This is a group of substances that selectively block H-ChRs of the autonomic ganglia, sinocarotid zone and adrenal medulla.
Blocking both sympathetic and parasympathetic ganglia, Gbl actually eliminate the influence of the VNS on organs and tissues.
Sympathetic ganglion blockade under the influence of GBL, it is especially noticeably reflected in the tone of peripheral vessels, especially arterioles - they expand, which leads to to lower blood pressure . This valuable property of GBL is used in the treatment of hypertension and the elimination of spasms of peripheral vessels. However, blockade of the sympathetic ganglia, carotid sinuses and adrenal medulla disrupts the physiological regulation of vascular tone and can lead to a sharp drop in blood pressure and loss of consciousness (collapse), especially with a rapid transition from a horizontal to a vertical position (orthostatic collapse). Therefore, after administration of GBL, patients are recommended to stay in bed for 1.5 - 2 hours.
By blocking the parasympathetic ganglia, GBL lower tone smooth muscles V internal organs (gastrointestinal tract, bladder, etc.) and reduce secretion digestive glands . This property of GBL is used in the treatment of gastric ulcer and duodenal ulcer, smooth muscle spasms internal organs. However, with prolonged administration of GBL, this can lead to intestinal dysfunction (atony, constipation).
Mechanism of action: GBL are capable of binding the mediator acetylcholine. In this case, the flow of impulses from the central nervous system to the executive organs is interrupted in the ganglia and the following pharmacological effects are observed:
Vasodilation, decreased blood pressure
Decreased tone of smooth muscles of internal organs (spasmolytic effect)
Decreased secretion of salivary, digestive, sweat, bronchial glands
Anti-edema effect
Anti-shock effect.
Indications for use of GBL:
GB, hypertensive (hypertensive) crises
Obliterating endarteritis (intermittent claudication) and other peripheral circulatory disorders
Peptic ulcer and duodenum
To prevent cerebral edema and pulmonary edema
For controlled hypotension to reduce bleeding from blood vessels during operations on the heart and blood vessels, during thyroidectomy, mastectomy, etc.
Side effects:
Orthostatic collapse.
Intestinal atony and constipation up to paralytic intestinal obstruction.
Dry skin and mucous membranes.
There may be mydriasis, disturbance of accommodation, dysarthria, dysphagia, urinary retention.
At long-term use addiction develops, which requires increasing doses.
Based on their duration, ganlioblockers are divided into two subgroups:
Long-lasting:benzohexonium(duration of action 3 - 4 hours), pyrylene(duration of action 12 hours), pentamine(acts somewhat shorter than benzohexonium), pachycarpine. They are used for diseases of internal organs associated with nervous regulation disorders. These drugs must meet the following requirements: high activity at in different ways introduction; long duration of action; low toxicity and no side effects.
Short acting:hygronium(10 – 15 minutes), imekhin(arfonad). Used in surgical practice for controlled hypotension. Administered intravenously; the effect occurs quickly, and after cessation of administration, the blood pressure level quickly (after 10–15 minutes) returns to its original level.
BENZOHEXONIUM,Benzohexonium, list “B”, 0.3 inside
White synthetic crystalline powder, salty-bitter taste, highly soluble in water, sensitive to light. The main effect of benzohexonium is a hypotensive effect, in addition, it relaxes smooth muscles, reduces the secretion of glands, lowers metabolic processes, can lower body temperature; inhibits the function of the pituitary gland.
Applicable:
1. for spasms of peripheral vessels (endarteritis, intermittent claudication).
2. to relieve hypertensive crises (rarely in hypertension),
3. for the treatment of peptic ulcer (ulcer and duodenal ulcer)
4. for bronchospasms
5. for controlled hypotension (IV)
6. when preparing patients for operations on thyroid gland, since, by inhibiting the pituitary gland, it eliminates the influence of the pituitary gland on the thyroid gland. Mainly used in hospitals.
FV – ampoules of 1 ml of 2.5% solution, tablets of 0.1.
PYRYLENE,Pirilenum, list “B”, 0.005
It is slightly inferior in activity to benzogexonium, but superior in duration of action. Used: for obliterating endarteritis, for gastrointestinal ulcers, for toxicosis of pregnant women, for hypertension in combination with other drugs. Penetrates through the BBB and has a blocking effect on central cholinergic receptors. It is better absorbed when administered orally.
FV – tablets of 0.005.
Contraindications to the use of benzohexonium and pyrylene.
1. Severe atherosclerosis.
2. For intestinal atony, bladder.
3. In case of dysfunction of the liver and kidneys.
4. For glaucoma, because may increase intraocular pressure.
PENTAMINE,Pentaminum, list “B”, VRD 3 ml 5% solution i.m.
It has a wider application: in anesthesiology (for controlled hypotension), effective in hypertensive crises, spasms of peripheral vessels; for renal, hepatic and intestinal colic, for relief acute attacks BA, with pulmonary and cerebral edema, with ulcerative gastric ulcer and duodenal ulcer.
FV: 5% solution in amps of 1 and 2 ml.
HYGRONIUM,Hygronium, list "B".
It has a short-term ganglion-blocking effect, and therefore is convenient for use in anesthesiology for controlled hypotension. It is administered intravenously in the form of a 0.1% solution.
PAKHIKARPIN,Pachycarpinihydroiodiumlist “B”, 0.2 orally, 5 ml of 3% solution s.c.
- salt of the alkaloid pachycarpine, found in the Sophora thick-fruited plant. Blocks ganglia without prior stimulation, reduces the sensitivity of adrenal tissue and receptors of the carotid glomeruli of the sinocarotid zone. Applicable:
1. for weakness labor activity, because increases the tone of the uterus and enhances its contractions.
2. with muscular dystrophy, 3. with spasms of peripheral vessels, with circulatory disorders in the lower extremities.
Contraindications: Pregnant women, with severe heart pathology, as well as with liver and kidney diseases.
FV – tablets 0.1; in ampoules of 2 ml of 3% solution.
Ganglion blockers are derivatives of either quaternary nitrogen - hexamethonium bromide (benzohexonium) , Azamethonium bromide (pentamine), Trepirium iodide (hygronium), or tertiary - pachycarpine hydroiodide. pempidine(pyrylene). All quaternary amines are poorly absorbed in the gastrointestinal tract and do not pass into the central nervous system, while tertiary amines - are easily resorbed in the intestine and penetrate the blood-brain barrier.
The mechanism of their action is associated with the blockade of H-cholinergic receptors of the ganglia and the adrenal medulla (evolutionarily - the ganglion). The conduction of impulses to organs through the sympathetic and parasympathetic nerves decreases or stops (pharmacological denervation of organs), the sympathetic and parasympathetic influence on organs and tissues decreases. Vascular tone (arterioles and venules) is mainly determined by the sympathetic nervous system and endogenous adrenaline produced by chromaffin cells of the adrenal gland. Blockade of the sympathetic ganglia and adrenal medulla reduces the amount of norepinephrine (in synapses) and adrenaline (in the blood), blood vessels dilate (both arterioles and venules) - blood pressure drops. Ganglion blockers dilate peripheral vessels, improve blood supply and microcirculation in the extremities (indicated for spasm of peripheral vessels).
Function of the heart, smooth muscles, gastrointestinal tract, bladder, glandular secretion are mainly maintained parasympathetic system. Blockade of intramural parasympathetic ganglia inhibits the stimulating effect of the vagus nerve and reduces contractions of the smooth muscles of internal organs (gastrointestinal tract, bladder, bronchi, etc.), that is, it gives a pronounced antispasmodic effect. For the same reason, the secretion of glands (salivary, gastrointestinal tract) decreases, heart contractions become more frequent, and paralysis of accommodation develops.
Indications for use:
1. Hypertensive crises. For this purpose, pentamine and benzohexonium are used.
2. Edema of the lungs and brain against the background of increased blood pressure. Ganglion blockers dilate peripheral vessels (both arterioles and venules), blood is deposited in the periphery, its flow to the “right” heart is reduced and the pulmonary circulation is unloaded, hydrostatic pressure in the vessels of the lungs and brain decreases. The expansion of venules helps to reduce the venous return of blood to the heart, which improves its working conditions.
3. Controlled hypotension. Artificial hypotension is used to bleed the surgical field during surgical interventions on the heart, cerebral vessels (the risk of edema is reduced), pelvic organs, dental operations(on tissues with abundant blood supply). Ganglion blockers dilate peripheral vessels, and blood is deposited in the periphery, which leads to a decrease in bleeding in the surgical field. At the same time, ganglionic blockers prevent the development of negative autonomic reactions to organs and blood vessels during surgical interventions. For controlled hypotension, short-acting drugs are mainly used (hygronium, imekhin - administered intravenously).
4. Treatment of peripheral vascular spasms (endarteritis, Raynaud's disease).
5. Gastric ulcer and duodenum. Ganglion blockers reduce secretion gastric juice and relax the smooth muscles of the stomach and intestines, creating functional peace of the ulcerated mucosa.
In addition, ganglion blockers are sometimes used as bronchodilators (as one of the components of treatment), apachycarpine, which stimulates contractile activity of the uterus, with weak labor.
Unfortunately, the use of ganglion blockers often leads to serious complications:
1) orthostatic collapsed state (a sharp drop in blood pressure when a person moves from a horizontal to a vertical position). Depositing blood in the vessels of the limbs and organs reduces systemic blood pressure in the vessels of the brain. When the position of the body changes due to gravity, the blood is redistributed - it goes to the underlying areas of the body, the brain bleeds, and the patient loses consciousness. For prevention, it is recommended to be in a horizontal position (lying down) for 1.5-2 hours after administration of the drug;
2) atony of the intestine (up to obstruction) and bladder. Due to the blockade of the parasympathetic ganglia and the pronounced antispasmodic effect, the motor and secretory functions of the gastrointestinal tract are disrupted, and constipation develops. Decline contractility bladder can lead to urinary retention.
In addition, the use of ganglion blockers may be accompanied by photophobia (dilated pupils), visual impairment (paralysis of accommodation), dry mouth, and tachycardia.
Ganglioblockers- drugs that block transmission nerve impulses V autonomic ganglia nervous system (With preganglionic fibers per postganglionic). Medical use is very limited. Used:
I already wrote that nerve endings of the autonomic nervous system, going from the brain and spinal cord to organs and tissues, are interrupted and switched from one neuron to another neuron in special autonomic ganglia nervous system (sympathetic and parasympathetic). Sympathetic ganglia are located in a chain along the spine, and parasympathetic ganglia are located in the wall of innervated organs (intestinal wall, blood vessels). In both types of ganglia, the transmission of nerve impulses is ensured by a mediator acetylcholine, which acts on nicotinic acetylcholine receptors (n-cholinergic receptors). These receptors are so named because they are activated not only acetylcholine, but also nicotine. Yes, that same nicotine, which makes up 0.3-5% by weight of dry tobacco. It is precisely because of the stimulation of n-cholinergic receptors by nicotine that the sympathetic nervous system is excited during smoking, which can temporarily improve your mood, heart rate (heart rate) and blood pressure increase due to vasoconstriction.
Diagram of the structure of the autonomic nervous system.
Comparison of the structure of the sympathetic and parasympathetic nervous systems.
Since n-cholinergic receptors are located in both the sympathetic and parasympathetic ganglia, ganglion blockers completely interrupt the autonomic effects on the organs and tissues of the body for some time. This fact makes ganglion blockers very interesting for scientific purposes ( pharmacological denervation), but have a lot of side effects and therefore are rarely used in medicine.
By duration of action ganglion blockers are divided into:
Due to blockade of the sympathetic ganglia small vessels dilate, blood pressure drops, the blood flow rate decreases, which may contribute to thrombosis in predisposed persons ( It is not advisable to prescribe to persons over 60 years of age). Blood accumulates in dilated vessels abdominal cavity and legs, venous return to the heart decreases, which alleviates the condition of patients with pulmonary edema. Heart function usually does not change, but with a significant drop in blood pressure it is possible reflex tachycardia(increased heart rate).
The body strives to compensate for lost capabilities internal regulation and gradually increases number and sensitivity of peripheral adrenergic and cholinergic receptors, which increases the latter’s response to catecholamines ( adrenaline, norepinephrine, dopamine) And acetylcholine. For this reason a absolute contraindication to the use of ganglion blockers - pheochromocytoma (benign tumor adrenal medulla or nodes of the sympathetic autonomic nervous system, secreting catecholamines; occurs in 1 in 10 thousand population and up to 1% of patients with hypertension). Because of hypersensitivity peripheral adrenergic receptors (primarily alpha1 receptors), possibly enhancing the vasopressor (vasoconstrictor with increasing blood pressure) effect catecholamines circulating in the blood with pheochromocytoma.
Typical complication when using ganglion blockers, due to inhibition of the sympathetic ganglia and disruption of the compensatory reactions of the nervous system to changes in vascular tone, - orthostatic hypotension(to the point of collapse and fainting). We have already considered this effect in our study. He has general mechanism development - alpha1-adrenergic receptors, which normally narrow small blood vessels and increase blood pressure, under the action of ganglion blockers they do not receive enough stimuli for full vasoconstriction in vertical position bodies.
Parasympathetic ganglion blockade reduces gland secretion(sweat, salivary, stomach, etc.), tone and peristalsis organs of the gastrointestinal tract (gastrointestinal tract) and bladder(pronounced antispasmodic effect). This is manifested by a slowdown in the movement of digested food in the intestines (up to intestinal obstruction), bloating, and constipation. Possible dry mouth due to decreased secretions salivary glands, blurred vision due to moderate dilation of the pupils and paralysis of accommodation, impotence, difficulty urinating due to decreased tone of the bladder (especially in persons with an initial disorder of urodynamics). At elevated temperature environment development is not excluded heatstroke due to non-functioning sweat glands.
Ganglion blockers are contraindicated at:
Drugs average duration(2-4 hours) actions are used to lower blood pressure in severe hypertensive crises when other means are ineffective. More often used in ambulances benzohexonium. After intravenous use benzohexonium hypotensive effect lasts about 3 hours, so 2-3 hours should be in a horizontal position for the prevention of orthostatic hypotension and temporary loss of consciousness.
Drugs short acting(10-30 minutes) occasionally used during surgical operations For controlled hypotension(artificially lowering blood pressure to reduce blood loss). Systolic (upper) blood pressure is reduced to 80-90 mm Hg. Art.
Indications for controlled hypotension:
However, for controlled hypotension, ganglion blockers are used quite rarely. For this purpose, during operations it is often used antipsychotic(neuroleptic) droperidol.
Ganglioblockers should not be confused with peripheral muscle relaxants(from mio- muscle and relaxans- debilitating). Peripheral muscle relaxants using blockade H-cholinergic receptors at the synapses, the flow of nerve impulses to the skeletal muscles stops, and the muscles stop contracting (death occurs from suffocation with full consciousness). This is how a famous South American poison works curare. Ganglion blockers and peripheral muscle relaxants act on the same type of receptors, but H-cholinergic receptors of the autonomic ganglia differ significantly from H-cholinergic receptors in skeletal muscles.
Comparison of the structure of the somatic and autonomic nervous systems.
In medicine, peripheral muscle relaxants used to create conditions for tracheal intubation (insertion of a breathing tube) And performing mechanical ventilation (artificial ventilation lungs), as well as during surgical operations.
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There are 2 main groups of substances that block H-cholinergic receptors: ganglion blockers and muscle relaxants.
Ganglioblockers - This medicinal substances, interrupting the transmission of excitation in the autonomic ganglia. They do not affect the synthesis and release of acetylcholine.
Mechanism of action ganglion blockers consist in blocking H-cholinergic receptors in a competitive manner, as a result of which these receptors of the postsynaptic membranes are shielded from acetylcholine, and the conformation of the receptors does not occur. As a result, the activity of the SH group of the transport ATPase decreases, and ultimately the development of an action potential does not occur.
Based on their chemical structure, they are divided into:
1. Quaternary ganglion blockers: the nitrogen atom of these substances has 4 chemical bonds through carbon. Due to this structure, they are poorly absorbed from the gastrointestinal tract (effective only when administered parenterally) and do not penetrate the BBB. Drugs in this group include benzohexonium, pentamine, dimecoline, hygronium, camphonium, and arfonade.
2. Non-quaternary (pyrylene, pachycarpine hydroiodide, ganglerone, temechin): the nitrogen atom has 2 or 3 chemical bonds through carbon. Drugs of this group are well absorbed and pass well through the BBB. They can be used both orally and parenterally.
Based on the duration of action, ganglion blockers are divided into drugs:
1. Short-acting: hygronium, arfonade - act for 20-30 minutes;
2. Medium duration actions: benzohexonium, pentamine, dimecoline - duration of action is 2-4 hours;
3. Long-lasting: pachycarpine hydroiodide, pyrylene are effective for 6-12 hours.
Ganglion blockers do not act directly on the executive organs; they only cause autonomic denervation. At the same time, sensitivity peripheral receptors to acetylcholine and norepinephrine increases.
The main effects of ganglion blockers:
1. Dilation of arterioles, venules, small veins, which leads to a decrease in blood pressure. The blood, under its own weight, is redistributed into the vessels of the mesentery and the lower half of the body, and the filling of the pulmonary circulation and the pressure in it decreases. Blood flow in the kidneys and urine filtration are also reduced. As a result of a decrease in central venous pressure and the return of blood to the heart, cardiac outflow is reduced by 15-20%. This reduces the load on the left ventricle. Ganglion blockers do not have a direct effect on the heart, although they cause a decrease in cardiovascular reflexes, including pathological ones during trauma, shock, and myocardial infarction. Blockade of H-cholinergic receptors in the adrenal medulla leads to inhibition of the release of norepinephrine, which helps lower blood pressure and reduce vascular reflexes to various influences.
2. Blockade of H-cholinergic receptors of the carotid glomeruli reduces reflex stimulation of the respiratory and vasomotor centers.
3. Blockade of the parasympathetic ganglia leads to weakened motility and secretion of the gastrointestinal tract. Therefore, ganglion blockers have been used in the past for peptic ulcers. For the same reason, long-term use of ganglion blockers for hypertension may lead to constipation.
4. Blockade of the parasympathetic ganglia also leads to pupil dilation and weakening of the secretion of the salivary and lacrimal glands.
5. Some ganglion blockers (Pachycarpin) stimulate labor and are used during obstetrics.
Mechanism of blood pressure reduction from ganglion blockers:
1. block of H-receptors of sympathetic ganglia
2. block of H-receptors of the adrenal cortex => adrenalin
3. block of H-receptors of the pituitary gland => vasopressin
4. block of H-receptors of skeletal muscles => vascular tension
5. block of H-receptors of the carotid sinus => tone SDC
Main indications: hypertensive crises, usually severe or complicated, peripheral vascular spasms (endarteritis, Raynaud's disease), artificial hypotension during surgical interventions, peptic ulcer(oral intake as reserve drugs), with weakness of labor, with acute pulmonary and cerebral edema.
Complications: orthostatic collapse, intestinal atony, constipation, urinary retention, dry mouth, blurred vision, dizziness.
Contraindicated ganglion blockers for hypotension of various origins, cerebral hemorrhages, liver and kidney dysfunction.
Mechanism of action: block H-ChRs of the sympathetic and parasympathetic ganglia, the adrenal medulla and the carotid glomerulus.
According to their chemical structure, ganglion blockers are divided into:
Quaternary ammonium compounds: benzohexonium, pentamine, dimecoline, hygronium.
Tertiary amines: pachycarpine, pyrylene.
According to the duration of action, ganglion blockers are divided into:
Long-acting ganglion blockers (6-10 hours or more): benzohexonium (hexonium), dimecoline, pyrylene (pempidine tonsilate).
When the sympathetic and parasympathetic ganglia are blocked, the flow of impulses from the central nervous system to peripheral tissues decreases, which leads to a decrease in vascular tone, intestinal motility, production of exocrine glands, etc.
Medium-acting ganlioblockers (4-6 hours): pentamine (azamethonium).
Short-acting ganglion blockers (10-15 minutes): hygronium, arfonade.
Indications for the use of ganglion blockers:
Edema of the lungs, brain (pyrylene, pentamine).
Controlled hypotension in anesthesiology (hygronia).
Eclampsia, causalgia (pentamine, pachycarpine).
Cupping hypertensive crises(pentamine, benzohexonium).
Peptic ulcer of the stomach and duodenum (benzohexonium, pyrylene).
Obliterating endarteritis, spasm of peripheral vessels (pyrylene, pachycarpine, benzohexonium, pentamine).
Toxicosis of pregnancy (pyrylene).
Rodostimulation (pachycarpine).
Intestinal spasm and biliary tract, renal colic (pentamine).
Baby Features: Children are prescribed only for hypertensive crises, edema of the brain, lungs, and left ventricular failure.
Side effects:
Constipation, bloating, intestinal atony (myasthenic syndrome) and bladder (urinary retention).
Tachycardia.
General weakness, dizziness.
Dry mouth.
Visual impairment.
Thrombosis.
Antidepolarizing Mixed Depolarizing
Pipecuronium bromide Dioxonium Dithiline
(arduan), pancuronium
bromide, atrocurium
(traquarium), mevacu-
riy (mevacron).
Mechanism of action of anti-depolarizing MRs: block H-ChRs of skeletal muscles and compete with ACh for interaction with receptors.
Mechanism of action of depolarizing MRs: first, skeletal muscle H-AChRs are briefly activated (cholinomimetic phase). As a result, depolarization of the receptor membrane occurs, accompanied by fibrillation of skeletal muscles with loss of K. Depolarization is then replaced by loss of sensitivity of the receptor to ACh - desensitization. It is considered as a consequence of changes in the conformation of the receptor and the inhibitory effect of K on K-Na-ATPase, which delays the repolarization of the postsynaptic membrane and the restoration of its response to incoming impulses.
Mechanism of action of mixed MR: first induces a depolarizing phase and then acts as an anti-depolarizing MR. In the second phase, prozerin weakens the effect of dioxonium. During anesthesia with ether and fluorothane, the effect of dioxonium increases. See Figure 4.
Fig.5. Mechanism of action of muscle relaxants.
Indications for use:
Anesthesiology: tracheal intubation, endoscopic procedures (ditilin, dioxonium).
Reposition of bones in case of fracture, reduction of dislocations (vecuronium bromide, pancuronium bromide).
Treatment of tetanus, convulsive conditions(alcuronium chloride, dithiline).
Immobilization eyeball(ditylin).
Side effects:
Respiratory depression.
Muscle postoperative pain.
Cardiac arrhythmias.
Bronchospasm.
Hypokalemia.
Hyperhidrosis.
Increased intraocular pressure.
Neuromuscular block.
Children's features: children of the first years of life are highly sensitive to antidepolarizing muscle relaxants, this is due to a small supply of ACh in presynaptic endings. When excitation arrives, less ACh is released into the synaptic cleft. But the effect of using these drugs disappears faster than in adults. Most often used in anesthesiology.
