intestinal motility (relatively often diarrhea) and the secretion of digestive glands (especially the stomach), bradycardia; note the number of patients in pain parotid gland swelling of the mucous membranes of the nasal cavity; typically there is a delay in the body fluid. Orthostatic collapse may occur when using oktadin (but much less frequently than in the appointment ganglioblokatorov) and practically not observed when using reserpine to treat hypertension (sometimes arises in the treatment of mentally ill patients with high doses of the drug).

In the application of reserpine possible side effects associated with the influence of the drug on the central nervous system: drowsiness, weakness. With prolonged use of the substance in large doses may experience depression, rarely - extrapyramidal disorders. Increased appetite also has central origin.

Increase on the background of simpatolitics secretion of digestive glands, as well as bradycardia can eliminate drugs of atropine. Stimulating effect on intestinal motility sometimes negate combination with ganglioblokatorami that reduce the motor activity of the gastrointestinal tract. Antagonists against reserpine its inhibitory effect on the central nervous system are inhibitors of monoamine oxidase (nialamide), restoring the balance of catecholamines and serotonin in the brain tissues. When extrapyramidal disorders appoint agents, effective in the treatment of Parkinson's disease (eg, tsiklodol).