3. CNS inhibitors Narcotic drugs.

Anesthesia - numbness, stunning. Reversible inhibition of the functions of the central nervous system, which is accompanied by loss of consciousness, loss of sensitivity, a decrease in reflex excitability and a decrease in muscle tone.

As a rule, anesthesia is used in surgical operations.

Funds for anesthesia affect the transmission of nerve impulses in the synapses of the CNS.

During anesthesia, breathing, palpitations, etc., are present and not disturbed.

The sensitivity of CNS synapses to narcotic substances is not the same. Example: Ether primarily acts on the cells of the cortex and the reticular formation. The cells that are more sensitive to anesthesia are depressed first of all and only then the less sensitive cells are suppressed.

All drugs are divided into:

- Means for inhalation anesthesia and non-inhalation anesthesia; substances of gaseous and volatile form, volatile, which are introduced through the respiratory tract;

- funds for non-inhalation anesthesia; substances that are administered intravenously and less intramuscularly.

INHALATION DRUGS. Ether, halothane, nitrous oxide (gas), methoxyflurane - substances are introduced by inhalation (inhalation). Inhalation devices are used for their introduction, are introduced into the body through special masks or intubation tubes through the trachea. These substances are volatile substances, in addition to nitrous oxide (gaseous form).

A) Liquid volatile substances. Ether has high drug activity and sufficient drug latitude (pain sensitivity is completely blocked).

There are several stages in the action of narcotic substances. During ether anesthesia, there are four stages:

Analgesia (no pain) . After absorption of ether into the blood, depression of the reticulum develops. formation, as well as the cells of the cortex GM, is observed decrease in pain sensitivity and gradual suppression of consciousness. at the same time, the unconditioned reflexes remain (breathing, pulse, pressure practically do not change), and by the end of the stage pain sensitivity is completely lost.

Stage of arousal . It develops with the further deepening of the action of the ether on the cortex of the GM. Consciousness is completely lost, but at the same time manifestations of certain types of nervous activity are observed: motor activity increases and speech activity can be observed. At the same time, muscle tone increases sharply, cough and vomiting reflexes are enhanced; breathing, pulse, pressure increased. All this is connected with the deactivation of the brake control on the part of the cortex with respect to the sub-root or stem centers.

Stage of anesthesia. The inhibitory effect of ether on GM is increasing, extends to the spinal cord. Excitement passes. The unconditioned reflexes are inhibited, the muscle tone decreases. Inside this stage there are four levels.

Stage of recovery or awakening . This stage begins when the drug is stopped; CNS functions are restored. Everything happens in reverse order. Awakening lasts 20-40 minutes, after which a long post-anesthetic sleep occurs.

In case of an overdose of anesthesia, the fourth stage is designated as agonal. In this case, the drug acts on all structures of the central nervous system, including the respiratory and vasomotor centers.

As a result, breathing is inhibited, the pulse quickens, blood pressure decreases.

Observed cyanosis - blue skin and mucous surfaces. The pupil of the eye is maximally expanded. Death comes when you stop breathing.

B) Narcotic gases.

The advantages in speed of onset of anesthesia, but requires the use of equipment (nitrous oxide) - "laughing, intoxicating gas" is the most common.

Disadvantage: weak effect of narcotic action, therefore it is used in combination with intravenous administration of narcotic substances.

Cyclopropane

Its disadvantage: it can have a toxic effect on the heart. As a result, arrhythmia will occur up to the flutter of the ventricles of the heart (contraindicated in patients with cardiovascular diseases).

Nitrous oxide is an optimal narcotic substance.

2. UNVEALABLE NARCOTIC SUBSTANCES.

The main method of administration is intravenous. Anesthesia quickly comes and you can clearly create a concentration in the blood.

For inhalation anesthesia, only those substances are used that are rapidly destroyed and quickly leave the brain tissue.

Non-volatile narcotic substances are widely used as sleeping pills and are taken orally (tablets by mouth).

All funds for non-inhalation anesthesia are divided into:

- barbituric acid derivatives (barbiturates). For example, hexenal, thiopental sodium.

- non-barbitic drugs: sodium oxybutyrate, propanidide, ketamine, etc.

Features of the action of barbiturates:

- when the chemical structure changes, the pharmacological effect changes, both persistent long-acting substances (used as a hypnotic) and short-acting substances (used as anesthesia) can be formed;

- lipid solubility and increased narcotic action associated with an increase in the number of carbon atoms.

Representatives:

Barbital (veronal) - a persistent compound that causes prolonged CNS depression, is used as a sleeping pill;

barbamil (amital) + etamininal (nembutal) - substances stronger, but shorter, are used for anesthesia;

Hexenal is a more short-term, strong, rapidly deteriorating drug;

thiopental - similar to 3-4;

luminal (phenobarbital) - used as a soporific and anticonvulsant.

By the duration of the action barbiturates are divided into :

- long-acting drugs: barbital and phenobarbital

- hypnotic drugs, almost never used as anesthesia;

- medium long-lasting agents: barbamyl and cyclobarbital, etamilan and hexabarbital;

- means of short-term action: hexenal, metahexital, thiopental. This group is used only for intravenous use!

The second group is used as a narcotic and hypnotic effect, but the dose is lower than the narcotic effect, and in this case they are the basic (main) anesthesia for inhalation anesthesia.

Intravenous barbiturates.

Sodium salts are used. In terms of blood pH, these compounds are well soluble in lipids and quickly penetrate from the blood into the brain. These funds lead to the third stage of anesthesia.

For anesthesia, the solution injected must be of a certain concentration and injected at a certain rate. At high rates of administration, respiratory arrest may occur. For such complications, it is necessary to administer excitatory substances + artificial respiration.

Positive qualities of intravenous anesthesia:

1. quick onset without discomfort;

2. lack of salivation (salivation);

3. quick awakening;

4. the absence of complications in the postoperative period.

Non-Barbiturates for Intravenous Administration.

Propanidide is an oily liquid that does not dissolve in water, therefore it is dissolved in a surfactant. It is fast and short-acting. After 30 seconds, anesthesia occurs, lasts 3-4 minutes. This is due to the active hydrolysis of its structure. No complicated consequences.

"-" effects:

drop in blood pressure;

tachycardia, increased breathing.

Ketamine - anesthesia occurs in 1-2 minutes, lasts 15 minutes. It is administered intravenously. Intramuscularly in 3-4 minutes, lasts 30 minutes.

Features:

1. quick attack;

2. deep analgesia;

3. preserves muscle tone and reflexes.

In the postoperative period, some adults, but not children, have delusional states and hallucinations. During the period of anesthesia: due to increased sympathetic tone, increased heart rate.

Sodium oxybutyrate - it is similar in its structure to the inhibitory mediators? -Aminobutyric acid, is slightly toxic, has a greater breadth of narcotic action.

The disadvantage is that it is not very manageable, because anesthesia is slow and lasts a long time (2-4 hours).

Steroid drugs.

They are similar in structure and properties to steroid hormones.

Positive features of steroid drugs

1. mild onset of anesthesia without arousal;

2. good muscle relaxation;

3. quick awakening without discomfort;

4. low toxicity

5. "soft" action

Representatives:

Predion (viadril).

After 3-5 minutes, anesthesia occurs and lasts 30-40 minutes.

Complications: irritation of the walls of the veins => the occurrence of thrombophlebitis => used in solution in the solution of glucose and novocaine.

Alfaxalon and alphadolone - low toxicity and mild action.

OUTSIDE MEANS.

Sleep by Pavlov - diffuse inhibition of the cortex and subcortex. Lack of sleep leads to the development of neurotic states and mental disorders. Orthodox phase 90 min, characterized by deep sleep; paradoxical - 15-20 min (shallow change 5 times per night).

Barbiturates and Noxiron have an effect, shortening the paradoxical and increasing the orthodox phase of sleep.

Chloral hydrate has no such effect on the paradoxical stage of sleep.

Characteristics of hypnotic drugs:

1. weakly inhibit the nervous system, reduce its excitability, as a result of which contribute to falling asleep;

2. suppressing the reaction to external stimuli with simultaneous preservation of movements, reflexes, sensations, pain;

Sleep is not anesthesia. Sleeping after taking a sleeping pill is longer and requires a long awakening.

The negative effect of hypnotics: as a rule, all hypnotic drugs are not removed from the body after the night. As a result, a decrease in mental performance, the occurrence of drowsiness, the whole day a feeling of "weakness."

In secondary techniques, the accumulation of sleeping pills occurs, and prolonged use leads to addiction.

The mechanism of action of hypnotic drugs is mainly mediated through the inhibition of the ascending part of the reticular formation.

Sleeping pills of barbiturates act on the subcortex, on the hypothalamic centers, and are capable of preventing the development of dystrophic lesions.

Drugs with hypnotic activity are classified based on the principle of their action and chemical structure.

I. Benzodiazepine receptor agonists

1) Benzodiazepine derivatives (nitrazepam, lorazepam, nozepam, temazepam, diazepam, phenazepam, flurazepam)

2) preparations of different chemical structure (zolpidem, zopiclone)

Ii. Hypnotic drugs with narcotic type of action

1) Heterocyclic compounds (derivatives of barbituric acid, more precisely, barbiturates of long and medium duration)

2) Aliphatic compounds (chloral hydrate)

Many anxiolytics related to benzodiazepine derivatives have pronounced hypnotic activity. The sedation that occurs with their action contributes to the development of sleep.

The widely used hypnotics include barbituric (long-acting) compounds: barbital (veronal), phenobarbital (luminal). Medium-duration barbiturates-hypnotics include: barbamyl, etaminal, cyclobarbital, and secabarbital.

Chloralhydrate belongs to the aliphatic sleeping pills, which contributes to the development of sleep for up to 8 hours.

ALIPHATIC ALCOHOLS

ETHANOL

Ethyl alcohol - by its chemical structure and pharmacological properties refers to narcotic substances.

Features of action:

- when using, various reflexes arise as a result of irritations of the mucous membranes, the heart rhythm changes, salivation occurs, and respiration is excited. High concentration (40% and above) leads to reflex separation of mucus, and in low concentrations (from 4-7%) the excretion of gastric juice increases;

- Alcohol is rapidly absorbed by the mucous membrane of the stomach and intestines;

the effect of alcohol on the cortex is manifested in the form of alcohol stimulation, is the result of the weakening of inhibition;

- performance drops, it is associated with a depressant effect on the ascending part of the reticular formation;

- The effect takes place with full preservation of consciousness, but with deep intoxication, the inhibitory effect spreads to the excitatory processes in the cortex; the result is drowsiness or loss of consciousness;

- the dorsal and medulla are less sensitive to alcohol than the cortex and subcortex; spinal reflexes are also impaired by deep intoxication, and the inhibitory effect on the vasomotor center refers only to the part that is responsible for skin vessels. As a result of alcohol intake, reddening of the skin is observed + a subjective sensation of heat, which does not correspond to the actual body temperature, with deep intoxication the heat transfer exceeds the heat production => death due to freezing;

- alcohol has a small narcotic breadth and the doses that cause depression of the spinal cord, can lead to disruption of the respiratory center, so alcohol is not used as anesthesia.

Alcohol in the body is oxidized to CO ₂ and water, but only 10% of the alcohol consumed is released, the rest is burned in the tissues, as a result of which energy is released. As a result of good absorption properties, which do not require the work of enzymes, alcohol is used as a nutrient in weak, depleted and febrile patients.

The resorptive effect of ethyl alcohol is directed mainly to the central nervous system. It has a suppressive effect on it, increasing with an increase in the concentration of ethyl alcohol in the blood and brain tissues. This manifests itself in the form of 3 main stages: 1) the stage of excitation; 2) anesthesia stages; 3) agonal stage.

The arousal stage is the result of the inhibition of the brain's inhibitory mechanisms. It is usually well defined and long lasting. There is euphoria, the mood rises, the person becomes overly sociable, talkative. At the same time, psychomotor reactions are disturbed, human behavior, self-control, an adequate assessment of the environment are sharply affected; performance reduced.

With an increase in blood concentration come analgesia, drowsiness, then consciousness is disturbed. Oppressed spinal reflexes. The stage of anesthesia begins, which, however, is short-lived and soon passes into the agonal stage. A small narcotic latitude, as well as a pronounced stage of arousal, do not allow the use of ethyl alcohol as a means for anesthesia.

One of the manifestations of the central action of ethyl alcohol is its effect on thermoregulation, which consists in increasing heat transfer. In the cold, ethyl alcohol contributes to hypothermia, the subjective sensation of heat after taking alcohol is not accompanied by a general increase in body temperature.

The diuretic effect of alcohol is caused by a decrease in the production of antidiuretic hormone of the posterior lobe of the pituitary.

It has an effect on the digestive system: it enhances the secretory activity of salivary and gastric glands, the activity of pepsin at low concentrations (up to 10%) does not change, and increases with an increase in its concentration; from 20% ethyl alcohol inhibits the secretion of hydrochloric acid and the digestive activity of gastric juice , especially when taking alcoholic beverages with a strength of 40% and above. In response to high concentrations of alcohol, the gastric glands produce a significant amount of mucus. Ethyl alcohol in high concentrations causes spasm of the pylorus and reduces the motility of the stomach.

In medical practice, it is used as an anti-shock agent (given its analgesic effect), rarely as a soporific or sedative. In some cases, the appointment of ethyl alcohol (in low concentrations) to debilitated patients is indicated.

With prolonged use of ethyl alcohol, addiction to it and drug dependence (mental and physical) develop.

Intoxication occurs approximately at a concentration of 1-2 g / l (100-200 mg%). At 3-4 g / l (300400 mg%) pronounced intoxication develops. Deadly concentrations range from 5 to 8 g / l (500-800 mg%).

In the treatment of alcohol coma should establish adequate breathing. Conduct toilet toilet, clean the upper respiratory tract. Atropine is injected to reduce the secretion of the salivary and bronchial glands. They prescribe inhalation of oxygen, carry out artificial ventilation of the lungs, administer analeptics (corazol, cordiamine, caffeine, etc.), carry out symptomatic therapy. It is also necessary to wash the stomach; correction of the acid-base state is necessary (sodium bicarbonate is injected intravenously) In case of a serious condition of the patient, hemodialysis is performed.

The normal blood alcohol concentration is 1 millimoles per liter (0.0004%).

In the case of mild intoxication, the concentration rises to 0.2-0.02%. Depends on the sensitivity of the NA to alcohol.

If the concentration reaches 0.4%, then a coma occurs; 0.7% - respiratory arrest. Death results from the cessation of breathing.

Unlike brain tissue, other tissues and organs are less sensitive to alcohol. In acute intoxication, the kidney function is disturbed a little, but the level of oxycorticosteroids increases in the blood, and as a result, the diuretic effect.

The treatment is performed by gastric lavage + stimulants on NA.

Along with gastric disorders (delirium tremens), disorders in various organs can be observed, but, as a rule, this happens during chronic alcoholism.

When alcohol is discontinued (chronic), abstinence occurs, resulting in an exacerbation of neurotic symptoms:

Stage 1 - tremor, passing into a convulsive seizure;

Stage 2 - hallucinations, delirium tremens with images of small and large sizes;

Stage 3 - occurs in 2-3 weeks, at this time a person may die as a result of collapse (decrease in pressure).

MEANS OF ELIMINATION FROM ALCOHOL DEPENDENCE.

Chronic poisoning is characterized by a particularly strong change in higher nervous activity, intelligence. Mental performance, attention, memory are reduced. Mental disorders can occur (delirium tremens, Korsakov's psychosis). Peripheral innervation is also affected (polyneuritis may occur).

Alcoholism is accompanied by chronic gastritis, liver cirrhosis, fatty degeneration of the heart and kidneys.

With alcoholism, there is a gradual mental and physical degradation of the individual.

The main task of treating alcoholism is to develop a negative attitude towards it. The elimination of ethyl alcohol should be gradual.

Drug treatment of alcoholism should always be combined with psychotherapy. Any methods of weaning are associated with the development of negative-conditioned reflexes, when the combination of alcohol intake occurs with an emetic agent (anomorphine).

One of the drugs used in the treatment of alcoholism is teturam (antabuse, disulfiram).

Assign teturam in combination with the intake of small amounts of ethyl alcohol. The mechanism of action of teturam is that it delays the oxidation of alcohol at the level of acetaldehyde. The accumulation of the latter in the body causes intoxication, which is accompanied by painful sensations. There is a feeling of fear, pain in the heart, headache, hypotension, excessive sweating, nausea, vomiting.

The course of treatment with teturam produces in patients a negative reflex to ethyl alcohol. It is not recommended for teturam over the age of 50 years, as well as for cardiovascular diseases, pathologies of the liver, kidneys and metabolism.

There is a teturam drug of prolonged action e with pepal (radoter). Esperaral tablets are implanted into the subcutaneous tissue.

Sometimes, an emetic tool of central action apomorphine is used to produce negative conditioned reflexes (also combined with ethyl alcohol intake).

In addition, in the treatment of alcoholism, the antagonist of opioid analgesics is widely used, but also various psychotropic drugs.

Unfortunately, there are no sufficiently effective drugs that suppress the craving for ethyl alcohol.

OTHER ALCOHOLS.

IZOAMILOVA ALCOHOL.

These are so-called fusel oils. Possess great toxicity and drug power. Fusel oils oxidize in the body more slowly than alcohol => cause a heavy hangover.

METHYL ALCOHOL (WOOD).

Formaldehyde and formic acid are formed in the body. This is associated with the duration of the drug. As a result of the use of depression, the NA lasts several days, paralysis of the medulla oblongata is possible, optic nerve neuritis is characteristic => blindness. 50 ml cause death.

Ethylene glycol .

Part of the technical fluids. Toxicity is associated with its transformation into oxalic acid. In addition to the central nervous system affects the kidneys.

ANTI-TRAFFIC MEANS.

The main indication is epilepsy. These funds differ by the nature of epilepsy. Some are used in the case of large seizures, others with small seizures, and others with psychomotor epilepsy.

The very first remedy for the treatment of epilepsy is bromine.

Then phenobarbital, which has a depressant effect on the central nervous system, in anticonvulsant doses lowers mental performance.

Diphenyl is a synthetic substance with a greater anticonvulsant and less soporific effect. Its mechanism is based on blocking the spread of excitation in the GM, and not suppressing the primary focus. In addition, the drug is able to inhibit impulses along the pyramidal (motor) paths.

For large epileptic seizures, etopgoin and phenytoin are used.

For small seizures, trimethine and ethosuxinide are used.

MEANS USED IN PARKINSON'S DISEASE.

Болезнь проявляется дисфункцией двигательных реакций, сопровождается ригидностью (повышенная двигательная активность, импульсация) и дрожанием (одновременный гипертонус мышц антагонистов: сгибание-разгибание).

Причина в нарушении передачи тормозных импульсов в системе: чёрная субстанция, полосатое тело, хвостатое ядро.

Болезнь связана с отсутствием или нарушением синтеза медиатора дофамина (мало ацетилхолина).

Причиной является дегенерация дофоминовых нейронов. Для лечения применяется дофаминоэргические и дофаминолитические препараты.

В качестве медикаментозного средства вводится ДОФА.