MINISTRY OF HEALTHCARE OF THE REPUBLIC OF UZBEKISTANTASHKENT MEDICAL ACADEMY

DEPARTMENT: PHARMACOLOGYSUBJECT: PHARMACOLOGY

On a theme:Ethanol. Hypnotics.

PLAN OF THE LECTURE

1. General characteristics of ethyl alcohol 2. Indications for use of ethyl alcohol. 3. Acute and chronic poisoning with ethyl

alcohol. 4. Treatment of alcoholism. 5. General characteristics of hypnotics. 6. By lassifikatsiya hypnotics. 7. Pharmacodynamics, The pharmacokinetics

of hypnotics. 8. Acute poisoning hypnotics. Aid for

poisoning.

THE AIM OF THE LECTURE:

generate knowledge of ethyl alcohol and sleeping pills.

LEARNING OUTCOMES:A STUDENT MUST:

- Tell us a general description of ethyl alcohol, hypnotics;

- List the indications for the use of ethyl alcohol and hypnotics;

- Describe the classification of hypnotics; - describe pharmacodynamics,

pharmacokinetics of ethyl alcohol and sleeping pills x funds.

- Talk about the principles of therapy for poisoning ethyl alcohol and sleeping pills.

 

Ethyl alcohol is a typical substance narcotic type of action. He has a general depressant effect on the central nervous system. In addition, ethyl alcohol has a strong antiseptic properties. For medical practices ethyl alcohol is of limited interest. It is used mainly as an antiseptic. Much greater attention is drawn to the ethyl alcohol with ¬ social dimension, as in connection with the use of alcoholic beverages, he is often the cause of acute and chronic poisoning. Ingestion ethyl alcohol is rapidly absorbed mainly in the small intestine and about 20% - in the stomach.

The absorption rate depends largely on the nature of the contents of the gastrointestinal tract motility and intensity. Particularly rapid resorptive effect of ethyl alcohol comes in the fasting state. Fats and carbohydrates significantly delay its absorption. In the body, 90% of the injected ethyl alcohol is metabolized to SOG and water. The oxidation is accompanied by liberation of ethyl ¬ tion considerable amount of energy (7.1 kcal / g). This occurs in the liver by approximately 10 ml / h Prolonged use of ethyl alcohol can be observed induction of liver enzymes in which the rate of inactivation of ethyl alcohol increased.

Unchanged ethyl alcohol stands lungs, kidneys and sweat glands ¬ mi. Resorptive effect of ethyl alcohol is directed mainly to the central nervous system. It exerts a dampening effect, which increases with the concentration of ethyl alcohol in the blood and tissues of the brain. This is manifested in three major steps: 1) excitation step 2) under anesthesia 3) atonal step.

Stage of excitation is the result of the oppression of brake mechanisms of the brain. It is usually well marked and long-lasting. There is euphoria, increased mood, he becomes overly sociable, talkative. Psychomotor reaction at this violated dramatically affected human behavior, self-control, adequate assessment of the environment, efficiency is reduced. With an increase in the blood concentration of ethyl alcohol come analgesia, drowsiness, then breaks out. Inhibited spinal reflexes. The stage of anesthesia, which, however, neprodolzhi ¬ tional and soon becomes atonal stage. A small drug ¬ cal latitude and expressed excitement stage not allow the use of ethyl alcohol as a means of anesthesia.

One of the manifestations of the central action of ethyl alcohol - its effect on thermoregulation, manifested by increased heat loss (due to vasodilatation of the skin, which is a consequence of the inhibition of the vasomotor center). As a result, the cold ethyl alcohol contributes to hypothermia, and does not preclude it, as is often said. The subjective feeling of warmth after receiving ethyl alcohol associated with the expansion of the cutaneous vessels, is not accompanied by a general increase in body temperature. In this regard, in order to create a feeling of warmth, acceptance of ethyl alcohol can be justified only after getting in from the cold into a warm room, when the danger of frost is excluded.

The diuretic action of ethyl alcohol also has a central origin (reduced production of antidiuretic hormone of the posterior pituitary). Ethyl alcohol has a pronounced effect on the digestive system. Thus, it enhances the secretory activity of the salivary and gastric glands ¬. This is the result of his Llyaetsya psychogenic, reflex, as well as direct action on the gland. Increased secretion of gastric glands under direct ethyl alcohol on the mucosa is obviously due to the release of humoral substances (gastrin, histamine). It should be borne in mind that ethyl alcohol increases the secretion of acid hloristovo ¬ stout.

Pepsin activity at low concentrations (10%) ethyl alcohol is not changed, and decreases with increasing concentration. Since about 20% concentration, ethyl alcohol not only inhibits the secretion of hydrochloric acid, but also food ¬ provisional activity of gastric juice, which is particularly pronounced when receiving alcoholic beverages with 40% and above. In response to stimuli ¬ tal effect on the mucous membrane of high concentrations of ethyl alcohol gastric glands produce large amounts of mucus. It coats the surface of the stomach, and also reduces the concentration of ethyl alcohol.

Changes and motility of the stomach. Ethyl alcohol in sufficient ¬ sufficiently high concentrations cause spasm of the pylorus and reduced gastric motility. On bowel function ethyl alcohol has little effect. Obviously, this is because it is diluted in the stomach and enters the intestine gradually. In medical practice resorptive effect of ethyl alcohol is rarely used. Sometimes it is used as a means protivoshokovoe (given its analgesic effect), rarely - as a hypnotic or sedative substances. In some cases, shows the assignment of ethyl alcohol (in low concentrations) depleted patients

In this case refers to its energy value. However, it should be noted that ethyl alcohol is not a nutrient substance ¬ tion. It does not provide a plastics material for forming fabrics are not deposited and has significant toxicity. With prolonged use of ethyl alcohol develop ¬ tion got used to it and drug abuse (physical and mental).

Reception alcohol can lead to acute poisoning, the degree of which depends on the concentration of ethyl alcohol in the blood. Intoxication occurs at a concentration of approximately 1-2 g / l (100 - 200 mg%). At 3-4 g / l (300-400 mg%) developed severe Institute ¬ intoxication. Lethal concentration is from 5 to 8 g / l (500 - 800 mg%). In the treatment of alcoholic coma should first establish a hell ¬ kvatnoe breath. Held WC oral purified upper airways. To reduce the secretion of salivary and bronchial glands atropine.

Assign oxygen. If necessary, carried ¬ stvlyayut mechanical ventilation. It is also useful introduction analeptikov (korazol, kordiamin, caffeine, etc.). When hemodynamic disorders, symptomatic therapy. It should also wash out the stomach. In addition, a correction of the acid-base equilibrium (intravenous sodium bicarbonate). In severe condition of the patient hemodialysis. In case of severe nausea possible use of antiemetics (metoclopramide, etc.). In connection with the violation of thermoregulation such patients should be warm

Chronic poisoning with ethyl alcohol (alcoholism) is characterized by a variety of symptoms. Particularly affected the higher nervous activity and knowledge. Reduced mental performance, attention, and memory. There may be mental disorders (Delirium tremens, Korsakoff's psychosis). Affected and peripheral innervation (polyneuritis can occur).

Serious disorders and marked by internal organ ¬ new. For example, accompanied by chronic gastritis, alcoholism, cirrhosis, fatty heart and kidneys. If alcoholism is a gradual mental and physical degradation of the individual. Alcoholism treatment is carried out in hospitals. The main task is to stop accepting ethyl alcohol and in the development of a negative attitude to it. Cancellation of ethyl alcohol must be gradual, as abrupt discontinuation of its use can cause severe phenomenon of deprivation, including exacerbation of mental disorders (eg, stroke, delirium tremens). One of the drugs used in the treatment of alcoholism is the teturam (Antabuse, disulfiram).

Assign teturam in conjunction with the acquisition of small amounts of ethyl alcohol. Teturama mechanism of action is that it delays the oxidation of ethyl alcohol to acetaldehyde level (presumably, it inhibits the aldehyde). The accumulation of the latter ¬ him in the body causes intoxication that followed. Extremely painful sensations. There is a feeling of fear, pain in the heart, headache, hypotension, diaphoresis, nausea, and vomiting

The course of treatment for patients Teturamom produces a negative reflection on ethyl alcohol. Teturamom treatment should be carried out with care, under the supervision of a physician. The patient should be well oriented in the fact that even a slight overdose of alcohol ethyl ¬ Vågå on the background of teturama can lead to death. Teturam not recommended for persons older than 50 years, as well as cardiovascular disease, liver disease, kidney disease and metabolism. There is a long-acting drug teturama, called esperal (radoter). Tablets esperal implanted in the sub ¬ cutaneous tissue.

Sometimes to generate negative conditioned reflexes use of centrally acting emetic - apomorphine (also melt ¬ A combination with the reception of ethyl alcohol). Furthermore, in the treatment of alcoholism are widely used various psychotropic drugs. The positive effect in the treatment of alcoholism ¬ SRI, especially in the development of polyneuritis, give thiamine.

Drug treatment of alcoholism should always be combined with psychotherapy. Existing drugs can reduce the consumption of ethyl alcohol ¬ Vågå only in some patients and only for a few months. Unfortu ¬ leniyu enough effective drugs that suppress the craving for ethyl alcohol, no.

Hypnotics By hypnotic include means to facilitate the development and provision ¬ zations sleep. They promote falling asleep and provide the necessary amount of sleep ¬ directly. By the nature of the influence of the central nervous system and the lack of selective classic hypnotics (barbiturates, Alif ¬ cal compounds) are substances such as drugs.

By the nature of the influence of the central nervous system and the lack of selective classic hypnotics (barbiturates, Alif ¬ cal compounds) are substances such as drugs. Hypnotics By hypnotic include means to facilitate the development and provision ¬ zations sleep. They promote falling asleep and provide the necessary amount of sleep ¬ directly. By the nature of the influence of the central nervous system and the lack of selective classic hypnotics (barbiturates, Alif ¬ cal compounds) are substances such as drugs.

Hypnotics are classified based on the principle of action and chemical structure.

I. Hypnotics with narcotic 1. Heterocyclic compounds  Barbituric acid derivatives (barbiturates)                                               Phenobarbital Barbital barbamyl Barbital sodium-sodium etaminal                       2. Aliphatic compounds                   Chloral hydrate bromisoval P. Hypnotics group of tranquilizers                          Benzodiazepines                                       Nitrazepam Sibazon                                                                                  (Diazepam)

Sleep disorders are also using separate preparations of the other groups that have hypnotic properties antihistaminic media ¬ properties (diphenhydramine), the means of anesthesia, effective oral (sodium hydroxybutyrate). Despite considerable research, the mechanism of action of hypnotics may speak only hypothetically. The main difficulties stem from the fact that the known mechanisms of physiological sleep. According to modern concepts, the dream - it is an active process in which the activity of gipnogennyh (synchro ¬ ating) structures of the brain is increased and the activation of the ascending reticular formation (called EEG desynchronization) ¬ on the lower.

Obviously influenced hypnotics changes the interaction of these two systems in favor gipnogennoy. Indeed, many of the hypnotic ¬ governmental funds, such as barbiturates, have a depressing effect on the activating reticular formation of the brain stem, which should favor the development of sleep. However, this is only one possible, but not the only mechanism of action of hypnotics. So, tranquillizers ¬ lytic benzodiazepine agents that promote sleep, in contrast to the barbiturates act on the limbic system and its relationship to functional systems, which provide a cyclic shift of wakefulness and sleep.

Over the past years, much attention is drawn to the endogenous substance ¬ properties isolated from the brain and possess hypnotic activity (eg ¬ measures peptide δ-sleep). It is natural that the selection of compounds with gipnogennymi properties is of great interest not only for understanding the mechanism of sleep, but also for the creation of new drug ¬ funds. It should be borne in mind that sleep induced by a majority of hypnotic drugs, in its current differs from the natural sleep. As you know, under normal conditions during sleep several times alternating so-called Vai ¬ "slow" sleep (orthodox, perednemozgovoy, synchronized ¬ Rowan) and "fast" sleep (REM, zadnemozgovoy, desynchronization-nizirovanny; sleep accompanied by rapid eye movements) .

The latter is 20-25% of total sleep time. Long ¬ tional violations during each of these phases are recognized adverse ¬ nicely on the condition of the body (there are behavioral, mental disorders). It turned out that most hypnotics (Barbie ¬ Turati, etc.) substantially change the "structure" of sleep. This is especially true of "rapid" sleep (increased latency of the appearance of the first phase of "rapid" sleep reduces the overall length of it). Cancel hypnotics may be accompanied by the so-called phenom ¬ nom "recoil", the severity of which depends on the dose and duration of their use.

The duration of the "fast" sleep some time exceeds the normal value, it shortens the latency period, marked an abundance of dreams, nightmares, frequent awakening. In this regard, special attention is paid to sleeping pills which do not affect or minimally affecting the phase relationship of sleep and contribute to the development of sleep, which is close to natural.

There was no impact on the "fast" sleep sodium hydroxybutyrate and chloral hydrate or this effect is negligible, but both drugs have a number of drawbacks. Also of interest from the benzodiazepine tranquilizers (nitrazepam, sibazon, etc.). The main effect of these as tranquilizers is to eliminate mental stress. Occurring at the same time promotes calm sleep. Drugs such nitrazepama to a lesser extent than barbiturates, shortened REM sleep.

Hypnotics With TYPE OF NARCOTIC A significant number of these hypnotics relates to derivatives of barbituric acid. The latter is a product of the interaction ¬ action of urea and malonic acid. The main chemical modifications of barbituric acid are associated with joining the C5 various structures. Some substances relative to syatsya ¬ thiobarbituric acid derivative (in this case, instead of the oxygen atom linked to the sulfur atom C2).

The duration of action of barbiturates used in practice corresponds to about 8 pm This group includes phenobarbital (Luminal, phenobarbitone). Barbital (veronal, barbiton), barbital n atrium (Medinai, barbital sodium), barbamil (amobarbital sodium, sodium amytal ) etaminal sodium (pentobarbital sodium Nembutal). Isolation of intermediate-acting drugs (Barba ¬ sweet etaminal sodium) is impractical because of clinical observations ¬ deniyam they similarly barbitalu phenobarbital and contribute to the development of sleep duration of about 8 hours

At the termination of hypnotic action of barbiturates take participation ¬ ment different processes. One of them - that enzymatic inactivation of substances microsomal liver enzymes. Most often, this oxidation. (Hydroxylation occurs radicals at C5). In this regard, the pathology of the liver, accompanied by decreased activity of its enzyme systems, the duration of action of barbiturates increases. The latter, of course, refers to those drugs that a major amount of biotransformation (etaminal sodium, Barbamyl). It should be borne in mind that barbiturates (particularly phenobarbital) cause induction of microsomal enzymes.

In this regard, upon repeated administration of barbiturates speed increases their metabolism. Perhaps this is one of the main causes of addiction to them. Furthermore, it affects the rate of biotransformation of compounds of other chemical groups. The duration of a number of derivatives of barbituric acid also depends on their rate of excretion by the kidneys. This refers to the connection ¬ neniyam that either in the ground (eg, barbital), or to a large ¬ erably (phenobarbital) excreted by the kidneys in unchanged form. If the kidney function effect of barbiturates markedly prolonged.

Duration soporific effect also depends on the redistribution of ¬ substances in the body. Refers mainly reduction of barbiturates in the brain tissue and their deposition in adipose tissue in high lipophilicity compounds. After the application of long-acting barbiturates, even when a single dose, the day after waking up can be a feeling of lethargy, weakness, impaired psychomotor reactions attention. This condition is commonly referred to as the aftereffect. The slower output (inactivated) product, the more pronounced after-effect. For example, reduction of phenobarbital, and barbital in blood plasma by 50% of the injected dose (t ½) is about 3 ½ days and concerning aftereffect relatively frequently observed

Phenobarbital is derived entirely from the body more rapidly ¬ yardarm than barbital. To a much lesser extent, the aftereffect noted ¬ acquired after application of barbital sodium and sodium-etaminal (t ½ of these drugs is 30-40 hours). For barbiturates at their repeated use of materials characterized by accumulation ¬ rial. It is most pronounced at the long-acting drugs, especially barbital and phenobarbital, because of their slow ¬ nym clearance from the body. In the application of barbiturates for days growing deficit phase of the "rapid" sleep. As noted, when the drugs are stopped, a so-called phenomenon of 'give', which may persist for several weeks.

Continuous barbiturates for a long period leads to habituation and may cause drug dependence ¬ GOVERNMENTAL (mentally and physically). With daily use of barbiturates getting used to it reveals about 2 weeks after the start of reception. The rate of drug dependence is largely determined by the dose preparations. If a large enough dose, drug dependence may develop after 1-3 months. Removal of the drug in the presence of drug dependence is accompanied by severe mental and physical disorders (withdrawal symptoms). Having anxiety, irritability, anxiety, vomiting, blurred vision, seizures, orthostatic hypotension, etc. In severe cases, death can occur. Enter barbiturates usually on the inside, at least - rectal or parenteral ¬ eral (water-soluble drugs). They are well absorbed from the Write debugging ventricular ¬ tract.

Partly bound to plasma proteins (primarily to albumin). Easily penetrate the tissue barriers. Excreted by the kidneys. Basically barbiturates prescribed as sleeping pills (30-60 minutes before bedtime). Widely used as barbiturates and sedatives (⅓ -1 / 5, and less of the hypnotic dose). Phenobarbital, moreover, is an antiepileptic drug active. When used in therapeutic doses, barbiturates no significant violations of the internal organs and their systems are not observed. However, allergic reactions (skin lesions, jaundice, fever, etc.).

Most often they arise in the administration of phenobarbital. Acute barbiturate poisoning occur as a result of accidental or intentional overdose of drugs. There comes a depression of the central nervous system. In severe poisoning coma develops, there is no consciousness, reflex activity is suppressed. Depress ¬ Xia centers of the medulla oblongata. Due to the inhibition of the respiratory center reduces the amount of breath. Falling blood pressure (hypotension is associated not only with the central action, but also to the influence of substances on the heart, ganglia, as well as direct miotropnym sosudorasshi ¬ fying action). Disrupted the function of the kidneys.

Treatment of acute poisoning is to accelerate the elimination of the drug from the body and to maintain vital functions. If you enter a barbiturate completely sucked from the gastro-intestinal tract ¬, do gastric lavage, give adsorbing agents, saline laxatives. In order to accelerate the elimination of already grown deep substance injected large amounts of fluid and prescribed an osmotic diuretic furosemide or causing a rapid and significant ¬ cant increase urine output (the so-called forced diuresis). The introduction of alkaline solutions can also help us derive ¬ NIJ barbiturates. At very high concentrations of barbiturates in the blood is carried hemosorption and peritoneal dialysis and hemodialysis ¬ sis.

One of the main objectives of the treatment of barbiturate poisoning conclude ¬ prises establishing adequate breathing and elimination or prevention of Denia ¬ hypoxia. In severe cases, artificial respiration. Analeptics (Bemegride, korazol, etc.) prescribed only in mild forms of poisoning, with severe poisoning, they do not contribute to the restoration of breathing, but may even worsen ¬ sew the patient's condition. Should consider the possibility of developing pneumonia. If you are experiencing hypotension, collapse, injected blood krovezame-fuse, and norepinephrine. In renal failure (oliguria, anuria) often shows hemodialysis. The prognosis depends on the dose of sedative agents, timeliness of treatment, the state organ ¬ ism. The above principles of treatment of acute barbiturate poisoning ¬ mi use and overdose of sleeping pills other groups

Chronic poisoning most often occurs when taking barbitu ¬ Ratov who have expressed cumulation (barbital, phenobarbital). This is manifested by apathy, drowsiness, weakness, a violation of equal ¬ equilibrium, slurred speech, dizziness. Possible hallucinations ¬ nation, psychomotor agitation, convulsions. May also suffer blood circulation, digestion, liver and kidneys. It should consider the possibility of drug addiction, in which can immediately stop the introduction of the drug, since it causes withdrawal syndrome. In this regard, the treatment of chronic poisoning ¬ tions gradually reduce the dose of sleeping pills and discontinued it. Simultaneously, symptomatic treatment and psychotherapy. The prognosis for rehabilitation of such patients is usually favorable.

To heterocyclic compounds also include derivatives of piperidine. The most common sleeping pills this series is noksiron (glyutetimid, Doris). According to the chemical structure, it is similar to phenobarbital. Noksiron has sedative and hypnotic effects. It promotes sleep up to 8 hours less active than barbiturates. Reduces the phase of "rapid" sleep. Atropine has properties. Stimulates the synthesis of microsomal liver enzymes ¬ Comrade. Noksiron well absorbed from the gastrointestinal tract. Readily crosses the blood-brain barrier.

Almost completely biotransformation. Its metabolites are excreted by the kidneys. With prolonged use noksirona him develop addictive, can arose ¬ nut drug abuse (physical and mental). Assign noksiron as a soporific (15-30 minutes before sleep) as well as a sedative. The drug is well tolerated. Sometimes, there are allergic reactions, dizziness, as well as the side effects associated with the m-anticholinergic properties ¬ mi (eg, dry mouth, etc.). In general, no special advantages CPA ¬ vneny with barbiturates noksiron not.

A number of hypnotics is to aliphatic compounds ¬ tions. One of them is the chloral hydrate. This is the first synthetic ¬ skoe sleeping pills used in the practice of medicine. A pronounced hypnotic effect. Contributes to the development of sleep for up to 8 hours of barbiturates is different from the fact that almost does not disturb sleep patterns. In large doses, causes anesthesia. Drug ¬ cal breadth of chloral hydrate in a small (comes quickly oppression centers of the medulla oblongata).

Rapidly absorbed from the intestine. Freely through tissue barriers. The body turns to trichloroethanol (chloral hydrate on similar properties). Chloral hydrate to a small extent stimulated ¬ ruet synthesis of microsomal liver enzymes. Chloral hydrate metabolites and conjugates excreted by the kidneys. With the re-introduction of chloral hydrate to it develops pref ¬ circuiting, possible drug dependence (physical and mental). Cumulation hardly occurs. Use the drug orally or rectally (enemas) as a sleep aid (for 15-30 minutes before sleep), sedative and anticonvulsant.

Chloral hydrate has a number of negative features. These attributes ¬ Xia possible adverse effects on parenchymal organs: liver, kidneys, heart. Data are shown toxic effects mainly on the background of the pathological changes in these organs, as well as intoxication with chloral hydrate. Chloral hydrate has a strong stimulating effect, so it is usually prescribed in combination with mucus. Mild sedative and hypnotic properties has also bromisoval (bromural). It is used mainly as a means of sedation ¬ tive. As relief is used only for the expressed little sleep disorders. GROUPS OF hypnotics Tranquilizers

Many tranquilizers belonging to the group of benzodiazepines, have expressed widespread activity (nitrazepam, sibazon, phenazepam, etc). For some of them it is the dominant feature, for example, in nitrazepama, which basically uses and ¬ Xia as a hypnotic. Nitrazepam (eunoktin) is similar to other benzodiazepine tranquilizers has a hypnotic, anxiolytic (tranquilizing, sedative), anticonvulsant and muscle-relaxing activity. Hypnotic and anxiolytic effects are associated mainly with nitrazepama depressing effect on the limbic system (hippocampus) and to a lesser extent in asset-regulating the reticular formation of the brain stem and cerebral cortex; Muscle-relaxing effect due to the suppression of spinal reflexes polneynapticheskih.

The mechanism of anticonvulsant (antiepileptic) of action is obviously linked to the activation of inhibitory mechanisms of the brain. Sleeping pills nitrazepama after its introduction into the coming 30-60 minutes and lasts up to 8 hours aftereffect is missing or expressed little. Boosts and prolongs the effect of drug money ¬ arithmetic type of action: for narcosis, ethyl alcohol, ¬ governmental hypnotic, narcotic analgesics. On the cardiovascular system healthy ¬ O people of almost no effect. Well absorbed from the intestine. Nitrazepama biotransformation occurs in the liver. The drug accumulates.

The barbiturates, nitrazepam different for the better by following ¬ blowing features: a) a lesser extent, changes the structure of sleep, and b) an ¬ possesses a greater breadth of therapeutic action and therefore less risk of acute poisoning, c) is less pronounced causes the induction of microsomal liver enzymes, and d) less risk of drug dependence ¬ (but consider it necessary). Currently, nitrazepam and similar benzodiazepines he considered the treatment of choice as hypnotics. Particularly effective means of such sleep disorders associated with emotional ¬ nym stress, anxiety

Despite the large number of sleeping pills, the creation of new and better drugs that contribute to the normalization of sleep, still remains one of the most important tasks of pharmacology. It is essential that along with high activity, the absence of side effects and possible therapeutic breadth of new hypnotics Dili does not lead to a breach of sleep cycles did not cause accumulation, pref ¬ Kania and drug addiction.