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INHALATION ANESTHESIA is a type of general anesthesia provided by the use of gaseous or volatile anesthetics that enter the body through the respiratory tract.

Desired effects of anesthesia Sedation Amnesia Analgesia Immobility in response to pain stimulation Muscle relaxation

What is General Anesthesia Amnesia (hypnotic component) Analgesia Akinesia (immobility) Autonomic reflex control (Snow, Guedel 1937, Eger 2006) Concept Perouansky, 2011: Amnesia Akinesia Hypnotic component Eger and Soner, 2006: Amnesia Immobility Excluded sleep (example ketamine) and hemodynamic control (moderate tachycardia is tolerated normally, everything can be leveled with vasoactive drugs)

The concept of multicomponent anesthesia Prosthetics of vital functions Monitoring Analgesia Hypnotic component Miorelaxation

The Concept of General Anesthesia-Clinical Targeting Stansky and Shafer, 2005 Suppression of response to verbal stimuli Suppression of motor response to traumatic stimuli Suppression of hemodynamic response to tracheal intubation From this point of view, inhalational anesthetics are true anesthetics

General Anesthesia - IA Capabilities Shutdown of consciousness - level of basal ganglia, cerebral cortex, disintegration of signals in the CNS Amnesia - effects on different areas Pain - pain (WHO) = an unpleasant sensory or emotional sensation associated with actual or potential tissue damage that can be describe at the time of the occurrence of this damage. During the operation, the nociceptive pathways are activated, but there is no sensation of pain (the patient is unconscious). PAIN control is relevant after recovery from anesthesia.

Inhalation anesthesia Advantages Disadvantages Ø Painless induction into anesthesia Ø Good controllability of the depth of anesthesia Ø Low threat of maintaining consciousness during anesthesia Ø Predictable rapid recovery from anesthesia Ø Powerful general anesthetic activity of the drug Ø Rapid awakening and the possibility of early activation of patients Ø Reduced use of opioids, muscle relaxants and faster recovery of gastrointestinal function Ø Relatively slow induction Ø Excitation stage problems Ø Threat of airway obstruction Ø High cost (when using conventional high-flow anesthesia) Ø Operating room air pollution

The main advantage of using IAs is the ability to control them at all stages of anesthesia. IAs are indicated for induction (especially in predicted difficult intubation, in patients with obesity, comorbidities and aggravated allergic history, in pediatric practice) and maintenance of anesthesia during long-term operations as part of a general combined anesthesia. An absolute contraindication to the use of IAs is the fact of malignant hyperthermia and a history of adverse (primarily allergic) reactions. A relative contraindication is short-term surgical interventions, when IAs are used in an open respiratory circuit with the patient spontaneously breathing or in a semi-closed circuit with mechanical ventilation under conditions of high gas flow, which does not harm the patient, but significantly increases the cost of anesthesia.

HISTORICAL DATA - ETHER Diethyl ether was synthesized in the 8th century AD. e. Arab philosopher Jabir ibn Hayyam in Europe was obtained in the 13th (1275) century by the alchemist Raymond Lullius in 1523 - Paracelsus discovered its analgesic properties 1540 - re-synthesized by Cordus and included in the European Pharmacopoeia William E. Clarke, medical student from Rochester (USA) in January 1842 was the first to use ether for anesthesia during a surgical operation (tooth extraction). A few months later, on May 30, 1842, the surgeon Crawford Williamson Long (USA) used ether for the purpose of anesthesia when removing two small tumors on the neck of a patient who was afraid of pain, but this became known only in 1952. Morton, a dentist who received a diploma in 1844 on the advice of the chemist Jackson, used ether first in an experiment on inhalation anesthesia // 10 for a dog, then for himself, then in his practice from August 1 and September 30 A. E. Karelov, St. Petersburg MAPO 1846.

Historical Dates of Anesthesia 16 October 1846 William Morton - First Public Demonstration of General Anesthesia with Ether William Thomas Green Morton (1819 -1868)

History of Inhalation Anesthesia - Chloroform Chloroform was first obtained in 1831 independently as a rubber solvent by Samuel Guthrie, then by Justus von Liebig and Eugène Soubeiran. The French chemist Dumas established the formula for chloroform. He also came up with the name "chloroform" in 1834, due to the property of this compound to form formic acid during hydrolysis (Latin formica translates as "ant"). In clinical practice, chloroform was first used as a general anesthetic by Holmes Coote in 1847, it was introduced into wide practice by obstetrician James Simpson, who used chloroform to reduce pain during childbirth. In Russia, the method for the production of medical chloroform was proposed by the scientist Boris Zbarsky in 1916, when he lived in the Urals in the village of Vsevolodo-Vilva in the Perm Territory.

James Young Simpson (James Yuong Simpson, 1811–1870) On November 10, 1847, at a meeting of the Medical and Surgical Society of Edinburgh, J. Y. Simpson made a public announcement about his discovery of a new anesthetic, chloroform. At the same time, he successfully used chloroform for the anesthesia of childbirth for the first time (on November 21, 1847, the article “On a new anesthetic, more effective than sulfuric ether” was published).

Nitrous oxide (N 2 O) was synthesized in 1772 by Joseph Priestley. Humphrey Davy (1778-1829) experimented with N 2 O on himself at Thomas Beddoe's Pneumatic Institute. In 1800, Sir Davy published an essay on his own feelings from the effects of N 2 O (laughing gas). In addition, he repeatedly expressed the idea of using N 2 O as an analgesic for various surgical procedures (“.... Nitrous oxide, apparently, along with other properties, has the ability to eliminate pain, it can be successfully used in surgical operations ....” ... As an anesthetic first used by Gardner Colton and Horace Wells (for tooth extraction) in 1844, Edmond Andrews in 1868 used in a mixture with oxygen (20%) after the first recorded death during anesthesia with pure nitrous oxide.

The American dentist Horace Wells (1815-1848) in 1844 happened to be at a demonstration of the effect of N 2 O inhalation organized by Gardner Colton. Wells drew attention to the absolute insensitivity of the patient to pain in the injured leg. In 1847, his book "History of the discovery of the use of nitrous oxide, ether and other liquids in surgical operations" was published.

The second generation of inhalational anesthetics In 1894 and 1923 there was a largely accidental introduction into practice of chloroethyl and ethylene Cyclopropane was synthesized in 1929 and introduced into clinical practice in 1934. All inhalational anesthetics of that period were explosive with the exception of chloroform, had hepatotoxicity and cardiotoxicity, which limited their use in clinical practice.

The era of fluorinated anesthetics Shortly after the Second World War, the production of halogenated anesthetics began In 1954, fluroxene was synthesized the first halogenated inhalation anesthetic In 1956, halothane appeared In 1960, methoxyflurane appeared In 1963-1965, enflurane and isoflurane were synthesized In 1992 The clinical use of desflurane began In 1994, sevoflurane was introduced into clinical practice Xenon was first experimentally used in the 50s of the 20th century, but is still not popular due to its extremely high cost

History of the development of inhalation anesthesia 20 Anesthetics used in clinical practice (total) Sevoflurane Isoflurane 15 Halothane Ethyl vinyl ether Vinethen 0 1830 Fluroxene Propyl methyl ether Isoproprenyl vinyl ether Trichlorethylene 5 Enfluran Methoxyflurane 10 Cyclopropane Ethylene Chloroform Ethyl chloride Ether NO 2 1918 1850 Dezflurane 1950 Year of entry into clinical practice 1970 1990

The most commonly used inhalational anesthetics Halothane Isoflurane Desflurane Sevoflurane Nitrous oxide Xenon

The action develops rapidly and is easily reversible; it seems that it largely depends on the properties of the anesthetic itself and the low-energy intermolecular interactions and bonds formed by it. IAs act on the synaptic membranes of neurons in the brain and spinal cord, predominantly affecting the phospholipid or protein components of the membranes.

Mechanism of action It is assumed that the mechanism of action of all inhalation anesthetics at the molecular level is approximately the same: anesthesia occurs due to the adhesion of anesthetic molecules to specific hydrophobic structures. By binding to these structures, the anesthetic molecules expand the bilipid layer to a critical volume, after which the membrane function undergoes changes, which in turn leads to a decrease in the ability of neurons to induce and conduct impulses between themselves. Thus, anesthetics cause excitatory depression both at the presynaptic and postsynaptic levels.

According to the unitary hypothesis, the mechanism of action of all inhalation anesthetics at the molecular level is the same and is determined not by the type, but rather by the number of molecules of the substance at the site of action. The action of anesthetics is more of a physical process than an interaction with specific receptors. A strong correlation with the potency of anesthetics has been noted in the oil/gas ratio (Meyer and Overton, 1899-1901). This is supported by the observation that the potency of an anesthetic is directly related to its fat solubility (Meyer-Overton rule). The binding of an anesthetic to the membrane can significantly change its structure. Two theories (the flow theory and the lateral phase decoupling theory) explain the action of the anesthetic by the effect on the shape of the membrane, one theory - by a decrease in conductivity. The way in which a change in the structure of the membrane causes general anesthesia can be explained by several mechanisms. For example, the destruction of ion channels leads to a violation of the permeability of the membrane for electrolytes. Conformational changes in hydrophobic membrane proteins may occur. Thus, regardless of the mechanism of action, depression of synaptic transmission develops.

The mechanism of action of inhalation anesthetics has not yet been studied, and the internal mechanisms of the occurrence of general anesthesia through their action currently remain completely unknown. "Theories" = hypotheses: Coagulation, Kuhn, 1864 Lipoid, Meyer, Overton, 1899-1901 Surface tension, Traube, 1913 Adsorption, Lowe, 1912 Critical volume Violations of redox processes in cells, hypoxic, Verworn, 1912 Water microcrystals, Pauling, 1961 Membrane, Hober, 1907, Bernstein, 1912, Hodgkin, Katz, 1949 Parabiosis, Vvedensky, Ukhtomky, Reticular.

Interaction of halogen-containing IAs with GABA receptors activates and potentiates the effects of γ-aminobutyric acid, while interaction with glycine receptors activates their inhibitory effects. At the same time, there is inhibition of NMDA receptors, H-cholinergic receptors, inhibition of presynaptic Na + channels and activation of K 2 P and K + channels. It is assumed that gaseous anesthetics (nitrous oxide, xenon) block NMDA receptors and activate K 2 P channels, but do not interact with GABA receptors.

The action of various anesthetics on ion channels is not identical. In 2008, S. A. Forman and V. A. Chin proposed to divide all general anesthetics into three classes: - Class 1 (propofol, etomidate, barbiturates) - these are "pure" GABA sensitizers (GABA - γ-aminobutyric acid); - 2nd class - active against ionotropic glutamate receptors (cyclopropane, nitrous oxide, xenon, ketamine); - 3rd class - halogen-containing drugs that are active against not only GABA-, but also acetylcholine receptors in the center and on the periphery. Halogen-containing anesthetics are, strictly speaking, rather hypnotics with pronounced analgesic activity than true anesthetics.

At the macroscopic level, there is no single area of the brain where inhalation anesthetics act. They affect the cerebral cortex, the hippocampus, the sphenoid nucleus of the medulla oblongata and other structures. They also suppress the transmission of impulses in the spinal cord, especially at the level of intercalary neurons of the posterior horns involved in the reception of pain. It is believed that the analgesic effect is caused by the action of the anesthetic primarily on the brainstem, and on the spinal cord. One way or another, the higher centers that control consciousness are the first to be affected, and the vital centers (respiratory, vasomotor) are more resistant to the effects of the anesthetic. Thus, patients under general anesthesia are able to maintain spontaneous breathing, heart rate and blood pressure close to normal. From the foregoing, it becomes clear that the "target" for the molecules of inhalation anesthetics are brain neurons.

The final (expected) effect of anesthetics depends on the achievement of their therapeutic (certain) concentration in the CNS tissue (anesthetic activity), and the speed of obtaining the effect depends on the speed at which this concentration is reached. The anesthetic effect of inhalation anesthetics is realized at the level of the brain, and the analgesic effect is realized at the spinal level.

Functions of Vaporizers Ensuring the vaporization of inhalation agents Mixing vapor with the carrier gas stream Controlling the composition of the gas mixture at the exit, despite variables Delivering safe and accurate concentrations of inhalation anesthetics to the patient

Classification of evaporators ♦ Type of supply In the first option, the gas is drawn through the evaporator by reducing the pressure in the final section of the system; in the second, the gas fills the evaporator, forcing through it under high pressure. ♦ Anesthetic nature Determines which anesthetic can be used in this vaporizer. ♦ Temperature compensated Indicates if this evaporator is temperature compensated. ♦ Flow stabilization It is important to determine the optimal gas flow rate for a given evaporator. ♦ Flow resistance Determines how much force is required to force the gas through the evaporator. In general, evaporators are most often classified by type of gas supply and by the presence of calibration (with and without calibration). Calibration is a term used to describe the accuracy of a procedure under certain conditions. Thus, vaporizers can be calibrated to supply anesthetic concentration with an error of ± 10% of the set values at a gas flow of 2-10 l/min. Outside these gas flow limits, vaporizer accuracy becomes less predictable.

Types of Vaporizers Drawover Vaporizers - Carrier gas is "pulled" through the vaporizer by reducing the pressure in the final section of the system (during the patient's inspiration)

Scheme of a flow evaporator Low resistance to the flow of the gas mixture Gas passes through the evaporator only on inspiration, the flow is not constant and pulsating (up to 30-60 l per minute on inspiration) No need to supply compressed gases

Fill Evaporators (plenum) Designed for use with a constant flow of pressurized gas and have a high internal resistance. Current models are specific to each anesthetic. Flow stabilized, operate with +20% accuracy at fresh gas flow from 0.5 to 10 l/min

Vaporizer safety Special labeling of the vaporizers Drug level indicator Proper placement of the vaporizer in the circuit: - Filling vaporizers are installed behind the rotameters and in front of oxygen - Flow vaporizers are installed in front of the bellows or bag Locking device to prevent multiple vaporizers from being switched on at the same time Monitoring of anesthetic concentration Potential Hazards: Inverting the vaporizer Reverse connection Evaporator tipping over Incorrect filling of the evaporator

Pharmacokinetics studies Ø Absorption Ø Distribution Ø Metabolism Ø Excretion Pharmacokinetics - studies the relationship between the dose of a drug, its concentration in tissues and duration of action.

Pharmacokinetics of inhalation anesthetics The depth of anesthesia is determined by the concentration of anesthetic in the brain tissue The concentration of anesthetic in the alveoli (FA) is related to the concentration of anesthetic in the brain tissues

Basic physical parameters of inhalation anesthetics Volatility or "Saturated Vapor Pressure" Solubility Power

The drugs we call "inhalation anesthetics" are liquids at room temperature and atmospheric pressure. Liquids are made up of molecules that are in constant motion and have a common affinity. If the surface of a liquid comes into contact with air or another gas, some molecules will break away from the surface. This process is evaporation, which increases with heating of the medium. Inhalation anesthetics are able to evaporate quickly and do not require heating in order to turn into vapor. If we pour an inhalation anesthetic into a container, such as a jar with a lid, over time, the vapor generated from the liquid will accumulate in the headspace of this jar. In this case, the vapor molecules move and create a certain pressure. Some of the vapor molecules will interact with the surface of the liquid and re-liquid. Eventually, this process reaches an equilibrium where equal numbers of molecules will leave the liquid and return to it. "Saturated vapor pressure" is the pressure exerted by the vapor molecules at the point of equilibrium.

Saturated Vapor Pressure (VVP) Saturated Vapor Pressure (VVP) is defined as the pressure generated by vapor in equilibrium with the liquid phase. This pressure depends on the drug and its temperature. If the saturation vapor pressure (VVP) is equal to atmospheric pressure, the liquid boils. Thus, water at sea level at 100°C has a saturated vapor pressure (DVP) = 760 mm Hg. Art. (101, 3 k. Pa).

Volatility This is a general term that is related to saturation vapor pressure (VVP) and latent heat of vaporization. The more volatile the drug, the less energy is required to convert the liquid into vapor and the more pressure is created by this vapor at a given temperature. This indicator depends on the nature of the temperature and on the drug. Thus, trichlorethylene is less volatile than ether.

The volatility or "Saturated Vapor Pressure" of the DNP reflects the ability of the anesthetic to evaporate, or in other words, its volatility. All volatile anesthetics have a different ability to evaporate. What determines the intensity of evaporation of a particular anesthetic. . ? The pressure that will be exerted on the walls of the vessel by the maximum number of evaporated molecules is called "saturated vapor pressure". The number of evaporated molecules depends on the energy status of a given liquid, that is, on the energy status of its molecules. That is, the higher the energy status of the anesthetic, the higher its DNP is an important indicator because, using it, you can calculate the maximum concentration of anesthetic vapors.

For example, the DNP of isoflurane at room temperature is 238 mm. hg. Therefore, in order to calculate the maximum concentration of its vapors, we make the following calculations: 238 mm. Hg / 760 mm. HG * 100 = 31%. That is, the maximum concentration of Isoflurane vapor at room temperature can reach 31%. Compared to isoflurane, the anesthetic methoxyflurane has a DNP of only 23 mm. HG and its maximum concentration at the same temperature reaches a maximum of 3%. The example shows that there are anesthetics characterized by high and low volatility. Highly volatile anesthetics are used only with the use of specially calibrated vaporizers. The saturation vapor pressure of anesthetics can change as the ambient temperature rises or falls. First of all, this dependence is relevant for anesthetics with high volatility.

Examples: Remove the lid from a can of paint and you can smell it. At first, the smell is quite strong, as the steam is concentrated in the jar. This vapor is in equilibrium with the paint, so it can be called saturated. The can has been closed for a long period of time and the vapor pressure (VAP) is the point at which equal amounts of ink molecules become vapor or return to the liquid phase (the ink). Very soon after you remove the lid, the smell disappears. The vapor has diffused into the atmosphere, and since the paint has a low volatility, only very small amounts are released into the atmosphere. If you leave the paint container open, the paint remains thick until it completely evaporates. When the cap is removed, the smell of gasoline, which is more volatile, continues to persist, as a large number of molecules evaporate from its surface. For a short period of time, no gasoline remains in the tank, it completely turns into steam and enters the atmosphere. If the container was filled with gasoline, when you open it on a hotter day, you will hear a characteristic whistle, and on a cold day, on the contrary, it will suck air into itself. Saturated vapor pressure (VVP) is higher on warm days and lower on cold days, as it depends on temperature.

Latent heat of vaporization Latent heat of vaporization is defined as the amount of energy required to convert 1 g of liquid into vapor without changing the temperature. The more volatile the liquid is, the less energy is needed for this. The latent heat of vaporization is expressed in kJ/g or kJ/mol, based on the fact that different preparations have different molecular weights. In the absence of an external source of energy, it can be taken from the liquid itself. This leads to cooling of the liquid (use of thermal energy).

Solubility A gas dissolves in a liquid. At the beginning of dissolution, gas molecules actively pass into solution and back. As more and more gas molecules mix with liquid molecules, a state of equilibrium gradually sets in, when there is no more intense transition of molecules from one phase to another. The partial pressure of the gas at equilibrium in both phases will be the same.

The rate of onset of the expected effect of inhalation anesthetic depends on the degree of its solubility in the blood. Anesthetics with high solubility are absorbed in large quantities by the blood, which does not allow reaching a sufficient level of alveolar partial pressure for a long time. The degree of solubility of an inhalation anesthetic characterizes the Oswald blood/gas solubility coefficient (λ is the ratio of the anesthetic concentrations in the two phases at equilibrium). It shows how many parts of the anesthetic should be in 1 ml of blood from the amount of anesthetic that is in 1 ml of the anesthetic-respiratory mixture in the alveolar space so that the partial pressure of this anesthetic is equal and the same in the blood and in the alveoli.

Vapors and gases with different solubility create different partial pressures in the solution. The lower the solubility of a gas, the greater the partial pressure it is able to create in solution compared to a highly soluble gas under the same conditions. An anesthetic with low solubility will create a higher partial pressure in solution than a highly soluble one. The partial pressure of an anesthetic is the main factor that determines its effect on the brain.

the solubility coefficient of sevoflurane is 0.65 (0.630.69), i.e., this means that at the same partial pressure, 1 ml of blood contains 0.65 of the amount of sevoflurane that is in 1 ml of alveolar gas, i.e. The blood capacity of sevoflurane is 65% of the gas capacity. for halothane, the blood / gas distribution coefficient is 2.4 (240% of the gas capacity) - to achieve equilibrium, 4 times more halothane must be dissolved in the blood than sevoflurane.

BLOOD / GAS Xenon Desflurane Nitrous oxide Sevoflurane Isoflurane Enflurane Halothane Methoxyflurane Trichlorethylene Ether – 0.14 – 0.42 – 0.47 – 0.59 – 1.4 – 1.9 – 2.35 – 2.4 – 9.0 – 12, 0 Inhalation anesthesia // A. E. Karelov, St. Petersburg MAPO 59

12 vials/ml of sevoflurane dissolved in blood Gaseous sevoflurane contains 20 vials/ml No diffusion when partial pressures are equal solubility ratio blood/gas sevoflurane = 0.65

Blood - 50 bubbles/ml Gas - 20 bubbles/ml No diffusion when partial pressures equal solubility ratio blood/halothane gas = 2.5

The solubility coefficient determines the possibilities of using an inhalation anesthetic. Induction - is it possible to carry out a mask induction? Maintenance - how quickly will the depth of anesthesia change in response to changes in vaporizer concentration? Awakening - how long will the patient wake up after the anesthetic is stopped?

Power of an inhalant anesthetic The ideal inhalant anesthetic allows anesthesia to be performed using high concentrations of oxygen (and a low concentration of inhalant anesthetic) The minimum alveolar concentration (MAC) is a measure of the power of inhaled anesthetics. MAC is identical to ED 50 in pharmacology. MAC is determined by measuring the concentration of the anesthetic directly in the exhaled gas mixture in young and healthy animals subjected to inhalation anesthesia without any premedication. MAC essentially reflects the concentration of the anesthetic in the brain, because when anesthesia occurs, there will be an equilibrium between the partial pressure of the anesthetic in the alveolar gas and in the brain tissue.

MAC MINIMUM ALVEOLAR CONCENTRATION MAC is a measure of activity (equipotency) of an inhalation anesthetic and is defined as the minimum alveolar concentration in the saturation phase (steady-state), which is sufficient to prevent 50% of patients from responding to a standard surgical stimulus (skin incision) at sea level (1 atm = 760 mm Hg = 101 k. Ra). Inhalation anesthesia // A. E. Karelov, St. Petersburg MAPO 65

The MAC concept is a dose-response approach for AIs Facilitates comparison between drugs Helps in studies of the mechanism of action Characterizes drug interactions

Why MAC? 1. Alveolar concentration can be measured 2. In a state close to equilibrium, partial pressures in the alveoli and brain are approximately the same 3. High cerebral blood flow leads to rapid equalization of partial pressures 4. MAC does not change depending on different painful stimuli 5. Individual variability extremely low 6. Gender, height, weight, and duration of anesthesia do NOT affect MACs 7. MACs of different anesthetics are summed

Comparing the concentration of different anesthetics required to achieve the MAC, one can tell which one is more powerful. For example: MAC. for isoflurane 1.3%, and for sevoflurane 2.25%. That is, to achieve the MAC, different concentrations of anesthetics are required. Therefore, drugs with a low MAC value are powerful anesthetics. A high MAC value indicates that the drug has a less pronounced anesthetic effect. Powerful anesthetics include halothane, sevoflurane, isoflurane, methoxyflurane. Nitrous oxide and desflurane are mild anesthetics.

FACTORS INCREASING MAC Children under 3 years of age Hyperthermia Hyperthyroidism Catecholamines and sympathomimetics Chronic alcohol abuse (induction of the P 450 system of the liver) Amphetamine overdose Hypernatremia Inhalation anesthesia // A. E. Karelov, St. Petersburg MAPO 69

FACTORS REDUCING MAC Neonatal period Old age Pregnancy Hypotension, decreased COO Hypothermia Hypothyroidism Alpha 2-agonists Sedative drugs Acute alcohol intoxication (depression - competitive - P 450 systems) Chronic amphetamine abuse Inhalation anesthesia // Litiy A. E. Karelov, St. Petersburg MAPO 70

FACTORS REDUCING MAC Pregnancy Hypoxemia (less than 40 torr) Hypercapnia (more than 95 torr) Anemia Hypotension Hypercalcemia Inhalation anesthesia // A. E. Karelov, St. Petersburg MAPO 71

FACTORS THAT DO NOT AFFECT MAC Hyperthyroidism Hypothyroidism Sex Duration of exposure Inhalation anesthesia // A. E. Karelov, St. Petersburg MAPO 72

MAK 1, 3 MAK - an effective dose for 95% of the subjects. 0, 3 -0, 4 MAC - awakening MAC. MACs of different anesthetics add up: 0.5 MAC of N 2 O (53%) + 0.5 MAC of halothane (0.37%) cause CNS depression comparable to the effect of 1 MAC of enflurane (1.7%). Inhalation anesthesia // A. E. Karelov, St. Petersburg MAPO 73

MAC AND FAT/GAS RATIO Methoxyflurane Trichlorethylene Halothane Isoflurane Enflurane Ether Sevoflurane Dezflurane Xenon Nitrous oxide – 0.16 // … – 0.17 // 960 – 0.77 // 220 – 1.15 // 97 – 1.68 / / 98 – 1.9 // 65 – 2.0 // … – 6.5 // 18.7 – 71 // … – 105 // 1.4 Measure of fat solubility Fat solubility correlates with anesthetic potency Higher fat solubility – higher power of anesthetic Inhalation anesthesia // A. E. Karelov, St. Petersburg MAPO 74

The anesthetic effect depends on the achievement of a certain partial pressure of the anesthetic in the brain, which in turn directly depends on the partial pressure of the anesthetic in the alveoli. Abstractly, this relationship can be thought of as a hydraulic system: the pressure generated at one end of the system is transferred through the fluid to the opposite end. The alveoli and brain tissue are "opposite ends of the system" and the fluid is blood. Accordingly, the faster the partial pressure in the alveoli increases, the faster the partial pressure of the anesthetic in the brain will also increase, which means that induction into anesthesia will occur faster. The actual concentration of the anesthetic in the alveoli, circulating blood, and in the brain is important only because it contributes to the achievement of the anesthetic partial pressure.

The most important requirement in the formation and maintenance of anesthesia is the delivery of an appropriate amount of anesthetic to the patient's brain (or other organ or tissue). Intravenous anesthesia is characterized by direct entry of the drug into the bloodstream, which delivers it to the site of action. When using inhalation anesthetics, they must first pass the pulmonary barrier to enter the bloodstream. Thus, the basic pharmacokinetic model for inhalation anesthetic should be supplemented by two additional sectors (respiratory circuit and alveoli) that are actually represented by the anatomical space. Due to the presence of these two additional sectors, inhalation anesthesia is somewhat more difficult to manage than intravenous anesthesia. However, it is the ability to regulate the degree of inhalation anesthetic entering and washing out of the blood through the lungs that is the only and main control element of this type of anesthesia.

Schematic diagram of anesthesia machine Breathing circuit Vaporizer CO2 adsorber Ventilator Control unit + monitor

Barriers between anesthesia machine and brain Lungs Fresh gas flow Arterial blood Dead space Respiratory circuit Brain Venous blood Fi Solubility FA Fa Alveolar blood flow Solubility and absorption Volatility (DNP) Power (MAC) Pharmacological effects SI

FACTORS AFFECTING PHARMACOKINETICS Factors affecting the fractional concentration in the inhaled mixture (FI). Factors affecting fractional alveolar concentration (FA). Factors affecting the fractional concentration in arterial blood (Fa).

Fi is the fractional concentration of the anesthetic in the inhaled mixture v Fresh gas flow v Volume of the breathing circuit - MRI hoses - 3 m v Absorption capacity of surfaces in contact with the mixture - rubber tubes absorb ˃ plastic and silicone → delay induction and recovery. The greater the fresh gas flow, the lower the volume of the breathing circuit and the lower the absorption, the more closely the concentration of anesthetic in the inhaled mixture corresponds to the concentration set on the vaporizer

FA - fractional alveolar concentration of anesthetic Ventilation. The effect of concentration. The effect of the second gas. The effect of increased inflow. Intensity of absorption by blood.

Factors affecting the flow of anesthetic into the alveoli Ventilation ▫ With an increase in alveolar ventilation, the flow of anesthetic into the alveoli increases ▫ Respiratory depression slows down the increase in alveolar concentration

N.B concentration. Increasing the fractional concentration of the anesthetic in the inhaled mixture not only increases the fractional alveolar concentration, but also rapidly increases the FA/Fi effect of the concentration. If, against the background of a high concentration of nitrous oxide, another inhalation anesthetic is administered, then the entry of both anesthetics into the pulmonary circulation will increase (due to the same mechanism). The influence of the concentration of one gas on the concentration of another is called the effect of the second gas.

Factors affecting the elimination of the anesthetic from the alveoli Solubility of the anesthetic in the blood Alveolar blood flow Difference between the partial pressure of the anesthetic in the alveolar gas and venous blood

The entry of anesthetic from the alveoli into the blood If the anesthetic does not enter the blood from the alveoli, then its fractional alveolar concentration (FA) will quickly become equal to the fractional concentration in the inhaled mixture (Fi). Since during induction the anesthetic is always absorbed to some extent by the blood of the pulmonary vessels, the fractional alveolar concentration of the anesthetic is always lower than its fractional concentration in the inhaled mixture (FA / Fi

High solubility (K=blood/gas) - FA - P partial in alveoli and blood grow slowly!!! Diffusion into blood Lungs (FA) Acting/dissolved tissue fraction Solubility low (K=blood/gas) - FA - P partial in alveoli and in blood grow fast!!! Diffusion into blood Tissue saturation Required gas concentration in inhaled gas Induction time

Factors affecting the elimination of anesthetic from the alveoli Alveolar blood flow ▫ In the absence of pulmonary or intracardiac shunting, the blood is equal to cardiac output ▫ With an increase in cardiac output, the rate of entry of anesthetic from the alveoli into the bloodstream increases, the increase in FA decreases, so induction lasts longer ▫ Low cardiac output, on the contrary, increases risk of overdose of anesthetics, since in this case FA increases much faster ▫ This effect is especially pronounced in anesthetics with high solubility and a negative effect on cardiac output

Factors affecting the elimination of anesthetic from the alveoli The difference between the partial pressure of the anesthetic in the alveolar gas and venous blood ▫ Depends on the absorption of the anesthetic by the tissues ▫ Determined by the solubility of the anesthetic in the tissues of the tissue (blood/tissue distribution coefficient) and tissue blood flow ▫ Depends on the difference between the partial pressure in the arterial blood and those in tissues Depending on the blood flow and solubility of anesthetics, all tissues can be divided into 4 groups: well vascularized tissues, muscles, fat, poorly vascularized tissues

The difference between the partial pressure of the anesthetic in the alveolar gas and the partial pressure in the venous blood - this gradient depends on the absorption of the anesthetic by various tissues. If the anesthetic is absolutely not absorbed by the tissues, then the venous and alveolar partial pressures will be equal, so that a new portion of the anesthetic will not come from the alveoli into the blood. The transfer of anesthetics from the blood to the tissues depends on three factors: the solubility of the anesthetic in the tissue (blood/tissue distribution coefficient), the tissue blood flow, the difference between the partial pressure in the arterial blood and that in the tissue. Characteristic Share of body mass, % Share of cardiac output, % Perfusion, ml/min/100 g Relative solubility Time to reach equilibrium 10 50 20 Weakly vascularized tissues 20 75 19 6 О 75 3 3 О 1 1 20 О 3 -10 min 1 -4 hours 5 days Good Muscle vascularized tissue Fat O

The brain, heart, liver, kidneys, and endocrine organs make up a group of highly vascularized tissues, and it is here that a significant amount of anesthetic enters in the first place. The small volume and moderate solubility of anesthetics significantly limit the capacity of the tissues of this group, so that a state of equilibrium quickly sets in in them (arterial and tissue partial pressures become equal). The blood flow in the muscle tissue group (muscles and skin) is less and the consumption of the anesthetic is slower. In addition, the volume of a group of muscle tissues and, accordingly, their capacity is much larger, so it may take several hours to achieve equilibrium. The blood flow in the adipose tissue group is almost equal to that in the muscle group, but the extremely high solubility of anesthetics in adipose tissue results in such a high total capacity (Total Capacity = Tissue/Blood Solubility X Tissue Volume) that it takes several days to reach equilibrium. In the group of weakly vascularized tissues (bones, ligaments, teeth, hair, cartilage), blood flow is very low and anesthetic consumption is negligible.

Rise and fall in alveolar partial pressure precede similar changes in partial pressure in other tissues, fa reaches Fi faster with nitrous oxide (anesthetic with low blood solubility) than with methoxyflurane (anesthetic with high blood solubility).

Factors affecting the fractional concentration of the anesthetic in the arterial blood (Fa) Violation of the ventilation-perfusion relationship Normally, the partial pressure of the anesthetic in the alveoli and in the arterial blood after reaching equilibrium becomes the same. Violation of the ventilation-perfusion relationship leads to the appearance of a significant alveolo-arterial gradient: the partial pressure of the anesthetic in the alveoli increases (especially when using highly soluble anesthetics), in the arterial blood it decreases (especially when using low-soluble anesthetics).

The anesthetic content in the brain rapidly equalizes with the arterial blood. The time constant (2-4 min) is the blood/brain distribution ratio divided by the cerebral blood flow. The blood/brain partition coefficients differ little among AIs. After one time constant, the partial pressure in the brain is 63% of the partial arterial pressure.

Time constant The brain takes about 3 time constants to reach equilibrium with arterial blood Time constant for N 2 O / Desflurane = 2 minutes Time constant for Halothane / ISO / SEVO = 3 -4 minutes

For all inhalational anesthetics, equilibrium between brain tissue and arterial blood is reached in approximately 10 minutes.

Arterial blood has the same partial pressure with the alveoli PP inspiratory = 2 A Complete equilibrium on both sides of the alveolar-capillary membrane PP alveolar = A = PP

Fet. IA = key value Currently measuring Fet. AI at steady state, we have a good way to determine the concentration in the brain, despite all the complexities of pharmacokinetics. When equilibrium is reached: End tidal = alveolar = arterial = brain

Summary (1) (Fi): (2) (FA): 1 - fresh gas flow 2 - circuit gas absorption 3 - breathing circuit volume Gas input: 1 - concentration 2 - MOAlv. Vent Gas removal: 1 - blood solubility (3) (Fa): V/Q disturbances 2 - alveolar blood flow 3 - tissue gas consumption

FA is a balance between the entry and exit of IAs from the alveoli. Increased entry of IAs into the alveoli: High % on the evaporator + MOD + fresh mixture flow. IA venous pressure (PA) = 4 mm Hg FI = 16 mm Hg FA = 8 mm Hg FA / FI = 8/16 = 0. 5 Agent arterial pressure (PV) agent = 8 mm Hg Increased IA excretion from the alveoli into the blood: Low venous P, high solubility, high CO

High solubility = slow build up FA N 2 O, low blood / gas Halothane, high blood / gas

The entry of IA from the alveoli into the blood - "absorption" FI = 16 mm Hg FA = 8 mm Hg Venous (PA) agent = 4 mm Hg Arterial (PV) agent = 8 mm Hg

The intake of gas from the alveoli (“uptake”) is proportional to the blood/gas ratio Input Inhaled “FI” PP = 16 mm Hg Alveoli “FA” PP = 8 mm Hg Output (“uptake”) is low Sevoflurane b/g = 0. 7 Blood and tissues PP = 6 mm Hg

The flow of gas from the alveoli (“uptake”) is proportional to the blood/gas ratio Input Inhaled “FI” PP = 16 mm Hg Alveoli “FA” PP = 4 mm Hg Output (“uptake”) is large Halothane b/g = 2. 5 Blood and tissues PP = 2 mm Hg

Delay time between turning on the vaporizer and accumulation of AI in the brain 4% sevoflurane Closed system (“hoses”) PP= 30 mm Hg PP = 24 mm Hg vaporizer At sea level Inhaled AI “FI” PP = 16 mm Hg Alveoli “FA” PP = 8 mm Hg Arterial blood PP = 8 mm Hg brain PP = 5 mm Hg

When venous pressure=alveolar, absorption stops and FA / FI = 1. 0 FI = 16 mm Hg FA = 16 mm Hg Venous (PA) agent = 16 mm Hg FA / FI = 16/16 = 1. 0 Arterial ( PV) agent = 16 mm Hg

Awakening depends on: - removal of exhaled gas, - high fresh gas flow, - small volume of the breathing circuit, - negligible anesthetic absorption in the breathing circuit and anesthesia machine, - low anesthetic solubility, - high alveolar ventilation

Advantages of modern inhalation anesthesia Ø Powerful general anesthetic activity of the drug. Ø Good handling. Ø Rapid awakening and the possibility of early activation of patients. Ø Reducing the use of opioids, muscle relaxants and faster recovery of gastrointestinal function.

“Inhalation anesthesia is most indicated for long-term and traumatic operations, while with relatively low-traumatic and short-term interventions, the advantages and disadvantages of inhalation and intravenous techniques are mutually compensated” (Likhvantsev V.V., 2000).

Conditions for the use of inhalation anesthetics: availability of narco-respiratory equipment intended for the use of inhalation anesthetics; availability of appropriate evaporators (“each volatile anesthetic has its own evaporator”); full-fledged monitoring of the gas composition of the respiratory mixture and functional systems of the body;

The main advantage of using IAs is the ability to control them at all stages of anesthesia, which ensures, first of all, the patient's safety during surgery, since their effect on the body can be quickly stopped.

minor gynecological operations with severe concomitant pathology (circulatory system, respiratory system) short-term interventions in obese patients

short-term diagnostic studies (MRI, CT, colonoscopy, etc.) New Drugs: Alternatives and Adjuncts to Bupivacaine in Pediatric Regional Anaesthesia Per-Arne Lönnqvist, Stockhom, Sweden - SGKA-APAMeeting 2004

with a limited possibility of using non-inhalation anesthetics - allergic reactions - bronchial asthma - difficulties in providing vascular access, etc.

in Pediatrics - Providing Vascular Access - Inducing Anesthesia - Conducting Short Term Rapid Sequence Induction in Pediatric Anaesthesia Peter Stoddart, Bristol, United Kingdom - SGKAAPA-Meeting 2004

An absolute contraindication to the use of IAs is the fact of malignant hyperthermia and a history of adverse (primarily allergic) reactions. A relative contraindication is short-term surgical interventions, when IAs are used in an open respiratory circuit with the patient spontaneously breathing or in a semi-closed circuit with mechanical ventilation under conditions of high gas flow, which does not harm the patient, but significantly increases the cost of anesthesia.

"Ideal inhalation anesthetic" Properties Physico-chemical stability - must not be destroyed by light and heat inertness - must not enter into chemical reactions with metal, rubber and soda lime no preservatives must not be flammable or explosive must have a pleasant odor must not accumulate in atmosphere have a high oil/gas partition coefficient (i.e. be fat soluble), correspondingly low MAC have a low blood/gas partition coefficient (i.e. low solubility in liquid) not metabolized - have no active metabolites and are excreted unchanged non-toxic Clinical have analgesic, antiemetic, anticonvulsant effects no respiratory depression bronchodilator properties no negative effect on the cardiovascular system no decrease in coronary, renal and hepatic blood flow no effect on cerebral blood flow and intracranial yes phenomenon not a trigger of malignant hyperthermia not having epileptogenic properties Economic relative cheapness availability for the health care system acceptability in terms of cost effectiveness and utility of costs economic feasibility of application for the health care system cost savings of the health care budget

Each of the inhalation anesthetics has its own so-called anesthetic activity or "power". It is defined by the concept of "minimum alveolar concentration" or MAC. It is equal to the concentration of anesthetic in the alveolar space, which in 50% of patients prevents a reflex motor reaction to a painful stimulus (skin incision). MAC is an average value, which is calculated for people aged 30-55 years and expressed as a percentage of 1 atm, reflects the partial pressure of the anesthetic in the brain and allows you to compare the "power" of different anesthetics. The higher the MAC, the lower the anesthetic activity of the awakening MAC drug - 1/3 MAC 1, 3 MAC - 100% lack of movement in patients 1, 7 MAC - MAC BAR (hemodynamically significant MAC)

MAC - partial pressure, not concentration Yes - MAC is expressed in %, but this implies % of atmospheric pressure at sea level

Can you survive with 21% oxygen in the air? Not if you are at the top of Everest!!! Also MAC reflects partial pressure and not concentration.

MAC At sea level, atmospheric pressure is 760 mm Hg. % MAC = 2.2%, and the partial pressure will be: 2. 2% X 760 = 16. 7 mm Hg At altitude, the pressure is lower and will be 600 mm Hg, and MAC% of sevoran will be = 2. 8% and pressure remains the same (16.7 / 600 = 2.8%)

Q: What is the % MAC of sevoran at 33 feet underwater? Answer: 1. 1%, since the barometric pressure is 2 atmospheres or 1520 mm Hg. And since the partial pressure of sevoran is constant, then: 16. 7 mm Hg / 1520 mm Hg = 1. one%

MAC value of inhalation anesthetics in a patient aged 30-60 years at atmospheric pressure Anesthetic MAC, % Halothane 0.75 Isoflurane 1. 15 Sevoflurane 1. 85 Desflurane 6.6 Nitrous oxide 105

Properties of an ideal inhalation anesthetic Sufficient strength Low solubility in blood and tissues Resistant to physical and metabolic degradation, no damaging effect on organs and tissues of the body No predisposition to develop seizures No irritant effect on the respiratory tract No or minimal effect on the cardiovascular system on the earth's ozone layer) Acceptable cost

Anesthetic solubility in the blood A low blood/gas partition coefficient indicates a low affinity of the anesthetic for blood, which is a desirable effect, as it provides a quick change in the depth of anesthesia and a quick awakening of the patient after the end of anesthesia The partition coefficient of inhaled anesthetics in the blood at t 37 ° C Blood-gas 0.45 Nitrous oxide Sevoflurane Isoflurane Halothane 0.47 0.65 1.4 2.5

Distribution coefficient of inhalation anesthetics in tissues at t 37°C Anesthetic Brain/blood Muscle/blood Fat/blood Nitrous oxide 1, 1 1, 2 2, 3 Desflurane 1, 3 2, 0 27 Isoflurane 1, 6 2, 9 45 Sevoflurane 1 , 7 3, 1 48 Halothane 1, 9 3, 4 51

Resistance to degradation When evaluating the metabolism of inhalational anesthetics, the most important aspects are:

Resistance to degradation Halothane, Isoflurane and Desflurane undergo biotransformation in the body with the formation of trifluoroacetate, which can cause liver damage Sevoflurane has an extrahepatic biotransformation mechanism, its metabolic rate is from 1 to 5%, which is slightly higher than that of isoflurane and desflurane, but significantly lower than at halothane

Resistance to metabolic degradation and potential hepatotoxic effects of some inhalational anesthetics Anesthetic Halothane Metabolism, % Incidence of liver injury 15 -20 1: 35000 Isoflurane 0.2 1: 1000000 Desflurane 0.02 1: 10000000 Sevoflurane 3.3 -

Resistance to degradation Nitrous oxide is practically not metabolized in the body, but it causes tissue damage by suppressing the activity of vitamin B 12 -dependent enzymes, which include methionine synthetase, which is involved in DNA synthesis Tissue damage is associated with bone marrow depression (megaloblastic anemia), as well as damage to the nervous system (peripheral neuropathy and funicular myelosis) These effects are rare and presumably only occur in patients with vitamin B12 deficiency and long-term use of nitrous oxide

Resistance to degradation Sevoflurane does not have hepatotoxicity Approximately 5% of sevoflurane is metabolized in the body to form fluorine ions and hexafluoroisopropanol Fluoride ion has potential nephrotoxicity at plasma concentrations above 50 µmol/L 10 -23 µmol/l and rapidly decreases after anesthesia has ended No cases of nephrotoxicity in children after anesthesia with sevoflurane have been noted

Protective effect of inhaled anesthetics Clinical studies of the use of propofol, sevoflurane and desflurane as anesthetics in coronary artery bypass CAD patients showed that the percentage of patients with elevated postoperative troponin I levels, reflecting damage to myocardial cells, was significantly higher in the propofol group compared with groups sevoflurane and desflurane

Predisposition to seizures Halothane, isoflurane, desflurane, and nitrous oxide do not cause seizures The medical literature describes cases of epileptiform activity on the EEG and convulsive movements during anesthesia with sevoflurane, however, these changes were transient and spontaneously resolved without any clinical manifestations in the postoperative period. cases at the stage of awakening in children there is increased arousal, psychomotor activity ▫ May be associated with a rapid recovery of consciousness against the background of insufficient analgesia

Irritant effect on the respiratory tract Halothane and Sevoflurane do not cause respiratory irritation The threshold for the development of respiratory irritation is 6% with desflurane and 1.8% with isoflurane Desflurane is contraindicated for use as mask induction in children due to the high incidence of adverse events. effects: laryngospasm, cough, breath holding, desaturation Due to the absence of an irritating odor and low risk of respiratory irritation, sevoflurane is the most commonly used inhalation anesthetic used for induction of anesthesia

The effect of inhalation anesthetics on hemodynamics With a rapid increase in the concentration of desflurane and isoflurane, tachycardia and an increase in blood pressure are more pronounced in desflurane compared to isoflurane, however, when these anesthetics are used to maintain anesthesia, there are no large differences in hemodynamic effects. Sevoflurane reduces cardiac output, but to a much lesser extent. less than halothane, and also reduces systemic vascular resistance A rapid increase in the concentration of sevoflurane (0.5 MAC, 1.5 MAC) causes a moderate decrease in heart rate and blood pressure Sevoflurane to a much lesser extent sensitizes the myocardium to endogenous catecholamines, serum adrenaline concentration, at which disturbances are observed heart rate, sevoflurane is 2 times higher than halothane and comparable to isoflurane

Choice of anesthetic: nitrous oxide Low power limits use, used as a carrier gas for other more powerful inhalation anesthetics Odorless (makes it easier to accept other inhaled anesthetics) Has a low solubility coefficient, which ensures rapid induction and rapid recovery from anesthesia Causes an increase in cardiodepressive effect halothane, isoflurane Increases pressure in the pulmonary artery system Has a high diffusion capacity, increases the volume of cavities filled with gas, therefore it is not used for intestinal obstruction, pneumothorax, operations with cardiopulmonary bypass During the period of recovery from anesthesia, it reduces the alveolar oxygen concentration, therefore, within 5-10 minutes after the anesthetic has been switched off, high concentrations of oxygen must be used

Choice of anesthetic: halothane Halothane has some of the characteristics of an ideal inhalation anesthetic (sufficient potency, no irritant effect on the respiratory tract). However, high solubility in blood and tissues, a pronounced cardiodepressive effect and the risk of hepatotoxicity (1: 350001: 60000) led to its displacement from clinical practice modern inhalation anesthetics

Choice of anesthetic: isoflurane Not recommended for induction into anesthesia ▫ Has an irritant effect on the respiratory tract (cough, laryngospasm, apnea) ▫ With a sharp increase in concentration, it has a pronounced effect on hemodynamics (tachycardia, hypertension) Has a potential hepatotoxicity (1: 1000000) Has a relatively high solubility in blood and tissues (higher than sevoflurane and desflurane) Has minimal impact on the Earth's ozone layer Cheaper drug than sevoflurane and desflurane Most common inhalation anesthetic

Choice of anesthetic: desflurane Not recommended for induction into anesthesia ▫ Has an irritating effect on the respiratory tract (cough, laryngospasm, apnea) ▫ With a sharp increase in concentration, it has a pronounced effect on hemodynamics (tachycardia, hypertension) Has the lowest solubility in organs and tissues compared to isoflurane and sevoflurane Does not have hepatotoxicity Has a cardioprotective effect Environmentally safe Has a relatively high cost, comparable to sevoflurane

The choice of anesthetic: sevoflurane Does not cause irritation of the respiratory tract Does not have a pronounced effect on hemodynamics Less soluble in blood and tissues than halothane and isoflurane Does not have hepatotoxicity Has a cardioprotective effect epileptiform activity on the EEG In some cases, it can cause the development of postoperative agitation The drug of choice for inhalation induction The most common inhalation anesthetic in pediatric practice

There are three phases of the first degree of anesthesia according to Artusio (1954): initial - pain sensitivity is preserved, the patient is in contact, memories are saved; medium - pain sensitivity is dulled, slight stunning, it is possible to preserve memories of the operation, their inaccuracy and confusion are characteristic; deep - loss of pain sensitivity, drowsiness, a reaction to tactile irritation or a loud sound is present, but it is weak.

Excitation stage During general anesthesia with ether, loss of consciousness at the end of the analgesia phase is accompanied by pronounced speech and motor excitation. Having reached this stage of ether anesthesia, the patient begins to make erratic movements, makes incoherent speeches, sings. A long stage of arousal, about 5 minutes, is one of the features of ether anesthesia, which made it necessary to abandon its use. The excitation phase of modern general anesthesia is weakly expressed or absent. In addition, the anesthetist may use their combination with other drugs to eliminate negative effects. In patients suffering from alcoholism and drug addiction, it is quite difficult to exclude the stage of arousal, since biochemical changes in brain tissues contribute to its manifestation.

Stage of surgical anesthesia It is characterized by complete loss of consciousness and pain sensitivity and weakening of reflexes and their gradual inhibition. Depending on the degree of decrease in muscle tone, loss of reflexes and the ability to spontaneous breathing, four levels of surgical anesthesia are distinguished: Level 1 - the level of movement of the eyeballs - against the background of restful sleep, muscle tone and laryngeal-pharyngeal reflexes are still preserved. The breathing is even, the pulse is somewhat quickened, the blood pressure is at the initial level. The eyeballs make slow circular movements, the pupils are evenly constricted, they react vividly to light, the corneal reflex is preserved. Surface reflexes (skin) disappear. Level 2 - the level of the corneal reflex. The eyeballs are fixed, the corneal reflex disappears, the pupils are constricted, their reaction to light is preserved. There are no laryngeal and pharyngeal reflexes, muscle tone is significantly reduced, breathing is even, slow, pulse and blood pressure are at the initial level, mucous membranes are moist, skin is pink.

Level 3 - the level of pupil dilation. The first signs of an overdose appear - the pupil expands due to paralysis of the smooth muscles of the iris, the reaction to light is sharply weakened, dryness of the cornea appears. The skin is pale, the muscle tone decreases sharply (only the tone of the sphincters is preserved). Costal breathing gradually weakens, diaphragmatic breathing prevails, inhalation is somewhat shorter than exhalation, the pulse quickens, blood pressure decreases. Level 4 - the level of diaphragmatic breathing - a sign of overdose and a harbinger of death. It is characterized by a sharp dilation of the pupils, the absence of their reaction to light, a dull, dry cornea, complete paralysis of the respiratory intercostal muscles; only diaphragmatic breathing was preserved - superficial, arrhythmic. The skin is pale with a cyanotic tint, the pulse is thready, rapid, blood pressure is not determined, paralysis of the sphincters occurs. The fourth stage - AGONAL STAGE - paralysis of the respiratory and vasomotor centers, manifested by respiratory and cardiac arrest.

Awakening stage - exit from anesthesia After the cessation of the flow of funds for general anesthesia in the blood, awakening begins. The duration of the exit from the state of anesthesia depends on the rate of inactivation and excretion of the anesthetic substance. For the broadcast, this time is about 10 -15 minutes. Awakening after general anesthesia with propofol or sevoflurane occurs almost instantly.

Malignant hyperthermia A disease that occurs during or immediately after general anesthesia, characterized by skeletal muscle hypercatabolism, manifested by increased oxygen consumption, lactate accumulation, increased production of CO 2 and heat First described in 1929 (Ombredan's syndrome) ▫ Succinylcholine

Malignant hyperthermia An autosomal dominant hereditary disease The average incidence is 1 in 60,000 general anesthesia with succinylcholine and 1 in 200,000 without its use Signs of MH can occur both during anesthesia with trigger agents and after several hours after its completion Any patient can develop MH, even if the previous general anesthesia was uneventful

Pathogenesis MH is triggered by inhaled anesthetics (halothane, isoflurane, sevoflurane) alone or in combination with succinylcholine Trigger substances release calcium from the sarcoplasmic reticulum, causing skeletal muscle contracture and glycogenolysis, increasing cellular metabolism, resulting in increased oxygen consumption, excess heat production, lactate accumulation Affected patients develop acidosis, hypercapnia, hypoxemia, tachycardia, rhabdomyolysis, followed by an increase in serum creatine phosphokinase (CPK), as well as potassium ions with a risk of developing cardiac arrhythmia or cardiac arrest and myoglobinuria with a risk of developing renal failure

Malignant hyperthermia, early signs In most cases, signs of MH occur in the operating room, although they may appear during the first postoperative hours ▫ Unexplained tachycardia, rhythm disturbances (ventricular extrasystoles, ventricular bigemia) ▫ Hypercapnia, increased RR if the patient is spontaneously breathing ▫ Spasm of masticatory muscles (unable to open mouth), generalized muscle rigidity ▫ Marbling of the skin, sweating, cyanosis ▫ Sudden increase in temperature ▫ Anesthesia machine adsorber becomes hot ▫ Acidosis (respiratory and metabolic)

Laboratory diagnosis of MH Changes in CBS: ▫ Low p. H ▫ Low p. O 2 ▫ High p. CO 2 ▫ Low bicarbonate ▫ Major base deficiency Other laboratory findings ▫ Hyperkalemia ▫ Hypercalcemia ▫ Hyperlactatemia ▫ Myoglobinuria (dark urine) ▫ Elevated CK levels Caffeine-halothane contractile test is the gold standard for diagnosing MH predisposition

Diagnosis of predisposition to MH Caffeine test Halothane test Muscle fiber is placed in a caffeine solution with a concentration of 2 mmol / l Normally, it breaks when a force of 0.2 g is applied to the muscle fiber In a predisposition to MH, break occurs with a force of > 0.3 g The muscle fiber is placed in a container of saline, through which a mixture of oxygen and carbon dioxide and halothane is passed. The fiber is stimulated by an electrical discharge every 10 seconds. Normally, it will not change the force of contraction of the application of force > 0.5 g during the entire time of the presence of halothane in the gas mixture. When the concentration of halothane in the environment of the muscle fiber decreases by 3%, the fiber break point drops from > 0.7 to > 0.5 G

Actions in case of development of masticatory muscle stiffness Conservative approach Stop anesthesia Obtain a muscle biopsy for laboratory testing Postpone anesthesia to a later date Liberal approach Switch to use of non-trigger anesthetic drugs Careful monitoring of O 2 and CO 2 Treatment with dantrolene

Differential diagnosis of masticatory muscle rigidity Myotonic syndrome Temporomandibular joint dysfunction Insufficient administration of succinylcholine

Neuroleptic malignant syndrome Symptoms similar to malignant hyperthermia ▫ Fever ▫ Rhabdomyolysis ▫ Tachycardia ▫ Hypertension ▫ Agitation ▫ Muscle stiffness

Neuroleptic malignant syndrome Seizure occurs after prolonged use of: ▫ Phenothiazines ▫ Haloperidol ▫ Abrupt withdrawal of Parkinson's drugs Possibly triggered by dopamine depletion Condition is not inherited Succinylcholine is not a trigger Dantrolene treatment is effective If the syndrome develops during anesthesia, treatment is carried out according to the protocol for the treatment of malignant hyperthermia

Treatment of malignant hyperthermia Mortality in fulminant form without the use of dantrolene is 60 - 80% The use of dantrolene and rational symptomatic therapy has reduced mortality in developed countries to 20% or less

Diseases associated with MH ▫ King-Denborough syndrome ▫ Central rod disease ▫ Duschenne muscular dystrophy ▫ Fukuyama muscular dystrophy ▫ Myotonia congenita ▫ Schwartz-Jampel syndrome High risk of alertness to the development of MH Trigger agents should be avoided

First steps 1. 2. 3. Call for help Alert the surgeon of the problem (abort operation) Follow treatment protocol

Treatment protocol 1. Stop the administration of trigger drugs (inhalation anesthetics, succinylcholine) Hyperventilation (MOV 2-3 times higher than normal) 100% oxygen with high flow (10 l/min or more), disconnect the vaporizer 2. ▫ change the circulation system and adsorbent not needed (waste of time) 3. Switch to use of non-trigger anesthetic drugs (NTA) 4. Administer dantrolene at 2.5 mg/kg (repeat if no effect, total dose up to 10 mg/kg) 5. Cool patient ▫ ▫ Ice on the head, neck, underarms, groin area Stop cooling at body temperature

Monitoring Continue routine monitoring (ECG, Sat, Et. CO 2, indirect BP) Measure core temperature (esophageal or rectal temperature probe) Place large diameter peripheral catheters Discuss placement of CVC, arterial line, and urinary catheter Electrolyte and blood gas analysis B/C analysis blood (liver, kidney enzymes, coagulogram, myoglobin)

Further treatment Correction of metabolic acidosis at p. H

Dantrolene The drug was introduced into clinical practice in 1974. Non-curare-like muscle relaxant Reduces the permeability of calcium channels of the sarcoplasmic reticulum Reduces the release of calcium into the cytoplasm Prevents the occurrence of muscle contracture Restricts cellular metabolism Nonspecific antipyretic

Dantrolene Intravenous formulation appeared in 1979. 20 mg bottle + 3 g mannitol + Na. OH Onset of action after 6-20 minutes Effective plasma concentration persists for 5-6 hours Metabolized in the liver, excreted by the kidneys Shelf life 3 years, ready-made solution - 6 hours

Side effects Muscle weakness up to the need for prolonged mechanical ventilation Reduces myocardial contractility and cardiac index Antiarrhythmic effect (prolongs the refractory period) Dizziness Headache Nausea and vomiting Severe drowsiness Thrombophlebitis

Therapy in the ICU Observation for at least 24 hours Administration of dantrolene at a dose of 1 mg/kg every 6 hours for 24-48 hours ▫ Up to 50 ampoules of dantrolene may be required for adult therapy Monitoring of core temperature, gases, blood electrolytes, CPK , myoglobin in blood and urine and coagulogram parameters

Cleaning the anesthesia machine Replacing the evaporators Replacing all parts of the machine circuit Replacing the absorber with a new one Replacing the anesthesia masks Ventilating the machine with pure oxygen at a flow of 10 l/min for 10 min.

Anesthesia in patients with a predisposition to MH Adequate monitoring: ▫ Pulse oximeter ▫ Capnograph ▫ Invasive BP ▫ CVP ▫ Central temperature monitoring

Anesthesia in patients with a predisposition to MH Dantrolene 2.5 mg/kg IV 1.5 h before anesthesia (now considered unreasonable) General anesthesia ▫ Barbiturates, nitrous oxide, opioids, benzodiazepines, propofol ▫ Use of non-depolarizing muscle relaxants Regional anesthesia Local anesthesia against the background of medical sedation Postoperative observation for 4-6 hours.

16453 0

Halothane(halothane). Synonyms: Fluorotan(Phthorothanum), drug addict(Narcotan).

pharmachologic effect: has a strong fast-passing narcotic effect, does not cause excitation and tension of the patient during anesthesia. Switching off consciousness occurs in 1-2 minutes after the administration of halothane at a concentration of 1:200 (0.5 vol.%) with oxygen, the surgical stage occurs in 3-5 minutes; awakening - 35 minutes after stopping the supply of halothane.

Indications: is a means of choice for many surgical interventions, different in volume and trauma. For a short-term intervention that does not require muscle relaxation, superficial anesthesia is acceptable.

Mode of application: Anesthesia with halothane can be carried out along any circuit, but it is better to use a semi-closed one. The halothane evaporator is always installed outside the circulation circle. Inhalation mononarcosis while maintaining spontaneous breathing is carried out in the following mode: the introductory phase occurs when 1:40-1:33 (2.5-3 vol.%) of halothane is given for 34 minutes, anesthesia can be maintained when 1:100-1 is received: 66 (1 - 1.5 vol.%) drug with oxygen or a mixture consisting of 50% oxygen and 50% nitrous oxide.

Side effect: possible inhibition of the function of the cardiovascular system, hepatotoxic effect (in case of impaired liver function), sensitization of the heart to catecholamines, increased bleeding in the area of surgical intervention, chills, pain.

: during anesthesia, adrenaline, norepinephrine, aminophylline, chlorpromazine should not be used. The use of an azetotropic mixture consisting of halothane and ether (2:1), at an oxygen concentration of at least 50%, makes it possible to reduce the amount of halothane used. Contraindications: hyperthyroidism, cardiac arrhythmia, hypotension, organic liver damage.

Release form: dark bottles of 50 and 250 ml. Storage conditions: in a dry, cool, dark place. List B.

Nitrous oxide(Nitrogenium oxydulatum). Synonym: Oxydum nitrosum.

pharmachologic effect: when inhaled pure gas causes a narcotic state and asphyxia. After cessation of inhalation, it is excreted completely unchanged through the respiratory tract. Possesses weak narcotic activity. For a more complete relaxation of the muscles, muscle relaxants are needed, while not only increasing the relaxation of the mouse, but also improving the course of anesthesia.

Indications: used in operations of the maxillofacial region and in the oral cavity.

Mode of application: administered in a mixture with oxygen using apparatus for gas anesthesia, in the process of anesthesia, the content of nitrous oxide in the mixture is reduced from 80 to 40%.

To obtain the required level of anesthesia, they are combined with other drugs - cyclopropane, halothane, barbiturates, and are also used for neuroleptanalgesia.

Side effect: possible nausea and vomiting after anesthesia.

see Droperidol, Hexenal, Methoxyflurane, Cyclopropane.

Contraindications: caution is necessary when prescribing to persons with severe hypoxia and impaired diffusion of gases in the lungs.

Release form: metal cylinders according to Yul under pressure in a liquefied state.

Storage conditions: In a separate room at room temperature away from heat sources.

Isoflurane(Isoflurane). Synonym: Foran(Forane).

Pharmachologic effect: has a rapid immersion in anesthesia and exit from it, a rapid weakening of the pharyngeal and laryngeal reflexes. During anesthesia, blood pressure decreases in proportion to its depth. The heart rate does not change. Anesthesia levels change easily. Muscle relaxation is sufficient for operations. Surgical anesthesia occurs in 7-10 minutes at a concentration of 1.5-3 vol.%.

Indications: agent for inhalation anesthesia.

Mode of application: The concentration of anesthetic created by a vaporizer calibrated to phorane must be observed very carefully. The value of the minimum concentration depends on age: for 20-year-old patients - 1.28% in oxygen, for 40-year-olds - 1.15%, for 60-year-old patients - 1.05%; newborns - 1.6%, children under 12 months - 1.8%. The initial recommended concentration is 0.5%. Maintaining anesthesia is recommended at a level of 1-2.5% in a mixture with oxygen or oxygen and nitrous oxide.

Side effect: in case of overdose - severe arterial hypotension, cardiac arrhythmias, changes in the blood (leukocytosis).

Contraindications: hypersensitivity to the drug. Use with caution in patients with increased intracranial pressure.

Interaction with other drugs: enhances the effect of muscle relaxants, especially with the simultaneous use of nitrous oxide.

Release form: liquid for anesthesia in vials.

Storage conditions: at a temperature of +15°-30° C for 5 years.

Methoxyflurane(Methoxyfluranum). Synonyms: Ingalan(1phalanum), Pentran(Pentran).

pharmachologic effect: surpasses ether and chloroform in narcotic activity. Inhalation of 1:200-1:125 (0.5-0.8 vol.%) of the drug leads to severe analgesia.

Anesthesia occurs slowly (10 minutes), the excitation stage is pronounced. Awakening after stopping the supply of methoxyflurane - up to 60 minutes. Narcotic depression persists for 2-3 hours.

Indications: used for sanitation of the oral cavity under anesthesia, preparation of teeth for fixed dentures in persons with hypersensitivity.

Mode of application: for induction anesthesia in its pure form is rarely used (the patient falls asleep only after 8-10 minutes). Analgesia with pentranom is possible with the help of a special evaporation system of the Tringal type. The technique is simple, safe and practically has no contraindications when using subnarcotic doses of the drug (up to 0.8 vol.%).

Side effect: when using the drug in the post-anesthetic period, headache, postoperative depression, inhibition of kidney function with the development of polyuria, sensitization of the heart to catecholamines are possible.

Interaction with other drugs: not used with epinephrine and norepinephrine. The combination of 1:200-1:100 (0.5-1.0 vol.%) methoxyflurane with nitrous oxide and oxygen l: I, as well as barbiturates and muscle relaxants, is used for long-term operations.

Contraindications: Be careful with kidney and liver disease.

release form: dark glass bottles of 100 ml.

Storage conditions: in tightly closed vials in a cool place. List B.

Trichlorethylene(Trichloraethylenum). Synonyms: Narcogen(Narcogen) trichlorene(Trichloren) Trilene(Trilen).

pharmachologic effect: is a powerful narcotic drug with a rapid onset of effect, the effect of the drug ends 2-3 minutes after the cessation of supply.

Small concentrations already in the first stage of anesthesia give a strong analgesia. Does not cause an increase in the secretion of the salivary and bronchial glands, does not affect blood circulation.

Mode of application: used for anesthesia in a semi-open system using special anesthesia machines with a calibrated evaporator ("Tritek") without an absorber at a concentration of 1:167-1:83 (0.6-1.2 vol.%). For short-term anesthesia, analgesia for minor operations and painful manipulations, it is used at a concentration of 1:333-1:167 (0.3-0.6 vol.%) in a mixture with oxygen or air or with a mixture containing 50% nitrous oxide and 50 % oxygen. Cannot be used in a closed or semi-closed system due to possible ignition of decomposition products in the absorber.

Side effect: in case of an overdose (concentration over 1:66-1.5 vol.%), a sharp respiratory depression develops with a violation of the heart rhythm.

Interaction with other drugs: due to trichlorethylene sensitization of the myocardium to catecholamines, it cannot be used in conjunction with epinephrine and norepinephrine.

Contraindications: caution is necessary in case of liver and kidney diseases, heart rhythm disturbances, lung diseases, anemia.

Release form: ampoules of 1, 2, 6 and 7 ml, bottles of 25, 50, 100, 250. 300 ml, aluminum containers.

Storage conditions: in a dry, cool place. List B.

Chloroethyl(Aethylii chloridum). Synonyms: Ethyl chloride(Aethylis chloridum). Ethyl chloride.

Pharmachologic effect: chloroethyl has a small therapeutic breadth, therefore, it is not currently used as a means for inhalation anesthesia. It is used for short-term superficial anesthesia of the skin due to rapid evaporation, which leads to a strong cooling of the skin, vasospasm and a decrease in sensitivity.

Indications: prescribed for the treatment of erysipelas (cryotherapy), neuralgia, neuromyositis, diseases of the temporomandibular joint; for small superficial operations (skin incisions), for painful dressings in the postoperative period, for the treatment of burns, for soft tissue bruises, insect bites.

Mode of application: applied externally, by irrigating the skin of the desired area of the maxillofacial region. The rubber cap is removed from the lateral capillary of the ampoule, the ampoule is warmed in the palm of the hand, and the emerging jet is directed to the skin surface from a distance of 25-30 cm. After the appearance of frost on the skin, the tissues become dense and insensitive. For medicinal purposes, the procedure is carried out 1 time per day for 7-10 days.

Side effect: with strong cooling, tissue damage, skin hyperemia is possible.

Contraindications: violation of the integrity of the skin, vascular disease.

Release form: ampoules of 30 ml.

Storage conditions: in a cool place. List B.

Cyclopropane(Cyclopropanum). Synonym: Cyclopropane.

Pharmachologic effect: has a strong narcotic effect. At a concentration of 1:25 (4 vol.%) causes analgesia, 1:16.7 (6 vol.%) - turns off consciousness, 1:12.5-1:10 (8-10 vol.%) - causes anesthesia ( Stage III), 1:5-1:3.3 (20-30 vol.%) - deep anesthesia. It is not destroyed in the body and is quickly (10 minutes after the cessation of inhalation) excreted from the body. Does not affect the function of the liver and kidneys.

Indications: is prescribed for short-term operations of the maxillofacial region in a hospital and polyclinics, for patients with diseases of the lungs, liver and diabetes.

Mode of application: for induction and main anesthesia mixed with oxygen in a closed and semi-closed system using devices with dosimeters. To maintain anesthesia, 1.6-1:5.5 (15-18 vol%) cyclopropane is used. In the Shane-Ashman mixture: after induction intravenous anesthesia with sodium thiopental, a mixture of gases is given (nitrous oxide - 1 part, oxygen - 2 parts, cyclopropane - 0.4 parts).

Side effect: causes some slowing of the pulse, an increase in the secretion of the salivary and bronchial glands. In case of an overdose, respiratory arrest and cardiac depression, headache, vomiting, and intestinal paresis are possible. Decreased diuresis. Possible arrhythmias, increased sensitivity of the myocardium to adrenaline, increased blood pressure (increased bleeding).

Interaction with other drugs: should not be used simultaneously with epinephrine, norepinephrine.

Release form: steel cylinders of 1 or 2 liters of liquid preparation under pressure.

Storage conditions: away from fire sources in a cool place.

Eifluran(Enflurant). Synonym: Etran(Ethrane).

Pharmachologic effect: the inhaled concentration of enflurane from 2% to 4.5% provides surgical anesthesia within 7-10 minutes. The level of blood pressure during the maintenance of anesthesia is inversely proportional to the concentration of the drug. The heart rate does not change.

Indications: means for inhalation anesthesia in combination with oxygen or with a mixture of oxygen + nitrous oxide.

Mode of application: for anesthesia, evaporators specially calibrated for enflurane are used. Premedication is selected individually. Anesthesia can be induced using enflurane with oxygen alone or in combination with an oxygen + nitrous oxide mixture, while a hypnotic dose of a short-acting barbiturate to induce unconsciousness must be administered to prevent arousal, after which the enflurane mixture is applied. The surgical level of anesthesia can be maintained at 0.5-3%.

Side effect: overexcitation of the central nervous system during hyperventilation, increase and decrease in blood pressure.

Contraindications: hypersensitivity to the drug.

Interaction with other drugs: enhances the effect of muscle relaxants.

Release form: liquid for inhalation anesthesia in amber-colored bottles of 150 and 250 ml.

Storage conditions: shelf life 5 years at 15-30°C.

Ether for anesthesia(Aether pro narcosi). Synonyms: Diethyl Ether.

pharmachologic effect: is an inhalation general anesthetic, a volatile liquid with a boiling point of + 34-36 ° C. The resorptive effect of the ether upon inhalation use is to disrupt the synaptic transmission of excitation to the central nervous system. The mechanism of action is associated with the stabilization of electrically excitable sections of neuronal membranes, blockade of the entry of sodium ions inside the cell, and impaired action potential generation. Analgesia and switching off of consciousness are observed at ether concentrations in the inhaled mixture of 1.50-1:25 (2-4 vol.%); superficial anesthesia is provided with a concentration of 1:20-12.5 (58 vol.%), deep 1:10-1:8.3 (10-12 vol.%).

In the stage of surgical anesthesia, it relaxes the skeletal muscles well. Narcotic latitude (the range between narcotic and toxic concentration in the blood) for ether is 50-150 mg/100 ml. Ether anesthesia develops slowly over 12-20 minutes, and is also characterized by a long period of elimination - awakening is observed 20-40 minutes after the cessation of the supply of ether. Possible post-narcotic depression within a few hours. When applied topically, the ether has a drying, irritating, and also a moderate antimicrobial effect.

Indications: used for general anesthesia in a hospital during plastic surgery, surgery for neoplasms of the maxillofacial region, as well as to maintain anesthesia.

The wound surface of dentin and enamel is degreased and dried with ether before filling, fixing locks, inlays, crowns, the surface of prostheses adjacent to the abutment teeth, as well as root canals before filling them, fixing artificial stumps with a pin or pin teeth.

How to use: in surgical practice it can be used in open, semi-open and closed systems. Combined anesthesia with halothane, nitrous oxide is possible.

Side effect: irritates the mucous membrane of the upper respiratory tract, at the beginning of anesthesia can cause reflex changes in breathing, up to its stop, bronchospasm, vomiting, cardiac arrhythmias. Increases the release of catecholamines into the blood. It has a toxic effect on the functions of parenchymal organs (liver, kidneys). After anesthesia with the use of ether, bronchopneumonia may develop. Interaction with other drugs: as mentioned above, combinations with halothane, nitrous oxide are possible. Barbiturates (hexenal, thiopental) can be used for induction anesthesia. Side effects of the ether are prevented by the introduction of anticholinergics (atropine, metacin). It should be remembered that ether vapors are explosive.

Contraindications: severe diseases of the cardiovascular system with cardiac decompensation, acute respiratory diseases, severe liver and kidney diseases, as well as acidosis and diabetes mellitus.

Release form: bottles of 100 and 150 ml.

Storage conditions: in a place protected from light. List B.

In case of violation of the tightness of the bottle under the influence of light and air, the formation of toxic substances (peroxides, aldehydes, ketones) is possible. For anesthesia, ether is used only from vials opened immediately before the operation.

The dentist's guide to medicines
Edited by Honored Scientist of the Russian Federation, Academician of the Russian Academy of Medical Sciences, Professor Yu. D. Ignatov

8. M-anticholinergic agents.

9. Ganglioblocking agents.

11. Adrenomimetic means.

14. Means for general anesthesia. Definition. Determinants of depth, speed of development and recovery from anesthesia. Requirements for an ideal drug.

15. Means for inhalation anesthesia.

16. Means for non-inhalation anesthesia.

17. Ethyl alcohol. Acute and chronic poisoning. Treatment.

18. Sedative-hypnotic drugs. Acute poisoning and measures of assistance.

19. General ideas about the problem of pain and anesthesia. Drugs used in neuropathic pain syndromes.

20. Narcotic analgesics. Acute and chronic poisoning. Principles and means of treatment.

21. Non-narcotic analgesics and antipyretics.

22. Antiepileptic drugs.

23. Means effective in status epilepticus and other convulsive syndromes.

24. Antiparkinsonian drugs and drugs for the treatment of spasticity.

32. Means for the prevention and relief of bronchospasm.

33. Expectorants and mucolytics.

34. Antitussives.

35. Means used for pulmonary edema.

36. Drugs used in heart failure (general characteristics) Non-glycoside cardiotonic drugs.

37. Cardiac glycosides. Intoxication with cardiac glycosides. Help measures.

38. Antiarrhythmic drugs.

39. Antianginal drugs.

40. Basic principles of drug therapy for myocardial infarction.

41. Antihypertensive sympathoplegic and vasorelaxant drugs.

I. Means affecting appetite

II. Remedies for reducing gastric secretion

I. Sulfonylureas

70. Antimicrobial agents. General characteristics. Basic terms and concepts in the field of chemotherapy of infections.

71. Antiseptics and disinfectants. General characteristics. Their difference from chemotherapeutic agents.

72. Antiseptics - metal compounds, halogen-containing substances. Oxidizers. Dyes.

73. Aliphatic, aromatic and nitrofuran antiseptics. Detergents. Acids and alkalis. Polyguanidines.

74. Basic principles of chemotherapy. Principles of classification of antibiotics.

75. Penicillins.

76. Cephalosporins.

77. Carbapenems and monobactams

78. Macrolides and azalides.

79. Tetracyclines and amphenicols.

80. Aminoglycosides.

81. Antibiotics of the lincosamide group. Fusidic acid. Oxazolidinones.

82. Antibiotics glycopeptides and polypeptides.

83. Side effect of antibiotics.

84. Combined antibiotic therapy. rational combinations.

85. Sulfanilamide preparations.

86. Derivatives of nitrofuran, oxyquinoline, quinolone, fluoroquinolone, nitroimidazole.

87. Anti-tuberculosis drugs.

88. Antispirochetal and antiviral agents.

89. Antimalarial and antiamebic drugs.

90. Drugs used in giardiasis, trichomoniasis, toxoplasmosis, leishmaniasis, pneumocystosis.

91. Antimycotic agents.

I. Means used in the treatment of diseases caused by pathogenic fungi

II. Drugs used in the treatment of diseases caused by opportunistic fungi (for example, with candidiasis)

92. Anthelmintics.

93. Antiblastoma drugs.

94. Means used for scabies and pediculosis.

15. Means for inhalation anesthesia.

basic means for inhalation anesthesia.

a) liquid drugs for inhalation anesthesia: halothane (halothane), enflurane, isoflurane, diethyl ether(non-halogenated anesthetic)

b) gas anesthetics: nitrous oxide.

Requirements for drugs for anesthesia.

rapid induction into anesthesia without the stage of excitation

ensuring sufficient depth of anesthesia for the necessary manipulations

good controllability of anesthesia depth

quick recovery from anesthesia without aftereffect

sufficient narcotic breadth (the range between the concentration of the anesthetic that causes anesthesia and its minimum toxic concentration that depresses the vital centers of the medulla oblongata)

no or minimal side effects

ease of technical application

fire safety of preparations

acceptable cost

The mechanism of the analgesic action of drugs for anesthesia.

General mechanism: a change in the physicochemical properties of membrane lipids and the permeability of ion channels → a decrease in the influx of Na + ions into the cell while maintaining the exit of K + ions, an increase in permeability for Cl - ions, a cessation of the flow of Ca 2+ ions into the cell → hyperpolarization of cell membranes → a decrease in the excitability of postsynaptic structures and impaired release of neurotransmitters from presynaptic structures.

Means for anesthesia

Mechanism of action

Nitrous oxide, ketamine

Blockade of NMDA receptors (glutamine) coupled to Ca 2+ channels on the neuron membrane →

a) cessation of Ca 2+ current through the presynaptic membrane → violation of mediator exocytosis,

b) cessation of Ca 2+ current through the postsynaptic membrane - a violation of the generation of long-term excitatory potentials

1) Blockade of Hn-cholinergic receptors coupled to Na + -channels → disruption of Na + current into the cell → cessation of the generation of spike APs

2) Activation of GABA A receptors associated with Cl - - channels → entry of Cl - into the cell → hyperpolarization of the postsynaptic membrane → decrease in neuron excitability

3) Activation of glycine receptors coupled to Cl - channels → entry of Cl - into the cell → hyperpolarization of the presynaptic membrane (reduced mediator release) and postsynaptic membrane (reduced neuron excitability).

4) Disrupts the processes of interaction of proteins responsible for the release of the mediator from the vesicles of the presynaptic ending.

Advantages of halothane anesthesia.

high narcotic activity (5 times stronger than ether and 140 times more active than nitrous oxide)

rapid onset of anesthesia (3-5 minutes) with a very short stage of excitation, severe analgesia and muscle relaxation

easily absorbed in the respiratory tract without causing irritation of the mucous membranes

inhibits the secretion of the glands of the respiratory tract, relaxes the respiratory muscles of the bronchi (the drug of choice for patients with bronchial asthma), facilitating the implementation of mechanical ventilation

does not cause disturbances in gas exchange

does not cause acidosis

does not affect kidney function

rapidly excreted from the lungs (up to 85% unchanged)

halothane anesthesia is easily managed

great narcotic latitude

fire safe

slowly decomposes in air

Advantages of ether anesthesia.

pronounced narcotic activity

ether anesthesia is relatively safe and easy to manage

pronounced myorelaxation of skeletal muscles

does not increase the sensitivity of the myocardium to adrenaline and norepinephrine

sufficient narcotic latitude

relatively low toxicity

Advantages of anesthesia caused by nitrous oxide.

does not cause side effects during the operation

does not have irritating properties

does not adversely affect parenchymal organs

causes anesthesia without prior excitation and side effects

fire safe (does not ignite)

excreted almost unchanged through the respiratory tract

quick recovery from anesthesia without aftereffects

Interaction of adrenaline and halothane.

Halothane activates the allosteric center of myocardial β-adrenergic receptors and increases their sensitivity to catecholamines. The administration of epinephrine or norepinephrine against the background of halothane to increase blood pressure can lead to the development of ventricular fibrillation, therefore, if it is necessary to maintain blood pressure during halothane anesthesia, phenylephrine or methoxamine should be used.

Interaction of adrenaline and ethyl ether.

Does not increase the sensitivity of the myocardium to the arrhythmogenic effect of catecholamines.

Disadvantages of halothane anesthesia.

bradycardia (as a result of increased vagal tone)

hypotensive effect (as a result of inhibition of the vasomotor center and direct myotropic effect on the vessels)

arrhythmogenic effect (as a result of a direct effect on the myocardium and its sensitization to catecholamines)

hepatotoxic effect (as a result of the formation of a number of toxic metabolites, therefore, repeated use is not earlier than 6 months after the first inhalation)

increased bleeding (as a result of inhibition of the sympathetic ganglia and expansion of peripheral vessels)

pain after anesthesia, chills (as a result of a quick exit from anesthesia)

enhances blood flow from the vessels of the brain and increases intracranial pressure (cannot be used in operations on people with head injury)

inhibits the contractile activity of the myocardium (as a result of a violation of the process of calcium ions entering the myocardium)

depresses the respiratory center and can cause respiratory arrest

Disadvantages of ether anesthesia

ether vapors are highly flammable, form explosive mixtures with oxygen, nitrous oxide, etc.

causes irritation of the mucous membranes of the respiratory tract  reflex changes in breathing and laryngospasm, a significant increase in salivation and secretion of bronchial glands, bronchopneumonia

a sharp increase in blood pressure, tachycardia, hyperglycemia (as a result of an increase in the content of adrenaline and norepinephrine, especially during arousal)

vomiting and respiratory depression in the postoperative period

long stage of arousal

slow onset and slow recovery from anesthesia

convulsions are observed (rarely and mainly in children)

depression of liver function, kidney function

development of acidosis

development of jaundice

Disadvantages of anesthesia with nitrous oxide.

low narcotic activity (can be used only for anesthesia in combination with other drugs and to provide surface anesthesia)

nausea and vomiting in the postoperative period

neutropenia, anemia (as a result of the oxidation of the cobalt atom in the composition of cyanocobalamin)

diffusion hypoxia after the cessation of inhalation of nitrous oxide (nitric oxide, poorly soluble in the blood, begins to be intensively released from the blood into the alveoli and displaces oxygen from them)

flatulence, headache, pain and congestion in the ears

Halothane (halothane), isoflurane, sevoflurane, dinitrogen, nitric oxide (nitrous).

FLUOROTAN (Рhthorothanum). 1, 1, 1-Trifluoro-2-chloro-2-bromoethane.

Synonyms: Anestan, Fluctan, Fluothne, Ftorotan, Halan, Halothane, Halothanum, Narcotan, Rhodialotan, Somnothane.

Fluorotan does not burn and does not ignite. Its vapors, mixed with oxygen and nitrous oxide in proportions used for anesthesia, are explosion-proof, which is its valuable property when used in a modern operating room.

Under the action of light, halothane slowly decomposes, so it is stored in orange glass flasks; thymol (O, O1%) is added for stabilization.

Fluorotan is a powerful narcotic, which allows it to be used alone (with oxygen or air) to achieve the surgical stage of anesthesia or as a component of combined anesthesia in combination with other drugs, mainly nitrous oxide.

Pharmacokinetically, halothane is easily absorbed from the respiratory tract and rapidly excreted by the lungs unchanged; only a small part of halothane is metabolized in the body. The drug has a rapid narcotic effect, which stops shortly after the end of inhalation.

When using halothane, consciousness usually turns off 1-2 minutes after the start of inhalation of its vapors. After 3-5 minutes, the surgical stage of anesthesia begins. After 3-5 minutes after stopping the supply of halothane, the patients begin to wake up. Anesthetized depression completely disappears in 5-10 minutes after short-term and 30-40 minutes after prolonged anesthesia. Excitation is observed rarely and is poorly expressed.

Vapors of halothane do not cause irritation of mucous membranes. There are no significant changes in gas exchange during anesthesia with halothane; arterial pressure usually decreases, which is partly due to the inhibitory effect of the drug on the sympathetic ganglia and the expansion of the peripheral vessels. The vagus nerve tone remains high, which creates conditions for bradycardia. To some extent, halothane has a depriming effect on the myocardium. In addition, halothane increases the sensitivity of the myocardium to catecholamines: the introduction of adrenaline and norepinephrine during anesthesia can cause ventricular fibrillation.

Fluorotan does not affect kidney function; in some cases, liver dysfunction with the appearance of jaundice is possible.

Under halothane anesthesia, various surgical interventions can be performed, including on the organs of the abdominal and thoracic cavities, in children and the elderly. Non-flammability makes it possible to use it when using electrical and X-ray equipment during surgery.

Fluorotan is convenient for use in operations on the organs of the chest cavity, as it does not cause irritation of the mucous membranes of the respiratory tract, inhibits secretion, relaxes the respiratory muscles, which facilitates artificial ventilation of the lungs. Fluorothane anesthesia can be used in patients with bronchial asthma. The use of halothane is especially indicated in cases where it is necessary to avoid excitation and stress of the patient (neurosurgery, ophthalmic surgery, etc.).

Fluorothane is part of the so-called azeotron mixture, which consists of two parts by volume of fluothane and one volume of ether. This mixture has a stronger narcotic effect than ether, and less powerful than halothane. Anesthesia occurs more slowly than with halothane, but faster than with ether.

During anesthesia with halothane, the supply of its vapors should be precisely and smoothly regulated. It is necessary to take into account the rapid change of stages of anesthesia. Therefore, halothane anesthesia is carried out using special evaporators located outside the circulation system. The concentration of oxygen in the inhaled mixture must be at least 50%. For short-term operations, halothane is sometimes also used with a conventional anesthesia mask.

In order to avoid side effects associated with excitation of the vagus nerve (bradycardia, arrhythmia), atropine or metacin is administered to the patient before anesthesia. For premedication, it is preferable to use not morphine, but promedol, which excites the centers of the vagus nerve less.

If it is necessary to enhance muscle relaxation, it is preferable to prescribe relaxants of a depolarizing type of action (ditilin); when using drugs of a non-depolarizing (competitive) type, the dose of the latter is reduced against the usual one.

During anesthesia with halothane, due to inhibition of sympathetic ganglia and expansion of peripheral vessels, increased bleeding is possible, which requires careful hemostasis, and, if necessary, compensation for blood loss.

Due to the rapid awakening after the cessation of anesthesia, patients may feel pain, so early use of analgesics is necessary. Sometimes in the postoperative period there is a chill (due to vasodilation and heat loss during surgery). In these cases, patients need to be warmed with heating pads. Nausea and vomiting usually do not occur, but the possibility of their occurrence in connection with the administration of analgesics (morphine) should be considered.

Anesthesia with halothane should not be used in case of pheochromocytoma and in other cases when the content of adrenaline in the blood is increased, with severe hyperthyroidism. Caution should be used in patients with cardiac arrhythmias, hypotension, organic liver damage. During gynecological operations, it should be borne in mind that halothane can cause a decrease in the tone of the muscles of the uterus and increased bleeding. The use of halothane in obstetrics and gynecology should be limited only to those cases where uterine relaxation is indicated. Under the influence of halothane, the sensitivity of the uterus to drugs that cause its contraction (ergot alkaloids, oxytocin) decreases.

When anesthesia with halothane, adrenaline and norepinephrine should not be used to avoid arrhythmias.

It should be borne in mind that people working with halothane may develop allergic reactions.

NITROGEN OXIDE (Nitrogenium oxudulatum).

Synonyms: Dinitrogen ohide, Nitrous oxyde, Oxydum nitrosum, Protohude d "Azote, Stickoxydal.

Small concentrations of nitrous oxide cause a feeling of intoxication (hence the name<веселящий газ>) and mild drowsiness. When pure gas is inhaled, a narcotic state and asphyxia quickly develop. In a mixture with oxygen at the correct dosage causes anesthesia without prior excitation and side effects. Nitrous oxide has a weak narcotic activity, and therefore it must be used in high concentrations. In most cases, combined anesthesia is used, in which nitrous oxide is combined with other, more powerful, anesthetics and muscle relaxants.

Nitrous oxide does not cause respiratory irritation. In the body, it almost does not change, it does not bind to hemoglobin; is in a dissolved state in plasma. After cessation of inhalation, it is excreted (completely after 10-15 minutes) through the respiratory tract in unchanged form.

Anesthesia with the use of nitrous oxide is used in surgical practice, operative gynecology, surgical dentistry, as well as for labor pain relief.<Лечебный аналгетический наркоз>(B.V. Petrovsky, S.N. Efuni) using a mixture of nitrous oxide and oxygen is sometimes used in the postoperative period to prevent traumatic shock, as well as to relieve pain attacks in acute coronary insufficiency, myocardial infarction, acute pancreatitis and other pathological conditions accompanied by pain that is not relieved by conventional means.

For a more complete relaxation of the muscles, muscle relaxants are used, while not only increasing muscle relaxation, but also improving the course of anesthesia.

After stopping the supply of nitrous oxide, oxygen should be continued for 4-5 minutes to avoid hypoxia.

Nitrous oxide should be used with caution in case of severe hypoxia and impaired diffusion of gases in the lungs.

To anesthetize childbirth, the method of intermittent autoanalgesia is used using a mixture of nitrous oxide (40 - 75%) and oxygen with the help of special anesthesia machines. The woman in labor begins to inhale the mixture when the harbingers of the contraction appear and ends the inhalation at the height of the contraction or towards its end.

To reduce emotional arousal, prevent nausea and vomiting, and potentiate the action of nitrous oxide, premedication by intramuscular administration of a 0.5% solution of diazepam (seduxen, sibazon) is possible.

Therapeutic anesthesia with nitrous oxide (with angina pectoris and myocardial infarction) is contraindicated in severe diseases of the nervous system, chronic alcoholism, alcohol intoxication (excitation, hallucinations are possible).

Means for inhalation anesthesia pharmacology

Inhalation agents are widely used in pediatric anesthesiology. The occurrence of anesthesia when using them depends on the value of the partial volume content of the anesthetic agent in the inhaled mixture: the higher it is, the sooner anesthesia occurs, and vice versa. The rate of onset of anesthesia and its depth to a certain extent depend on the solubility of substances in lipids: the larger they are, the sooner anesthesia develops.

In young children, inhalants should be used very carefully. They, especially in the first months of life, have more tissue hemoperfusion than older children and adults. Therefore, in young children, a substance administered by inhalation is more likely to enter the brain and can cause a deep depression of its function within a few seconds - up to paralysis.

Comparative characteristics of drugs for inhalation anesthesia

Ether for anesthesia (ethyl or diethyl ether) is a colorless, volatile, flammable liquid with a boiling point of + 34-35 ° C, which forms explosive mixtures with oxygen, air, nitrous oxide.

The positive properties of diethyl ether are its large therapeutic (narcotic) latitude, ease of controlling the depth of anesthesia.

The negative properties of diethyl ether include: explosiveness, pungent odor, slow development of anesthesia with a long second stage. Introductory or basic anesthesia avoids the second stage. A strong irritating effect on the mucosal receptors leads to the occurrence of reflex complications during this period: bradycardia, respiratory arrest, vomiting, laryngospasm, etc. postoperative period. The risk of these complications is especially high in young children. Sometimes in children in whom anesthesia was caused by ether, a decrease in the content of albumins and y-globulins in the blood is noted.

Ether increases the release of catecholamines from the adrenal medulla and presynaptic endings of sympathetic fibers. This can result in hyperglycemia (undesirable in diabetic children), relaxation of the lower esophageal sphincter, which facilitates regurgitation (passive leakage of stomach contents into the esophagus) and aspiration.

Do not use ether in dehydrated children (especially under the age of 1 year), since after anesthesia they may experience dangerous hyperthermia and convulsions, often (in 25%) ending in death.

All this limits the use of ether in children under 3 years of age. At an older age, it is still sometimes used.

Means for inhalation anesthesia advantages and disadvantages

Fluorotan (halothane, fluotan, narcotan) is a colorless liquid with a sweet and pungent taste, its boiling point is +49-51 °C. It does not burn or explode. Fluorotan is characterized by high lipid solubility, so it is rapidly absorbed from the respiratory tract and anesthesia occurs very quickly, especially in young children. It is rapidly excreted from the body through the respiratory tract in unchanged form. However, about a quarter of the halothane that enters the body undergoes biotransformation in the liver. It forms the fluoroethanol metabolite, which binds strongly to the components of cell membranes, nucleic acids of various tissues - the liver, kidneys, fetal tissues, germ cells. This metabolite is retained in the body for about a week. With a single exposure to the body, there are usually no serious consequences, although cases of toxic hepatitis have been noted. With the repeated ingestion of at least traces of halothane (in employees of anesthesia departments) into the human body, this metabolite accumulates in the body. There is information about the occurrence in connection with this mutagenic, carcinogenic and teratogenic effect of halothane.

Fluorotan has H-anticholinergic and a-adrenolytic properties, but does not reduce, but even increases the activity of B-adrenergic receptors. As a result, peripheral vascular resistance and blood pressure decrease, which is facilitated by the inhibition of myocardial function caused by it (as a result of inhibition of glucose utilization). This is used to reduce blood loss during surgery. However, in young children, especially those with dehydration, it can lead to a sudden drop in blood pressure.

Fluorotan relaxes the smooth muscles of the bronchi, which is sometimes used to eliminate an intractable asthmatic condition in children.

Against the background of hypoxia and acidosis, when the release of catecholamines from the adrenal glands increases, halothane can contribute to the occurrence of cardiac arrhythmias in children.

Fluorotan relaxes skeletal muscles (the result of N-anticholinergic action), which, on the one hand, facilitates operations, and, on the other hand, due to the weakness of the respiratory muscles, it reduces the volume of lung ventilation, often not exceeding the volume of the "dead" space of the respiratory tract. Therefore, during halothane anesthesia, as a rule, tracheal intubation is performed and the child is transferred to controlled or assisted breathing.

Fluorotan is used with the help of special evaporators both independently and in the form of the so-called azeotropic mixture (2 parts by volume of halothane and 1 volume part of ether). Its combination with nitrous oxide is rational, which makes it possible to reduce both its concentration in the inhaled mixture from 1.5 to 1-0.5 vol.%, and the risk of undesirable effects.

Halothane is contraindicated in children with liver diseases and in the presence of severe cardiovascular pathology.

Flammable agent for inhalation anesthesia

Cyclopropane is a colorless combustible gas with a characteristic odor and a pungent taste (under a pressure of 5 atm and a temperature of + 20 ° C it turns into a liquid state). It is poorly soluble in water and well - in fats and lipids. Therefore, cyclopropane is rapidly absorbed from the respiratory tract, anesthesia occurs after 2-3 minutes, without the stage of excitation. He has a sufficient breadth of narcotic action.

Cyclopropane is considered a flammable agent for inhalation anesthesia. Cyclopropane is used with the help of special equipment and very carefully due to the extreme flammability and explosiveness of its combinations with oxygen, air and nitrous oxide. It does not irritate the lung tissue, is exhaled unchanged, with the correct dosage, has little effect on the function of the cardiovascular system, but increases the sensitivity of the myocardium to adrenaline. In addition, it increases the release of catecholamines from the adrenal glands. Therefore, when using it, cardiac arrhythmias often occur. Due to the rather pronounced cholinomimetic effect of cyclopropane (manifested in bradycardia, increased secretion of saliva, mucus in the bronchi), atropine is usually used for premedication.

Cyclopropane is considered the drug of choice for traumatic shock and blood loss. It is used for induction and basic anesthesia, preferably in combination with nitrous oxide or ether. Liver diseases and diabetes mellitus are not contraindications to its use.

Classification of drugs for inhalation anesthesia

Nitrous oxide (N20) is a colorless gas, heavier than air (at a pressure of 40 atm it condenses into a colorless liquid). It does not ignite, but supports combustion and therefore forms explosive mixtures with ether and cyclopropane.

Nitrous oxide is widely used in anesthesia in adults and children. To induce anesthesia create a mixture of 80% nitrous oxide with 20% oxygen. Anesthesia occurs quickly (the high concentration of nitrous oxide in the inhaled gas mixture matters), but it is shallow, the skeletal muscles are not sufficiently relaxed, and the surgeon's manipulations cause a reaction to pain. Therefore, nitrous oxide is combined with muscle relaxants or with other anesthetics (halothane, cyclopropane). In lower concentrations (50%) in the inhaled gas mixture, nitrous oxide is used as an analgesic (for reducing dislocations, for painful short-term procedures, incisions of phlegmon, etc.).

In small concentrations, nitrous oxide causes a feeling of intoxication, which is why it is called laughing gas.

Nitrous oxide is of low toxicity, but when the oxygen content in the gas mixture is less than 20%, the patient develops hypoxia (signs of which may be skeletal muscle rigidity, dilated pupils, convulsive syndrome, and a drop in blood pressure), severe forms of which lead to the death of the cerebral cortex. Therefore, only an experienced anesthetist who knows how to use the appropriate equipment (NAPP-2) can use nitrous oxide.

Nitrous oxide is 37 times more soluble in blood plasma than nitrogen, and is able to displace it from gas mixtures, while increasing their volume. As a result, the volume of gases in the intestines, in the cavities of the inner ear (protrusion of the tympanic membrane), in the maxillary (maxillary) and other cavities of the skull associated with the respiratory tract may increase. At the end of inhalation of the drug, nitrous oxide displaces nitrogen from the alveoli, almost completely filling their volume. This interferes with gas exchange and leads to severe hypoxia. For its prevention, after stopping the inhalation of nitrous oxide, it is necessary to give the patient 3-5 minutes to breathe 100% oxygen to the patient.

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Medical College

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Deputy Director for SD

T.Z. Galeyshina

"___" ___________ 20____

METHODOLOGICAL DEVELOPMENT of a lecture on the topic: “Means affecting the central nervous system

Discipline "Pharmacology"

Specialty 34.02.01. nursing

Semester: I

Number of hours 2 hours

Ufa 20____

Topic: "Means affecting the central nervous system

(general anesthetics, hypnotics, analgesics)"

based on the work program of the academic discipline "Pharmacology"

approved by "_____" _______20____

Reviewers for the presented lecture:

Approved at a meeting of the educational and methodological council of the college from "______" _________ 20____.

1. Topic: "Means affecting the central nervous system

(general anesthetics, hypnotics, analgesics)"

2. Course: 1 semester: I

3. Duration: combined lesson 2 hours

4. The contingent of students - students

5. Learning goal: to consolidate and test knowledge on the topic: “Means that affect the efferent nervous system (adrenergic drugs)”, to acquire knowledge on a new topic: “Means that affect the central nervous system

(general anesthetics, hypnotics, analgesics)"

6. Illustrative material and equipment (multimedia projector, laptop, presentation, test tasks, information block).

7. The student should know:

· Means for inhalation anesthesia (ether for anesthesia, halothane, nitrous oxide).

The history of the discovery of anesthesia. stages of anesthesia. Features of the action of individual drugs. Application. Complication of anesthesia.

Means for non-inhalation anesthesia (thiopental sodium, propanide, sodium oxybutyrate, ketamine). The difference between non-inhalation drugs for anesthesia and inhalation. Routes of administration, activity, duration of action of individual drugs. Application in medical practice. Possible complications.

· Ethanol (ethyl alcohol) Influence on the central nervous system. Influence on the functions of the digestive tract. Action on the skin, mucous membranes. Antimicrobial properties. Indications for use.

Sleeping pills

Barbiturates (phenobarbital, etaminal - sodium, nitrazepam);

Benzodiazepines (temazepam, triazolam, oxazolam, lorazepam)

Cyclopyrrolones (zopiclone)

Phenothiazines (diprazine, promethazine)

Sleeping pills, principle of action. Influence on the structure of sleep. Application. Side effects. The possibility of developing drug dependence.

· Analgesics:

Narcotic analgesics - opium preparations (morphine hydrochloride omnopon, codeine). Synthetic narcotic analgesics (promedol, fentanyl, pentosacin, tramadol) their pharmacological effects, indications for use, side effects.

Non-narcotic analgesics, non-steroidal anti-inflammatory drugs (metamisole sodium (analgin), amidopyrine, acetylsalicylic acid). Mechanism of analgesic action. Anti-inflammatory and antipyretic properties. Application. Side effects.

Formed competencies: the study of the topic contributes to the formation

OK 1. Understand the essence and social significance of your future profession, show a steady interest in it.

OK 7. Take responsibility for the work of team members (subordinates), for the result of completing tasks.

OK 8. Independently determine the tasks of professional and personal development, engage in self-education, consciously plan and implement advanced training.

PC 2.1. Present information in a way that is understandable to the patient, explain to him the essence of the intervention.

PC 2.2. Carry out medical and diagnostic interventions, interacting with participants in the treatment process.

PC 2.3. Collaborate with collaborating organizations and services.

PC 2.4. Apply medications in accordance

with rules for their use.

PC 2.6. Maintain approved medical records.

CHRONOCARD OF THE COMBINED LESSON on the topic: "Means acting on the central nervous system (general anesthetics, hypnotics, analgesics)"

No. p / p	Content and structure of the lesson	Time (min.)	Teacher activity	Student activities	Methodological substantiation
1.	Organizing time		- greeting students - checking the readiness of the audience for the lesson - marking absent	- teacher's greeting - duty report about absent students	-implementation of the psychological attitude to educational activities, education of organization, discipline, business approach -activization of students' attention
2.	Determining the objectives of the lesson		- presenting the lesson plan	- think over the course of the stages of educational activity	-creation of a holistic view of the lesson -concentration of attention on the upcoming work -formation of interest and understanding of the motivation for learning activities.
3.	Control and correction of knowledge on the previous topic: "Means acting on efferent innervation (adrenergic drugs)"		- interrogation frontal - the decision of KIM for the current control	- answer questions on the previous topic - demonstrate the level of independent preparation for the lesson - collectively correct gaps in knowledge	-determination of the level of self-preparation of students for the lesson, completeness of homework -correction of gaps in knowledge -development of self and mutual control
4.	Theme Motivation		- emphasizes the relevance of the topic	- write down the topic in a notebook	- formation of cognitive interests, concentration of attention on the topic under study
5.	Lecture-conversation with elements of interactivity		-provides awareness of the formation of knowledge on the topic	note-taking of the topic in a notebook	-formation of knowledge on the topic "Means affecting the blood system"
6.	Summing up the lesson, consolidating the material		- reflects the main issues of the topic; - with the help of students, analyzes the achievement of the objectives of the lesson;	-determine the level of mastering the material and achieving the objectives of the lesson	-development of analytical activity -formation of self-control and mutual control
7.	Homework, assignment for independent work		-suggests to write down homework: to prepare the topic "Means acting on the central nervous system (general anesthetics, hypnotics, analgesics)" for the next theoretical lesson.	- write down homework	-stimulation of cognitive activity of students and interest in the development of educational material

All medicinal substances acting on the central nervous system can be conditionally divided into two groups:

1. oppressive CNS functions (anesthetics, hypnotics, anticonvulsants, narcotic analgesics, some psychotropic drugs (neuroleptics, tranquilizers, sedatives);

2. exciting CNS functions (analeptics, psychostimulants, general tonic, nootropic drugs).

Means for anesthesia

Narcosis is a reversible depression of the central nervous system, which is accompanied by loss of consciousness, the absence of all types of sensitivity, inhibition of spinal reflexes and relaxation of skeletal muscles while maintaining the function of the respiratory and vasomotor centers.

The official date of the discovery of anesthesia is considered to be 1846, when the American dentist William Morton used ether to anesthetize the operation of removing a tooth.

In the action of ethyl ether, 4 stages:

I - stage of analgesia is characterized by a decrease in pain sensitivity, a gradual depression of consciousness. Respiratory rate, pulse and blood pressure are not changed.

II - stage of excitation, the cause of which is the switching off of the inhibitory effects of the cerebral cortex on the subcortical centers. There is a "rebellion of the subcortex." Consciousness is lost, speech and motor excitation develops. Breathing is irregular, tachycardia is noted, blood pressure is increased, pupils are dilated, cough and gag reflexes increase, vomiting may occur. Spinal reflexes and muscle tone are increased.

III - stage of surgical anesthesia. It is characterized by suppression of the function of the cerebral cortex, subcortical centers and spinal cord. The vital centers of the medulla oblongata - the respiratory and vasomotor continue to function. Breathing normalizes, blood pressure stabilizes, muscle tone decreases, reflexes are inhibited. The pupils are constricted.

There are 4 levels in this stage:

III 1 - superficial anesthesia;

III 2 - light anesthesia;

III 3 - deep anesthesia;

III 4 - superdeep anesthesia.

IV - stage of recovery. Occurs when the drug is discontinued. Gradually, the functions of the central nervous system are restored in the reverse order of their appearance. With an overdose of drugs for anesthesia, the agonal stage develops, due to the inhibition of the respiratory and vasomotor centers.

Requirements for drugs for anesthesia:

speed of onset of anesthesia without pronounced arousal

Sufficient depth of anesthesia, allowing the operation to be carried out under optimal conditions

good controllability of the depth of anesthesia

Quick and painless recovery from anesthesia

Sufficient narcotic breadth - the range between the concentration of a substance that causes the stage of deep surgical anesthesia, and the minimum toxic concentration that causes respiratory arrest due to depression of the respiratory center

Do not cause tissue irritation at the injection site

minimal side effects

must not be explosive.

Means for inhalation anesthesia

Volatile liquids

Diethyl ether, Halothane (Ftorotan), Enflurane (Etran), Isoflurane (Foran), Sevoflurane.

Gaseous substances

nitrous oxide

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