On a theme:

GENERAL PHARMACOLOGY

MINISTRY OF HEALTHCARE OF THE REPUBLIC OF UZBEKISTANTASHKENT MEDICAL ACADEMY

Department: PHARMACOLOGYSubject: PHARMACOLOGY

Purposes

• learning a general idea of antituberculosis and antisperochetal drugs to their destination;

• give a classification of antituberculosis and antisperochetal antituberculosis and antisperochetal drugs;

• give a notion of effects of the antituberculosis and antisperochetal drugs;

• give a notion of mechanisms of action of the antituberculosis and antisperochetal drugs;

• give a notion of side effects of the antituberculosis and antisperochetal drugs;

• give a notion about indications and contraindication of the antituberculosis and antisperochetal drugs.

Tasks

•Student should know:•- route of administration and excretion of

drugs;• - the interaction of drugs;• - The types of action of drugs;• - side effects and complications caused by

medicinal substances.

•Student should be able to: •Perform practical skills - perform tasks for

the recipe (prescription to furatsilin (solution for outdoor applications), diotsid (bottle.), brilliant green (bottle), chloramine B (bottle), alcohol-iodine solution (bottle), peroxide hydrogen (bottle), boric acid (bottle, ointment).

Motivation

• In general of Pharmacology provides general pattern of pharmacokinetics and pharmacodynamics of drugs. Effects of drugs are the result of their interaction with the organism, in this context covers not only the basic properties of substances, but also the dependence of the effect on the application of these substances and the state of the body, discusses the most important types of pharmacotherapy, general rules of side and toxic effects of drugs. Therefore, knowledge of this topic is necessary for physicians of all specialties, especially the general practitioner.

• Pharmacology - the science of the interaction of chemical compounds from living organisms. In general pharmacology studies drugs used to treat and prevent various diseases and pathological conditions. One of the major problems of pharmacology is to find new drugs.

• The search for new drugs developed in the following areas.

• The chemical synthesis of drugs• II. Receipt of drugs from medicinal plants and the

selection of individual substances:• 1) animal origin;• 2) vegetable origin;• 3) mineral.• III. Isolation of drugs, which are products of vital

activity of fungi and microorganisms.

•As a biomedical science, pharmacology closely related to the different areas of experimental and practical medicine. Thus, pharmacology has a great influence on the development of many other biomedical sciences, especially physiology and biochemistry. For example, using Wegetotropona substances could reveal subtle mechanisms of synaptic transmission is carried out with the participation of neurotransmitters acetylcholine and norepinephrine.

• Many complex functions of the central nervous system have become available for the study due to psychotropic drugs: the discovery of hallucinogenic drugs has led to the creation of animal models of psychosis. For experimenters core value of pharmacological agents is that they represent a great deal of control many biochemical and physiological processes. Very large value of Pharmacology for practical medicine. As a result, creating a large range of high-performance products pharmacotherapy has become a universal treatment for many diseases.

• Broader meaning in medicine have received funds, depressing and stimulating the central and peripheral nervous system, raising and lowering blood pressure, stimulates heart activity, breathing, regulating blood, metabolism, etc. The important role played by antimicrobial and anti-parasitic drugs used for the treatment and prevention of infectious diseases. Progress pharmacology inevitably affects the development of clinical disciplines. Thus, the emergence of tools for anesthesia, anesthetics, curariform funds ganglioblokatorov and other drugs contributed to the success of surgery. A qualitatively new stage in the development of mental health associated with the discovery of psychotropic substances. Isolation and synthesis of hormonal methods have significantly changed the results of treatment of patients with endocrine diseases.

•General pharmacology is the study of the common patterns of drugs pharmacokinetics and pharmacodynamics. Pharmacokinetics (from the Greek. pharmacon - medicine, kineo - move) - this section pharmacology of absorption, distribution in the body, depositing, metabolism and excretion of substances. The main content of the pharmacodynamics (from the Greek. pharmacon - medicine, dynamis - force) - the biological effects of substances, as well as localization and mechanism of action.

•Drug administration routes. Existing ways of bringing in is usually divided into enteral (through the digestive tract) and parenteral (bypassing the digestive tract).

•For enteral routes include introduction through the mouth under the tongue, buccally, the duodenum, rectum (rectal).

•For parenteral introduction of routes include subcutaneous, intramuscular, intravenous, intra-arterial, intrasternalny, intraperitoneal, inhalation, subarachnoid, sub occipital and some other.

• Effective treatment of bacterial infections has become possible only after receiving antibiotics and sulfa drugs. Organ transplant managed to carry out mainly in connection with the creation of immunosuppressive agents. Such examples are many. All of them indicate the paramount role of pharmacology in medicine today. Progress pharmacology characterized by a continuous search for and creation of new and better drugs. Drug development begins with research chemists and pharmacologists, creative community that is absolutely necessary for "design" of new drugs.

• The search for new drugs developed in the following areas. 1. Chemical synthesis of drugs A. The direct synthesis: 1) reproduction of nutrients; 2) creation of anti-metabolites; 3) the modification of the molecules of compounds with known biological activity; 4) a combination of structures of two compounds with the desired properties; 5) synthesis based on the study of chemical transformations of the body. B. empirical way: 1) random findings; 2) "screening". II. Getting drugs from medicinal plants and isolation of individual substances: 1) of animal origin; 2) of plant origin; 3) of the minerals.

• This is the most convenient and simple way of introduction. Sterile preparation in this case not needed. Absorption (absorption) of a number of substances (for example, acetylsalicylic acid, barbiturates, and other weak electrolytes that are acidic in nature) is part of the stomach (in the acidic environment of the stomach, these compounds are found mainly in the non-ionized (lipophilic) form and are absorbed by diffusion). However, the vast majority of drug is absorbed mainly in the small intestine. This favorable large suction surface of the intestinal mucosa (approx. 200 m2) and its intense perfusion. Known basic mechanisms of absorption:

• 1. Passive diffusion across the cell membrane. Determined by the gradient of concentration of substances. In this way easily absorbed lipophilic (mostly nonpolar) substance. The more lipophilic substances, they are more easily penetrate through the cell membrane (so-called isolated facilitated diffusion. It involves transport system functioning without energy loss). 2. Filtration through membrane pores. The pore diameter of the membrane of the intestinal epithelium is small (about 0.4 nm). Therefore, water diffuses therethrough, some ions and small hydrophilic molecules (e.g., urea). 3. Active transport (involved in this process of cell membrane transport systems) is characterized by selectivity for certain compounds, the possibility of competition between two substances in a single transport mechanism saturability (at high concentrations), the possibility of transport against a concentration gradient and energy expenditure (metabolic poisons inhibit active transport) . Active transport provides hydrophilic absorption of polar molecules, some inorganic ions, sugars, amino acids, pyrimidines.

• 4. When pinocytosis cell membrane invagination occurs with the consequent formation of the bubble (vacuoles). Last full of liquid with entrained large molecules of substances. Bubble migrates through the cytoplasm to the opposite side of the cell, wherein the contents by exocytosis bubble is expelled. These mechanisms of passage of substances through the membrane are universal in nature and are not only important for the absorption of substances, but also for their distribution in the body and excretion. The main mechanism of drug absorption in the small intestine is passive diffusion. Minor role played by active transport. Filtration through a cellular membrane pores virtually irrelevant. Absorption of certain proteins and complex cyanocobalamin (vitamin B12) to biermerin is apparently by pinocytosis. Absorption from the small intestine is relatively slow. It depends on the functional state of the intestinal mucosa and its motility and pH, the quantity and quality characteristics of the intestinal contents. It is important to bear in mind that the substance from the small intestine to the liver (where part of inactivated or excreted in bile) and only then - in general circulation. Note that some substances inside ineffective when assigning as degraded by the enzymes of the gastrointestinal tract (e.g., insulin), as well as the particular reaction medium, especially in acidic environment of the stomach (e.g., penicillin).

• If the drug is destroyed by stomach acid or is irritating to the mucous membrane of the stomach, it is prescribed in special dosage forms (capsules, pills) that are soluble only in the small intestine. Absorption of substances regulated as a special membrane transporter - P-glycoprotein. It promotes the excretion of substances into the lumen of the intestine and prevents their absorption. P-glycoprotein pump is also blood-brain barrier, kidney, liver, placenta and other tissues. Therefore, this transportation system affects many processes: absorption, distribution, elimination. Known inhibitors of P-glycoprotein - cyclosporin A, quinidine, verapamil, itraconazole, and many others. There is evidence that rifampin, an inducer of this transporter.

• Due to the fact that the substance developing a systemic effect only after getting into the bloodstream, where it enters the tissue is provided, the term "bioavailability". It reflects the amount of unchanged substance has reached the blood plasma, relative to the initial dose. In this case the bioavailability of enterally value determined lossy substance at its absorption from the digestive tract and first-pass hepatic barrier. To assess the bioavailability usually measure the area under the curve, which reflects the relationship between the concentration of the substance in the blood plasma and the time since the rate is directly proportional to the number of substances introduced into the systemic circulation. Also determine the maximum concentration of free (active) of the substance in the blood plasma and the time required to achieve it. Biodostupnost substance when administered intravenously as 100%. On bioavailability can be judged by the release of the drug in the urine, provided it is not subject to biotransformation. In some cases, the criterion may be the amount bioavailability pharmacological effect if applicable its precise quantitative measurement.

• With the introduction of the substance under the tongue - sublingual (tablets, granules, drops) - suction starts pretty quickly. In this case, the drugs have general action, bypassing the first hepatic passage barrier and contact with enzymes and the environment of the gastrointestinal tract. Sublingual designate certain substances with high activity (single hormonal agents, nitroglycerin) where the dose is low. Sometimes drugs are administered by gavage to the duodenum (e.g., magnesium sulfate as a choleretic), which allows to quickly create a high concentration of gut connection.

• When administered into the rectum (per rectum) substantial part of the substance (about 50%) goes into the bloodstream, bypassing the liver. Moreover, in this way the introduction substance is not exposed to enzymes of the digestive tract. Absorption from the rectum occurs by simple diffusion. Rectally administered drugs into suppositories or enemas drug (volume 50 ml). If the substance is irritating effect, they are combined with mucus. Medicinal substances having the structure of proteins, fat and polysaccharides in the colon are not absorbed. Rectal use of substance and for local effects. For parenteral routes of administration include subcutaneous, intramuscular, intravenous, intraarterial, intrasternal, intraperitoneal, inhalation, subarachnoid, suboccipital and others. Parenteral routes of the most common is the introduction of substances under the skin, into the muscle and veins. Effect occurs especially quickly when administered intravenously, is somewhat slower - intramuscular and subcutaneous administration. In order to prolong the effect of pharmacotherapeutic drugs injected into a muscle in the form of poorly soluble (suspension) in oil or other grounds, delaying absorption of substances from the site of administration. Intramuscular and subcutaneous should not introduce substances which have a pronounced irritant effect, as this can cause inflammatory reactions and even necrosis infiltrates.

• Intravenously administered drugs are usually slow. Possible single, fractional, and a drip infusion. Should not be administered intravenously insoluble compounds, oil solutions (possibility of embolism), funds with a strong irritant (could lead to the development of thrombosis, thrombophlebitis), drugs that cause blood clotting or hemolysis. Negative aspects of these three routes of administration are their relative complexity and morbidity, the need for sterile preparations and participation of medical personnel. Intra-arterial injection can create in the area of the artery that supply blood to high concentrations of the substance. In this way, sometimes introducing an antineoplastic. In order to reduce their overall toxicity blood flow may be artificially difficult (by compression of veins). Also administered intra-radiopaque agents that can accurately determine the location of the tumor, blood clot, constriction of blood vessels, the aneurysm. Intrasternal injection path (in the sternum) is usually used in technical impossibility intravenous (children, elderly people). Intraperitoneal formulations administered infrequently (for example, antibiotics during celiac operations). Sometimes the medicines prescribed intrapleural (the pleural cavity). For gaseous and volatile compounds is a major inhalation route of administration. In the same way, and some are administered aerosols. Light - a vast absorption band (90-100 m2), receives abundant blood supply, so the absorption of substances from inhalation is rapid. The severity of the effect is easily controlled by changing the concentration of substances in the breathing air.

• Deposition After absorption of the substance into the blood and then to various organs and tissues. Most drugs are unevenly distributed and only a small part - relatively evenly (for example, some funds for inhalation anesthesia). Significant impact on the distribution of substances have biological barriers, which are found in the way of their distribution: the capillary wall, cell (plasma) membrane, the blood-brain and placental barriers. Through the wall of the capillaries, which has the character of a porous membrane (pore size in a person's average is 2 nm), the majority of drugs takes place quite easily. Exception of plasma proteins and their complexes with drugs. Hydrophilic compounds are readily soluble in water, pass through pores of the capillary walls and fall into the interstitial space. A protein-phospholipid cell membranes they practically do not diffuse (inside the cells can enter only if participation transport systems). Lipophilic compounds pass through the fine capillary endothelium and the cell membrane.

• Difficult passage of many substances through the blood-brain barrier. This is due to the structure of the capillaries of the brain. Prezhde of their endothelium has pores through which the capillaries extend to many common materials. In the capillaries of the brain is practically no pinocytosis. Have a certain value and glial elements (astroglia) lining the outer surface of the endothelium and, obviously, playing the role of an additional lipid membrane. After the blood-brain barrier poorly polar compounds tested. Lipophilic molecules penetrate into the brain tissue easily. Basically substances pass through the blood-brain barrier by diffusion, and some compounds - by active transport. There are some small parts of the brain (the region epiphysis, posterior pituitary, and others) in which the blood-brain barrier is practically ineffective. It should also be borne in mind that in some pathological conditions (e.g. inflammation of the meninges) increased permeability of the blood-brain barrier.

• Some drugs (in particular, quinacrine), especially in large quantities in the cell detected depot. Binding of the cells possibly due to protein, nucleoprotein and phospholipids. Fat depots are of particular interest because they may be retained lipophilic compound (in particular, some means for anesthesia). Deposited drugs, usually at the expense of convertible bonds. Length of stay in the tissue depots varies widely. Thus, some sulfonamides (sulfadimethoxine, etc.) form stable complexes with plasma proteins, with which a considerable part of the length of their associated actions. Very long trapped in the body of heavy metals ions. Note that the distribution of substances not usually characterizes the direction of their action. The latter depends on the sensitivity of tissues to them, i.e. the affinity of the drug to those biological substrates, which determine the specificity of their action. In clinical pharmacology often use the-apparent volume of distribution - Vd. It reflects the hypothetical volume of liquid in which material is distributed (arbitrarily assumed that the concentration in plasma and other body fluids the same).  The volume of distribution gives an indication of the fraction of a substance in the blood plasma. For lipophilic compounds easily penetrate tissue barriers and having a broad distribution (plasma, interstitial fluid, intracellular fluid in) are characterized by high value Vd. If a substance mainly circulates in blood, Vd has low values. This parameter is important for efficient dispensing of substances, as well as to determine the elimination rate constant (Ke | jm) and "half-life" of a substance (t1 / 2).

• Chemical conversions (biotransformation, metabolism) of drugs in the body Most drugs undergoes biotransformation in the body. Unchanged for vysokogidrofilnyh mostly ionized compounds. Of lipophilic substances, with the exception of funds for inhalation anesthesia, most of them in the chemical reactions in the body does not enter. These light output in the same form in which have been introduced. In the biotransformation of drugs involved many enzymes, of which the most important role is played by the liver microsomal enzymes (located in the endoplasmic reticulum). They are foreign to the body metabolize lipophilic compounds (different structure), making them more hydrophilic. Substrate specificity they do not. Are essential and different localization nemikrosomalnye enzymes (liver, intestine and other tissues and plasma), especially in the case of hydrophilic substances biotransformation. Allocate two main types of drugs conversion: 1) metabolic transformation, and 2) the conjugation. Metabolic transformation - is the transformation of substances due to oxidation, reduction and hydrolysis. Thus, oxidation are imipramine, ephedrine, chlorpromazine, histamine, codeine. Oxidation occurs mainly due to the microsomal mixed oxidase activity with the participation is necessary, oxygen, and cytochrome P-450.

• Conjugation - is a biosynthetic process, accompanied by adherence to the drug substance or its metabolites or grupirovok number of chemical molecules endogenous compounds. For example, methylation may be substances (histamine, catecholamines) or acetylation (sulfanilamidy) interaction with glucuronic acid (morphine, oxazepam), sulfates (chloramphenicol, phenol), glutathione (paracetamol), etc. In the process of conjugation involves many enzymes: glyukuroniltransferazy, sulfotransferase, transatsilaza, methyl transferase, glutathione-5-transferase, etc. Conjugation may be the only way of transformation of substances or she follows its predecessor metabolic transformation.

• When metabolic transformation and conjugation agents pass more polar and more soluble metabolites and conjugates. It is conducive to their further chemical transformations, if they are needed, and promotes their excretion from the body. It is known that the kidneys are derived hydrophilic compounds, whereas the lipophilic highly exposed to the renal tubular reabsorption of (reabsorption) As a result of metabolic transformation, and conjugation of drugs usually lose their biological activity. Thus, this process is limited in time action substances. In the pathology of the liver, accompanied by decreased activity of microsomal enzymes, the duration of action of a number of substances increases. Known inhibitors and various enzymes such as microsomal (chloramphenicol, phenylbutazone) and nemikrosomalnyh (anticholinesterase agents, MAO inhibitors, etc.). They prolong the effects of drugs which are inactivated by these enzymes. However, a compound (e.g., phenobarbital) that increase (induce) the synthesis rate of microsomal enzymes. In some cases, chemical reactions of drugs in the body may lead to increased activity of the compound (imipramine <desipramine), increased toxicity (phenacetin <phenetidine), change mode of action (one of the metabolites is iprazida antidepressant isoniazid having antitubercular activity), as well as conversion of one other active compound (partially converted codeine to morphine). Ways elimination of drugs from the body

• Drugs, their metabolites and conjugates are primarily excreted in the urine and bile. In the kidney, low molecular weight compounds dissolved in the plasma (non-protein), filtered through the membrane capillaries and glomerular capsule. In addition, the significant role played by active secretion of substances in the proximal tubules with transport systems. These are distinguished by organic acids and bases, penicillins, salicylates, sulfonamides, quinine, histamine, thiazides, etc. Some lipophilic compounds can migrate from the blood into the lumen of the tubules (proximal and distal) by simple diffusion through the walls thereof. Removing materials largely depends on the process of reabsorption (reuptake) in the renal tubules. Drugs reabsorbed mainly by simple diffusion. This consists mainly of non-polar lipophilic compounds penetrate well through biological membranes. The polar compounds are poorly reabsorbed from the renal tubules. In this regard, for removing weak acids and bases important in urine pH. Thus, in alkaline urine increased excretion of acidic compounds (for example, salicylic acid, phenobarbital), when acidic - increased excretion bases (imipramine, etc.). This is due to the fact that in these conditions the compound ionized and virtually reabsorbed from the renal tubules.

•  Furthermore, in some reabsorption endogenous substances (amino acids, glucose, uric acid) participates actively transport. A number of drugs (tetracyclines, penicillins, phenytoin, colchicine, etc.) and especially the products of their transformation in a significant amount excreted in the bile into the intestine, where partially excreted in the feces and can be re-absorbed and subsequently re-released into the intestines, etc. . (The so-called enterohepatic circulation, or hepatic recirculation). Gaseous and many volatile matter (for example, the means for inhalation anesthesia) are displayed in the main light. Some drugs are excreted salivary glands (iodide), sweat (protivoleproznoe means ditofal) glands of the stomach (quinine, nicotine) and intestines (weak organic acids), lacrimal glands (rifampicin). It should also be borne in mind that in lactating mammary gland secretes many substances that receives nursing mother (hypnotics, sedatives, ethyl alcohol, nicotine, etc.). In this regard, care is required to appoint the mother of drugs, since the milk they can get into the child's body and have an adverse effect on him. Elimination (removal) of the substance of the body is provided by biotransformation and excretion. To quantify elimination process uses a series of parameters: elimination rate constant (K elim), «half life» (t1 / 2) and total clearance (CL T). The elimination rate constant (K eljm) reflects the rate of material removal from the body.

• To assess the clearance rate of substances from the body is used as the parameter "half-life" (elimination half-life) - t1 / 2, which reflects the time required for reducing the concentration of a substance in blood plasma by 50%. This parameter is used for the selection of doses of substances and intervals of administration to create steady-state concentration of the drug. It is known that the removal of substances of more than 90% is carried out for a time equal to four tl / 2, which is taken into account when dispensing. It should be borne in mind that the t1 / 2 is determined not only breeding material from the body, but also its biotransformation and deposition. Furthermore, to quantify the elimination rate substances used parameter clearance (CL) from the English. clearance - cleaning, reflecting the rate of plasma cleaning of the substance (expressed in volume per unit time, if necessary with the body weight or surface: ml / min ml / kg / min l/m2/ch etc.) . Allocate general (total), clearance (CL T), and kidney (CL R) and hepatic (CL H) clearance. The total clearance is associated with parameters such as volume of distribution (Vd), «half life» (t 1/2) and the elimination rate constant (K elim).

• Resorptive effect depends on the route of administration of drugs and their ability to cross biological barriers.At the local and resorptive effect drugs have either a direct or reflex effect. First implemented in place of direct contact of the substance with a cloth. When the reflex action of matter affect exteroanterocone or interoceptors and the effect is the change of state or the corresponding nerve centers, or executive. Thus, the use of yellow cards in the pathology of respiratory ref-reflex improves their trophic (mustard essential oil stimulates exteroceptors skin). The drug lobelia, injected intravenously, has a stimulating effect on the carotid chemoreceptors glomerulus and stimulating the reflex center of respiration, increases the volume and respiratory rate.The main objective of the pharmacodynamics - find out where and how the drugs are causing these or other effects. Thanks to the improvement of instructional techniques, these issues are not only at the system and organ, but also on the cellular, sub-cellular, molecular and submolecular levels.

• So, for neurotropic drugs applies the structure of the nervous system, synaptic formation of which have the most by a high sensitivity to these compounds. For substances that affect the metabolism is determined by the localization of enzymes in different tissues, cells and subcellular entities whose activity changes is particularly important. In all cases, we are talking about the biological substrates, "targets", which interact with the drug.As the "target" for the drug are receptors, ion channels, enzymes, transport systems and genes.Receptors called active groups of the macromolecules of substrates with which a substance. Receptors, providing the manifestation of substances called specific.There are the following 4 types of receptors.

• I. Receptors direct control over the function of ion channels. This type of receptor directly associated with ion channels, include n-cholinergic receptors, GABA receptors, glutamate receptors.II. Receptors associated with effector through «G-proteins - the secondary transmitter" or «G-protein-gated ion channels". These receptors are available for many hormones and neurotransmitters (m-cholinergic receptors, adrenergic receptors).III. Receptors directly control the effector function of the enzyme. They are directly related to tyrosine phosphorylation of proteins and adjusted. According to this principle arranged insulin receptors several growth factors.IV. Receptors controlling transcription of DNA. In contrast to membrane receptors type I-III is intracellular receptors (soluble cytosolic or nuclear proteins). With these receptors interact with steroid and thyroid hormones.Most fruitful study of receptor subtypes and associated effects. Among the first studies of this type include work on the synthesis of many in-blockers are widely used in various diseases of the cardiovascular system. Then came the histamine H2-blockers receptor - effective for the treatment of gastric ulcer and duodenal ulcer. Later it was synthesized in a variety of other drugs that act on different subtypes of alpha-adrenergic receptors, dopamine, opioid receptors, etc. These studies have played a major role in the creation of new groups of selective drugs, which are widely used in medical practice.

• Pharmacological interaction due to the fact that one substance or alters the pharmacokinetics (s) other components of the mixture pharmacodynamics. Pharmacokinetic interaction type can be associated with malabsorption, biotransformation, transport, deposition and removal of the substances. Pharmacodynamic type of interaction is the result of direct or indirect interaction of matter at the level of receptor cells, enzymes, organ or physiological systems. In this case, the main effect may vary quantitatively (amplified, attenuated) or qualitatively. In addition, the possibility of chemical and physico-chemical interaction of substances in their joint application.Pharmacokinetic type of interaction can occur at the stage of absorption of substances, which may vary for different reasons. Thus, in the digestive tract may be binding substances absorbent material (activated carbon, white clay) or anion-exchange resin (e.g. cholestyramine hypolipidemic agent), the formation of inactive chelate or chelates (for example, according to the principle tetracycline group of antibiotics interact with the ions of iron, calcium, magnesium). All of these forms of interaction prevents the absorption of drugs and thus reduce their pharmacological effects. For some substances absorption from the digestive tract is essential pH. So by changing the reaction of digestive juices, can significantly affect the rate and completeness of absorption of weakly acidic and weakly basic compounds

• General principles of treatment of acute poisoning by drugs Acute poisoning by chemicals, including drugs, are quite common. Poisoning may be accidental, intentional (suicide (from Lat. Suicidum - suicide (sui - myself, caedo - kill)) and associated features of the profession. Most common acute poisoning with ethyl alcohol, hypnotics, psychotropic drugs, opioid and non-opioid analgesics, organophosphate insecticides and other compounds. For the treatment of poisoning by chemicals created special poison control centers and offices. The main objective in the treatment of acute poisoning is to remove substances from the body, causing the toxicity. In severely ill patients it must be preceded by general therapeutic and resuscitative measures aimed at ensuring the functioning of vital systems - respiration and blood circulation. The principles of detoxification are as follows. First of all it is necessary to delay the absorption of the substance on the routes of administration. If the substance is partially or fully grown deep, should accelerate its excretion from the body, as well as take advantage of antidotes for its neutralization and elimination of adverse effects. a) delay absorption of the toxic substance in the blood

• If the substance to cause intoxication, is applied to the skin or mucous membranes, wash them thoroughly (preferably flowing water). After contact with toxic substances through the lungs should stop their inhalation (to remove the victim from the poisonous atmosphere or wear a gas mask on him). When subcutaneous absorption of toxic substances from its insertion site can slow injection of adrenaline solution around the site of administration, as well as by cooling in the area (the skin surface placed on an ice pack). If possible, the tourniquet is applied, obstructing blood flow and creating venous stasis in the administration of the substance. All of these measures reduce systemic toxic effects of the drug. b) removing the toxic substances from the body If a substance has grown deep and resorptive effect, major efforts should be directed to the early elimination from the body.

• For this purpose use diuresis, peritoneal dialysis, hemodialysis, hemosorption, blood substitution, etc. The method is forced diuresis combined aqueous active load using diuretics (furosemide, mannitol). In some cases the urine acidification or alkalization (depending on the properties of the material) contributes to more rapid removal of material (by reducing its reabsorption in the renal tubules). The method of forced diuresis can display only free agents not associated with proteins and lipids blood. Using this method should maintain electrolyte balance, which may be disrupted due to excretion of large amounts of ions. In acute cardiovascular insufficiency, severe renal dysfunction and the risk of developing cerebral edema or pulmonary forced diuresis is contraindicated. In addition to forced diuresis, using hemodialysis or peritoneal dialysis (dialysis (from the Greek. Dialysis - Branch) - separation of colloidal particles of the solute).

• In hemodialysis (artificial kidney) blood passes through the dialyzer with the semipermeable membrane and largely freed from non-toxic proteins (e.g., barbiturates). Hemodialysis is contraindicated with a sharp decrease in blood pressure. Peritoneal dialysis is peritoneal cavity lavage solution of electrolytes. Depending on the nature of poisoning use certain dialysis fluid to facilitate the most rapid excretion of substances in the peritoneal cavity. Simultaneously, dialysis solution is administered for prevention of infection with antibiotics. Despite the high effectiveness of these methods, they are not universal, since not all chemical compounds are well dialyzed (i.e., do not pass through the semipermeable membrane of the dialyzer for hemodialysis, or through the peritoneum in peritoneal dialysis). One of the methods of detoxification is hemosorbtion. In this case, the toxic substances in the blood are adsorbed on the specific sorbents (for example, granular activated charcoal coated with blood proteins). This method can successfully carry out detoxification in cases of poisoning antipsychotics, anxiolytics, organophosphorus compounds and etc. It is important that the method is effective in cases where drugs poorly dialyzed (including substance-related plasma proteins) and hemodialysis not give a positive result

• In the treatment of acute poisoning is used as replacement of blood. In such cases, the bleeding is combined with transfusion of donor blood. Most demonstrates the use of this method for poisoning substances acting directly on the blood, e.g. causing metgemoglobinoobrazovanie (acting as nitrites, nitrobenzene, etc.). In addition, the method is very effective in cases of poisoning macromolecular compounds, strongly bind to plasma proteins. Blood replacement surgery is contraindicated in severe violations of circulation, thrombophlebitis. Over the past few years in the treatment of poisoning with certain substances has spread plasmapheresis (from the Greek. Plasma - plasma, aphairesis - taking away, taking), under which a removal of plasma without loss of blood cells followed by the replacement of its donor plasma or albumin solution of electrolytes. Sometimes the purpose of detoxification through the thoracic duct lymph removed (chylorrhea). Limfodializ possible, limfosorbtsiya. These methods are of great importance in the treatment of acute poisoning by medicinal substances have not. If the poisoning occurred substances that emit light, the forced ventilation is one of the important ways of treating such toxicity (for example, by the inhalation anesthetic). Hyperventilation can cause stimulant carbogen breathing, as well as artificial respiration.

• Strengthening the biotransformation of toxic substances in the body for the treatment of acute poisoning not essential. c) the elimination of toxic action has grown deep If it is determined what the substance is caused by poisoning, then resort to detoxify the body by using antidotes (from the Greek. Antidoton - the antidote). Antidotes called agents used for the specific treatment of poisoning by chemicals. These include substances that inactivate toxins by chemical or physical interaction or by pharmacological antagonism (at physiological systems, receptor, etc.) (more precisely referred to as safeners only antidote which interact with poisons in physico-chemical principle ( adsorption, precipitation or formation of inactive complexes). Antidotes, whose operation is based on the physiological mechanisms (eg, antagonistic interaction at the level of the substrate, "target"), in this nomenclature indicate antagonists. However, the practical application of all antidote regardless of the principle of their action is usually called antidotes). Thus, heavy metal poisoning used compounds which form complexes with them non-toxic (e.g. unitiol, D-penicillamine, SaNa2EDTA).

• Known antidote, which react with the material and release the substrate (eg, oximes - cholinesterase reactivators, and similarly there are antidotes used for poisoning metgemoglobinobrazuyuschimi substances). Widely used in acute poisoning pharmacological antagonists (atropine poisoning anticholinesterase agents, naloxone and morphine poisoning, etc.). Usually pharmacological antagonists competitively interact with the same receptors as the substance that caused the poisoning. Promising is the development of specific antibodies against substances which are particularly common cause of acute poisoning. The earlier the treatment of acute poisoning antidote, so it is more efficient. If you develop damage to the tissues, organs and systems of the body and in the terminal stages of poisoning antidote therapy effectiveness is low. d) symptomatic treatment of acute poisoning An important role in the treatment of acute poisoning plays symptomatic therapy. Of particular importance it acquires poisoning substances which have no specific antidotes.

• First, you need to support vital functions - circulation and respiration. For this purpose, use cardiac glycosides, substances that regulate blood pressure, facilities, improve microcirculation in the peripheral tissues, often use oxygen therapy, sometimes - respiratory stimulants, etc. When the unwanted symptoms that aggravate the patient's condition, remove them with appropriate products. So, seizures can arrest the anxiolytic diazepam, which has potent anticonvulsant activity. When cerebral edema dehydration treatment is carried out (using mannitol, glycerol). Eliminate pain analgesics (morphine, etc.). Great attention should be paid to the acid-base status and emerging violations carry out the necessary correction it. In the treatment of acidosis used solutions of sodium bicarbonate, trisamin, while alkalosis - ammonium chloride. It is equally important to maintain fluid and electrolyte balance. Thus, the treatment of acute poisoning drug detoxification activities includes a set in combination with symptomatic and if need arises, resuscitation therapy. d) the prevention of acute poisoning

• The main task - the prevention of acute poisoning. To do this reasonably prescribe drugs properly and keep them in hospitals and at home. So, do not keep medicines in cabinets, refrigerator, where the food is. Designated storage of medicines should be available for children. It is not practical to keep the house preparations in which there is no need. You can not use drugs that have expired. The preparations used must have appropriate labels with names. Naturally, the majority take drugs should only be on the advice of a doctor, strictly observing their dosage. This is especially important for the toxic and potent drugs. Self-medication is generally inadmissible, as it is often the cause of acute poisoning and other adverse effects. Important to respect the rules of storage of chemicals and use them with the chemical and pharmaceutical plants and laboratories engaged in the manufacture of drugs. Performing all of these requirements can significantly reduce the incidence of acute drug poisoning.

Thanks for your attention !!!