Comparative study of the action of local anesthetics.

17. Local anesthetics: classification, mechanism of action, comparative characteristics. Resorptive action of local anesthetics. Application.

M local anesthesia - switching off sensitivity during direct contact of the drug with nerve conductors and receptors without turning off consciousness, reflexes and muscle tone(as opposed to drugs). Local anesthetics - these are drugs that cause a reversible inhibition of the conductivity and excitability of receptors and conductors when applied to them.

Classification by chemical structure : 1) complex esters of amino alcohols and aromatic acids cocaine (benzoic acid derivative), novocaine, dicaine, anestezin (para-aminobenzoic acid derivatives) , 2) substituted acid amides .- xicaine (lidocaine) and trimecaine (xylidine derivatives), sovcaine (cholinecarboxylic acid derivative). Drugs with an amide bond have more long-term action than anesthetics with an ether bond, which is destroyed by blood and tissue esterases.

For the manifestation of the anesthetic effect, anesthetics must undergo the following transformation steps: 1) the anesthetic salt used is highly soluble in water, but poorly in lipids, therefore it droops weakly through the membranes and does not have an anesthetic effect; 2) in tissue fluid the anesthetic salt is converted into a non-ionized lipophilic base that penetrates well through membranes; 3) the base of the anesthetic acquires a cationic form, which interacts with receptors inside the sodium channels of the membranes, as a result of which the passage of sodium (and potassium) ions through the channels of the membranes is disrupted. This prevents the occurrence of the action potential and causes a block in the conduction and generation of impulses. Competitive interaction with calcium ions, which regulate the "opening-closing" of ion channels, is also important. This shows an analogy with the action of local and general anesthetics: both block the generation of excitation in the membranes. That's why narcotic substances(ether, etc.) can cause local anesthesia, and local anesthetics, when administered intravenously, can cause general anesthesia. This is obviously related to the potentiating effect at joint application local anesthetics. narcotic, hypnotic and analgesic drugs.

Local anesthetics block the conduction of excitation in all types of nerve fibers: sensitive, motor, vegetative, but at different speeds and in different concentrations. Thin non-fleshy fibers are most sensitive to them, along which pain, tactile and temperature sensitivity is carried out, then - sympathetic fibers, which is accompanied by vasodilation, and in last turn motor fibers are blocked. Restoration of impulse conduction goes to reverse order.

Local anesthesia develops only with direct contact with the anesthetic. With a resorptive action, the central nervous system is paralyzed before local sensitivity is eliminated.

Neutralization of anesthetics carried out by biotransformation. Substances with an ether bond are hydrolyzed by esterases: novocaine by plasma cholinesterase, cocaine, dicaine, anestezin by liver esterases. Biotransformation of anesthetics with an amide bond occurs in the liver by its destruction (eg, lidocaine). The decay products are excreted by the hepatic circulation. Decreased hepatic blood flow leads to a prolonged half-life and an increase in blood concentration, which can lead to intoxication. Anesthetics easily penetrate the lungs, liver, kidneys, central nervous system, through the placenta. If a significant amount of a substance enters the blood, there is toxic effect: excitation, then paralysis of the centers of the medulla oblongata. This is manifested first by anxiety, shortness of breath, increased blood pressure, pallor of the skin, fever, and then - respiratory and circulatory depression. In case of intoxication, oxygen, artificial ventilation of the lungs, intravenous administration of barbiturates, sibazon, adrenaline, norepinephrine are used. allergic reactions most often cause anesthetics with an ether bond, especially novocaine. The most dangerous of these is anaphylactic shock.

Local anesthetics are used for the following types of anesthesia:

Terminal (terminal, surface, application) - by applying an anesthetic to the mucous membranes. Apply anesthetics that are well absorbed through the mucous membranes (cocaine, dicaine, lidocaine, anestezin). They are used in otorhinolaryngology, ophthalmology, urology, dentistry, in the treatment of burns, wounds, ulcers, etc. Conductor (regional) - blockade nerve fibers. In this case, the conduction of impulses to the central nervous system is disrupted and sensitivity is lost in the area that is innervated by this nerve. Novocaine, lidocaine, trimecaine are used. One of the options for this anesthesia is spinal, which is carried out by introducing an anesthetic into the subdural space. infiltration anesthesia is carried out by layer-by-layer impregnation of tissues with anesthetic solution. This turns off the receptors and conductors. Novocaine, lidocaine and trimecaine are used. This type of anesthesia is widely used in surgery. Intraosseous anesthesia is carried out by introducing an anesthetic into the cancellous bone, a tourniquet is applied above the injection site. The distribution of the anesthetic occurs in the tissues of the limb. The duration of anesthesia is determined by the allowable period of application of the tourniquet. This type of anesthesia is used in orthopedics and traumatology. Choosing the type of anesthesia depends on the nature, volume and trauma of the surgical intervention. For each type of anesthesia, there are drugs of choice and technique of execution. The choice of anesthetic depends on the ability to droop into the mucous membranes, on the strength and duration of action and toxicity. For diagnostic and low-traumatic interventions on superficially located areas, terminal anesthesia is used. For infiltration, conduction and intraosseous anesthesia, low-toxic and relatively safe agents are used. For spinal anesthesia usually use sovkain, which has a strong and long-lasting effect, as well as lidocaine. It is important to choose the right concentration of the solution. Weak concentrated solutions entered in in large numbers, spread widely in tissues, but diffuse poorly through membranes, while concentrated solutions in small quantities spread worse, but diffuse better. The effect does not depend on the total amount of anesthetic, but on that part of it that penetrates into the nerve formations. Therefore, an increase in the amount of solution does not yet mean an increase in the anesthetic effect, often this only leads to an increase in the toxic effect.

During anesthesia of well-vascularized tissues (face, oral cavity, pharynx, larynx, etc.), the anesthetic is absorbed quickly, which can lead to intoxication. To reduce this effect and prolong the effect of the drug, vasoconstrictor drugs (adrenaline, norepinephrine) are added. In this case, the concentration of adrenaline should not exceed 1:200000 (1 ml per 200 ml of anesthetic), since adrenaline itself can cause tachycardia, hypertension, headache, anxiety.

Characteristics of individual anesthetics. Cocaine - alkaloid from the leaves of Erythroxylon Coca, which grows in South America. It is well absorbed, anesthesia occurs in 3-5 minutes, the duration of the effect is 30-60 minutes. It has a pronounced sympathomimetic effect, inhibiting the reverse neuronal uptake of norepinephrine, dopamine and serotonin in synapses. This is accompanied by stimulation of the cardiovascular system and central nervous system and the development of addiction. The action on the central nervous system is manifested by euphoria, anxiety, agitation, which can progress to psychosis with hallucinations, confusion, paranoid thinking, convulsions, vomiting, cardiac arrhythmias. This is due to the dopaminergic and serotonergic effects of cocaine. Vascular spasms, increased blood pressure, tachycardia, decreased appetite are the result of an adrenomimetic effect. Symptoms of excitation during intoxication are quickly replaced by depression of the central nervous system, respiration and blood circulation. Children are especially sensitive to cocaine. Death usually occurs from paralysis of the respiratory center. To provide emergency care thiolental sodium, diazepam, chlorpromazine are injected intravenously, artificial ventilation of the lungs is carried out. Cocainism occurs with prolonged use of cocaine and leads to intellectual and moral degradation. Abstinence (abstinence disease) is manifested by mental and vegetative disorders. Novocaine in terms of the strength of the anesthetic effect, it is 2 times inferior to cocaine, but 4 times less toxic. Used for infiltration (0.25-0.5%), conduction (1-2%) anesthesia and for various kinds blockade. Valid for about 30 minutes. In case of an overdose, it causes an increase in reflex excitability, nausea, vomiting, a drop in blood pressure, weakness, and respiratory failure. Often there is idiosyncrasy (rash, itching, swelling of the subcutaneous tissue, dizziness). In case of intoxication, thiopental sodium, diazepam, ephedrine, strophanthin, and artificial respiration are prescribed.

Decain it is 15 times more potent than novocaine, but 10 times more toxic than it and 2 times more toxic than cocaine. Used for superficial anesthesia of the mucous membranes, children under 10 years of age are contraindicated. Lidocaine (Xycaine) acts stronger and longer than novocaine 2-3 times. It is used for all types of anesthesia. Well tolerated, but with rapid absorption may cause collapse. Trimecain 2.5-3 times stronger than novocaine and less toxic. Its properties are close to lidocaine. Used for infiltration and conduction anesthesia, sometimes for the terminal (2-5%). scoops 15-20 times stronger than novocaine and 6-8 times longer than its duration of action, therefore it is convenient for spinal anesthesia. However, the toxicity exceeds novocaine by 15-20 times, and therefore it is dangerous for infiltration and conduction anesthesia.

A drug	Relative power	Systemic toxicity	actions	Duration of anesthesia
Novocaine			Slow	A short
			Slow	long
Trimecain
Lidocaine
Artikain
Bupivacaine				long
Ropivacaine				long

1. Compare procaine and trimecaine in terms of chemical structure, metabolic features,

duration of action, activity, toxicity, use in various types

local anesthesia.

What are we comparing?		Trimecain
Chemical structure	Ester of aromatic acids	Aromatic amine amide
Peculiarity metabolism	Rapidly destroyed in the blood by butyrylcholinesterases (pseudocholinesterases or false esterases)	Degraded much more slowly by microsomal enzymes in the liver
Time of action	0.5 - 1 hour	2 – 3 hours
Activity
Toxicity
Application for various types of local anesthesia	1. Infiltration 0.25-0.5%% 3. Spinal – 5% 4. Terminal - 10%	1. Infiltration - 0.125- 2. Conduction and epidural 3. Spinal – 5% 4. Terminal - 2-5%%

From an anesthesiology textbook

local anesthetics. These funds, depending on the characteristics of the chemical structure, are divided into two groups: esters of aromatic acids with amino alcohols (novocaine, dicaine) and amides, mainly of the xylidine series (lidocaine, trimecaine, bupivacaine, etc.). Anesthetics of the second group have a stronger and longer-lasting effect with relatively low toxicity and the possibility of long-term preservation of their properties when stored in solutions. These qualities contribute to their wide application.

Novocaine is the hydrochloride of diethylaminoethyl ester of para-aminobenzoic acid. For infiltration anesthesia, 0.25 - 0.5% novocaine is used. For conduction anesthesia, novocaine is rarely used, in 1-2% solutions. The maximum allowable bolus doses of novocaine: 500 mg without adrenaline, 1000 mg with adrenaline.

Lidocaine(xicaine ) compared with novocaine, it has a more pronounced anesthetic effect, a short latent period, and a longer duration of action. Toxicity in the applied doses is small, it biotransforms more slowly than novocaine. The following solutions of xycaine are used: for infiltration anesthesia - 0.25%, conduction, epidural and spinal - 1 - 2%, terminal - 5 - 10%. Xicaine, like other local anesthetics of the amide group, has less allergenic properties than novocaine. Lidocaine is destroyed in the liver and only 17% of it is excreted unchanged in the urine and bile. The maximum allowable doses of lidocaine: 300 mg without adrenaline, 1000 mg with adrenaline.

Trimecain(mesocaine) in terms of anesthetic effect is somewhat inferior to lidocaine. According to the main properties, as well as indications for use, it is almost similar to it. The maximum allowable doses: without adrenaline 300 mg, with adrenaline -1000 mg.

Pyromecaine is also a representative of anesthetics of the amide group. It has a strong anesthetic effect on mucous membranes, is not inferior to dikain and significantly exceeds cocaine. Its toxicity is lower than that of the named anesthetics. For terminal anesthesia, it is used in the form of a 2% solution, not more than 20 ml.

Bupivacaine(marcain) also refers to anesthetics of the amide group. Compared to lidocaine and trimecaine, it has a stronger and longer-lasting effect, but is more toxic. The anesthetic is used in the form of a 0.5% solution for conduction, epidural and spinal anesthesia methods. He, like other anesthetics of this group, is biotransformed relatively slowly.

Bupivacaine is one of the anesthetics with the longest (up to 12 hours) duration of analgesic effect. By using various concentrations of bupivacaine for drug blockade of the nerve stem plexuses, it is possible to achieve different depth blockade: for example, when performing a blockade of the brachial plexus with a 0.25% solution of bupivacaine, complete “surgical” analgesia of the limb is achieved with preserved muscle tone. For anesthesia with concomitant complete muscle relaxation, bupivacaine is used at a concentration of 0.5%.

Ropivacaine(naropin) differs little in chemical structure from bupivacaine. But, unlike the latter, it has much less toxicity. The positive qualities of the drug also include the rapid cessation of motor block when long-term preservation touch. It is used in the form of a 0.5% solution for conduction, epidural and spinal anesthesia.

The mechanism of action of local anesthetics is currently explained from the standpoint of the membrane theory. In accordance with it, anesthetics in the zone of contact with nerve fibers violate the transmembrane permeability for sodium and potassium ions. As a result, depolarization in this section of the membrane is impossible, and, accordingly, the excitation propagating along the fiber is extinguished. In nerve fibers that conduct excitatory impulses of various modalities, when the nerve comes in contact with an anesthetic solution, the blocking effect does not appear simultaneously. The less pronounced the myelin sheath of the fiber, the faster the violation of its conduction occurs and vice versa. Thin unmyelinated fibers, which, in particular, include sympathetic ones, are blocked first. They are followed by a blockade of the fibers that carry pain sensitivity, then, sequentially, temperature and protopathic. Lastly, the conduction of impulses in the motor fibers is interrupted. The restoration of conductivity occurs in the reverse order. The time from the moment the anesthetic solution is applied to the nerve to the onset of the blocking effect varies for different anesthetics. It depends mainly on their lipoidotropy. The concentration of the solution also matters: with its increase in all anesthetics, this period decreases. The duration of the blocking effect is directly dependent on the affinity of the anesthetic for lipids and inversely on the blood supply to the tissues in the area of ​​anesthetic injection. The addition of adrenaline to the anesthetic solution prolongs its specific action due to a decrease in the blood supply to the tissues and a slowdown in the resorption of the drug from them.

The fate of the administered local anesthetics of the two considered groups in the body is significantly different. Anesthetics of the ester series undergo hydrolysis with the participation of cholinesterase. The mechanism of biotransformation in this group is well studied in relation to novocaine. As a result of its decomposition, para-aminobenzoic acid and diethylaminoethanol are formed, which has some local anesthetic effect.

Local anesthetics of the amide group are inactivated relatively slowly. The mechanism of their transformation is not well understood. It is believed that biotransformation occurs under the influence of liver enzymes. In unchanged form, only a small amount of these anesthetics is released.

With all methods of local and regional anesthesia, the anesthetic from the injection site constantly enters the bloodstream. Depending on the concentration created in it, it has a more or less pronounced general effect on the body, which manifests itself in inhibition of the function of interoreceptors, synapses, neurons and other cells. When using acceptable doses, the resorptive effect of anesthetics does not pose a danger. Moreover, a small general effect, summing up with a local one, increases the anesthetic effect. In cases where the prescribed dosage is not observed or the patient's sensitivity to the anesthetic is increased, signs of intoxication may appear to one degree or another.

CHARACTERISTICS OF LOCAL ANESTHETICS

Local anesthetics of the ester group

Anesthetics of the ester group are more rapidly hydrolyzed in tissues, since the ester bonds are unstable. In the blood, their hydrolysis is accelerated by pseudocholinesterase. Anesthetics of this group act briefly.

DIKAIN. Synonyms: Amethocaine, Anethaine, Decicain, Felicain, Foncaine, Intercain, Medicain, Pantocain, Pontocaine hydrochloride, Rexocaine, Tetracaini hydrochloridum, Tetracaine hydrochloride, etc.

Due to the high toxicity (10 times more toxic than novocaine), the drug is used only for application anesthesia mucous membranes of the mouth and nose. It is advisable to use 0.25%, 0.5% and
1% solutions. In some cases, most often with anesthesia of small areas, 2-3% dicaine solutions can be used. The highest single dose of the drug for adults is 0.09 g (3 ml of a 3% solution). Since the drug is easily absorbed and a slight excess of the therapeutic dose can cause severe intoxication and even fatality, it is not used in pediatric dentistry.

ANESTHESIN. Synonyms: Benzocaine, Aethylis aminobenzoas, Anaesthalgin, Anaesthicin, Anaesthin, Benzocain, Ethoforme, Ethylis aminobenzoas, Ethyl aminobenzoate, Norcain, Parathesine, Rhaetocain, Topanalgin, etc.

The substance is insoluble in water. Can be used for surface anesthesia in the form of powders or 5-20% oil solutions. For anesthesia of wound and ulcerative surfaces, it can be used in the form of a 5–10% ointment. Highest dose for adults: single 0.5 g, daily 1.5 g.

NOVOCAINE. Synonyms: Aethocain, Allocaine, Ambocain, Aminocaine, Anesthocaine, Atoxicain, Cerocain, Chemocain, Citocain, Ethocaine, Genocaine, Herocaine, Isocain, Jenacain, Marecaine, Minocain, Naucain, Neocaine, Pancain, Paracaine, Planocaine, Polocainum, Procaine, Procaini hydrochlor idum , Procaine hydrochloride, Protocaine, Sevicaine, Syncaine, Syntocain, Topocaine, etc.

In terms of activity, novocaine is 4–5 times inferior to dicaine. For infiltration anesthesia, 0.25%, 0.5% and 1% solutions are used, and for conduction anesthesia, 1% and 2% solutions are used. It should be borne in mind that with the same total dose of the drug, the higher the concentration of the solution used, the higher the toxicity. The drug has moderate vasodilating properties.

The highest single dose for adults: when using a 0.25% solution, not more than 500 ml (1.25 g); 0.5% solution - 150 ml (0.75 g); 1% solution - 75–100 ml (0.75 g) and 25–30 ml of a 2% solution (0.5 g). The total dose should not exceed 2 g.

With resorptive action (action medicines or toxic substances, which manifests itself after their absorption into the blood), novocaine is marked by depression of the central nervous system, a moderate analgesic, anti-shock effect. The drug has a ganglioblocking, vasodilating, antiarrhythmic effect, improves microcirculation. Novocaine has low toxicity, but often causes allergic reactions (stomatitis, dermatitis, Quincke's edema, and even anaphylactic shock). At hypersensitivity to novocaine, the patient experiences dizziness, weakness, falling blood pressure, collapse, shock. Therefore, when taking an anamnesis, attention should be paid to the patient's tolerance not only to novocaine, but also to other anesthetics similar to novocaine in structure (anesthesin and dicaine), since there may be cross-allergy to them. Novocaine reduces the activity of sulfa drugs, since one of its metabolites is para-aminobenzoic acid, and the antimicrobial effect of sulfonamides is based on competitive antagonism with para-aminobenzoic acid.

Local anesthetics of the complex amide group

Local anesthetics of the amide group are more slowly inactivated in the body, are not destroyed by blood cholinesterase, act for a longer time, and therefore are more effective. Their main advantage is that they diffuse better into the tissues at the injection site, act faster, have a larger area of ​​anesthesia and stronger interaction with tissues, which prevents the local anesthetic from entering the bloodstream.

LIDOCAINE. Synonyms: Xicaine, Xylocaine, Lidestine, Acetoxyline, Alocaine, Anestacon, Anestecain, Astracaine, Dolicaine, Dulcicaine, Esracaine, Fastocaine, Leostesin, Lidestin, Lidocaine, Lidocard, Lidocaton, Lignocain, Maricain, Nulicaine, Octocaine, Remicaine, Solcain, Stericaine, Xycain, Xylesin, Xylocain, Xylocard, Xylocitin, Xyloton, Xylotox, etc.

Lidocaine is the first amide anesthetic used in dentistry, it is four times more effective than novocaine and approximately twice as toxic, it has a deeper and longer anesthetic effect than novocaine. This allowed him, in the 50s, to become one of the most popular anesthetics used in dentistry.

By chemical structure lidocaine is a derivative of acetanilide. Unlike novocaine, it is not an ester, it is metabolized more slowly in the body and acts longer than novocaine. Due to the fact that during its metabolism in the body there is no formation of para-aminobenzoic acid, it does not have an antisulfanilamide effect and, unlike novocaine, can be used in patients receiving sulfanilamide preparations.

Along with local anesthetic activity, lidocaine has pronounced antiarrhythmic properties.

Lidocaine is a strong local anesthetic that causes all types of local anesthesia: terminal, infiltration, conduction, and is considered the ancestor of all amide drugs. Compared to novocaine, it acts faster, stronger and longer. The relative toxicity of lidocaine depends on the concentration of the solution. In low concentrations (0.5%), it does not differ significantly in toxicity from novocaine; with an increase in concentration (1% and 2%), toxicity increases (by 40–50%).

For infiltration and conduction anesthesia in dentistry, a 2% anesthetic solution is used, and for terminal (application) anesthesia of the oral mucosa, a 10% aerosol solution produced abroad (lidestin) is used, in surgery, an aerosol is used when changing dressings, opening abscesses etc. The aerosol can contains 750 doses of 10 mg of lidocaine. The amount of sprayed drug depends on the surface to be anesthetized. In adults, do not exceed a dose of 200 mg, i.e. 20 sprays; in children older than 2 years, 1-2 doses of the drug are prescribed once.

Aerosol should not be allowed to enter the eyes.

Lidocaine, used in doses that do not cause seizures, has a sedative effect. The drug is contraindicated in patients with severe liver disease. The highest single dose for adults is 2% solution up to 20 ml. With the rapid entry of the drug into the bloodstream, there may be a decrease in blood pressure and collapse; decrease hypotensive effect achieved by the administration of vasoconstrictors.

Contraindications for the use of lidocaine are as follows:

sick sinus syndrome in elderly patients;

severe bradycardia;

cardiogenic shock;

severe liver disorders;

hypersensitivity to the drug.

Lidocaine should be prescribed to pregnant and lactating women according to strict indications.

In children under 2 years of age, the use of lidocaine aerosol is allowed only after it has been previously applied to a cotton swab.

In case of overdose, there are psychomotor agitation, tremor, clonic-tonic convulsions, collapse, CNS depression. Barbiturates are used to treat this complication. short action, benzodiazepine tranquilizers.

With the simultaneous appointment of lidocaine and beta-blockers (drugs used for paroxysmal tachycardia, extrasystoles, angina pectoris, hypertension - inderal, trazikorkor) resorptive effects (including toxic ones) of lidocaine may be enhanced due to the weakening of its inactivation in the liver. The dose of the drug in this case is reduced.

It is irrational to prescribe lidocaine simultaneously with antiarrhythmic drugs - drugs used to treat paroxysmal tachycardia, atrial fibrillation and extrasystole (aimalin, quinidine, etc.) due to increased cardiodepressive action. Combined use with novocainamide (an antiarrhythmic agent) can cause CNS excitation and hallucinations. It is also contraindicated to co-administer lidocaine with MAO inhibitors (antidepressants, for example, iprazide), polymyxin B (the antibiotic is used for staphylo-, strepto-, pneumo-, gono- and meningococcal infection), diphenin ( anticonvulsant used to treat epilepsy).

Storage: the drug should be stored in a dark place at room temperature.

MEPIVACAIN. Synonyms: Scandicain, Scandonest, Carbocain, Isocain, Mepivastesin, Mepicaton, Mepidont. It is used for infiltration and conduction anesthesia in the form of a 3% solution, a 2% solution with adrenaline (1/100,000) and norepinephrine (1/100,000). In terms of efficacy and toxicity, a 2% solution of mepivacaine is approximately equal to a 2% solution of lidocaine (the drug does not cause an allergic cross-reaction with ether anesthetics). Unlike most active substances in anesthetic solutions, which have vasodilating properties, mepivacaine has vasoconstrictor action, which allows the use of a solution with reduced content vasoconstrictor. In this regard, a 3% solution of mepivacaine hydrochloride in therapeutic dentistry today is the drug of choice for patients who are contraindicated in the use of vasoconstrictors.

Contraindications for the use of mepivacaine are as follows:

allergy to local anesthetics belonging to the same group;

severe myasthenia;

low plasma cholinesterase levels;

serious liver disorders: cirrhosis, hereditary or acquired porphyria.

The maximum single dose of the drug is 2.7 mg per 1 kg of body weight or 162 mg (3 capsules) with a weight of 60 kg. For children, the total dose should not exceed 1 capsule and is 1.33 mg per 1 kg of body weight.

In case of overdose, clonic convulsions appear as a result of intoxication of the nervous system.

ARTICAIN. Synonyms: ultracain, karticain, septonest, ubistezin, etc. Drug for local anesthesia in dentistry. Articaine is a local anesthetic of the amide type of the thiafene group. The drug provides a reliable anesthetic effect. Wound healing after surgical interventions proceeds without complications, due to good tissue tolerance and minimal vasoconstrictive effect.

Due to the low content of adrenaline in articaine preparations, its effect on the cardiovascular system is little expressed: there is almost no increase in blood pressure and an increase in heart rate.

Articaine preparations have low toxicity. However, articaine preparations produced by various companies under different trade names differ to some extent from each other in composition:

Ultracain D-S- 1 ml of the drug contains: articaine hydrochloride 40 mg, adrenaline hydrochloride 6 mcg.

Other Ingredients:

Ultracain D-SForte

Other Ingredients: sodium metabisulphite, sodium chloride, water for injection.

Ubistezin Forte- 1 ml of the drug contains: articaine hydrochloride 40 mg, adrenaline hydrochloride 12 mcg.

Other Ingredients: sodium metabisulphite, sodium chloride, water for injection

Septanest- 1 ml of the drug contains: articaine hydrochloride 40 mg, adrenaline hydrochloride 10 mcg.

Other Ingredients: sodium metabisulfite, sodium chloride, EDTA, water for injection

Articaine acts faster than lidocaine, the effect of the drug begins after 1-3 minutes, the duration of anesthesia is 60-180 minutes. It has a high diffusion capacity and degree of binding to plasma proteins (95%), low fat solubility. Articaine penetrates well into tissues, can provide pain relief of the palate after buccal infiltration anesthesia and pulp pain relief after infiltration anesthesia in the lower jaw from 35 to 45. The lipophilicity of articaine is less than that of other amide anesthetics, however, low toxicity compared to lidocaine and mepivacaine allows the use of this drug in the form
4% solution of articaine hydrochloride with adrenaline (epinephrine) in dilutions of 1:100,000 and 1:200,000. Because articaine formulations generally do not contain parabens (an antibacterial preservative), these anesthetics can be used in patients who are allergic to parahydroxybenzoates or chemically related entities. The stability of the anesthetic is achieved by the high quality of packaging (ampoules and cartridges) and the high chemical purity of the active substance. However, it should be remembered that "Ultracain", produced in 20 ml vials, contains
0.05 mg methylparaben.

The maximum single dose of the drug solution is 12.5 ml (7 cartridges) for an adult weighing 70 kg (7.0 mg/kg of articaine).

When using articaine preparations, the following side effects are possible:

From the side of the central nervous system: depending on the applied dose, cases of impaired consciousness are described up to its loss; respiratory disorders; muscle tremor, involuntary muscle twitches, sometimes progressing to generalized convulsions; nausea, vomiting.

On the part of the organs of vision: blurred vision, transient blindness, diplopia (rarely).

From the side of the cardiovascular system: moderate hemodynamic disturbances, manifested by a decrease in blood pressure, tachycardia or bradycardia.

Allergic reactions: swelling or inflammation at the injection site; in other areas - skin redness, itching, conjunctivitis, rhinitis, angioedema varying degrees severity (including swelling of the upper and/or lower lip and/or cheeks, glottis with difficulty swallowing, urticaria, difficulty breathing). All these phenomena can progress to the development of anaphylactic shock.

Local reactions: swelling or inflammation at the injection site.

Other: headaches (probably associated with the presence of adrenaline in the preparation). Other side effects caused by the action of adrenaline (tachycardia, arrhythmia, increased blood pressure) are rare, since the concentration of adrenaline is negligible.

Drug Interactions: The hypertensive effect of sympathomimetic amines such as adrenaline may be enhanced by tricyclic antidepressants and MAO inhibitors. Interactions of this type have been described for epinephrine and noradrenaline when used as vasoconstrictors at concentrations of 1:25,000 and 1:80,000, respectively. Although the concentration of adrenaline in articaine preparations is significantly lower, this possibility should nevertheless be considered.

Sometimes an accidental intravascular injection can lead to the development of ischemic zones at the injection site, in some cases progressing to tissue necrosis.

Damage to the facial nerve, up to the development of paralysis of the facial nerve, occurs only if the injection technique is violated.

Absolute contraindications:

introduction to children up to 4 years;

recent myocardial infarction;

paroxysmal tachycardia and other tachyarrhythmias;

uncontrolled increase in blood pressure;

angle-closure glaucoma;

hyperthyroidism not controlled by drugs;

diabetes mellitus not controlled by drugs;

bronchial asthma, which is treated with corticosteroids;

pheochromocytoma (tumor of the adrenal glands);

allergic reactions to sulfites or auxiliary components of the anesthetic.

Speaking about allergic reactions to articaine preparations, it should be noted that an allergy to adrenaline is impossible, because it is a hormone that is produced by every person. As for articaine, according to the literature, no cases of an allergic reaction to the drug in its pure form have been documented.

Relative contraindications:

simultaneous use of tricyclic antidepressants, MAO inhibitors, ß-blockers, cocaine.

special instructions

Due to the sulfite content, some patients may develop acute attack suffocation, impaired consciousness, shock. In patients with bronchial asthma, the risk of developing this complication is very high. Pregnant women are also shown the sparing use of these drugs, since there is evidence of a small penetration of them through the placenta. IN breast milk Articaine solutions do not penetrate in a significant amount and therefore are used during lactation.

When conducting infiltration and conduction anesthesia in dentistry in patients with diseases of the cardiovascular system (chronic heart failure, pathology of the coronary vessels, angina pectoris, rhythm disturbances, a history of myocardial infarction, arterial hypertension), cerebrovascular disorders, with a history of paralysis, chronic bronchitis, emphysema, diabetes, hyperthyroidism, as well as in the presence of severe anxiety, it is advisable to use articaine preparations with low content adrenaline, which is ultracaine D-S (adrenaline content 6 μg per 1 ml).

In special tests, no clear effect of the drug on operator activity was revealed. However, due to the fact that the patient's preoperative anxiety and the stress caused by surgery can affect the effectiveness of the activity, the dentist must individually decide on the admission of the patient to management in each specific case. vehicle or to work with mechanisms.

Comparative characteristics of local anesthetics

	Novocaine	Lidocaine	mepivacaine	Artikain
Plasma protein binding
Half-life in min.
Anesthetic activity*
Toxicity*
Duration of anesthesia (in minutes) without vasoconstrictor
Duration of anesthesia (in minutes) with a vasoconstrictor
Maximum allowable dose(mg/kg) with vasoconstrictor
Maximum allowable dose (mg/kg) without vasoconstrictor
Speed ​​of action	Slow			Very fast

The use of local anesthetics in recommended doses is relatively safe (with the exception of allergic reactions). Complication statistics and side effects during local anesthesia is not very accurate and is associated rather with an error in the choice of the drug and its dosage.

The practice of using local anesthetics should take into account the individual maximum dose of the drugs used. Usually it is determined according to the body weight of the patient.

The dentist should always strive to achieve effective pain relief using minimal amount anesthetic. Recommendations, in this regard, suggest the use of a dose not exceeding 50% of the maximum value of the toxic dose.

In cases where the volume of dental intervention requires the use of local anesthetics in a dosage exceeding 50% of the maximum dose, it is necessary to provide the patient with an anesthetic benefit, including free access for intravenous injections, oxygen inhalation, assisted or artificial ventilation of the lungs.

It is very important to collect the following anamnestic data before applying local anesthesia:

clinic therapeuticdentistry. 2 1.3.1.1. 1.3.1.4. 1.3.2.1. 1.3.2.3. 1.3.3.3. 1.3.4.1. 1.3.4.6. 2 Organization therapeutic dental care...

I goals and objectives of the discipline "therapeutic dentistry" 1 goals of teaching the discipline 2 tasks of studying the discipline

Document

Application, infiltration and conduction anesthesia with the aim of painless treatment... 2. Additional Methods examination of the patient in clinictherapeuticdentistry. Temperature diagnostics and electroodontodiagnostics. Sighting...

1 The main stages in the development of dentistry Purpose and objectives The role of domestic scientists in the development of dentistry Dentistry as a single section of general medicine The main problems of therapeutic dentistry

Document

2nd year students Tasks therapeuticdentistry. General familiarity with clinictherapeuticdentistry, its main and... Phantom Course therapeuticdentistry(atlas). - M.: Medicine, 1996.- 304 p. 13. Petrikas A.Zh. Anesthesia teeth. ...

Dental-revue IX International Conference of Oral and Maxillofacial Surgeons and Dentists "New Technologies in Dentistry" Russia St. Petersburg May 25-27, 2004

Program

Moskovets (Moscow) Application of periodontal methods anesthesia V clinictherapeuticdentistry. - 10 min. A.K. Iordanishvili... and assessment of the psycho-emotional status of patients in clinic surgical dentistry. 34. A.P. Grigoryan, R.A. ...

LOCAL DEVELOPMENT

PAIN RELIEF IN

DENTISTRY

More than 100 years ago, the local anesthetic cocaine was discovered. (first generation anesthetic) and, since 1884, it has been used in all areas of medicine, including dentistry. Since 1886, infiltration anesthesia of the teeth began to be used. At first, cocaine was used in high concentrations- 10-20% solutions, which quite often caused adverse reactions including deaths. Later, 0.5-1% cocaine solution was used for pain relief, which reduced the number of complications.

In 1901, adrenaline was synthesized, and in 1902, Vgain began to add it to a cocaine solution. This made it possible to achieve better pain relief due to the slow absorption of cocaine and significantly reduced its toxicity.

A special injection instrumentation was created: at the beginning of the 20th century, dental syringes appeared, on which the cannula of the needle was screwed and there were stops for fingers and palms (Fig. 1). In 1921, Cook proposed a carpule syringe, which was loaded with a cylindrical carpule (Fig. 2).

For anesthesia, a 0.5-1% solution of cocaine was used, to which adrenaline was later added.

In 1905, A. Enpogp discovered an anesthetic of the ether series - novocaine (second generation anesthetic). Began "competitive struggle" between cocaine and novocaine.

Cocaine is more toxic than novocaine, besides, it played a significant role drug addiction. Novocaine won, which is much safer than cocaine. But the weak novocaine could not satisfy

Rice. 1. Fisher's dental syringe (A.Zh. Petrikas, 1987)

Rice. 2. Cook's dental syringe (loaded with a carpula through the back of the hinged body) (A.Zh. Petrikas, 1987)

rite doctors, infiltration

Noe anesthesia carried out by him was ineffective. The era of conduction anesthesia began, the founder of which in our country was S.N. Weissb-lat.

An important step in the development of local anesthesia was the discovery in 1943 of N. bo^amide anesthetics third generation -yashsh- ina and trimecaine. Lidocaine has become one of the leading anesthetics, and in our country the anesthetic trimecaine, tested by Yu.I. Vernadsky (1972).

The next step was anesthetics. fourth generation - prilocaine (C. Tegner, 1953), mepivacaine and bupivacaine (A.F. EkeShat, 1957), which are less dependent on a vasoconstrictor, have a better analgesic effect.

Improvement of the properties of local anesthetics continued: new anesthetics appeared fifth generation- etidocaine (B. Takman, 1971) and articaine (J.E. Winter, 1974), according to their data, significantly superior to their predecessors;

°| ................. .________________

stvennikov. The development of new anesthetics continues today.

Summing up the 100-year development of local anesthesia, it can be divided into 3 stages:

FIRST- the use of a strong anesthetic (cocaine), dental and carpool syringes for high-quality infiltration anesthesia. It must be admitted that the technique of infiltration anesthesia and the prototype of injection instruments were developed at the beginning of the 20th century.

SECOND- Weak novocaine has become the main anesthetic and therefore conduction anesthesia is widely used. Even when the teeth of the upper jaw are removed, conduction (infraorbital and tuberal) anesthesia is used, in which a relatively large number of complications associated with damage to the blood and nerve trunks are observed. But conduction anesthesia with novocaine did not always satisfy dentists, especially with complex tooth extractions, treatment of pulpitis under anesthesia, etc.

THIRD PERIOD began in the 70s of the XX century. with the use of lidocaine and other strong anesthetics. The widespread use of carpool syringes and modern anesthetics in our country began in the 90s.

The development perspective is focused on the safety and efficacy of local anesthesia:

1) the use of powerful anesthetics of a new generation that can be used independently (without vasoconstrictors);

2) introduction into clinical practice of the most modern designs of syringes and needles;

3) development and improvement of local anesthesia methods that can provide high-quality anesthesia with minimal doses of anesthetic.

Currently, to enhance the action of the anesthetic and exsanguination operating field use the vasoconstrictor adrenaline, which causes a number of common complications.

Sometimes it is replaced with synthetic drugs posterior pituitary gland: filipresin, ornipressin and others, which have much less effect on general state organism, but more often use an anesthetic with a low content of adrenaline (1:200,000).

Due to the significant analgesic effect of the standard anesthetic, a simpler and safer method of infiltration anesthesia will continue to progress in the future. There is a prospect of replacing infiltration conduction (mandibular) anesthesia for anesthesia of the lower molars.

In parallel with the creation of new local anesthetics, injection tools are also being improved: the so-called self-aspirating cartridge syringes have been developed, the design of which prevents the introduction of anesthetic into the vessel. There are carpool injectors that inject a small amount of anesthetic solution (0.06 ml) under high pressure and provide high-quality performance of intraligamentary and intrapulpal anesthesia.

Currently, an injector with a dosing wheel for intraligamentary anesthesia has been created, which provides high-quality anesthesia of the teeth and prevents the occurrence of post-injection complications.

The created injection instrumentation allows for anesthesia minimal doses of anesthetic, which prevents the occurrence of common complications, as well as more economical use of expensive modern anesthetics, which, in addition to medical, gives a significant economic effect.

CHARACTERISTICS OF ANESTHETICS

Local anesthetics

Local anesthesia - the main method of anesthesia, carried out during an outpatient dental appointment. Local anesthetics are subject to the following requirements:

1) they must have a strong analgesic effect, easily diffuse into tissues and stay there for as long as possible;

2) have low toxicity and, accordingly, cause a minimum number of both general and local complications.

Behind last years About 100 local anesthetics appeared, mainly based on lidocaine, mepivacaine, articaine and bupivacaine hydrochloride. This makes it possible to choose the most effective and safe drug for pain relief.

Local anesthetics are divided into 2 groups according to their chemical structure: esters and amides.

I. Esters:

1) anesthesin; 2) dikain; 3) novocaine.

II. Amides:

1) trimekain; 2) pyromecaine; 3) lidocaine; 4) mepivacaine; 5) prilocaine; 6) articaine; 7) bupivacaine; 8) etidocaine. Anesthetic molecules are weak bases and consist of three parts:

Lipophilic pole (aromatic group);

Hydrophilic pole (amino group);

An intermediate chain with an ether or amide compound (with other molecules).

CHARACTERISTICS OF ANESTHETICS

Essential compounds are relatively unstable. Rapidly degraded in plasma, low toxicity. Amide compounds are much more stable, better withstand the decrease in pH that occurs during inflammation, have a higher degree of penetration into tissues and provide more effective pain relief (Table 1).

Table 1. Modern dental local anesthetics

Aromatic Intermediate Amino Group

chain group

i^\ ESSENTIAL x.N,

! /k^Sr---- coaxial^----- m< на Тетрака

(ABOUT)""gmnsosn, n4 on -sn, with" n =

AMIDE
CH, / "- H

H,S \0)^ ~ TCHNSOSgG; NN

Na Meeokyann
"SN, CH n; (trvim: ■

@---- insoog-g/,

On Mepiwhain ■sn,

sn, s, n "Bupivzhinp

\y^^~ mk fsn;m\ on

1CHNSOSN"; N4 ""On Egndokani

sn, ^^ sn, s > n "

n, s-- p--- -p - knsosdg- m \ „

And

^coosn sn -

12 ______________ ^ = ^ == ________

Similar information.

M local anesthesia - switching off the sensitivity during direct contact of the drug with nerve conductors and receptors without turning off consciousness, reflexes and muscle tone (unlike anesthesia). Local anesthetics - these are drugs that cause a reversible inhibition of the conductivity and excitability of receptors and conductors when applied to them.

Classification by chemical structure : 1) complex Esthers of amino alcohols and aromatic acids cocaine (benzoic acid derivative), novocaine, dicaine, anestezin (para-aminobenzoic acid derivatives) , 2) substituted acid amides .- xicaine (lidocaine) and trimecaine (xylidine derivatives), sovcaine (cholinecarboxylic acid derivative). Drugs with an amide bond have a longer duration of action than anesthetics with an ether bond, which is destroyed by blood and tissue esterases.

For the manifestation of the anesthetic effect, anesthetics must undergo the following transformation steps: 1) the anesthetic salt used is highly soluble in water, but poorly in lipids, therefore it droops weakly through the membranes and does not have an anesthetic effect; 2) in the tissue fluid, the anesthetic salt turns into a non-ionized lipophilic base, which penetrates well through the membranes; 3) the base of the anesthetic acquires a cationic form, which interacts with receptors inside the sodium channels of the membranes, as a result of which the passage of sodium (and potassium) ions through the channels of the membranes is disrupted. This prevents the occurrence of the action potential and causes a block in the conduction and generation of impulses. Competitive interaction with calcium ions, which regulate the "opening-closing" of ion channels, is also important. This shows an analogy with the action of local and general anesthetics: both block the generation of excitation in the membranes. Therefore, narcotic substances (ether, etc.) can cause local anesthesia, and local anesthetics, when administered intravenously, can cause general anesthesia. With this, obviously, the potentiating effect is associated with the combined use of local anesthetics. narcotic, hypnotic and analgesic drugs.

Local anesthetics block the conduction of excitation in all types of nerve fibers: sensitive, motor, vegetative, but with different speed and at different concentrations. The most sensitive to them are thin non-fleshy fibers, along which pain, tactile and temperature sensitivity is carried out, then sympathetic fibers, which is accompanied by vasodilation, and lastly motor fibers are blocked. Restoration of impulse conduction proceeds in the reverse order.

Local anesthesia develops only with direct contact with the anesthetic. With a resorptive action, the central nervous system is paralyzed before local sensitivity is eliminated.

Neutralization of anesthetics carried out by biotransformation. Substances with an ether bond are hydrolyzed by esterases: novocaine by plasma cholinesterase, cocaine, dicaine, anestezin by liver esterases. Biotransformation of anesthetics with an amide bond occurs in the liver by its destruction (eg, lidocaine). The decay products are excreted by the hepatic circulation. Decreased hepatic blood flow leads to a prolonged half-life and an increase in blood concentration, which can lead to intoxication. Anesthetics easily penetrate the lungs, liver, kidneys, central nervous system, through the placenta. If a significant amount of a substance enters the blood, there is toxic effect: excitation, then paralysis of the centers of the medulla oblongata. This is manifested first by anxiety, shortness of breath, increased blood pressure, pallor of the skin, fever, and then - respiratory and circulatory depression. In case of intoxication, oxygen, artificial ventilation of the lungs, intravenous administration of barbiturates, sibazon, adrenaline, norepinephrine are used. Allergic reactions are most commonly caused by ester-linked anesthetics, especially novocaine. The most dangerous of these is anaphylactic shock.

Local anesthetics are used for the following types of anesthesia:

Terminal (terminal, surface, application) - by applying an anesthetic to the mucous membranes. Apply anesthetics that are well absorbed through the mucous membranes (cocaine, dicaine, lidocaine, anestezin). They are used in otorhinolaryngology, ophthalmology, urology, dentistry, in the treatment of burns, wounds, ulcers, etc. Conductor (regional) - blockade of nerve fibers. In this case, the conduction of impulses to the central nervous system is disrupted and sensitivity is lost in the area that is innervated by this nerve. Novocaine, lidocaine, trimecaine are used. One of the options for this anesthesia is spinal, which is carried out by introducing an anesthetic into the subdural space. infiltration anesthesia is carried out by layer-by-layer impregnation of tissues with anesthetic solution. This turns off the receptors and conductors. Novocaine, lidocaine and trimecaine are used. This type of anesthesia is widely used in surgery. Intraosseous anesthesia is carried out by introducing an anesthetic into the cancellous bone, a tourniquet is applied above the injection site. The distribution of the anesthetic occurs in the tissues of the limb. The duration of anesthesia is determined by the allowable period of application of the tourniquet. This type of anesthesia is used in orthopedics and traumatology. Choosing the type of anesthesia depends on the nature, volume and trauma of the surgical intervention. For each type of anesthesia, there are drugs of choice and technique of execution. The choice of anesthetic depends on the ability to droop into the mucous membranes, on the strength and duration of action and toxicity. For diagnostic and low-traumatic interventions on superficially located areas, terminal anesthesia is used. For infiltration, conduction and intraosseous anesthesia, low-toxic and relatively safe agents are used. For spinal anesthesia, scowcaine, which has a strong and long-lasting effect, as well as lidocaine, is usually used. It is important to choose the right concentration of the solution. Weakly concentrated solutions, introduced in large quantities, spread widely in tissues, but diffuse poorly through membranes, while concentrated solutions in small quantities spread worse, but diffuse better. The effect does not depend on the total amount of anesthetic, but on that part of it that penetrates into the nerve formations. Therefore, an increase in the amount of solution does not yet mean an increase in the anesthetic effect, often this only leads to an increase in the toxic effect.

During anesthesia of well-vascularized tissues (face, oral cavity, pharynx, larynx, etc.), the anesthetic is absorbed quickly, which can lead to intoxication. To reduce this effect and prolong the effect of the drug, vasoconstrictor drugs (adrenaline, norepinephrine) are added. In this case, the concentration of adrenaline should not exceed 1:200,000 (1 ml per 200 ml of anesthetic), since adrenaline itself can cause tachycardia, hypertension, headache, and anxiety.

Characteristics of individual anesthetics. Cocaine - alkaloid from the leaves of Erythroxylon Coca, native to South America. It is well absorbed, anesthesia occurs in 3-5 minutes, the duration of the effect is 30-60 minutes. It has a pronounced sympathomimetic effect, inhibiting the reverse neuronal uptake of norepinephrine, dopamine and serotonin in synapses. This is accompanied by stimulation of the cardiovascular system and central nervous system and the development of addiction. The action on the central nervous system is manifested by euphoria, anxiety, agitation, which can progress to psychosis with hallucinations, confusion, paranoid thinking, convulsions, vomiting, cardiac arrhythmias. This is due to the dopaminergic and serotonergic effects of cocaine. Vascular spasms, increased blood pressure, tachycardia, decreased appetite are the result of an adrenomimetic effect. Symptoms of excitation during intoxication are quickly replaced by depression of the central nervous system, respiration and blood circulation. Children are especially sensitive to cocaine. Death usually occurs from paralysis of the respiratory center. To provide emergency care, thiolental sodium, diazepam, chlorpromazine are administered intravenously, artificial ventilation of the lungs is carried out. Cocaine addiction occurs when long-term use cocaine and leads to intellectual and moral degradation. Abstinence (abstinence disease) is manifested by mental and autonomic disorders. Novocaine in terms of the strength of the anesthetic effect, it is 2 times inferior to cocaine, but 4 times less toxic. Used for infiltration (0.25-0.5%), conduction (1-2%) anesthesia and for various types of blockades. Valid for about 30 minutes. In case of an overdose, it causes an increase in reflex excitability, nausea, vomiting, a drop in blood pressure, weakness, and respiratory failure. Often there is idiosyncrasy (rash, itching, swelling of the subcutaneous tissue, dizziness). In case of intoxication, thiopental sodium, diazepam, ephedrine, strophanthin, and artificial respiration are prescribed.

Decain it is 15 times more potent than novocaine, but 10 times more toxic than it and 2 times more toxic than cocaine. Used for superficial anesthesia of the mucous membranes, children under 10 years of age are contraindicated. Lidocaine (Xycaine) acts stronger and longer than novocaine 2-3 times. It is used for all types of anesthesia. Well tolerated, but with rapid absorption may cause collapse. Trimecain 2.5-3 times stronger than novocaine and less toxic. Its properties are close to lidocaine. Used for infiltration and conduction anesthesia, sometimes for terminal (2-5%). scoops 15-20 times stronger than novocaine and 6-8 times longer than its duration of action, therefore it is convenient for spinal anesthesia. However, the toxicity exceeds novocaine by 15-20 times, and therefore it is dangerous for infiltration and conduction anesthesia.

M-, N-cholinomimetic drugs: classification, mechanisms of action, main effects, use, side effects. Clinic of acute poisoning with muscarine and M-, N-cholinomimetics indirect action. Help measures. Anticholinesterase agents.

M -cholinergic receptors are excited by fly agaric venom muscarine and blocked by atropine. They are located in nervous system And internal organs receiving parasympathetic innervation (cause depression of the heart, contraction of smooth muscles, increase the secretory function of the exocrine glands) (Table 15 in lecture 9). M-cholinergic receptors are associated with G-proteins and have 7 segments that cross, like a serpentine, the cell membrane.

Molecular cloning made it possible to isolate five types of M-cholinergic receptors:

1. M 1 -cholinergic receptors CNS (limbic system, basal ganglia, reticular formation) and autonomic ganglia;

2. M 2 -cholinergic receptors hearts (reduce heart rate, atrioventricular conduction and myocardial oxygen demand, weaken atrial contractions);

3. M 3 -cholinergic receptors:

smooth muscles (cause constriction of the pupils, spasm of accommodation, bronchospasm, spasm of the biliary tract, ureters, contraction Bladder, uterus, increase intestinal motility, relax sphincters);

glands (cause lacrimation, sweating, copious separation of liquid, protein-poor saliva, bronchorrhea, secretion of acidic gastric juice).

· extrasynaptic M 3 -cholinergic receptors are located in the vascular endothelium and regulate the formation of a vasodilator factor - nitric oxide (NO).

4. M 4 - and M 5 -cholinergic receptors have less functional significance.

M 1 -, M 3 - and M 5 -cholinergic receptors, activating through G q /11-protein phospholipase C of the cell membrane, increase the synthesis of secondary messengers - diacylglycerol and inositol triphosphate. Diacylglycerol activates protein kinase C, inositol triphosphate releases calcium ions from the endoplasmic reticulum,

M 2 - and M 4 -cholinergic receptors with the participation G i - And G 0-proteins inhibit adenylate cyclase (inhibit cAMP synthesis), block calcium channels, and also increase the conductivity of the potassium channels of the sinus node.

· Additional effects M-cholinergic receptors - mobilization of arachidonic acid and activation of guanylate cyclase.

· N-cholinergic receptors excited by the tobacco alkaloid nicotine in small doses, blocked by nicotine in large doses.

Biochemical identification and isolation of H-cholinergic receptors became possible due to the discovery of their selective high-molecular ligand -bungarotoxin, the venom of the Taiwan viper Bungarus multicintus and cobras Naja naja. H-cholinergic receptors are located in ion channels, within milliseconds they increase the permeability of the channels for Na +, K + and Ca 2+ (5 - 10 7 sodium ions pass through one channel of the skeletal muscle membrane in 1 s).

1. Cholinomimetic drugs: a) m-n-cholinomimetics of direct action (acetylcholine, carbachol); b) m-n-cholinomimetics of indirect action, or anticholinesterase (physostigmine, prozerin, galantamine, phosphacol); b) m-choliomimetics (pilocarpine, aceclidin); c) n-cholinomimetics (lobelin, cytiton).

2. Anticholinergic drugs: a) m-anticholinergics (atropine, platifillin, scololamin, hyoscyamine, homatropine, metacin); b) n-anticholinergic ganglion blockers (benzogexonium, pentamine, pahikarpine, arfonad, hygronium, pyrilene); muscle relaxants (tubocurarine, dithylin, anatruxonium).

Cholinomimetic drugs. Mn-cholinomimetics of direct action. ACH is rapidly destroyed by cholinesterase, therefore, it acts for a short time (5-15 minutes with s / c administration), carbacholin is destroyed slowly and acts up to 4 hours. These substances produce all the effects associated with the excitation of cholinergic nerves, i.e. muscarine- and nicotine-like.

Excitation m-XR leads to an increase in the tone of smooth muscles, an increase in the secretion of the digestive, bronchial, lacrimal and salivary glands. This is manifested by the following effects. There is a narrowing of the pupil (miosis) as a result of contraction of the circular muscle of the iris of the eye; a decrease in intraocular pressure, since when the iris muscle contracts, the helmet canal and fountain spaces expand, through which the outflow of fluid from the anterior chamber of the eye increases; spasm of accommodation as a result of contraction of the ciliary muscle and relaxation of the ligament of zon, regulating the curvature of the lens, which becomes more convex and is set to the near point of vision. The secretion of the lacrimal glands increases. On the part of the bronchi, there is an increase in the tone of smooth muscles and the development of bronchospasm, an increase in the secretion of bronchial glands. The tone increases and the peristalsis of the gastrointestinal tract increases, the secretion of the digestive glands increases, the tone of the gallbladder and biliary tract increases, the secretion of the pancreas increases. The tone of the bladder, ureters, urethra increases, the secretion of sweat glands increases. Stimulation of m-ChR of the cardiovascular system is accompanied by a decrease in heart rate, slowing of conduction, automaticity and contractility of the myocardium, and vasodilation skeletal muscle and pelvic organs, lowering blood pressure. Excitation n-XR manifested by increased and deepening of breathing as a result of stimulation of the receptors of the carotid sinus (carotid glomeruli), from where the reflex is transmitted to the respiratory center. The release of adrenaline from the adrenal medulla into the blood increases, however, its cardiotonic and vasoconstrictive action is suppressed by inhibition of the heart and hypotension as a result of m-ChR stimulation. The effects associated with increased transmission of impulses through the sympathetic ganglia (vasoconstriction, increased heart function) are also masked by the effects due to the excitation of m-ChR. If you first enter atropine, blocking m-XR, then the effect of m-n-choliomimetics on n-ChR is clearly manifested. ACH and carbacholine increase skeletal muscle tone and can cause fibrillation. This effect is associated with increased transmission of impulses from the endings motor nerves on muscles as a result of n-ChR stimulation. In high doses, they block n-ChR, which is accompanied by inhibition of ganglionic and neuromuscular conduction and decreased secretion of adrenaline from the adrenal glands. These substances do not penetrate through the BBB, since they have ionized molecules, therefore, in usual doses do not affect the CNS. Carbacholin can be used to reduce intraocular pressure in glaucoma, with bladder atony.

· M-n-cholinomimetics of indirect action (anticholinesteoase). These are substances that stimulate m- and n-ChR due to the accumulation of ACH in synapses. MD is caused by inhibition of cholinesterase, which leads to a slowdown in ACh hydrolysis and an increase in its concentration in synapses. The accumulation of ACh under their influence reproduces all the effects of ACh (with the exception of respiratory stimulation). The above effects associated with the stimulation of m- and n-ChR are characteristic of all cholinesterase inhibitors. Their action on the central nervous system depends on penetration through the BBB. Substances containing tertiary nitrogen(physostigmine, galantamine, phosphacol), penetrate well into the brain and enhance cholinergic effects, and substances with quaternary nitrogen (prozerin) penetrate poorly and act mainly on peripheral synapses.

By the nature of the action on cholinesterase they are subdivided into reversible and irreversible action. The first ones are physostigmine, galantamine and prozerin. They cause reversible inactivation of cholinesterase, as they form an unstable bond with it. The second group consists organophosphate compounds (FOS), which are used not only in the form of drugs (phosphacol), but also for the destruction of insects (chlorophos, dichlorvos, karbofos, etc.), as well as as chemical warfare nerve agents (sarin, etc.). they form a strong covalent bond with cholinesterase, which is very slowly hydrolyzed by water (about 20 days). Therefore, the inhibition of cholinesterase becomes irreversible.

Anticholinesterase drugs apply with the following diseases: 1) residual effects after poliomyelitis, skull trauma, cerebral hemorrhage (galantamine); 2) myasthenia - a disease characterized by progressive muscle weakness (prozerin, galantamine); 3) glaucoma (phosphacol, physostigmine); 4) atony of the intestines, bladder (prozerin); 5) overdose of muscle relaxants (prozerin). These substances are contraindicated in bronchial asthma and heart disease with conduction disorders. poisoning most often occur when FOS, which have an irreversible effect, enter the body. Initially, miosis develops, disturbance of accommodation of the eye, salivation and difficulty in breathing, increased blood pressure, urge to urinate. Muscle tone increases, bronchospasm increases, breathing becomes difficult, bradycardia develops, blood pressure decreases, vomiting, diarrhea, fibrillar muscle twitching, attacks of clonic convulsions occur. Death, as a rule, is associated with a sharp violation of breathing. First aid consists in the introduction of atropine, cholinestease reactivators (diperoxime, etc.), barbiturates (to relieve convulsions), hypertensive drugs (mezaton, ephedrine), artificial lung ventilation (preferably with oxygen). M-cholinomimetics. Muscarine is not used due to its high toxicity. It is used in scientific research. Used as LS pilocarpine and aceclidine. MD of these drugs is associated with direct stimulation of m-ChR, which is accompanied by pharmacological effects due to their excitement. They are manifested by a constriction of the pupil, a decrease in intraocular pressure, a spasm of accommodation, an increase in the tone of the smooth muscles of the bronchi, gastrointestinal tract, bile and urinary tracts, an increase in the secretion of the bronchial, digestive glands, sweat glands, a decrease in automatism, excitability, conductivity and contractility of the myocardium, vasodilatation of skeletal muscles , genital organs, decreased blood pressure. Of these effects, a decrease in intraocular pressure and an increase in intestinal tone are of practical importance. Other effects are most often undesirable consequences: spasm of accommodation disrupts the adaptation of vision, depression of the heart can cause circulatory disorders and even sudden stop heart (syncope). Therefore, it is not recommended to administer these drugs intravenously. Lowering blood pressure is also undesirable. bronchospasm, hyperkinesis.

The action of m-cholinomimetics on the eye is of great importance in the treatment of glaucoma, which often gives exacerbations (crises), which are common cause blindness and therefore need emergency treatment. Instillation of solutions of cholinomimetics into the eye causes a decrease in intraocular pressure. They are also used for intestinal atony. Used for glaucoma pilocarpine, with atony aceclidine, which gives less side effects. M-cholinomimetics are contraindicated in bronchial asthma, impaired conduction in the heart, serious illnesses heart, with epilepsy, hyperkinesis, pregnancy (due to the risk of miscarriage). In case of poisoning m-cholinomimetics(most often fly agaric) first aid consists in gastric lavage and the introduction of atropine, which is an antagonist of these substances due to the blockade of m-ChR.

· N-holinominetics. Nicotine medicinal value does not have. When smoked together with tobacco combustion products, it contributes to the development of many diseases. Nicotine has high toxicity. Other substances are inhaled along with smoke from smoking. poisonous products: resins, phenol, carbon monoxide, hydrocyanic acid, radioactive polonium, etc. The craving for smoking is due to the pharmacological effects of nicotine associated with the excitation of n-ChRs of the central nervous system (cortex, oblongata and spinal cord), which is accompanied by a subjective feeling of increased performance. The release of adrenaline from the adrenal glands, which increases blood circulation, is also important. A large role in the development of attraction is played by habit and the psychological impact of the environment. Smoking contributes to the development of cardiovascular diseases (hypertension, angina pectoris, atherosclerosis, etc.), bronchopulmonary diseases(bronchitis, emphysema, lung cancer), gastrointestinal diseases ( peptic ulcer, gastritis). Getting rid of this bad habit depends primarily on the smoker himself. Some drugs (eg, tabex) containing cytisine or lobeline can help with this.

· lobelin And cytiton selectively stimulate n-ChR. Practical value has excitation of n-XR carotid glomeruli, which is accompanied by reflex excitation of the respiratory center. Therefore, they are used as respiratory stimulants. The effect is short-term (2-3 minutes) and is manifested only with a / in the introduction. At the same time, the work of the heart increases and blood pressure rises as a result of the release of adrenaline from the adrenal glands and the acceleration of impulse conduction through the sympathetic ganglia. These drugs are indicated for respiratory depression caused by carbon monoxide poisoning, drowning, neonatal asphyxia, brain injury, for the prevention of atelectasis and pneumonia. However, their medical value is limited. More often used analeptics of direct and mixed action.