Side effects of ganglion blockers. Introduction, Ganglioblockers - Ganglioblockers. Curariform agents. Muscle relaxants. Classification by mechanism of action

These drugs cause blockade of conduction in the autonomic ganglia without a previous phase of excitation. Substances of very different chemical structures belong to this group; some examples are shown in fig. 9.6.

History reference. Structural-functional dependence

Figure 9.6. Structural formulas of ganglioblockers.

Despite the fact that the "anticotinic" effect of tetraethylammonium on the autonomic ganglia was first described by Marshall in 1913 (Marshall, 1913), this compound was not given much attention for a long time. Only in 1946 Aikson and My (Ache-son and My, 1946) published a work with a detailed analysis of the action of tetraethylammonium on the cardiovascular system and autonomic ganglia. Bisquaternary ammonium bases have been independently developed and studied by Barlow and Ing (1948) and Paton and Zaimis (Paton and Zaimis, 1952). A typical representative of these compounds - hexamethonium - consists of two quaternary nitrogen atoms linked by a palimethylene chain of 6 carbon atoms (Fig. 9.6). Its influence on skeletal muscles and M-cholinergic receptors is insignificant.

Triethylsulfonium compounds, such as trimetafan camsilate, also have a ganglioblocking effect (Fig. 9.6). In the mid 1950s. The secondary amine mecamylamine was introduced as an antihypertensive agent.

Pharmacological properties

Almost all the effects of ganglion blockers can be predicted based on the direction (Table 6.1) and severity (Table 9.4) of the effects of the autonomic nerves on the internal organs. Thus, the blockade of the sympathetic ganglia leads to the elimination of the vasoconstrictive sympathetic tone and, as a result, to vasodilation, a decrease in blood pressure, and in some cases to an improvement in the blood supply to certain organs.

With systemic action, ganglioblockers can cause atony of the bladder and intestines, accommodation paralysis, dry mouth, decreased sweating and (due to suppression of hemodynamic reflexes) orthostatic hypotension. These side effects severely limit the clinical use of ganglion blockers.

The cardiovascular system. The hypotensive effect of ganglion blockers depends primarily on the vasoconstrictor sympathetic tone. So, in persons with normal blood pressure in the supine position, ganglioblockers almost do not have a hypotensive effect, but in the sitting or standing position this effect is pronounced. The main side effect of ganglion blockers in non-bedridden patients is orthostatic hypotension. It is relieved to some extent with physical exertion and completely eliminated with the transition to bed rest.

Changes in heart rate under the action of ganglioblockers largely depend on the tone of the vagus nerves. In humans, orthostatic hypotension is accompanied by moderate tachycardia, which indicates incomplete ganglionic blockade. If the initial heart rate was high, then ganglionic blockers can cause it to decrease.

In patients with normal cardiac function, ganglionic blockers often cause a decrease in cardiac output. The reason is a decrease in venous return due to the expansion of the veins and peripheral accumulation of blood. On the contrary, in heart failure, cardiac output under the action of ganglionic blockers often increases due to a decrease in peripheral vascular resistance. In patients with arterial hypertension, cardiac output, stroke volume and left ventricular work are reduced.

Although OPSS decreases under the influence of ganglioblockers, the vascular resistance of different organs (and, accordingly, the blood supply to these organs) changes in different ways. Cerebral blood flow almost does not decrease until blood pressure falls below 50-60 mm Hg. Art. The blood supply to skeletal muscles also does not change, while renal blood flow and blood flow in the gastrointestinal tract decrease.

Pharmacokinetics

Absorption of quaternary ammonium and sulfonium bases from the gastrointestinal tract is incomplete and unpredictable, both because of the low membrane permeability for these compounds and because they inhibit intestinal motility and the evacuation of gastric contents. Mecamylamine is better absorbed, but can cause intestinal atony up to paralytic ileus.

After entering the blood, quaternary ammonium and sulfonium bases reside mainly in the extracellular space and are removed mainly unchanged by the kidneys. Mecamylamine accumulates in the liver and kidneys and is also excreted unchanged, but slowly.

Side effects

Moderate side effects of ganglioblockers include visual disturbances, dry mouth, conjunctival hyperemia, difficulty initiating urination, decreased potency, chilliness, mild constipation (sometimes diarrhea), abdominal discomfort, decreased appetite, heartburn, nausea, belching, and a bitter taste in the mouth. , as well as the first signs of pre-syncope conditions due to orthostatic hypotension. More severe side effects are severe orthostatic hypotension with fainting, paralytic ileus, urinary retention, accommodation paralysis.

Table 9.4. Autonomic nerve tone and effects of ganglionic blockers

	Dominant tone	Effects of ganglionic blockers
Argerioles	Sympathetic	Expansion, decrease in OPSS, decrease in blood pressure
	Sympathetic	Dilation, peripheral blood pooling, decreased venous return, decreased cardiac output
	Parasympathetic	Tachycardia
Pupil sphincter	Parasympathetic	pupil dilation
ciliary muscle	Parasympathetic	Accommodation paralysis (focusing on distant objects)
	Parasympathetic	Decreased tone and peristalsis, constipation, decreased secretion of the stomach and pancreas
Bladder	Parasympathetic	Urinary retention
Salivary glands	Parasympathetic	Dry mouth
sweat glands	Sympathetic cholinergic	Anhidrosis
Sex organs	Sympathetic	Decreased sexual reflexes

Application

Of all the ganglion blockers ever used in the United States, only mecamylamine and trimethaphan camsylate are now used.

As antihypertensive agents for continuous use, ganglioblockers have given way to more effective and safe drugs (Ch. 33). In hypertensive crisis, other drugs are also usually used (Murphy, 1995; see also Ch. 33), although sometimes - for example, as the first remedy for a rapid decrease in blood pressure in aortic dissection, especially with contraindications to p-blockers, ganglionic blockers are administered. (Varon and Marik, 2000). The advantages of ganglioblockers in such cases are due to the fact that they reduce not only blood pressure, but also (due to the elimination of sympathetic tone) the rate of its increase in the area of delamination. When dissecting the aorta, trimetafan camsilate is administered by intravenous infusion at a rate of 0.5-3 mg/min with constant monitoring of blood pressure. If there are no signs of ischemia of the kidneys, heart and brain, then the infusion rate is increased until the blood pressure normalizes. A sign of the cessation of delamination is the disappearance of pain. The disadvantage of trimetafan camsylate is the development of addiction to it within 48 hours; this habituation is partly due to fluid retention.

Ganglion blockers are also used for controlled arterial hypotension in surgery: lowering blood pressure reduces blood loss and facilitates manipulations on blood vessels (Fukusaki et al., 1999). At the same time, trimetafan camsylate infusion is used instead of sodium nitroprusside or simultaneously with it: firstly, some patients do not respond to sodium nitroprusside, secondly, trimetafan camsylate blocks the increase in sympathetic tone caused by sodium nitroprusside, and, thirdly, this combination reduces dose of sodium nitroprusside (Fahmy, 1985).

Finally, trimetafan camsylate is used for autonomic hyperreflexia. This condition is commonly seen in patients with high spinal cord interruption. At the same time, there is no control of spinal sympathetic reflexes from higher centers, and a sharp reflex increase in sympathetic tone periodically occurs.

Literature

Acheson, G.H., and Mine, G.K. The action of tetraethylammonium ion on the mammalian circulation. J Pharmacol. Exp. Then, 1946, 87:220-236.
Adams, P.R., Brown, D.A., and Constanti, A. Pharmacological inhibition of the M-current. J. Physiol., 1982, 332:223-262.
Drenck, N.E., Lfeda, N., Olsen, N.V., Engbaek, J., Jensen, E., Skov-gaard, L.T., and Viby-Mogensen, J. Manual evaluation of residual curari-
Katz, B., and Thesleff, S. A study of the "desensitization' produce! ! by acetylcholine at the motor end-plate. J. Physiol. (Lond.), 1957,13J-63-80.
Langley, J.N., and Dickinson, W.L. On the local paralysis of peripheral j ganglia, and on the connexion of different classes of nerve fibers with them. Proc. R. Soc. Lond. , 1889, 46:423-431.
Marshall, C.R. Studies on the pharmaceutical action of tetra-alkyl-ammonium compounds. Trans. R. Soc. Edinb., 1913, 1:17-40.
Primo-Parmo, S.L., Bartels, C.F., Wiersema, B., van deer Spek, A.F., Innis, J.W., and La Du, B.N. Characterization of 12 silent alleles of the human butyrylcholinesterase (BCHE) gene. Am. J. Hum. Genet., 1996, 58:52-64.
Sine, S.M., and Claudio, T. y- and 8-subunits regulate the affinity and cooperativity of ligand binding to the acetylcholine receptor. J Biol. Chem. 1991.266:19369-19377.

Ganglion blockers block H-cholinergic receptors of neurons of sympathetic and parasympathetic ganglia and thus disrupt the transmission of excitation from preganglionic to postganglionic fibers. As a result, the influence of both sympathetic and parasympathetic innervation on effector organs and tissues is reduced or eliminated. In addition, ganglion blockers block the H-cholinergic receptors of the chromaffin cells of the adrenal medulla, reducing the release of adrenaline and noradrenaline, as well as the H-cholinergic receptors of the carotid glomeruli, which prevents reflex excitation of the respiratory and vasomotor centers.

The blockade of the ganglia of the sympathetic system leads to a decrease in the stimulating effect of the sympathetic system on the heart and vascular tone (arteries and veins), while the stroke volume decreases, the arteries and veins expand - as a result, arterial and venous pressure decreases. A decrease in the release of adrenaline and norepinephrine by the adrenal glands under the influence of ganglionic blockers also helps to reduce arterial and venous pressure.

The blockade of the ganglia of the parasympathetic system leads to a violation of accommodation (accommodation paralysis), an increase in heart contractions (tachycardia), a decrease in the tone of the smooth muscles of the gastrointestinal tract and bladder, and inhibition of the secretion of the salivary, bronchial glands, glands of the stomach and intestines. Unlike M-cholinoblockers, ganglioblockers dilate pupils to a lesser extent and do not significantly affect bronchial tone.

Currently, in medical practice, mainly the hypotensive effect of ganglionic blockers is used. The drugs of this group are used to relieve hypertensive crises (rapid pressure reduction), with pulmonary edema against the background of high blood pressure, with spasm of peripheral vessels. Short-acting ganglioblockers are used in surgical operations for controlled hypotension. Substances are administered intravenously by drip, while lowering blood pressure helps to reduce bleeding from the vessels of the surgical field, and during neurosurgical operations it prevents the development of cerebral edema. In addition, in this way it is possible to reduce unwanted reflex reactions to the heart and blood vessels that occur during surgery.

Side effects of ganglion blockers are mainly associated with the blockade of the sympathetic and parasympathetic ganglia. Thus, the expansion of venous vessels associated with the blockade of sympathetic ganglia is the cause of orthostatic hypotension - a sharp decrease in blood pressure when the body position changes from horizontal to vertical. As a result, fainting may occur. To prevent this side effect after the introduction of a ganglion blocker, patients are advised to lie down for at least 1.5-2 hours. bubble. Reduced intestinal motility leads to obstipation and can even be the cause of paralytic ileus (intestinal obstruction), and decreased bladder tone leads to urinary retention. With such complications, M-cholinomimetic (aceclidine) or anticholinesterase (neostigmine) agents are administered. Due to severe side effects, ganglioblockers are not used for a long time.

With an overdose of ganglioblockers, hypotension develops, to eliminate which α-agonists are used, which increase blood pressure. The use of analeptics that restore breathing is shown.

Ganglioblockers are contraindicated in severe hypotension, shock, myocardial infarction, liver and kidney damage. Ganglion blockers should not be used in patients with angle-closure glaucoma, since due to pupil dilation, fluid outflow from the anterior chamber of the eye worsens, which can lead to an increase in intraocular pressure. Due to the slowing of blood flow, ganglionic blockers are contraindicated in patients with an increased tendency to thrombosis.

According to the chemical structure, ganglioblockers are divided into:

Bis Quaternary Ammonium Compounds: hexamethonium benzosulfonate (Benzohexonium), azamethonium bromide (Pentamine), trepyrium iodine (Higronium).

Sulfonium Compound: trimetafan camphorsulfonate (Arfonad).

Tertiary amines: pempidine tosylate (Pyrilene).

The bis-quaternary ammonium compounds and the sulfonium compound are hydrophilic polar substances and therefore are poorly absorbed from the gastrointestinal tract and do not penetrate the blood-brain barrier. They differ in duration of action. Hexamethonium and azamethonium, when administered intramuscularly and subcutaneously, act for 2-3 hours and are mainly used to relieve hypertensive crises. Trimethaphan and hygronium cause a short-term effect lasting 10-20 minutes. Therefore, these drugs are administered by intravenous drip for controlled hypotension.

The longest action (8-10 hours) has pempidine tosylate.

It is a tertiary ammonium compound (lipophilic non-polar substance) that is well absorbed when taken orally and penetrates the blood-brain barrier, therefore, with prolonged use, it can cause unwanted side effects from the central nervous system. Currently, the drug is rarely used.

These drugs block the action of acetylcholine and similar agonists on nicotinic receptors in both parasympathetic and sympathetic autonomic ganglia. Some members of the group also (or perhaps exclusively) block ion channels that are closed by nicotinic acetylcholine receptors. Due to their ability to block all autonomic pathways, ganglionic blockers are still of exceptional interest for pharmacological and physiological research. However, the lack of selectivity leads to such a wide range of side effects that these drugs are rarely used in the clinic.
Ganglioblockers include:
- Short-acting drugs (trimethophane kamsilat, hygroniy, imekhin);
- Drugs of medium duration of action (benzohexonium, pentamine).

Tab. Drug interactions of anticholinergics

main drug	co-administered drug	Type and level of interaction	Interaction mechanism	Result of interaction
Ganglioblockers	Indomethacin and its analogues		Decreased synthesis of vasodilating prostaglandins
	Pyrazolone derivatives (phenylbutazone)	FD, functional system of blood pressure regulation	Retention of Na+ ions and water	Decreased hypotensive effect
	Glucocorticosteroids	FD, functional system of blood pressure regulation	Retention of Na+ ions and water	Decreased hypotensive effect
	Thiazide diuretics	FD, functional system of blood pressure regulation	Excretion of Na+, K+ and water ions
	Adrenomimetics	PD, α and β adrenoreceptors	Antagonism due to stimulation of adrenergic receptors (narrowing of the vessels of the abdominal organs, skin, and to a lesser extent skeletal muscles)	Weakening of the action of ganglioblockers: an increase in the strength and frequency of heart contractions, an increase in blood pressure
	H1 - histamine blockers, hypnotics, antipsychotics, narcotic analgesics, tricyclic antidepressants, local anesthetics	PD, functional system of blood pressure regulation (CNS, peripheral vessels)	Synergy	Strengthening the hypotensive effect
	Anticholinesterase agents (prozerin, physostigmine, neostigmine methyl sulfate)	FD, cholinergic receptors	Antagonistic interaction: the blockade of H-cholinergic receptors of the autonomic ganglia is weakened by an indirect cholinomimetic effect due to the potentiation of the action of endogenous acetylcholine	Can be used in case of an overdose of ganglioblockers to reduce the effects caused by these drugs: accommodation disturbance, bronchial dilatation, decreased gastrointestinal motility, increased heart rate, decreased bladder tone, decreased blood pressure, etc. Can be used in case of an overdose of ganglioblockers to reduce the effects caused by these drugs: accommodation disturbance, bronchial dilatation, decreased gastrointestinal motility, increased heart rate, decreased bladder tone, decreased blood pressure
	N-cholinomimetics	FD, cholinergic receptors	Antagonistic interaction: blockade of H-cholinergic receptors of autonomic ganglia is weakened by direct cholinomimetic action	Can be used in overdose of ganglioblockers to reduce the pharmacodynamic effects caused by these drugs: disturbances of accommodation, bronchial dilatation, decreased motility of the gastrointestinal tract, increased heart rate, decreased bladder tone, decreased blood pressure
	Other antihypertensive drugs	FD, functional system of blood pressure regulation	Effect summation	Strengthening the hypotensive effect

In addition to the central nervous system in the human body, there is another one that controls the work of many internal organs. Relatively recently, scientists have developed a new group of chemicals called ganglion blockers. Drugs from this group can control the work of the autonomic nervous system, improve the patient's condition in many diseases.

Basic information

Thanks to numerous nerve endings, the autonomic system controls the activity of almost all internal organs (lungs, heart, intestines, etc.). The work of the autonomic nervous system itself is regulated by the brain. The transmission of nerve impulses is carried out thanks to special chemicals. In some clinical cases, it may be necessary to block the transmission of nerve impulses, that is, to suspend the production of these substances. This problem can be solved by ganglionic blockers.

Preparations can be short, medium and long-acting. Such agents are used in anesthesiology, for the treatment of complex cases of toxicosis of pregnant women, hypertension. However, the action of ganglioblockers is not always effective and may be accompanied by side effects. Therefore, it is absolutely impossible to use such drugs without consulting a doctor. Most drugs are not dispensed in pharmacies without a prescription.

"Higronium"

The drug is available in the form of a powder for the preparation of a solution. The drug is administered by injection intravenously or intramuscularly. You can’t just buy it at the Gigroniy pharmacy. The prescription must be written by the attending physician. Due to the ganglioblocking action, the drug is used in anesthesiology, when it is necessary to control the patient's pressure. In addition, the drug is used in obstetric practice. With its help, it is possible to stop attacks of eclampsia.

"Gigronium" has a number of contraindications. These include thrombosis, hypotension, acute myocardial infarction, renal or hepatic failure. In old age (after 65 years), the medication is used with caution. Some patients may develop hypersensitivity.

Ganglioblocking effect is observed already 5 minutes after intravenous administration of the drug and persists for 15-20 minutes. This is sufficient for short-term control of blood pressure (with simple surgical interventions).

"Azamethonium bromide"

The drug is a potent ganglionic blocker. The active ingredient selectively blocks autonomic nerve receptors. "Azamethonium bromide" is widely used in hypertensive crises, bronchial asthma, pulmonary and cerebral edema. With the help of the drug, it is possible to control blood pressure in anesthesiology, to normalize the condition of pregnant patients suffering from eclampsia.

The drug is used in the form of injections (intramuscularly or intravenously). The exact dosage is set by the doctor in accordance with the patient's disease, the individual characteristics of the body. In this case, contraindications must be taken into account. These include the following conditions: angle-closure glaucoma, central nervous system, impaired functioning of the kidneys and liver, acute period of myocardial infarction. The drug is used with caution in the elderly, as well as in patients suffering from bronchial asthma, thrombophlebitis.

"Gangleron"

Due to the blocking of vegetative impulses, the drug has an anesthetic and antispasmodic effect. With peptic ulcer of the stomach and duodenum, the remedy "Gangleron" is widely used. The instruction indicates that the drug can also be prescribed for angina pectoris, impaired mobility of the gastrointestinal tract. The medicine is administered intramuscularly or subcutaneously. The dosage is determined by the doctor.

The drug has its own contraindications, like other ganglionic blockers. Drugs of this type are not used for arterial hypotension, in the presence of degenerative changes in the central nervous system. In rare cases, hypersensitivity to the active ingredient may develop. In no case should the drug be administered intravenously. This can lead to a sharp drop in blood pressure.

"Benzohexonium"

The tool is considered one of the most popular in the treatment of arterial hypertension. Allows you to quickly stop the hypertensive crisis "Benzohexonium". Instructions for use indicate that the drug can also be prescribed for chronic gastritis, some forms of bronchial asthma, peptic ulcer of the stomach and duodenum. For the treatment of mild pathologies, Benzohexonium tablets are used. Instructions for use indicate that the drug is also available in the form of a solution for injection.

The drug is used to lower blood pressure in surgical practice (anesthetic effect). In this case, the drug is used in the form of a solution, it is administered intravenously. For the treatment of diseases of the stomach, a solution for intramuscular injection can be used.

Incorrect prem medication can lead to the development of side effects (weakness, dizziness, dry mouth). Deterioration of well-being is associated with a sharp decrease in blood pressure. The use of the drug is recommended to be carried out in a hospital, where the patient can be provided with timely assistance in case of collapse.

"Pentamine"

The drug has a pronounced hypotensive effect. The drug "Pentamine" is widely used in hypertensive crises. The instruction indicates that it is produced in the form of a solution for intramuscular or intravenous injection. The active ingredient is azomethonium bromide.

The drug is used in a hospital setting and can be prescribed for the following pathological processes: cerebral edema, pulmonary edema, a sharp increase in blood pressure, acute attacks of bronchial asthma, intestinal spasms, renal colic. To create controlled hypotension, Pentamine can also be used in anesthesiology. The instruction indicates that the medicine is dispensed exclusively by prescription.

The drug has the same contraindications as other ganglionic blockers. These are myocardial infarction, hypotension, thrombophlebitis, angle-closure glaucoma.

"Imekhin"

The drug produces a pronounced hypotensive effect, like other ganglionic blockers. Preparations from this group are widely used in surgical practice, as well as to relieve hypertensive crises. However, it will not be possible to remove high blood pressure with this medicine at home. The drug is used exclusively under the supervision of a physician. Means "Imekhin" is also used to treat swelling of the brain and lungs, relief of acute attacks of bronchial asthma.

The drug has many side effects. One of them is which is characterized by a sharp decrease in blood pressure when changing body position (from vertical to horizontal). In addition, during therapy, the patient may complain of dry mouth, general weakness, and frequent dizziness.

"Temekhin"

This ganglionic blocking agent is available in the form of tablets. The medicine is prescribed for Raynaud's syndrome, gastric and duodenal ulcers, arterial hypertension. The active ingredient produces a pronounced analgesic effect. Tablets are recommended to be taken after meals. The dosage and duration of the course of therapy are determined by the doctor.

Contraindications include the acute period of myocardial infarction, hypotension, liver and kidney damage, angle-closure glaucoma. The drug is not suitable for self-medication. You can buy pills only with a doctor's prescription.

Outcome

Ganglioblocking agents are indispensable in many areas of medicine. However, the use of drugs from this group should be strictly controlled by a specialist. An overdose can lead to serious side effects, even death. Therefore, ganglioblockers are used in hospitalization or in the provision of emergency medical care. It is impossible to use such drugs on your own even after carefully studying the instructions.

The main drugs-ganglioblockers are arfonad, benzohexonium, pentamine.

ARFONAD(Arfonad, BP - trimetaphan, camphorosulfamate) - a derivative of thiophane. In medical practice, 0.1 or 0.05% arfonad is most often used. To obtain the last 1 ml of the contents of the ampoule, add to 50-100 ml of 5% glucose or saline. It has a powerful ganglioblocking effect. By the strength of its inhibitory effect on the vegetative nodes, hexonium is 6 times superior. The inhibitory effect of arfonad and other ganglion blockers on the vegetative nodes is due to the fact that these drugs capture those receptors in the ganglia that are affected by acetylcholine, i.e. ganglion blockers are its competitors. Unlike other ganglioblockers, arfonad not only inhibits transmission in synaptic ganglia, but also has a direct effect on vascular smooth muscle. The latter is obviously the predominant one. In addition, arfonad promotes the release of histamine. By blocking the transmission of impulses from the vasomotor center and having a direct effect on the muscles of the vessels, arfonad causes the expansion of their walls, vasodilation, mainly of arteries, arterioles and venules. This reduces the rate of blood flow and the blood is deposited in the vessels of the underlying organs. Therefore, by applying a postural position, it is possible to achieve that in some parts of the body located above others, blood flow and bleeding will be significantly reduced. The pressure in the veins with the use of Arfonade has only a slight tendency to decrease. Therefore, venous bleeding with the use of arfonad is possible. Of great practical importance is the question of the permissible level of reduction in systolic pressure. The exchange of oxygen and carbon dioxide in the tissues is normal when the pressure at the arterial end of the capillary slightly exceeds 32 mm Hg. Art. Normal metabolism in the brain is provided only at a systolic pressure of 40 mm Hg. Art., and glomerular filtration is disturbed if it is below 50 mm Hg. Art. Therefore, systolic blood pressure should not be lowered below 70 mm Hg. Art., especially since, in combination with the postural position, this level of blood pressure always provides a “dry” surgical field. However, it would be a mistake to always lower blood pressure to this level. The criterion for the required degree of hypotension is a "dry" surgical field, and this can be achieved in combination with a postural position and at a systolic pressure of 80 and 90 mm Hg. Art.

When using arfonad, when blood pressure is not lower than a critical level (70 mm Hg), the skin is warm, pale pink, the pulse is somewhat faster, soft, but satisfactory filling, the pupils are sharply dilated, do not react to light. With controlled hypotension, good oxygenation is important, therefore, in most cases, ganglionic blockers should be used in combination with muscle relaxants and controlled breathing. It must be remembered that against the background of arfonade, the effect of muscle relaxants, especially dithylin, is greatly prolonged.

The advantage of arfonade over other ganglionic blockers is its fast onset and short action. With intravenous administration, it occurs in 3-5 minutes. The hypotensive effect continues while the drug is administered. After the cessation of the introduction of arfonad, after 4-6 minutes, an increase in blood pressure begins, which comes to the original after 10-25 minutes. Such a short duration of action is explained by the fact that part of the arfonade is destroyed in the body, and the other part is excreted unchanged by the kidneys 3 minutes after administration. Usually, Arfonad is administered drip (0.05% solution in 5% glucose) at a rate of 30-120 drops/minute, starting with the introduction of a test dose of 30-50 drops/minute, then, depending on the decrease in blood pressure, increase the dose. As soon as the desired level of blood pressure is reached, the introduction of arfonad is reduced to a minimum that maintains the desired pressure. Sometimes (very rarely) there is no hypotensive effect in response to the administration of the drug. In such cases, the dose should not be excessively increased, but another ganglionic blocker should be used.

Arfonad is administered intravenously; when applied per os, it is ineffective; when administered intramuscularly, subcutaneously, it causes persistent and poorly controlled hypotension.

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After the use of ganglioblockers, complications such as anuria, oliguria, collapse, thrombosis of cerebral vessels are possible. Thrombosis can occur from a slowdown in blood flow, other complications due to tissue anoxia. After the end, bleeding may begin. Sometimes prolonged hypotension is possible.

The use of ganglionic blockers is indicated during operations accompanied by large bleeding: surgical interventions on the brain, lungs with separation of adhesions, interventions for highly vascularized tumors, operations on large vessels, pancreas, spleen. Arfonad is useful in the treatment of pulmonary edema.

The use of ganglioblocking agents is contraindicated in shock, degenerative changes in the central nervous system, organic lesions of the kidneys and liver, with severe arteriosclerosis and impaired coronary circulation. In the event of profuse bleeding, it is necessary to immediately stop the introduction of arfonad.

BENZOHEXONIUM(Benzohexonium). Synonyms: hexabenzate and hexonium B. According to its chemical and pharmacodynamic properties, hexonium (hexamethonium, hexamethon, metonium) is close to it. Benzohexonium is less toxic and chemically more stable. In a closed package, the powder can be stored for a very long time. The solution is sterilized by boiling for 30 minutes and can also be stored for a long time.

Benzohexonium has an inhibitory effect on impulses in the sympathetic and parasympathetic ganglia, therefore, along with a hypotensive effect and blockade of reflexes, it causes side effects such as dry mouth, decreased intestinal tone, and tachycardia. In addition to the blockade of the ganglia, it has a weak inhibitory effect on the vasomotor center, in addition, an inhibitory effect on the chromaffin tissue of the adrenal glands, carotid glomeruli.

When administered per os, only 10% is absorbed. It is excreted in this case by the kidneys unchanged. With intravenous administration, 50% of benzohexonium is excreted unchanged by the kidneys, and the rest is removed from the body during the day.

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To obtain hypotension, benzohexonium is administered intravenously as a 2% solution (1 ml) for 2 minutes. Its action does not begin immediately, so the drug should be administered 12-15 minutes before the moment when it is desirable to get hypotension. If the effect does not come, then the drug is administered again. If excessive hypotension occurs, then the introduction of vasoconstrictors is necessary.

PENTAMINE. Synonyms: Pendiamide, Pentamethazine, Pentomethonium. Its solution is sterilized in water by boiling for 30 minutes. Close in structure and pharmacodynamics to benzohexonium. Somewhat inferior in strength to its gangliolytic action.

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For controlled hypotension, a 5% solution is used. Usually, 40-60 mg of pentamine is slowly injected intravenously 15-20 minutes before the time when controlled hypotension is needed. If this dose is ineffective, then the drug is administered additionally up to a total of 120-180 mg. The duration of action and the rate of restoration of a normal level of blood pressure in pentamine is approximately the same as in benzohexonium.