Education students in the department are the third course on the subject “Pharmacology”. From subject “Pharmacology” student of pediatric and Medico-pedagogical faculty have 58 hours of lectures and 94 hours of practical lessons and 82 hours self study work. The chair is the main building of the institute, 4th floor right wing.
THE CONTENT OF PHARMACOLOGY AND ITS TASKS, AMONG OTHER MEDICAL DISCIPLINES, A BRIEF HISTORY OF THE DEVELOPMENT OF
Pharmacology is one of the most important and essential disciplines for the education of doctors. In the literal translation of “pharmacology” is the science of drugs (gr. pharmacon is drug, and logos is science). In the broad sense of the word pharmacology is the science that studies the qualitative and quantitative changes that occur in humans and animals under the influence of drugs. Pharmacological agents, once in the body of humans and animals, cause functional and morphological changes that can occur throughout the body or in specific organs, tissues, cells, cellular elements and biochemical structures. The pharmacology is closely related toxicology, the study of poisons. It should be noted that the exact boundaries between medicines and poisons can be arbitrary, as almost all drugs in high doses produce toxic effect. In order to objectively assess the success of pharmacology, correct to refer to history. To explain fully the history is not possible, as the pharmacology is one of hi most ancient branches of human knowledge and its beginning is lost in the mists of time. The history of pharmacology has the same length as the history of the human race. Papyrus, written for 3600 years B. C., and bearing the title “the Book of preparation of medicines for all parts of the body,” says applied at the time the substances of plant and animal origin for the treatment of various ailments. In the development of pharmacology, the large role played by ancient Oriental countries: India, Tibet, China and the Arab countries, widespread treatment of medicinal plants. Appreciating the works of scientists of all countries of the world, I would like to focus on the works of ancient scientists of Uzbekistan, made a great contribution to the development of pharmacology. Famous Tabib East Ibn Abbos (died 997) 9 centuries before the development of experimental pharmacology in his writings emphasized the necessity of studying new drugs on animals. Before we got 36 works from the field of medicine, including pharmacology, polymath and famous Tabib East Abu Bakr ar-Razi (865-928. An invaluable contribution to the development of the pharmacology of encyclopedic knowledge in the field of medicine, the famous doctor of all time Abu Ali Ibn Sina. In his work “the Canon of medicine”, “Book of healing” are medicines used in the XI century. In the first book “Canon of medicine” described about 900 common drugs, of which 612 vegetable origin, in the fifth book describes the methods of preparation and application of complex drugs. Ibn Sina emphasized the need for the use of medication depending on “miso” — nature of the patient and nature of the drug. Great contribution to the development of the pharmacology made famous encyclopaedist, known thinker Khorezm Abu Rayhan Beruni. In his work “his Empire”, which is an encyclopedia of the pharmacology of the East, he led all known in the eleventh century medicines from plants, minerals, animals. Scientist and Tabib Khorezm Ismoil Jurjani (1080-1141 he wrote more than 15 books on medicine. His treatise on pharmacology consists of two parts: the first provides a simple, second — sophisticated drugs and methods for their preparation. Umar Cimini (died in 1221) wrote a small Canon “Conuna”, devoted to medicine, which until the early twentieth century used not only at home scholar in Khorezm, Iran. Samarkand scientist and Tabib Nazimuddin of Samarqandi (died 1222) was composed of 8 scientific papers medicine but, one devoted to “methods for preparing complex drugs.” Yusuf al-Heravi (XV century) was a court physician celebrity Babur, the ruler of India..XVI century European scientist Paracelsus was the founder of chemical vitalistic direction of jatrohimii (ACROS doctor) has enriched medicine chemicals. In Russia even before the printing press existed handwritten “herbalists” in which were listed the methods of preparation and use of medicines. Great contribution to the development of various areas of pharmacology introduced by I. P. Pavlov, who led the experimental laboratory at the clinic of S. P. Botkin. He was the first Professor who taught a course in experimental pharmacology. Within 1891 1895, I. P. Pavlov headed the Department of pharmacology at the Military medical Academy.The founder of the national pharmacology is N. P. Maga-cov, which created the largest school of pharmacists. He developed many methods pharmacological studies. N. P. Kravkov wrote the textbook “Fundamentals of pharmacology”, which was reprinted 14 times. N. P. Kravkov, his students S. V. Anichkov, V. V. and nine others are the basis of modern pharmacology.The book is academician M. D. Mashkovsky “drugs” is a reference book for physicians. Academician D. A. Kharkevich written and many times reprinted the textbook “Pharmacology” for medical students. In Uzbekistan, the greatest development of this science associated with the opening of the laboratory of pharmacology at the Institute of chemistry of plant substances, Academy of Sciences of Uzbekistan, headed by Professor I. K. Kamilov. Currently in the field of pharmacology has over 20 doctors and 100 candidates of Sciences. As a result of scientific researches of the Uzbek pharmacologists in the clinic introduced a number of new drugs. One of the main tasks of pharmacology is the development of new drugs, comprehensively study and their introduction into medical practice. THE MAIN TOPICS OF PHARMACOLOGY. PRINCIPLES OF CLASSIFICATION OF MEDICINAL SUBSTANCES. Pharmacology is divided into General and private. General pharmacology studies the General laws of action of drugs, their pharmacokinetics and pharmacodynamics. Private pharmacology examines specific pharmacological groups and certain medications.Pharmacokinetics is exploring ways of drug administration, mechanisms of absorption, distribution, escrow, metabolism and excretion from the body.Pharmacodynamics studies the effects of drugs on the body, mechanism, types and location of operation, conditions that affect the development of the action of drugs.Classification of drugs is of great difficulty, as if they leeeeeroy on chemical structure, one group will get substances with different mechanism of action; be classified according to the effect on individual organs too difficult, as a number of drugs acting in different directions.Medicinal substances are classified according to their influence on a number of systems. They can be represented by the following groups: — substances that affect the peripheral innervation; — substances that regulate the function of the Central nervous system; — substances that regulate the function of the Executive bodies and their systems; — substances that regulate the metabolism. Shared by drugs that affect pathological processes such as atherosclerosis, inflammation, immunity, Allergy. In a special section proteomic detailed, antiparasitic agents, chemotherapy of malignant tumors. ROUTE OF DRUG ADMINISTRATION. Route of drug administration can be divided into two large groups. 1. Enteral path through the gastrointestinal tract. 2. Parenteral route — bypassing the gastrointestinal tract. Depending on ways of introduction of medicinal substances change the speed of their entry into the General circulation, strength, duration and nature of the action and speed their removal from the body. The choice of routes of administration depends on the condition of the patient, physical-chemical properties and duration of action of drugs. When enteral the way drugs are administered under the tongue sublingually, are not affected by enzymes in the gastrointestinal tract, they do not undergo metabolism in the liver and absorbed from the injection site into the blood. Oral route is the most used because is simple, convenient for the patient and allows for the introduction of different dosage forms without requiring their sterility. Drugs with an unpleasant odor and taste, and substances collapsing in the intestinal juice, is not administered orally. Almost without changes in the oral cavity, drugs come into the stomach; for the rate of absorption is significantly affected by the degree of filling of the stomach with food, its composition and the duration of stay. Drugs taken on an empty stomach (before eating), are absorbed faster and are stronger compared to taken after meals. The drugs are mostly absorbed in the small intestine. In children, especially in early age, the absorption is more intense, which is associated with the structural features of the walls of their intestines.Serous cavities (pleura, pericardium, peritoneum) have high suction capacity; through the abdominal cavity Medications are absorbed faster than pleural.Relatively the exact dosage and the rapid introduction of medicinal substances Into the General circulation provide subcutaneous, intramuscular and intravenous routes of administration. Subcutaneously injected aqueous solutions of medicinal substances, their absorption happens! after 10-15 minutes, the force of action is 2-3 times higher than when administered orally. Suspensions and oily solutions are not recommended to be administered subcutaneously, as they are slowly absorbed and can form infiltrates in tissues, up to necrotic changes.Intramuscular absorption of drugs from the muscle faster than in subcutaneous, due to the abundance of capillaries. Muscle tissue is less sensitive to irritating agents than subcutaneous tissue, intramuscularly injected water, oil solutions, suspensions.At intravenous introduction of the drug directly into the blood stream. They should be introduced slowly, as with the rapid introduction of blood high concentrations, which may have toxic effects. Using this way of introducing the effect of the drugs starts very quickly, even during the injection, but it is shorter in comparison with subcutaneous and intramuscular introduction. Intravenously, you cannot enter the substances that cause the formation of sludge and possess hemolytic properties.In the spinal canal is entered substance that does not penetrate the blood-brain barrier, subarachnoid and PE-ridaranno. Medicinal substances are introduced nutriental-sexual, as well as directly to the heart, joints, bones and by iontophoresis.When it comes to injecting, I mean mostly subcutaneous, intramuscular, intravenous routes of administration. THE ABSORPTION, DISTRIBUTION, METABOLISM AND EXCRETION OF DRUGS. Drugs, once in the gastrointestinal tract, pass through biological membranes and absorbed into the bloodstream. The absorption is a complex physiological process. Biological semi-permeable membrane, so some drugs pass through it, and some don’t. The membrane of the intestinal epithelium is permeable in one direction only, so the vast majority lekarstvennyh substances, souvlis in the blood and lymph, unable to get back into the intestinal lumen.The process of absorption of drugs entered the pen is taken orally, is carried out through the following mechanisms: passive diffusion, facilitated diffusion, filtration, pinoci the Tosa and active transport. The vast majority of drugs are absorbed by passive diffusion. Passive diffusion. These are absorbed by the lipophilic drug (non-polar) substances, and the higher Lee-povinnosti, so they are easier to penetrate the cell membrane. The light diffusion. When her drug molecules bind to a specific part of cell membranes and their absorption is facilitated in comparison with passive diffusion. The light diffusion also occurs without the expenditure of energy on the concentration gradient. In this way absorbed purine and pyrimide-new grounds, nucleic acids. Filtering. When her drugs pass through the pores of the membranes. Due to the fact that the lumen of the small (0.4 nm) after they absorbed the liquid, some ions and small hydrophilic molecules (urea). The absorption by filtering also does not require expenditure of energy and depends on the degree of concentration. When pinocytosis in the cell membrane intussusception occurs, bubbles are formed, they receive the drug substance and the liquid, which go inside the cage and out of the bubbles. This process is also passive. Active transport. It medicines are absorbed against a concentration gradient that requires energy and participation transports enzyme systems, so when metabolic absorption by active transport slows down. By active transport of absorbed water-soluble hydrophilic polar molecules, inorganic ions, sugars, amino acids and pyrimidine bases. In children of early age immature enzyme system, therefore the process of absorption of medicinal substances by active transport them underdeveloped. After absorption into the blood medicinal substances introduced orally, the liver. It is a physiological barrier that protects the body from foreign substances, and filter the blood. In the liver of the drug substance disinfected, undergo metabolism, changing their chemical structure, as in the liver, are all of these processes, the circulation in it mainly venous, venous blood flows slowly, the medicinal substances are in them for a long time and undergo metabolism. Sucked into the blood, they are in free or bound to proteins (albumin). The drug contained in plasma in the free state, permeates through the walls of blood vessels in tissue. Protein-bound drug does not penetrate into the tissues, accumulates in the vessels, then, gradually freeing itself from proteins already in the free state penetrates the tissues. If for some reason reduced albumin content (premature infants, diseases of the liver, impaired synthesis of albumin, increased their allocation), then it reduces the number of related forms and increases the amount of drug in the free state. In the tissues of medicinal substances bind to receptors. This is an active group of macromolecules substrates interacting with the substance. Receptors, which manifests the effect of drugs, called specific. This adenosine, benzodiazepine, angiotensin, the histo-minovia, opioid, serotonine, bradykinesia receptors, adrenergic receptors, cholinergic receptors, GABA receptors, and others. In turn, specific receptors have subtypes, such as distinguish d, C, subtypes of opioid receptors. Substances that interact with specific receptors cause changes that lead to a biological effect, are called agonists. If the agonist, interacting with the receptor causes the maximum effect, it is called a full agonist. Substance that binds to a receptor but do not cause their stimulation, reduce or prevent the action of agonists, are called antagonists. For example, the ACO-milholin and atropine bind the same receptor (M-choline receptors), but the opposite effect, so they are antagonists. A substance that acts as an agonist on one subtype and the antagonist at different subtypes of receptor, called agonist-antagonist. In the body there are also non-specific receptors, which bind the drug. This is a plasma proteins, Moo-copolyamide connective tissue and others. When communicating with non-specific receptors drugs do not take effect, therefore, these receptors are called “space loss” substances, to be exact — “places nonspecific binding”. Medicinal substance after absorption evenly distributed in the body and uneven. So, inhaled drugs are distributed evenly. There is no certain connection between the distribution of drugs in the body and induced effects, the accumulation of a substance does not always lead to the strengthening of its action on that organ. On the distribution of drugs has an impact occurring on their way biological barriers, which include: the wall of the capillaries, the blood-brain barrier, a membrane serous cavities and, of course, in all of them is a barrier membrane of cells. Medicinal substances taken by pregnant women, pass through the placental barrier. Lipophilic substances penetrate well through it. Most drugs undergo in the body metabolism. This process involves microsomal liver enzymes, lipophilic substances can turn into water-soluble metabolites. Biotransformation occurs by metabolic transformation and conjugation. When metabolic transformation changes occur due to oxidation, recovery and hydrolysis of drugs. In the process of conjugation of the drug substance or their metabolites combine with other chemical groups —methyl, acetylamino, sulfate and glchronology acid. Together with the absorption and distribution begins the process of excretion of drugs from the body in an unmodified form and in the form of products of their transformation. The excretion of drugs from the body occurs through excretion by the kidneys, intestines, lungs, and tear, digestive, mammary glands, and the epidermis of the skin. Elimination — total result of inactivation of drugs in body tissues and their excretion in different ways. To characterize the elimination determine the half life of the drug, i.e. the time from the body to eliminate half the administered dose, and the quota elimination — the amount of the drug (in percent) allocated a day after a single dose. Medicines have a local resorptive action, reflex, basic, reversible, irreversible. side effects on other organs and systems. Types of drug therapy. Etiotropic therapy. When the effect of the drugs aimed at eliminating the causes of the disease. For example, the effect of antibiotics is focused on microorganisms that cause one or another infectious disease. Etiotropic drug therapy is the most effective.Symptomatic therapy aimed at the elimination of certain symptoms, for example, the elimination of pain, reduction of temperature. The disappearance of pain as a result of analgesics or reducing high temperature antipyretics improves the General condition of patients, but does not eliminate the cause of the disease. So, eliminating severe pain in myocardial infarction, it is possible to prevent the development of painful shock. Sometimes, the use of symptomatic therapy may obscure the clinical picture and make diagnosis of the disease. Replacement therapy is used in diseases associated with a lack of natural metabolites which are active in physiological processes in the body. As a substitution therapy used hormonal, vitamin preparations in diseases associated with their deficiency in the body.For example, in diabetes mellitus (lack of insulin) administered hormonal drug insulin, hypovitaminosis D — rickets, prescribed drug vitamin ergocalciferol. When pathogenetic therapy effect of the drug is aimed at the individual links of the pathogenesis of the disease. Prophylactic therapy aimed at preventing diseases, especially infectious (action proteomica-tions, disinfectants, antiseptics), with especially dangerous infections.
LECTURE number 2
THE MECHANISM OF ACTION OF DRUGS
The mechanism of action of drugs is studied on re-Capernaum, biomolecular, membrane level and poses a challenge, evidenced by the fact that the mechanism of action of some substances not yet installed. There are the following mechanisms of action of drugs. Due to the similarity of chemical structure to the natural metabolites of the body — hormones, vitamins, neurotransmitters involved in conducting nerve impulses, they participate in biochemical processes and have a corresponding pharmacological effect. Some drugs have a similar chemical structure to natural metabolites produced during the metabolism, and due to the competitive antagonism take their place and stop for normal biochemical processes. For example, such is the mechanism of action of sulfonamides, antihistamines, anticholinergic drugs. Any medicine due to its physico-chemical properties associated cellular proteins that modify the solubility, molecular structure, resulting in disturbed functional activity up to complete cell death. This is the mechanism of action of many antimicrobial agents. Drugs can inhibit the activity of enzyme (cholinesterase, monoamine oxidase) and to protect from destruction of natural neurotransmitters —acetylcholine, noradrenaline and increase their functional activity. The mechanism of action of drugs may be due to their effect on the ratio of the electrolytes Na, K, CA, Mg, etc., they change the environment, against which manifests the action of enzymes, proteins and other cellular components. As a result changes the excitability of the cells, the contractility of muscle fibers and in some cases violated biochemical processes, such a mechanism of action characteristic of diuretics, cardiac glycosides. The mechanism of action of certain drugs can be explained by their effects on ion channels. For example, local anaesthetics, by binding to the receptor, block the voltage gated sodium channels; some anti-septicemia drugs also block voltage gated sodium channels and inhibit irradiation of excitation. Of great practical importance are drugs that block the slow voltage gated calcium channels. The action of drugs depends on the dose. Dose is the amount of substance having a therapeutic effect after a single use. Doses in which the drug is called primary therapeutic effect, called a threshold, or minimum current. In the practice of medicine generally use the average therapeutic dose, which have a pronounced therapeutic effect in most patients. If you assign average therapeutic doses the effect of drugs is expressed is not sufficient, increase the dose to the highest therapeutic. Higher doses of toxic and potent substances described in the State Pharmacopoeia. Denote yet toxic doses that cause acute poisoning them, as well as a lethal dose. In the application of medicines, the importance of the breadth of pharmacological action — the difference between the minimum toxic and therapeutic dose, the larger it is, the safer the drug. Depending on the multiplicity of doses are distinguished: single-single (pro dosi), daily (pro die); if a single dose is divided into several stages, it is called split. If an appointment is assigned dose, 2-3 times higher than the therapeutic, it’s called shock; the dose intended for a course of treatment, are referred to as foreign exchange. The action of drugs depends on the time of reception during the day — circadian rhythms. Chronopharmacology — section of pharmacology that studies the effects of drugs depending on daily perio-Disma. So, it is established that the analgesic effect of morphine more pronounced in the second half of the day, and nitroglycerin — when taken in the morning. Depending on the time of day the effect of the drugs may change not only quantitatively, and sometimes qualitatively. Chronopharmacology includes both chronopharmacokinetics and chronopharmacokinetics. The action of drugs depends on their content in blood and quantities held in the free state. So, introduced oral medications are subjected to the action of enzymes in the gastrointestinal tract, metabolized in the liver, thereby reducing the amount that enters the blood, increased “bioavailability”. As indicated above, the action of drugs depends on the condition of the body. The action of drugs depends on gender: women are more sensitive to them in connection with the physiological characteristics of the organism (menstrual cycle, pregnancy, breastfeeding).The action of drugs depends on the mass of the body — face overweight are less sensitive to them than skinny. The action of drugs depends on the individual characteristics of the organism — “micasa”, literally translating the word difficult, most closely fits the word nature. The dependence of the action of drugs from the “micasa” known since the time of Hippocrates and Galen. Further development of the theory of “micasa” was in the works of Abu Ali Ibn Sino. Type “micasa” sum of the ratios of the following body fluids: blood, phlegm, yellow and black bile. The blood represents the warmth and humidity, mucus — coldness and wet, yellow bile — cold and dry, black bile — the warmth and dryness. According to Ibn Sina, there are 2 types of “micasa”: the first type is a balanced, calm, in such a case the liquid is distributed evenly, the second type of unbalanced, irritable, when fluid is not evenly distributed. Types “of miasa” can be simple or complex, depending on this there are 8 kinds of “micasa”: hot — cold, dry —wet, hot —dry, hot — humid, cold —dry, cold —wet. Most common complicated “migos”. Ibn Sina notes that each body, each body having its “migos”. For example, brain cold —wet “migos”, spleen — cold-dry, heart —warm-wet, liver — hot-dry. “Migos” depends on the gender, age, place of residence. In women more common cold-wet “migos” the teenagers — hot-wet, older — cold-dry “migos”. REPEATED AND COMBINED USE OF DRUGS. With repeated use of drugs there is a strengthening or weakening their effect. Chronic administration of the drugs weakened their therapeutic action, it is addictive or tolerance; tolerance is more likely to occur to some sleeping pills, cathartic means. Its occurrence is related to slower absorption and metabolism, excretion, and^ decreased sensitivity of receptors to certain drugs.’The effect of drugs also decreases with repeated use them over short periods of time. This is called tachyphylaxis (gr. tachys fast, phylaxis — protection) — fast organism protection. For example, with a sharp decrease in blood pressure is assigned to intravenous ephedrine. When you first apply pressure markedly increases with repeated use after 5-10 minutes the action of ephedrine already expressed to a lesser extent than in the first establishment. With repeated use of drugs may increase the sensitivity to them, which is called sensitization. Some of the drugs with repeated moves accumulate in the body — this condition is called cumulation, thereby increasing their strength and duration. Cumulation can be of two types: material at which there is an accumulation of the substance, and functional, which accumulates when the effect of the drug. For example, qualiwed effect of ethanol, while he himself, oxidized, rapidly excreted from the body, not lingering in the tissues. Some of the drugs with repeated applications, acting on the human psyche, cause a pleasant euphoria, slight agitation, indifference, resulting in a desire to take them again — so developing an addiction to them. It is often observed to drugs that affect the Central nervous system — morphine, caffeine, morphine, cocaine, ethyl alcohol, barbiturates, and some other. In these cases it develops mental and physical dependence to the drug — addiction. If you cancel the drug there is a feeling of deprivation is abstinence, however, there are mental disorders, mood changes, severe anxiety, tachycardia, feeling hot. Even heavier physical dependence occurs when a drug becomes a natural metabolite of the body. In this case, deprivation leads to profound changes in organs and systems, can even be fatal. Preventing mental and physical dependence on drugs is of national significance. COMBINED USE OF MEDICINES. The combined use of medicines as a result of their interaction may increase the effect — this process is called synergy (gr. syn —together, ergo —work). When synergy occurs summation and potentiation of the action. If the overall effect of two or more drugs is enhanced by simple arithmetical summation of each of them separately, this is called summation. If the overall effect of the combined drugs is superior to a simple summation, this is called potentiation. Synergies can be direct and indirect. Direct synergies the action of the drugs is enhanced by their influence on the same biochemical structure, if their action is enhanced by the effect on different biochemical structure, such synergies is called indirect. If you use two or more drugs their action is weakened, it is termed antagonism (gr. anti — against, ago — the struggle). Antagonism may be direct or indirect. If the effect of drugs is reduced at the expense of their influence on the same biochemical structure, are in direct antagonism, if the reduction is due to the effect on different biochemical patterns — indirect antagonism. Depending on the strength of oppositely-acting drugs antagonism is one-sided and two-sided.The antagonism between the drugs used in first aid in case of acute poisoning.
When prescribing two or more drugs at the same time needed to consider their pharmaceutical, pharmacokinetic, Phar-macodynamics interoperability and compatibility.
LECTURE – 3
SUBSTANCES THAT AFFECT THE AFFERENT INNERVATION
SUBSTANCES WHICH REDUCE SENSITIVITY IN THE AREA OF AFFERENT NERVES ENDINGS
These include local anesthetic, astringent, enveloping, emollient and absorbent means.
LOCAL ANESTHETIC MEANS.
Cocaine hydrochloride, tetracaine, novocaine, trimekain, lidocaine (xtain), bupivacaine, benzocaine.
Local anesthetic means reversibly inhibit the conductivity and excitability in sensory nerve endings. In the first turn, reduces pain sensitivity, while higher doses inhibited and the other kinds of sensitivity. Acting on the end of the sensitive nerves, local anesthetics prevent the generation and conduction of excitation. For obtaining local anesthesia in surgical practice used volatile liquid. In 1879 Russian scientist V. K. EN-rap suggested for local anesthesia alkaloid cocaine isolated from the Coca plant Erytroxylon, native to South America. In 1884 cocaine became used in ophthalmologic operations. However, due to toxicity and the development of addiction to it, cocaine has been applied in the as-neoestetologica products in other surgical interventions. The joint efforts of chemists and pharmacologists synthesized above local anesthetic funds. In chemical structure, they are aromatic esters (benzoic and p-aminobenzoic acids): procaine, di-Cain, benzocaine, and their Amida — lidocaine (xtain), trimekain (forms. 1). They do not dissolve in water, as are tertiary amines, their hydrochlorides are used is a water — soluble salt. To obtain a local anesthesia is required the hydrolysis of this salt and the formation of the base; hydrolysis of the salts takes place in the alkaline environment of the tissues (pH of 7.35 and 7.4), in acidic medium they are not guided relisource. In the inflamed tissue hydrolysis and excretion of anesthetic in the free state does not occur, therefore it anesthesia almost does not occur. Anesthetic in the free state to settle in the sensory nerve endings in the form of microcrystals, and because they dissolve in lipids, are absorbed by the membranes of nerve cells. To came local anesthesia, the anesthetic must cross in ionic-cationic form, and then starts its communication with the receptor. The mechanism of action of local anesthetics is not completely understood, although it is believed that the locking action chuvstvitelnosti appears to be associated with a decrease in the permeability for sodium ions, cell membranes, it VI are blockers of sodium channels and prevent the formation of the action potential and needsnew pulses. In addition, in the ionized cationic form of the local anesthetics have the antagonism to calcium ions binding to the slow calcium channels of their protein molecules, they prevent the passage of hqhob calcium inside the cell membrane. Local anesthetics impede the flow of calcium ions not only into the nerve cells, but the cells of smooth muscles, myocardium, the cardiac conduction system. There is a stabilization of cell membranes, and when applying stimulating impulses sodium channels are opened, the sodium does not penetrate the cells, with the result that there is no action potential, conduction is blocked. Local anesthetics not only block the sensory nerves, they inhibit nerve fibres of motor and autonomic nerves. Such action depends on the availability of malinovoe shell, its thickness and chemical structure of substances. To local anesthetics particularly sensitive thin bezmalinovic fiber. Anesthesia is the result of direct binding of anesthetic to the nerve fibers, they also block the passage of nerve impulses in the Central and autonomic ganglia, prevents the release of neurotransmitters acetylcholine, norepinephrine. The following types of anesthesia.1. Surface, terminal, anesthesia. When local anesthetics are applied to the surface of mucous membranes, wounds, thereby loss of sensation in nerve endings, where surgical intervention is performed. Terminal anesthesia used in ophthalmology, otorhinolaryngology, urology, in the treatment of surgical wounds and burns. For this kind of anesthesia using cocaine in tetracaine, lidocaine, since they easily penetrate through the mucous membranes to the sensory nerve endings. For terminal anesthesia is also used the drug benzocaine, insoluble in water, it is applied to the affected wound surface. Moreover, benzocaine is used to treat gastric ulcer and duodenal ulcer in the form of powders and pills, and suppositories for the rectal fissures, hemorrhoids/pediatric surface anaesthesia is widely used for analgesia of the eye, intranasal-BUT, during intubation, during the examination by the probe of the stomach, the urethra, and the treatment of burns. 2. infiltration anesthesia. Under this type of anesthesia local anesthetic infiltrate the layers ranging from the skin to deep tissue, which will be made the incision for the surgery, the anesthetic blocks the nerve fibers and their endings. For this type of anesthesia is used novocaine, trimekain, xican. 3. Regional or conduction anesthesia. The anesthetic is inserted into the barrel and along the nerve, the result is a block of conduction of excitation along the nerve fibers and is anaesthesia throughout the region innervated by them. For regional anesthesia are used novocaine, trimekain and xican. This type of anesthesia often used in dentistry and for the treatment of neuralgia. 4. Spinal anesthesiarelated injected into the spinal canal in the subarachnoid cavity, the epidural in the space above the hard shell of the spinal cord. The anesthetic affects the front and rear roots of the spinal cord. This type of pain include the paravertebral and sacral anesthesia. When spinal anesthesia blocks sensation in the lower divisions of the body, pelvic organs, lower limbs, therefore it is used in surgical operations in this area. For this purpose, trimekain, xican and bupivacaine. 5. Intraosseous anesthesia. The anesthetic is introduced into the cancellous bone, above the place of application of superimposed elastic harness. This type of anesthesia is used in orthopedics, traumatology, anesthesia is used mainly novocaine and trimekain. Pharmacokinetics of local anesthetics depends on their chemical structure. Anesthetics related to complex esters (procaine and tetracaine), dissolved in the blood about cholinesterase. Especially rapidly hydrolyses the procaine, which goes into almost inactive para-aminobenzoic acid (PABA) and AMI-nosplit — Diethylaminoethanol (DEAE). Resorptive effect of novocaine is related to this linesperson, the hydrolysis product of Novocain is less toxic than novocaine. If you enter into the body 2 g of novocaine, then after 30 min, the amount of the blood is reduced in 3 times in an hour he has,is not detected in the blood. During the day in the hydrolysis of procaine is formed of 70-80% of PABA and 20— 33% of daaa, which is excreted through the kidneys. The hydrolysis of tetracaine 5 times slower, so it is more toxic. Amides esters — xican, trimekain are not destroyed by cholinesterase, so they are slowly metabolized in the body and have a more lasting effect. They can accumulate in the body, some are excreted through the kidneys in unchanged form, the remainder undergoes metabolism in the liver. Many anesthetics may be absorbed from the wet spot and provide resorptive effect. Cocaine has a high anaesthetic power. It is used n ophthalmic practice, as along with a pronounced surface anesthesia, it narrows the blood vessels of the sclera, expanding the pupil, in some cases, increased intraocular pressure. However, cocaine can be absorbed into the bloodstream and have toxic effects. 11осле suction it acts on the Central nervous system, causes euphoria, and there is psychomotor agitation, fatigue is eliminated. With further absorption of cocaine in the blood excited the respiratory, vasomotor, and emetic centers of the medulla oblongata, increases the tone of spinal ‘ -tion of reflexes, may cause convulsions. With further increase in dose stimulation of the nervous system gives way to depression, paralysis of the vital centers. Cocaine causes stimulation of the adrenergic innervation, increases the effects of Adra-poemetto.^In case of acute poisoning by cocaine ingestion requires gastric lavage with potassium permanganate, the introduction of adsorbing and laxatives; when administered through the mucous membranes — rinse with isotonic solution; when injected into tissue it is necessary to stop the suction by applying the tourniquet above the insertion site. In severe poisoning is tracheotomy, artificial respiration, when convulsions, intravenous administration of seduksen. Chronic use of cocaine (through the nose, chewing Coca leaves, intravenously) develops a addiction, addiction, drug addiction, cocainism. The reason for the development of addiction is cocaine-induced euphoria in which improves mood, negative emotions are decreasing, the apparent surge of power and energy. The euphoria lasts about two hours, then the mood is dramatically reduced, there comes depression. In the future, addicts deteriorates memory, attention, appears apathy, comes the degradation of the individual. Discontinuation of cocaine they have observed symptoms of withdrawal, and the sense of deprivation, accompanied by mental disorders, anxieties, fear, palpitations, severe sweating. Abstinence observed when cocainism, is better tolerated than morfina abstinence because the cocaine develops mainly psychological dependence further as to morphine, both mental and physical dependence. The tetracaine is used for anaesthesia of the mucous membrane of the eye. On anaesthetic activity and toxicity “is superior to cocaine, in contrast, has no effect on intraocular pressure, accommodation. Dicain slightly annoying rainbow ugolochka and the injection dilates the blood vessels, so it is administered together with adrenaline. It must be remembered that the drug is well absorbed into the blood and at higher doses causes severe poisoning, therefore, the use of tetracaine is contraindicated for children under 10 years of age. Novocaine is the most widely used local anesthetic, anesthetic effect of 2 times weaker than cocaine, and 4 times less toxic (table. 3)0Новокаин mainly used for infiltration anesthesia, which lasts 30-60 minutes. In the body the drug is destroyed by serum esterases in the blood and tissues. In the area of injection of novocaine is not happening by dilating the blood vessels so to reduce absorption from the site of injection it is injected together with the agonists epinephrine. Ad-renomination, narrowing blood vessels, reduce intake, increase the duration of action and reduce the toxicity of novocaine. Novocaine is used for anesthesia, surface anesthesia was not used because it is rapidly destroyed. Resorptive effect of novocaine is most pronounced during slow intravenous administration, we observed an inhibitory action on the Central nervous system loses its sense of weight, of gravity of the body. With a further introduction occurs sleep novocaine, novocaine anesthesia. Especially pronounced inhibitory effect of novocaine on the ways polysynaptic in the spinal cord, the ascending activating system and the cortex, on the criminal brain. Procaine has an inhibitory effect on laryngeal, and cough reflexes, it slows down interarea Torah blood vessels by blocking autonomic ganglia, has spazmoliticheskoe action. Novocaine depressing effect on the conduction system, reduces conduction of impulses in sinocarotidna and atrioventricular node reduces heart rate, anxiety attacks, has antiarrhythmic effect. The drug has an-histamine and anti-inflammatory properties. Novocaine is used to produce various kinds of blockades of the cervical, vagosimpaticescoy, paranefralnaya, presacral, with slowed reflexes from the interoreceptors of the affected foci. Novocaine blockade used in Pediatrics. The side effects seen when using novocaine depend on sensitivity to the body, dizziness, rash, itching, fluid accumulation in the subcutaneous tissue. With increasing doses increased reflex excitability, observed pallor, nausea, vomiting, cold sweat, decreased blood pressure, possible collapse, convulsions, and respiratory arrest. In cases of poisoning by procaine administered drugs, which improves respiratory and cardiac stimulant (ephedrine, strofantin), do artificial respiration. Introduction of analgesics is dangerous because of the possibility of seizures. Xican (lidocaine), trimekain on anesthetic action and duration are superior to novocaine (table. 3). Drugs stands in a chemical relation may long-term storage and sterilization. (Trimekain used for infiltration, regional, epidural anesthesia. Lidocaine is a universal anesthetic, is applied in all kinds of anes-tezhi, anaesthetic activity 2.5 times stronger than novocaine and a few toxic it does not cause irritation of the skin, it is recommended to use it together with adrenaline. Digoxin well absorbed into the blood, has a pronounced antiarrhythmic properties. With increasing doses observed drowsiness, disturbed vision, nausea, tremor, convulsions. In severe cases, impair breathing, heart activity and blood vessels. The drug bupivacaine (marcain) chemical structure and action similar to lidocaine. A highly potent and long-acting local anesthetic used for infiltration, conduction and epidural anaesthesia. When epidural by the introduction of anesthesia lasts 3-4 h, with the blockade of the intercostal nerves is 7-14 hours. Benzocaine is not soluble in water, is assigned locally in the form of powders, pastes, ointments and orally in the form of powders and tablets in the rectum in the form of candles, when it comes under sedation.