Pharmaceutical care: clinical and pharmaceutical aspects of the use of alcohol in medicine. The effect of ethyl alcohol on various organs and functional systems

(C 2 H 5 OH). Based on the nature of its resorptive effect on the central nervous system, it can be classified as a narcotic-type substance. Its action on the central nervous system is divided into three stages: excitation, anesthesia and agonal stage.

However, ethyl alcohol is of little use as a means of anesthesia, since it causes a long stage of excitation and has an extremely small breadth of narcotic action (the anesthesia stage is very quickly replaced by the agonal stage). Research by I.P. Pavlov’s collaborators has shown that even small amounts of ethyl alcohol suppress inhibition processes in the cerebral cortex, resulting in a stage of excitation (intoxication). This stage is characterized by emotional arousal, a decrease in critical attitude towards one’s own actions, and disorders of thinking and memory.

Like other narcotic substances, ethyl alcohol has analgesic activity (reduces pain sensitivity).

With an increase in the dose of ethyl alcohol, the stage of excitation is replaced by phenomena of central nervous system depression, impaired coordination of movements, confusion, and then complete loss of consciousness. Signs of depression of the respiratory and vasomotor centers of the medulla oblongata appear: weakening of breathing and a drop in blood pressure. Severe poisoning with ethyl alcohol can lead to death due to paralysis of these centers.

Ethyl alcohol has a pronounced effect on thermoregulation processes. Due to the expansion of the blood vessels of the skin during intoxication, heat transfer increases (subjectively this is perceived as a feeling of warmth) and body temperature decreases. The increase in heat transfer, in particular, explains the fact that in conditions of low temperature, persons in a state of alcohol intoxication, freeze faster than sober people.

At local action Ethyl alcohol, depending on the concentration, causes an irritating or astringent effect. Irritating properties are most pronounced in 40% alcohol, astringent - in 95%. In addition, ethyl alcohol has an antimicrobial effect, and therefore is widely used externally as an antiseptic. For this purpose, 70%, 90% or 95% alcohol is used.

The astringent and antimicrobial properties of ethyl alcohol are associated with its ability to denature proteins (cause their coagulation). This ability increases with increasing concentration of ethyl alcohol.

Due to its irritating effect, ethyl alcohol, when taken orally, has a pronounced effect on the functions of gastrointestinal tract. In a small concentration (up to 20%), ethyl alcohol increases appetite and enhances the secretion of the digestive glands (in particular, the stomach glands). In high concentrations, ethyl alcohol destroys digestive enzymes, which leads to digestive disorders. Ethyl alcohol improves absorption various substances(including medicinal) in the gastrointestinal tract.

In organism most of(90-98%) ethyl alcohol is oxidized to carbon dioxide and water, releasing a significant amount of energy. When 1 g of alcohol is oxidized, about 29.28 kJ (7 kcal) of heat is released. In this respect, it is superior to carbohydrates: 1 g of carbohydrates forms 17.15 kJ (4.1 kcal) and is only slightly inferior to fats; 1 g of fat produces 38.9 kJ (9.3 kcal). Despite this, ethyl alcohol, unlike fats and carbohydrates, cannot be recommended as an energy product. Firstly, unlike carbohydrates and fats, alcohol is not deposited in the body and does not participate in the construction of tissues; secondly, its systematic use is accompanied by the development of chronic poisoning.

Ethyl alcohol finds practical use due to its antimicrobial, astringent, irritant and analgesic properties. Most often in practical medicine ethyl alcohol is used as antiseptic for disinfection of medical instruments, surgical field, surgeon's hands. The antimicrobial effect of ethyl alcohol is due to its ability to cause denaturation (coagulation) of microbial proteins and increases with increasing concentration. Thus, 95% ethyl alcohol has the greatest antimicrobial activity. In this concentration, the drug is used to treat surgical instruments, needles, catheters, etc. However, 70% alcohol is more often used to treat the surgeon’s hands and the surgical field. This is due to the fact that alcohol of a higher concentration intensively coagulates protein substances, poorly penetrates into the deep layers of the skin and disinfects only its superficial layer.

The ability of ethyl alcohol in high concentrations to cause protein coagulation, i.e. its astringent effect is used in the treatment of burns. For this purpose, 95% alcohol is used. Low concentration alcohol (40%) should not be used to treat burns, since, as already indicated, ethyl alcohol only has pronounced irritating properties and does not have a noticeable astringent and antimicrobial effect.

The irritating effect of 40% ethyl alcohol is used in practical medicine when using alcohol compresses in cases of inflammatory diseases of internal organs, muscles, nerve trunks, joints. As an irritant, ethyl alcohol has a “distracting” effect, that is, it reduces pain and improves the functional state of the affected organ.

The analgesic effect of ethyl alcohol can be used to prevent pain shock in injuries and wounds. In these cases, alcohol is administered intravenously as part of anti-shock fluids.

Pharmaceutical care: clinical and pharmaceutical aspects of the use of alcohol in medicine

I. A. Zupanets, N. V. Bezdetko, L. V. Derimedved
National Pharmaceutical University

Alcohol is a substance that combines the properties of a medical drug, a natural metabolite of the human body, a toxic xenobiotic, a food product and a nutritional factor that can significantly affect the effectiveness of drug therapy. Alcohol and alcoholic beverages can have an adverse effect on the metabolism of many drugs in the human body. Single or chronic use of ethyl alcohol is a direct contraindication to the prescription of a number of medications. Ethyl alcohol poisoning has been a topic of concern for many years. leading place among household poisonings in our country in terms of the absolute number of deaths. All this determines the relevance of the problem of the influence of ethyl alcohol on the human body, the interaction of drugs and alcohol for the pharmacist.

Clinical and pharmacological characteristics of ethyl alcohol

Ethanol (ethyl alcohol, wine alcohol) is a transparent, colorless, volatile and flammable liquid with a characteristic odor and a burning taste. Mixes with water in any ratio. Is a good solvent.

Like any drug, ethyl alcohol has characteristic pharmacokinetics and pharmacodynamics.

Pharmacokinetics of ethanol

Suction. Ethanol is well (quickly and completely) absorbed from the gastrointestinal tract. The rate of entry of the drug into the systemic circulation depends on its concentration and is regulated by the duration of contact with the mucosa. Absorption of ethanol begins in the oral cavity and esophagus, about 20% is absorbed in the stomach and about 80% in the duodenum. When the concentration increases to 30%, the absorption rate increases, and at a concentration of 40% and above it slows down. This is due to the astringent effect of the 40% solution on the mucous membrane, stimulation of increased mucus formation, enveloping the walls of the stomach and slowing down absorption, local vasoconstriction, and impaired evacuation of stomach contents.

After administration on an empty stomach, the maximum concentration of ethanol in the blood is reached after 30 minutes.

If before taking ethanol the stomach was filled with food, especially those with enveloping properties (potatoes, butter, porridge, etc.), absorption slows down significantly. Sugar and tannins, which are contained in sweet wines, also inhibit the flow of ethanol into the blood. Drinks containing carbon dioxide, on the contrary, significantly increase the absorption of ethyl alcohol, as they stimulate blood circulation in the intestines.

The concentration of ethanol in the blood (in ‰) can be calculated by multiplying the amount (in ml) of alcohol consumed (40%) by a factor of 0.0064. On the contrary, knowing the concentration of ethanol in the blood (in ‰), you can determine the amount of alcohol consumed (in ml) by multiplying by a factor of 156. If alcohol intake occurred several hours before the determination, the rate of biotransformation is also taken into account (25 ml/hour for a healthy man weighing 70 kg).

Ethanol vapor can be absorbed into the lungs.

To a certain extent, absorption of ethanol through the skin is possible, especially in children of the neonatal period and early childhood.

Distribution ethanol removal occurs quickly, and the level in the blood and tissues becomes approximately the same. Ethanol penetrates from the blood into the tissues and fluids of the body by passive diffusion. The volume of distribution is 0.6-0.7 ml/kg. Ethanol has a pronounced organotropic effect: in the brain its concentration exceeds that in the blood. High concentrations of ethanol are also observed in prostate secretions, testicles and sperm, having a toxic effect on germ cells. Ethanol very easily passes through the placenta and penetrates into milk.

Biotransformation Ethanolization mainly occurs in the liver.

When taking normal doses, the oxidation rate corresponds to zero-order kinetics, i.e., does not depend on time and concentration of the substance. The amount of alcohol oxidized per unit time is approximately proportional to body or liver weight. With hepatectomy or liver failure, the rate of biotransformation and elimination of alcohol from the body is significantly reduced, and sometimes even stops completely. An adult can metabolize 7-10 g of alcohol per hour (8 g ethanol = 25 ml vodka).

The biotransformation of ethanol in the liver occurs in two stages.

First stage oxidation of ethanol to acetaldehyde (acetic aldehyde). Normally, this reaction is catalyzed by three different enzyme systems.

1. Alcohol dehydrogenase pathway. Main way Ethanol oxidation is associated with alcohol dehydrogenase (ADH), a specific zinc-containing and NAD-dependent enzyme. ADH is found mainly in the cytosol of hepatocytes. A small amount of ADH is present in the stomach and brain. ADH oxidizes endogenous and exogenous ethanol, as well as a number of other substances with an alcohol structure: methanol, ethylene glycol. Alcohol dehydrogenase of all tissues exists in three isoforms.

In the above reaction, a hydrogen ion passes from alcohol to the coenzyme nicotine adenine dinucleotide (NAD) to form NADH. As a result of the oxidation of ethanol in the liver, an excess of reduced equivalents is created in the form of NADH.

ADH itself is not a rate-limiting factor. The intensity of the alcohol dehydrogenase reaction depends on the availability of the cofactor NAD+ and is limited by the reoxidation of NADH to NAD+.

At the stage of alcoholic liver dystrophy, ADH activity increases. This can be seen as defensive reaction body. With the formation of alcoholic hepatitis and liver cirrhosis, the overall activity of the ADH enzyme decreases, but continues to remain high in regenerating hepatocytes.

2. Microsomal ethanol oxidation system (MEOS). This enzymatic frequency system is called nonspecific mixed-function oxidases. It oxidizes ethanol with the participation of cytochromes P-450. In this case, NADPH is used as a cofactor instead of NAD.

The MEOS system does not take part in the oxidation of endogenous ethanol. It is included in the oxidation of ethanol only in cases where its concentration in the blood exceeds 0.1‰. In this situation, ADH is not enough.

With the systematic consumption of ethyl alcohol, cytochromes P-450 are subject to induction, resulting in an acceleration of the biotransformation of ethanol. At the same time, the biotransformation of many other endogenous and exogenous substances, including drugs, is accelerated.

3. Catalase pathway. Oxidation using catalase, tissue oxidases and peroxidases.

About 10% of ethanol is oxidized via this route. With chronic ethanol consumption, the role of this pathway increases. Catalase is 4-5 times more active than ADH.

When ethanol is oxidized along the second and third pathways, free radicals and peroxide products are formed in significant quantities, which increase the level of lipid peroxidation and lead to even greater disruption of the function of lipid membranes.

Second phase oxidation of acetaldehyde (acetic aldehyde) into acetic acid. The reaction is catalyzed by NAD-dependent aldehyde dehydrogenase (aldDH).

Subsequently, acetic acid, turning into acetyl-Co-A, is oxidized to carbon dioxide and water with the formation of energy. Acetyl-Co-A is also involved in the synthesis of fatty acids, cholesterol and steroid hormones.

It has now been established that there are three isoforms of aldehyde dehydrogenase. 90% of AlDG is located in liver mitochondria, 10% in the cytosol.

Chronic consumption of ethanol leads to a decrease in the rate of acetaldehyde oxidation.

Factors influencing the biotransformation of ethanol

The isoenzyme spectrum of ADH is genetically determined; the activity of various ADH isoforms has clearly defined differences in representatives of different races.

In men, a significant part of ethanol is metabolized by gastric ADH, therefore, when taken orally in equal doses, the blood alcohol level in women is significantly higher than in men; with intravenous administration of ethanol, gender differences are leveled out.

Frequency and regularity of alcohol consumption: in persons who systematically drink alcohol, the level of its biotransformation increases by 1.5-2 times (as a result of the phenomenon of induction of microsomal liver enzymes).

Functional state of the liver: if it is impaired, the biotransformation of alcohol is significantly reduced.

Elimination 90% of ethanol is carried out by biotransformation (see above), 10% by excretion unchanged. Unchanged ethanol is removed mainly by the lungs, in small quantities by the kidneys and sweat glands, as well as with milk (in women during lactation). The ratio of ethanol concentrations in the blood and milk of a nursing woman is the same (ratio is 1.0).

Pharmacodynamics of ethanol

In medical practice, the local, reflex and resorptive effects of ethanol are used.

Local and reflex action of ethanol

When applied topically, ethanol exhibits irritating, astringent and antiseptic effects.

Irritant effect ethanol is closely related to its ability to easily dissolve in lipids and quickly penetrate into the deep layers of the skin. Here, ethanol irritates sensitive nerve endings, causing a burning sensation, tingling and tingling, as well as hyperemia. Through the mechanism of segmental trophic reflexes, which are closed in the sympathetic centers of the spinal cord, regional hemodynamics changes as a result of the irritating effect of ethanol.

This action of ethanol is used:

• for colds (the area is rubbed chest 30-40% alcohol), the dominant focus of irritation on the skin reflexively reduces the cough effect, as a result of changes in hemodynamics in the lung tissue and bronchi, the inflammatory reaction is reduced and bronchial ventilation improves;
• for frostbite (improves blood circulation in upper layers skin);
• for joint pain, bruises, muscle pain, radiculitis (reflex pain reduction).

Irritation of the taste buds of the tongue with low concentrations of ethanol helps to increase appetite (when using high concentrations, spasm of the pyloric sphincter occurs, overirritation of the gastric mucosa and vomiting).

Astringent action ethanol is due to its ability to cause denaturation of tissue proteins. The tanning effect of alcohol on the skin reduces its sensitivity, helps reduce pain, sweating, and itching. This property is used:

• for the prevention of bedsores;
• to prevent the formation of blisters during burns.

Antiseptic effect associated with denaturation of cytoplasmic and membrane proteins of microbial cells. Unlike most aqueous solutions of antiseptics, ethanol penetrates well through the epidermis into the deep layers of the dermis. The bactericidal effect is manifested at a concentration of 70%. At higher concentrations (90 and 95%), the tanning effect prevents the penetration of ethanol into deep layers and the antiseptic effect is reduced. 70% ethanol is used for:

• treatment of the surgeon’s hands and surgical field;
• treatment of the initial stages of local purulent lesions (felon, paronychia, boil, etc.).

The ability of ethyl alcohol to lower the surface tension of liquids allows it to be used as an antifoam in pulmonary edema (a 30-40% alcohol solution is poured into a Bobrov jar with warm water, through which a gas mixture with additional oxygen content is passed to humidify; spend for 10-15 minutes inhalation: there may be little liquid in the lungs, but the resulting foam fills the airways, disrupting the passage of air and gas exchange).

Resorptive effect of ethanol

The resorptive effect of ethanol occurs when ethanol is taken orally or administered intravenously. In medicine, resorptive action is used extremely rarely in the following situations:

• in case of poisoning with methanol (methyl alcohol, wood alcohol);
• for parenteral nutrition of patients with cachexia who are in critical condition (50-70 g/day. 5% ethanol solution is included in anti-shock fluids);
• to stop premature birth (in emergency cases in the absence of other medicines);
• for pain relief (only in special emergency situations, in the absence of other drugs with an analgesic effect).

Although the medical indications for prescribing ethanol are limited, due to the widespread use of alcoholic beverages, both the doctor and the pharmacist encounter the results of the resorptive effect of ethyl alcohol on various organs and systems quite often.

Pharmacodynamic effects of ethanol after a single dose occur at the subcellular, cellular and tissue levels.

Effects of ethanol at the subcellular and cellular levels. Small organic molecules, like ethanol, can easily dissolve in the lipid bilayer of cell membranes. Ethanol reduces the viscosity of membranes of many types of cells and even artificial systems such as liposomes. The general reaction of all biological membranes to ethanol is a change in their viscosity and an increase in fluidity. Changes in the viscoelastic properties of biomembranes cause whole line various effects: changes in the structure and function of receptors for a number of mediators (dopamine, norepinephrine, opiates, etc.), changes in the structure and function of enzyme systems (Na+ -K+ -ATPase, acetylcholinesterase, adenylate cyclase, etc.), receptor-dependent ion channels and transport molecules, associated with cell membranes.

At the organ level The resorptive effect of ethanol is directed mainly to the central nervous system.

On the central nervous system ethanol has an inhibitory effect, which increases with increasing concentration of ethyl alcohol in the blood and brain tissue. This manifests itself in three main stages.

Excitation stage is the result of inhibition of the inhibitory mechanisms of the brain. Euphoria occurs, mood improves, the person becomes overly sociable and talkative. In this case, psychomotor reactions are disrupted, behavior, an adequate assessment of the environment, self-control and self-esteem, and a critical attitude towards one’s own actions suffer. Against the background of euphoria, fragments of memories and false conclusions are perceived as reality and can become a stimulus for inappropriate statements and actions. In the future, under the influence of provoking factors in the environment, aggression may occur. The logic of manifestations of aggressiveness is unpredictable, since it is based on the internal delusional ideas of a drunk person.

With a further increase in blood alcohol concentration, sleep stage. Alcoholic sleep superficially resembles natural human sleep, but it is based not on the activation of inhibitory mediator systems, but on the suppression by ethanol of both excitatory and inhibitory processes in the cerebral cortex and subcortical formations. During alcoholic sleep, the phase structure of sleep is significantly disrupted; there is no alternation of periods of fast and slow sleep. Sleeping after alcohol intoxication does not bring any relief.

A further increase in the concentration of alcohol in the blood leads to a decrease in the functional activity of neurons not only in the brain, but also in the spinal cord and develops stage of surgical anesthesia. Reflexes that close at the level of the posterior and anterior horns of the spinal cord are suppressed and gradually fade away. Significantly reduced muscle tone. Unlike true anesthetics, ethanol has a very small narcotic range: its concentration, which turns off the spinal cord, is very close to that which paralyzes the centers of the medulla oblongata, in particular the vital respiratory and vasomotor centers. The stage comes complete paralysis of the central nervous system, or agonal stage. An indicator of the transition from the stage of surgical anesthesia to the agonal stage is the size of the pupils: in the anesthesia stage, the pupils are moderately constricted, and in the terminal stage they dilate paralytically due to paralysis of the center of the motor nerve of the orbicularis oculi muscle.

The stage of surgical anesthesia is observed at a concentration of ethanol in the blood of 3‰ (300 ml/l), and concentrations of 3.5‰ and higher are considered fatal in forensic examination.

The cardiovascular system. Even with the consumption of a moderate amount of ethanol, there is a significant inhibition of myocardial contractile function, which is most likely due to the accumulation of acetaldehyde in myocardiocytes.

On vessels ethanol has a vasodilating effect. This is due to inhibition of the vasomotor center, as well as the direct relaxing effect of the ethanol metabolite acetaldehyde on vascular smooth muscle.

As a result of vasodilation by ethanol, blood moves into the capacitance vessels of the abdominal cavity and extremities (especially when the body is in an upright position), which can cause a collapsed state. The first warning sign may be a sharp pallor of the skin as a result of blood redistribution.

Effect of ethanol for thermoregulation consequence of inhibition of the vasomotor center. The dilation of skin vessels creates a false sensation of warmth, which is not accompanied by an increase in body temperature. On the contrary, due to vasodilation and sweating, heat transfer significantly increases, which can lead to severe hypothermia. The use of ethanol as a warming agent is permissible only after hypothermia has occurred and under the obligatory condition that the person is in a warm room.

Diuretic the effect of ethanol also has a central genesis: the production of antidiuretic hormone by the pituitary gland is reduced.

Ethanol relaxes smooth muscles of the uterus. This effect, in addition to the muscle relaxant effect of ethanol, is also associated with its ability to inhibit the secretion of oxytocin. Previously, intravenous ethanol was widely used in obstetric practice to terminate premature labor. However, the danger of using ethanol for the mother and fetus is too great, and currently there are much less dangerous and more effective drugs (calcium channel blockers, β-adrenergic agonists).

Effect on the digestive system ethanol is also quite pronounced. It enhances the secretion of the salivary and gastric glands. This is the total result of its psychogenic, reflex, and also direct action to the glands. With the direct effect of ethanol on the gastric mucosa, the secretion of hydrochloric acid and humoral stimulants of gastric secretion - gastrin and histamine - increases. Low (up to 10%) alcohol concentrations do not affect pepsin activity; higher (20%) concentrations reduce pepsin activity and secretion of hydrochloric acid. When taking alcohol in a concentration of 40% or higher, there is an irritating effect on the gastric mucosa, in response to which the gastric glands produce a large amount of mucus. Mucus coats the surface of the stomach, reduces the concentration of ethanol and, to a certain extent, reduces its absorption.

When exposed to ethyl alcohol in high concentrations, the motor function of the stomach also decreases, a spasm of the pylorus occurs, and vomiting is possible as a result of the irritating effect on the mucous membrane.

Energy action. Ethanol has a high calorie content; when 100 g of ethyl alcohol is burned in the body, 710 calories are released. In some cases, this property of ethanol is used when prescribing it (in low concentrations 5% solution, 50-70 g per day) to debilitated patients (patients with cachexia in critical condition). It should be remembered that ethanol is not a nutrient, it does not serve as a plastic material for the formation of tissues, it is not deposited, and at the same time it is highly toxic.

Acute ethanol poisoning

Acute poisoning with ethyl alcohol takes a leading place among household poisonings and is the cause of more than 60% of all deaths from various intoxications.

The development of acute alcohol poisoning is usually associated with the consumption of various drinks with an ethyl alcohol content of more than 12%. The degree of intoxication depends on three factors: the concentration of ethanol in the blood, the rate at which the alcohol level rises and the time during which it persists. increased level ethanol in the blood. The degree of intoxication is also influenced by the state of the gastrointestinal mucosa and the presence of other drugs in the body (primarily those that have a depressant effect on the central nervous system).

The lethal dose of alcohol for adults varies widely depending on the degree of tolerance. An ordinary intolerant adult (who does not regularly drink alcohol in significant quantities) can metabolize 7-10 g of alcohol per hour (the amount of ethanol in 30 ml of vodka, a mug of beer, a glass of dry wine).

The lethal dose of ethanol after a single dose ranges from 4 to 12 g per 1 kg of body weight (on average 300 ml of 96% ethanol). Alcoholic coma develops at a blood alcohol concentration of about 3 g/l, and a concentration of 5-6 g/l is fatal.

Of primary importance in the development of acute ethanol intoxication is a violation of the exchange of brain mediators. Acetaldehyde (a metabolite of ethyl alcohol) condenses with the neurotransmitters norepinephrine, dopamine and serotonin. This produces a number of highly toxic compounds (tetrahydropapaverines, tetrahydroisoquinolines and tetrahydrobetacarbolines). They are able to interact with opiate receptors, activate them and release endorphins, inhibit COMT and MAO in the brain, and block the uptake of dopamine and norepinephrine by nervous tissue. Some of these compounds are powerful hallucinogens.

Acetaldehyde also has a toxic effect on other organs. Thus, it increases the release from adrenergic nerve endings, resulting in the development of tachycardia, an increase in the need for oxygen in the myocardium and other tissues, an increase in the tone of the arteries and arterioles, and an increase in blood pressure.

Acetaldehyde disrupts liver function, resulting in the accumulation of fatty acids, lactic and pyruvic acids, and glycerol in the blood; metabolic acidosis develops. This, in turn, contributes to the development of pulmonary edema. Hypoglycemia and hypocalcemia often develop, which leads to the development of seizures.

Death occurs from paralysis of the respiratory center.

Of particular danger is acute ethanol poisoning in children. For children early age A toxic dose of ethanol is a single dose of 20 g of a 40% solution, and taking 50 g at once can lead to death.

Clinical symptoms alcohol poisoning in children are:

• nausea, vomiting (from any method of exposure to poison), diarrhea, possible signs of dehydration;
• CNS depression, visual hallucinations, convulsions;
• hemodynamic disturbances, hypoxia, acidosis, hyperkalemia.

CNS depression begins with disinhibition, but in young children immediately with pronounced depression. Early regulation of vascular tone is inhibited: skin vessels dilate, heat transfer increases, and blood pressure decreases. Acetaldehyde formed as a result of ethanol metabolism further disrupts the functioning of the heart and contributes to an even greater decrease in blood pressure. As a result of brain dehydration, hypocalcemia, and hypoglycemia, children often develop seizures.

As in adults, death occurs as a result of respiratory paralysis.

Due to the increase in the number of women who abuse various narcotic or other medications during pregnancy, it is now not uncommon to give birth to children who have developed a dependence on substances taken by the mother in utero. Ethanol can cause such dependence and cause the development of withdrawal syndrome (deprivation phenomena) in newborns.

Clinical signs of alcohol withdrawal syndrome in newborns are hyperreactivity, irritability, crying without apparent reason, impaired sucking, tremors, convulsions, bad dream and pathologically increased appetite. These symptoms appear immediately after birth and persist for 18-20 months.

Interaction of ethanol with drugs

The influence of ethanol on the pharmacodynamics and pharmacokinetics of drugs occurs in several ways.

• Changes in the structure and function of cellular and subcellular membranes.
• Changes in the permeability of histohematic barriers (as a result of impaired fluidity of lipid membranes).
• Changes in the structure and function of various receptors (opioid, dopamine, norepinephrine, GABAergic).
• Changes in the structure and function of enzymes (Na+ -K+ -ATPase, Ca++ -ATPase, 5-nucleotidase, acetylcholinesterase, adenylate cyclase, enzymes of the mitochondrial electron transport chain).
• Changes in the structure of voltage-gated ion channels (like calcium channels).
• “Switching” of the MEOS system to ethanol oxidation (resulting in a decrease in the level of oxidation of other endogenous and exogenous ligands).
• Induction of microsomal liver enzymes change in the rate and level of biotransformation of other substances.
• Increased secretion of gastric mucus and decreased absorption of drugs in the stomach.
• Summarized and/or potentiated synergism with all drugs that have a depressant effect on the central nervous system; with vasodilators; with oral hypoglycemic agents.

When drugs and ethyl alcohol are prescribed simultaneously, their interaction can occur through several mechanisms at once, which is of important clinical significance.

Interaction of ethanol with certain drugs

Literature

1. Basic and clinical pharmacology / Ed. Bertram G. Katzung. - M.-SPb: Binom-Nevsky Dialect, 1998. - 670 p.
2. Viktorov A.P., Perederiy V.G., Shcherbak A.G. Interaction of drugs and food. - K.: Health, 1991. - 240 p.
3. Derimedved L.V., Pertsev I.M., Shuvanova E.V., Zupanets I.A., Khomenko V.N. Interaction of drugs and the effectiveness of pharmacotherapy. - Kh.: Megapolis, 2002. - 784 p.
4. Zmushko E.I., Belozerov E.S. Drug complications. - St. Petersburg: Peter, 2001. - 448 p.
5. Karkishchenko N. N., Khoronko V. V., Sergeeva S. A., Karkishchenko V. N. Pharmacokinetics. - Rostov-on-Don: Phoenix, 2001. - 383 p.
6. Clinical toxicology of children and adolescents / Ed. I. V. Markova, V. V. Afanasyev, M. V. Nezhentseva. - St. Petersburg: Intermedica, 1998. - 304 p.
7. Compendium 2001/2002 medications/ Ed. V. N. Kovalenko, A. P. Viktorova. - K.: Morion, 2002. - 1476 p.
8. Lawrence D. P., Benitt P. N. Clinical pharmacology: In 2 volumes. - M.: Medicine, 1993. - T. 1. - 640 p., T. 2. - 672 p.
9. Luzhnikov E. A. Clinical toxicology. - M.: Medicine, 1999. - 416 p.
10. Mikhailov I. B. Fundamentals of rational pharmacotherapy. - St. Petersburg: Foliant, 1999. - 480 p.
11. Pertsev I.M., Derimedved L.V., Shevchenko L.D. Are medicine and alcohol compatible? // Pharmacist.- 2000.- No. 5.- P. 37-38.
12. Selevich M.I., Lelevich V.V. Changes in lipid metabolism when using anti-alcohol drugs // Experimental and clinical pharmacology. - 1999. - No. 1. - P. 70-74.
13. Modern over-the-counter drugs / Ed. A. L. Tregubova.- M.: Gamma-S LLC. A.”, 1999.- 362 p.
14. Haberman E. Drug interaction // Pharmacist.- 1997.- No. 16.- P. 21-25.

Based on the nature of its effect on the central nervous system, ethyl alcohol (ethanol; C2H5OH) can be classified as an anesthetic. Acts on the central nervous system

similar to diethyl ether: it causes analgesia, a pronounced stage of excitation, and in large doses - anesthesia and the atonal stage.

However, unlike diethyl ether, ethyl alcohol has virtually no narcotic potential: in doses that cause anesthesia, ethyl alcohol depresses the respiratory center. Therefore, ethyl alcohol is not suitable for surgical anesthesia.

Ethyl alcohol inhibits the production of antidiuretic hormone and therefore can increase diuresis.

Reduces the secretion of oxytocin and has a direct inhibitory effect on myometrial contractions; therefore, it may delay the onset of labor (tocolytic effect).

Reduces testosterone secretion; when used systematically, it can cause testicular atrophy, decreased spermatogenesis, feminization, and gynecomastia.

Dilates blood vessels (influence on the central nervous system and direct vasodilator effect).

When taken orally, ethyl alcohol is rapidly absorbed (20% in the stomach, 80% in the intestines). Approximately 90% of ethyl alcohol is metabolized in the liver under the influence of alcohol dehydrogenase; about 2% are exposed to microsomal liver enzymes. The resulting acetaldehyde is oxidized by aldehyde dehydrogenase; 5-10% of ethyl alcohol is excreted unchanged by the lungs, kidneys, and with the secretions of the sweat, lacrimal, and salivary glands.

In medical practice, stage I of the narcotic effect of ethyl alcohol can be used - the stage of analgesia. In particular, ethyl alcohol is used to prevent pain shock in injuries and wounds (intravenous administration of 5% ethyl alcohol is possible).

When applied topically, ethyl alcohol has an irritating effect. At a concentration of 40% (20% for children), ethyl alcohol is used for compresses for inflammatory diseases of internal organs, muscles, and joints. Alcohol compresses are applied to healthy areas of the skin that have conjugate innervation with the affected organs and tissues. Like other irritants (for example, mustard plasters), such compresses reduce pain and improve trophism of the affected organs and tissues.

At a concentration of 95%, ethyl alcohol has an astringent effect, which is associated with its ability to denature proteins.

For pulmonary edema, the antifoaming effect of ethyl alcohol vapor is used. The patient breathes air that is passed through ethyl alcohol. Ethyl alcohol vapor reduces the surface tension of the exudate and prevents its foaming.

Ethyl alcohol is especially often used in practical medicine as an antiseptic (antimicrobial) agent. The antimicrobial effect of ethyl alcohol is due to its ability to cause denaturation (coagulation) of microorganism proteins and increases with increasing concentration. Thus, 95% ethyl alcohol has the greatest antimicrobial effectiveness. In this concentration, the drug is used to treat surgical instruments, catheters, etc. To clean the surgeon's hands and the surgical field, 70% ethyl alcohol is often used. At higher concentrations, ethyl alcohol intensively coagulates protein substances and does not penetrate well into the deep layers of the skin.

Ethyl alcohol is used for methyl alcohol poisoning. Methyl alcohol (methanol), like ethyl alcohol, is subject to the action of alcohol dehydrogenase. Formaldehyde is formed (more toxic than acetaldehyde), which turns into another toxic product - formic acid. The accumulation of formic acid (not utilized in the tricarboxylic acid cycle) leads to the development of acidosis. When taking methyl alcohol internally, the intoxicating effect is less pronounced than when taking ethyl alcohol. The toxic effect develops gradually over 8-10 hours. Irreversible visual impairment is characteristic. In severe cases, convulsions, coma, and respiratory depression develop.

Alcohol dehydrogenase exhibits a significantly greater affinity for ethyl alcohol compared to methyl alcohol. In case of methyl alcohol poisoning, 200-400 ml of 20% ethyl alcohol is prescribed orally or 5% ethyl alcohol is administered intravenously in a 5% glucose solution. The metabolism of methyl alcohol slows down, which prevents the development of toxic effects.

With the everyday use of ethyl alcohol as part of alcoholic beverages, a stage of excitement (intoxication) quickly develops, which is characterized by a decrease in critical attitude towards one’s own actions, disorders of thinking and memory.

Ethyl alcohol has a pronounced effect on thermoregulation. Due to the expansion of the blood vessels of the skin during intoxication, heat transfer increases (subjectively this is perceived as a feeling of warmth) and body temperature decreases. Intoxicated people freeze faster in low temperatures than sober people.

With an increase in the dose of ethyl alcohol, the stage of excitation is replaced by phenomena of central nervous system depression, impaired coordination of movements, confusion, and then loss of consciousness. There are signs of depression of the respiratory and vasomotor centers, weakening of breathing and a drop in blood pressure. Severe ethyl alcohol poisoning can lead to death due to paralysis of vital centers.

Acute poisoning with ethyl alcohol (alcohol) is characterized by signs of deep depression of central nervous system functions. In severe alcohol poisoning, complete loss of consciousness and different types sensitivity, muscle relaxation, inhibition of reflexes. There are symptoms of depression of vital functions - breathing and heart activity, decreased blood pressure.

First aid for acute poisoning drinking alcohol comes down primarily to gastric lavage through a tube to prevent the absorption of alcohol. To accelerate the inactivation of alcohol, a 20% glucose solution is administered intravenously, and to correct metabolic acidosis, a 4% sodium bicarbonate solution is administered. In cases of deep coma, hemodialysis, a method of forced diuresis, is used to accelerate the removal of ethyl alcohol from the body.

Chronic alcohol poisoning (alcoholism) develops with the systematic consumption of alcoholic beverages. It manifests itself in various disorders of the central nervous system, functions of the circulatory, respiratory, and digestive organs. Thus, with alcoholism, there is a decrease in memory, intelligence, mental and physical performance, and mood instability. Alcoholism often causes serious mental disorders (alcoholic psychoses). Drinking alcohol during pregnancy can lead to the development of “fetal alcohol syndrome,” which is characterized by external manifestations (low forehead, wide-set eyes, decreased skull circumference), and later such children experience delayed mental and physical development and antisocial behavior.

With an abrupt cessation of systematic alcohol intake, withdrawal symptoms develop after about 8 hours - tremor, nausea, sweating, and later there may be clonic convulsions and hallucinations. In severe cases, a condition referred to as delirium tremens (“delirium tremens”) develops: confusion, agitation, aggressiveness, severe hallucinations. To reduce withdrawal symptoms, it is recommended to use benzodiazepines (diazepam), and to reduce symptoms of sympathetic activation - propranolol.

Alcoholism, as a rule, leads to moral and physical degradation of the individual. This is facilitated by damage to the central nervous system and diseases of internal organs during chronic alcohol poisoning. Myocardial dystrophy, chronic damage to the stomach (gastritis) and intestines (colitis), liver and kidney diseases develop. Alcoholism is often accompanied by a decline in nutrition, exhaustion, and decreased resistance to infectious diseases. With alcoholism in men and women, the functions of the reproductive system are significantly impaired. A connection has been established between parental alcoholism and certain birth defects of mental and physical development offspring (congenital dementia, growth retardation, etc.).

Patients with alcoholism are treated in specialized drug treatment departments of medical institutions. Most modern methods of treating alcoholism are aimed at inducing an aversion to alcohol in the patient. The treatment methods are based on the development of negative conditioned reflexes to alcohol. For example, they combine the technique not large quantities alcohol with the introduction of apomorphine (emetic). As a result, the mere sight or smell of alcohol causes nausea and vomiting in patients.

A similar principle is used in the treatment of alcoholism, using disulfiram (Teturam, Antabuse). Ethyl alcohol, under the influence of alcohol dehydrogenase, is converted into acetaldehyde, which is significantly more toxic than ethyl alcohol. Typically, acetaldehyde is quickly oxidized by acetaldehyde dehydrogenase. Disulfiram inhibits acetaldehyde dehydrogenase and delays the oxidation of ethyl alcohol at the acetaldehyde stage.

In a specialized hospital, patients with alcoholism are systematically prescribed disulfiram tablets. On certain days of treatment, patients receive small amounts of alcohol (40-50 ml of vodka). The resulting acetaldehyde causes an “antabuse reaction” - facial flushing, throbbing headache, arterial hypotension, dizziness, palpitations, difficulty breathing, muscle tremors, anxiety, sweating, thirst, nausea, vomiting. In this way, patients gradually develop a negative conditioned reflex (aversion) to alcoholic beverages.

THE CARDIOVASCULAR SYSTEM

A moderate amount of ethanol causes dilation of skin vessels (a central effect, since depression of the central nervous system leads to inhibition of the vasomotor center), which is accompanied by hyperemia and a feeling of warmth. A person who has taken ethanol has a red face and his eyes “burn.” The effect of vasodilation under the influence of ethyl alcohol prevents the normal reaction of constriction of skin vessels during cooling, so using alcohol as a warming agent in cold weather is harmful, since it contributes to increasing heat loss. Possible hypothermia.

In large doses, alcohol depresses cardiac activity like chloroform or ether. Long-term use of large amounts of ethanol causes damage to the heart muscle, leading to alcoholic myocardiopathy. In patients with diseases of the coronary vessels or heart valves, taking even small doses of ethanol inhibits myocardial function.

EFFECT OF ETHANOL ON THE LIVER

Ethyl alcohol disrupts gluconeogenesis in the liver, reduces the synthesis of albumin and transferrin, increases the synthesis of lipoproteins, and inhibits the oxidation of fatty acids. All this leads to uncoupling of oxidative phosphorylation in liver cells.

During alcohol intoxication, inhibition of hepatic microsomal enzymes occurs, and its chronic use stimulates the activity of these enzymes, which is accompanied by an increase in the rate of metabolism of many drugs and alcohol itself.

The most typical clinical symptoms are hypoglycemia and hepatomegaly. Fatty degeneration, alcoholic hepatitis, and liver cirrhosis may develop. Alcohol liver damage is a direct effect of ethanol. Women are more sensitive to the effects of alcohol, which is associated with a genetic predisposition based on the HLA phenotype.

Alcohol increases urination, which is a consequence of reduced reabsorption of water in the renal tubules, caused by inhibition of ADH (antidiuretic hormone) production.

EFFECT ON THE GASTROINTESTINAL TRACT

In small doses, when taken orally, ethanol causes a local sensation of warmth and increases the secretion of saliva and increases appetite. Due to the release of histamine and gastrin in the antrum, the secretion of the gastric glands increases.

At a concentration of more than 15 percent, alcohol inhibits both secretion and motor function. This effect can last for many hours. Even higher concentrations have a pronounced irritating effect on the mucous membranes and can cause the development of gastritis, provoke nausea and vomiting. At concentrations of more than 20 percent, the enzymatic activity of both gastric and intestinal juice decreases. When drinking alcohol in a concentration of over 40 percent, there is a burn of the mucous membrane, its swelling, swelling, destruction of the boundary layer of the mucous membrane, and the release of mucus in large quantities.

Ethyl alcohol affects thermoregulation by increasing heat transfer (suppression of the vasomotor center, dilation of skin vessels). As a result, ethyl alcohol in the cold promotes hypothermia of the body, and does not prevent it, as is commonly believed. Taking ethyl alcohol is justified only when coming from a cold place to a warm room.

Indications. In medical practice, the resorptive effect of ethyl alcohol is practically not used.

1) Most often it is used as a solvent for various medicinal substances (herbal preparations).

2) At a concentration of 70 percent, it can be used as an antiseptic and disinfectant (disinfection). It has a bactericidal effect only on vegetative forms of microorganisms (not on spores).

3) It is sometimes used in cases of fever, as it causes a cooling effect when applied to the skin (alcohol rubs).

4) On the contrary, alcohol wraps in the form of compresses are used as a warming measure.

5) Alcohol is used as an antifoam to relieve attacks of bronchial asthma.

6) Ethanol has previously been used to destroy nerve fibers, for example, in trigeminal neurogia. Now this method is practically not used.

7) To prevent bedsores, lubricating the patient’s skin.

Due to the wide spectrum of action of ethyl alcohol, and also due to the fact that many people drink alcohol for a long time, they develop mental and physical dependence. When addiction has developed, good health is associated with the presence of alcohol in liquid media and body tissues. Such a person’s craving for alcohol is so strong that the desire to drink it becomes the only interest in life.

Scheme 3.2.1. Effect of disulfiram (teturam) on the biotransformation of ethyl alcohol

NAD Ethanol NADP

CH3CH2OH