The nervous system regulates the interaction of organs and organ systems with each other, as well as the entire organism with the environment. The nervous system is divided into central and peripheral. The central nervous system (CNS) includes the brain and spinal cord, while the peripheral nervous system consists of 12 cranial and 31 spinal nerves.

According to the morphological structure, the central nervous system is a collection of individual neurons, the number of which in humans reaches 14 billion. Communication between neurons is carried out through contact between their processes with each other or with the bodies of nerve cells. Such interneuron contacts are called synapses (viparviv- connection). The transmission of nerve impulses at the synapses of the nervous system is carried out using chemical carriers of excitation - mediators, or transmitters (acetylcholine, norepinephrine, dopamine, etc.).

In medical practice, medications are used to change, suppress or stimulate the transmission of nerve impulses at synapses. The effect on the synaptic transmission of nerve impulses leads to changes in the function of the central nervous system, resulting in various pharmacological effects. Medicines are classified according to their main effects: anesthetics, ethyl alcohol, hypnotics, antiepileptics, antiparkinsonians, analgesics, analeptics, psychotropics.

Anesthetics

Anesthesia - where are the drugs, as a result of the administration of which a state of anesthesia occurs in the body (narcosis- numbness).

Anesthesia is a reversible depression of central nervous system function, which is accompanied by loss of consciousness, loss of pain and other types of sensitivity, inhibition of reflex activity and relaxation of skeletal muscles while maintaining cardiovascular activity and breathing.

Anesthesia- one of the methods of general anesthesia.

The pharmacodynamics of anesthetic agents has not been fully studied. All drugs disrupt synaptic transmission in the central nervous system. According to the sequence of central nervous system depression, four stages of anesthesia are distinguished:

I. Stage of analgesia. First, pain sensitivity decreases, and then amnesia occurs. Other types of sensitivity, skeletal muscle tone and reflexes are preserved.

II. Excitement stage. This stage is characterized by language and motor activation, increased blood pressure, respiratory distress, and increased all reflexes (there may be cardiac arrest, vomiting, bronchospasm and laryngospasm).

III. Stage of surgical anesthesia. The patient lacks all types of sensitivity, suppressed muscle reflexes; Normal breathing is restored and blood pressure stabilizes. The pupils are dilated, the eyes are open. There are four levels at this stage.

After the cessation of the administration of anesthesia, stage IV begins - awakening - restoration of the functions of the central nervous system, but in the reverse order: reflexes appear, muscle tone and sensitivity are restored, consciousness returns.

Classification of drugs for anesthesia

1. Means for inhalation anesthesia:

a) volatile liquids - ether, fluorothan (halothane), methoxyflurane, desflurane, enflurane, isoflurane, sevoflurane and the like;

b) gases - dinitrogen oxide, cyclopropane and the like.

2. Means for non-inhalation anesthesia:

a) powders in bottles - sodium thiopental b) solutions in ampoules - sodium hydroxybutyrate, propanidide (Somba-Revin), tropofol (diprivan), ketalar (ketamine, calypsol).

Means for inhalation anesthesia:.

They are administered using special equipment;

Anesthesia is easy to manage;

Most drugs cause irritation of the mucous membrane of the respiratory tract, a feeling of suffocation, and traumatize the patient’s psyche;

They enter the atmosphere and can adversely affect the health of medical personnel.

Ether for anesthesia- a volatile liquid with a pungent odor, quickly deteriorates in light, so it is necessary to check the quality of the drug before use. Boiling point - 35 ° C. Flammable. The ether is highly soluble in water, fats and lipids. Is a strong anesthetic. It has a wide spectrum of narcotic effects and a high safety factor.

Side effects: pronounced stage of excitement; promotes the release of catecholamines, which can lead to arrhythmia and increased blood glucose levels; after anesthesia, nausea, vomiting and constipation may occur; Due to the rapid evaporation of ether from the surface of the respiratory tract, pneumonia may develop in children and may cause convulsions. To eliminate them, thiopental is used.

Ftorotan(halothane) is a volatile liquid. It is destroyed in light, the boiling point is 50 ° C. Ftorotan does not burn and, when mixed with ether, prevents the combustion of the latter. Ftorotan is poorly soluble in water, but well soluble in fats and lipids. A strong anesthetic (exceeds the properties of ether as an anesthetic three times, and nitrous oxide by 50 times), but has a moderate analgesic effect.

Side effects: respiratory depression arrhythmia associated with excitation of myocardial beta-adrenergic receptors, therefore catecholamines (adrenaline, norepinephrine) should not be administered during anesthesia. In case of arrhythmia, β-blockers (propranolol) are administered; heart failure; arterial hypotension; mental changes; hepatotoxic, nephrotoxic, mutagenic, carcinogenic and teratogenic effect; Persons working with fluorotane may have allergic reactions.

Isoflurane, enflurane, desflurane- have less effect on the cardiovascular system.

Dianitrogen oxide- gas, does not explode, but supports combustion. The drug does not irritate the mucous membranes of the respiratory tract. A mixture of 80% nitrous oxide and 20% oxygen is introduced. Anesthesia occurs within 3-5 minutes. There is no stage of excitement. The anesthesia is superficial, so nitrous oxide is used for basic anesthesia and neuroleptic analgesia. The drug is used for pain relief for severe injuries, acute pancreatitis, myocardial infarction, during childbirth, and the like.

Side effects: rarely - nausea, vomiting, arrhythmia, arterial hypertension; hypoxia occurs as a result of prolonged administration of nitrous oxide. It is important to maintain the oxygen content in the gas mixture at a level of at least 20%. After the end of the nitrous supply, the oxides continue to give oxygen for 4-5 minutes.

Means for non-inhalation anesthesia:

They are administered intravenously, intramuscularly or rectally;

Anesthesia occurs immediately without the stage of excitement;

Does not pollute the atmosphere;

Anesthesia is poorly managed.

Classification of inhalation anesthesia drugs by duration of action.

1. Short-acting drugs (duration of anesthesia - 5-10 minutes): propandide (sombrevin), ketamine (ketalar, calypsol).

2. Medium-duration drugs (duration of anesthesia - 20-40 minutes): sodium thiopental, hexenal.

3. Long-acting drugs (duration of anesthesia - 90-120 minutes): sodium hydroxybutyrate.

Thiopental sodium- yellowish or yellowish-green powder, easily soluble in water. The solution is prepared ex tempore in sterile water for injection. Administered intravenously (slowly) or rectally (for children). Anesthesia occurs immediately and lasts 20 minutes.

Side effects: respiratory depression, arterial hypotension, laryngospasm, bronchospasm, reflex cardiac arrest, increased secretion of the bronchial glands.

Sodium hydroxybutyrate is a white powder, easily soluble in water. Available in ampoules of 10 ml of 20% solution. It is administered intravenously slowly, occasionally intramuscularly or administered orally. As a result of administration, the anesthesia stage begins after 30 minutes and lasts 2-4 hours.

Side effects: motor agitation, convulsive tremors of the limbs and tongue due to rapid administration; vomiting, motor and speech agitation upon recovery from anesthesia.

Ketamine(ketalar, calypsol) - white powder, easily soluble in water and alcohol. Ketamine causes dissociated general anesthesia, which is characterized by catatonia, amnesia and analgesia. The drug is administered intravenously or intramuscularly. The duration of anesthesia is 10-15 minutes, depending on the method of administration. Used for induction of anesthesia, as well as for its maintenance. Ketamine can also be used on an outpatient basis for short surgical procedures.

Side effects: arterial hypertension, tachycardia, increased intracranial pressure; hypertonicity, muscle pain; Hallucinatory syndrome (patients need observation after surgery).

CNS depressants

Drug name	Release form	Directions for use	Higher doses and storage conditions
Means for inhalation anesthesia
Ether for anesthesia (Aether pro narcosi)	Liquid in bottles of 100 and 150 ml	2-4 vol. % - Analgesia and loss of consciousness; 5-8 vol. % - Superficial anesthesia; 10-12 rev. % - Deep anesthesia; inhalation
Ftorotan (Halothane) (Phthorothapit)	Liquid in 50 ml bottles	3-4 vol. % - For induction of anesthesia; 0.5-2 vol. % - To support the surgical stage of anesthesia by inhalation
Dianitrogen oxide (Nitrogenium oxydulatum)	Gas in steel cylinders	70-80 rpm % Inhalation	Store in original packaging in a dark, cool place, away from fire and heating devices.
Means for non-inhalation anesthesia
Propanidid (Propanidi-	5% solution in 10 ml ampoules (50 mg/ml)	Intravenously at 0.005-0.01 g/kg
Thiopental sodium (Thiopenta-lumnatrium)	Powder in bottles of 0.5 and 1 g	Intravenously 0.4-0.6 g	List B In a cool, dry, dark place
Sodium hydroxybutyrate (Natru oxybutyras)	Powder 20% solution in ampoules of 10 ml (200 mg/ml); 5% syrup in 400 ml bottles	Intravenously at 0.07-0.12 g/kg; orally 0.1-0.2 g/kg (1-2 tablespoons)	In a dark place at room temperature
Ketamine (Ketaminum)	Liquid in 20 ml bottles (containing 0.05 g of the drug in 1 ml)	Intravenously at 0.002 g/kg; intramuscularly at 0.006 g/kg	Protected from light place

Ketamine anesthesia should not be administered to patients with mental disorders and epilepsy.

Propanidid(sombrevin) - administered intravenously slowly. Anesthesia occurs in 20-40 seconds and lasts 3-5 minutes. The drug is used for induction of anesthesia, as well as on an outpatient basis during short operations and for diagnostic studies (biopsy, suture removal, catheterization).

Side effects: bradycardia, arterial hypotension, heart failure, bronchospasm, anaphylactic shock, thrombophlebitis.

Pharmacosafety:

- Thiopental sodium and other barbiturates cannot be mixed in the same syringe with ketamine, ditilin, pentamin, aminazine and pipolfen, since a precipitate is formed as a result of physico-chemical interaction;

- It is prohibited to write prescriptions for anesthetic drugs.

Measures to prevent complications resulting from the use of anesthesia:

Explosive substances are combined with fluorothane;

Non-inhalational anesthetics are combined with inhalational anesthetics to reduce or eliminate the stage of agitation, sensations of suffocation, and mental trauma;

Before anesthesia, to reduce reflex reactions and limit the secretion of glands, patients are given premedication (preparation for surgery) - atropine (or another M-anticholinergic blocker) is administered to eliminate pain - analgesics (fentanyl, promedol, etc.); to enhance the relaxation of skeletal muscles - muscle relaxants (tubocurarine); to reduce the manifestations of allergies - antihistamines (diphenhydramine, pipolfen) drugs. For premedication, tranquilizers, neuroleptics, ganglion blockers, clonidine and other drugs are also prescribed.

Drugs affecting the central nervous system.

Anesthetic agents.

Narcosis (narcosis - numbness, stunning) is a condition that is characterized by reversible depression of the central nervous system, manifested by loss of consciousness, loss of sensitivity (primarily pain), suppression of reflexes, and decreased tone of skeletal muscles.

History of anesthesia. The discovery of anesthesia is associated with the discovery of the analgesic properties of ether. “Ether” is a word of Greek origin, which means “heavenly fire.” It was discovered as a substance in Spain in 1200. Lullius, and only in 1540 Paracelsus established the analgesic properties of this substance, and Cordus carried out its synthesis. The ether was re-synthesized in 1730 by Frobenius.

Nitrous oxide was obtained by Priestley in 1772, and the English chemist Davy described its analgesic properties, and in 1945 the American doctor Wells used it for tooth extraction. In 1849, the Russian doctor S.K. Klikovich successfully used a mixture of nitrous oxide and oxygen to anesthetize childbirth.

The generally accepted date of birth of anesthesia is considered to be October 16, 1846, when the American dentist Morton publicly gave ether anesthesia to a patient during dental extraction. He was awarded the Prize of the Paris Academy of Sciences, and many countries awarded him orders.

A great contribution to the study of anesthesia was made by A.I. Pirogov, who widely used anesthesia in the field and studied various methods of its administration. His monograph was published in 1947.

Subsequently, many new drugs for anesthesia were found.

Classification of anesthesia

Means for inhalation Means for non-inhalation

anesthesia anesthesia

1.Volatile liquids 2. Gaseous 1. Short acting

Ether for anesthesia - nitrous oxide - Propanidid

Ftorotan - Ketamine

2. Average cont. actions

Thiopental - sodium

3. Long-lasting

Sodium hydroxybutyrate

Inhalation anesthesia agents are administered through the respiratory tract (inhalation).

Non-inhalation anesthesia agents are most often administered intravenously or intramuscularly.

During anesthesia there are different four stages(see ether anesthesia):

I stage of analgesia (3-5 minutes). First of all, the cerebral cortex is depressed: pain sensitivity decreases, consciousness is gradually lost. Reflexes and muscle tone are preserved. Breathing, pulse, blood pressure are not changed, the pupils react to light.

Stage II of excitation (20 min). In the figurative expression of I.P. Pavlov, a “revolt of the subcortex” arises. Sensitivity and consciousness are completely lost. At the same time, motor and speech excitement develops (the patient begins to sing, speak, scream, cry or laugh). Reflexes (cough, gag) and muscle tone increase. Breathing, pulse are increased, blood pressure is increased. The pupils dilate and do not respond to light.

Stage III of surgical anesthesia is characterized by a lack of sensitivity, consciousness, suppression of reflexes, decreased muscle tone, other indicators decrease gradually.

IV Recovery stage (awakening) – 20-40 min.

The functions of the central nervous system are restored in the reverse order. After waking up, post-anesthesia sleep continues for several hours.

Anesthesia must meet the following requirements:

cause deep and prolonged anesthesia

have sufficient narcotic latitude

be well managed

cause rapid development and rapid recovery from anesthesia

do not cause complications

the application technique should be simple and convenient

be fire safe

Characteristics of drugs for inhalation anesthesia

Ether for anesthesia (Aether pro narcosi) - a liquid with a peculiar odor. Fire - explosive. Available in bottles of 100ml and 150ml.

Possesses high activity, wide range of action, easy to control, relaxes skeletal muscles well. Used for all types of operations.

The disadvantages are: slow induction of anesthesia, irritation of the mucous membranes of the respiratory tract, increased salivation and secretion of the bronchial glands, which makes breathing difficult; a long stage of excitement (10-20 minutes), during which cough, vomiting, tachycardia, and increased blood pressure are possible; during the stage of surgical anesthesia, a decrease in blood pressure and respiratory depression are possible; awakening is slow (20-40 minutes), pneumonia and bronchitis may develop in the postoperative period due to irritation of the mucous membranes of the respiratory tract with ether, sometimes nausea and vomiting occur.

To prevent complications, M-x.b (atropine) should be administered before anesthesia.

Ftorotan(Phtorothanum, Narcotan) – a liquid with a peculiar odor in a 50 ml bottle does not burn or explode.

Characterized by high activity (3-4 times higher than ether), rapid introduction to anesthesia (in 3-5 minutes) without the stage of excitation, has a wide range of action, is easy to control, and relaxes skeletal muscles well. Relatively little toxic, does not irritate the respiratory tract, inhibits the secretion of the salivary and bronchial glands. Awakening occurs after 3-5 minutes. after cessation of anesthesia. Nausea and vomiting are rare. Convenient for operations in children.

Flaws: bradycardia (prevented by atropine), arrhythmia, hypotension (mezaton is administered, but adrenaline and norepinephrine cannot be administered due to the increased sensitivity of the myocardium to them). Not recommended for cardiogenic shock. Synthesized in England and introduced into clinical practice in 1956.

Nitrous oxide colorless gas in cylinders of 5-12 liters. Not flammable. Used in a mixture with oxygen (80% nitrous oxide + 20% O 2) to prevent hypoxia. In lower concentrations of nitrogen, nitrous oxide causes a superficial narcosis, reminiscent of intoxication (formerly called “laughing gas”).

Characteristic rapid onset of anesthesia with a short and unexpressed stage of excitation, wide range of action, good controllability, quick recovery from anesthesia, no side effects.

Main disadvantage is low activity, therefore, to enhance the effect and obtain deep anesthesia, it is combined with other drugs.

Can be used for short-term interventions in traumatology, cardiology, dentistry, and obstetrics.

Characteristics of drugs for non-inhalation anesthesia

Preparation	Release form	Start of action	Duration	Side effects
Propanidid (sombrevin)	Solution in ampoules 5% - 10ml, IV			Nausea, tachycardia, muscle twitching, respiratory depression
(ketalar, calypsol)	Solution in bottles of 10 ml IV			tachycardia, increased Blood pressure, delirium, hallucinations after anesthesia
Thiopental sodium	Powder in a bottle of 0.5 and 1 g, greenish-yellow, intravenous			Inhibition of the respiratory and vasomotor centers.
Sodium hydroxybutyrate	Solution in ampoules 20% - 10ml, IV, IM			With rapid administration of convulsions, motor agitation.

Propanidide, ketamine, sodium thiopental used mainly for induction of anesthesia, for short-term operations, for burns, painful instrumental examinations, biopsies, fractures, drainage removal, in dentistry, etc.

Sodium hydroxybutyrate used for introductory and basic anesthesia in patients in a state of hypoxia, in the elderly and children.

Comparative characteristics of inhaled and non-inhaled anesthetics

Ethyl alcohol ( Spiritus acthylicus )

A transparent, volatile liquid with a characteristic odor that is flammable. According to the effect on the central nervous system, 3 stages are distinguished: excitement, anesthesia, agonal.

Normal Arousal Narcosis Paralysis

state

Alcohol is of little use as an anesthetic, because causes a long stage of excitation, and the period of anesthesia quickly turns into the agonal stage, i.e. it has a small range of action.

In medical practice, the irritating and antimicrobial properties of alcohol are used. Alcohol 40% has a pronounced irritant effect and is used for rubbing the skin in liquids, for example, Menovazin, for myositis, arthritis, neuritis, radiculitis, as well as for the prevention of bedsores. With the help of warming compresses for otitis, sore throat, bruises on the second day, when infiltrates occur, etc.

Alcohol 70%, 96% has an antimicrobial effect and is used for treating instruments, etc. Previously, it was widely used as an antiseptic for treating the surgical field and the hands of medical staff.

Alcohol is used as a solvent to prepare solutions, tinctures, and extracts.

Ingestion of alcohol is initially characterized by intoxication. A long stage of excitement is manifested by euphoria, increased mood, excessive talkativeness, and sociability. Psychomotor

reactions are disrupted, behavior, self-control, and performance suffer. Coordination of movement is impaired, reaction slows down, and unsteadiness of gait appears. A feeling of warmth appears. The skin is red, sweating is increased, pulse is frequent, blood pressure is increased. As the dose increases, signs of acute ethyl alcohol poisoning appear. Analgesia, drowsiness, and impaired consciousness occur. The skin is pale or cyanotic, moist, cold (increased heat transfer), breathing is rare, shallow; the pulse is frequent, weak, blood pressure is low, muscle tone and reflexes are decreased. In case of severe poisoning, fecal and urinary incontinence is possible.

I Prevent the absorption of alcohol into the gastrointestinal tract (see earlier)

II Purify the Blood

III Symptomatic treatment:

Analeptics: caffeine, cordiamine, bemegride, B vitamins (B 1 B 6), vitamin C intravenously or intramuscularly.

Chronic alcoholism and its treatment - see student abstracts

Lecture No. 23

Lecture topic: Sleeping pills. Anticonvulsants.

Hypnotics that can cause a person to experience a state resembling physiological sleep. By the nature of their effect on the central nervous system, they are classified as inhibitory substances.

As you know, sleep is absolutely necessary for a person. Prolonged insomnia leads to death sooner than fasting (after 4-6 days).

There are two phases in the sleep process; slow" and REM sleep. The slow-wave sleep phase is characterized by a slowdown in brain activity. It accounts for 75-80% of an adult's total sleep time. The REM sleep phase is characterized by increased brain activity and takes up 20-25% of total sleep time.

Sleeping pills facilitate the onset of sleep, increase its duration, and ensure its depth.

Correlation of stages of action of narcotic substances (scheme)

Anesthetic agents Excitation stage Anesthesia stage Agonal stage

Hypnotics Stage of sleep Stage of anesthesia Agonal stage

Ethyl alcohol Stage of excitation Stage of anesthesia Agonal stage

Classification of sleeping pills, based on their chemical structure

1. Derivatives 2. Derivatives 3. Various drugs

barbituric benzodiazepine chemical structure

acids -nitrazepam - zopiclone

- phenobarbital - rohypnol

In small doses they have a sedative (calming) effect, in medium doses they have a hypnotic effect, and in large doses they have a narcotic effect.

Indications for the use of sleeping pills are various sleep disorders, which can be of three types:

1. disturbance of the process of falling asleep - “insomnia of the young”, occurs in young people with overwork, neuroses, etc.; in this case, drugs of short and medium duration of action are recommended;

2. normal falling asleep, but quick awakening “insomnia of the elderly”, occurs in elderly people with severe cerebral vascular sclerosis; Long-acting sleeping pills are recommended.

3. disturbance of the processes of falling asleep and staying asleep - occurs at any age with various neurotic conditions, sleep can be superficial, not bringing rest, long-acting sleeping pills are recommended, depressing the REM sleep phase

Fenbarbitalo ( Phenobarbitalum)

Long-acting barbiturate. Sleep comes in ½-1 hour, because... poorly soluble and slowly absorbed from the gastrointestinal tract; lasts about 8 hours. Makes it easier to fall asleep, but disrupts the phase structure of sleep. Only 35% is inactivated by the liver and with repeated doses cumulation is possible, which is manifested by aftereffects (weakness, depression, drowsiness, decreased ability to work). With prolonged use, addiction and addiction develop, and with withdrawal, withdrawal syndrome develops.

Contraindications: severe liver and kidney diseases.

Nitrazepam ( Nitrazepamum, Radedorm)

Sleep occurs within 20-30 minutes and lasts 6-8 hours. Difference from phenobarbital: a) changes the structure of sleep to a lesser extent; b) has a wide range of therapeutic effects; c) lower risk of developing drug addiction.

It is used for sleep disorders of various etiologies.

P.d.: in large doses – drowsiness, lethargy, headache.

Contraindications: myasthenia gravis, pregnancy.

Rohypnol (Rohypnol)

Release form: tablets of 0.001 and 0.002, solution in ampoules of 1 ml

Prescribed immediately before bedtime. Accelerates the period of falling asleep, reduces the number of night awakenings

P.d: see nitrazepam

Zopiclone ( Jmovan )

Release form: tablets

Application: insomnia (difficulty falling asleep, night awakenings, early awakenings, chronic insomnia).

Contraindications: children under 15 years of age, pregnancy, nursing.

The sedative effect of hypnotics is used in small doses to treat neuroses, angina pectoris, hypertension, etc. By reducing the excitability of the motor centers of the brain, hypnotics (especially phenobarbital) have an anticonvulsant effect and are used to treat epilepsy.

All sleeping pills slow down reactions to external stimuli, so some categories of people (drivers, pilots, high-altitude workers, dispatchers, etc.) cannot take them while working, and they are prohibited from taking them with alcohol.

Acute poisoning by sleeping pills

In the initial stage, the victim complains of weakness, drowsiness, and headache. In severe poisoning, there is loss of consciousness, respiratory depression, a drop in blood pressure, relaxation of skeletal muscles, the skin is pale, cold, moist, the pupils first constrict and then dilate. Death occurs from paralysis of the respiratory center and cardiac arrest.

Help with poisoning: see ethyl alcohol poisoning.

Antiepileptic drugs

Epilepsy – seizure. Drugs in this group prevent the onset of seizures in epilepsy.

1. grand mal seizures are characterized by convulsions that cover the entire body, accompanied by loss of consciousness, followed by prolonged sleep.

2. Minor seizures are characterized by a short-term loss of consciousness without noticeable convulsions.

3. psychomotor seizures are manifested by impaired consciousness, motor and mental anxiety, and inappropriate actions.

Preparation	Indications for use			Side effects
	Grand mal seizures	Minor seizures	Psychomotor seizures
Phenobarbital tab. 0.05 and 0.1 Ethosuximide (suksilep) Clonazepam tab. 0.0005.0.001 Carbamazepine (finlepsin) Depakine tab.0.3				Drowsiness, headache, mental depression Nausea, vomiting, itching, rash, gingivitis Nausea, headache, dizziness, rash Drowsiness, headache, nausea, ataxia Nausea, headache, drowsiness, blood picture disturbances, arrhythmia. Nausea, vomiting, diarrhea, liver dysfunction, blood patterns, ataxia

Admission rules:

1. The drugs should be used regularly and for a long time; discontinuation may lead to withdrawal syndrome; the dose is reduced gradually.

2. the drug should be prescribed individually, taking into account the form of the disease.

3. It should be remembered that drugs prevent epilepsy attacks, slow down the process of mental degradation, but do not cure the disease.

To relieve status epilepticus, diazepam (Seduxen) IV or IM 0.5%-2 ml is most often used

Antiparkinsonian drugs used to treat illness Parkinson's (shaking palsy).

The disease is associated with damage to the substantia nigra of the brain. At the same time, the content of dopamine, which regulates the activity of motor neurons, decreases, cholinergic receptors are excited - the tone of skeletal muscles increases.

Symptoms: stiffness of movements, mincing gait, mask-like face, muscle rigidity, tremors.

Treatment of the disease can be aimed at either enhancing dopaminergic effects or reducing cholinergic ones.

Levodopa penetrates the brain, where it is converted into dopamine.

Release form: capsules of 0.25 and 0.5

P.d: nausea, vomiting, orthostatic collapse, arrhythmia.

Cycladol has a pronounced central and peripheral anticholinergic effect.

Release form: tablets of 0.002 List A

P.d.: dry mouth, impaired accommodation, tachycardia

In case of an overdose, motor and mental agitation and hallucinations are possible.

P.p.: glaucoma, pregnancy.

On the topic: “Medicines affecting the central nervous system”

Introduction

Antidepressants

Neuroleptics

Literature used

Introduction

This group of drugs includes substances that change the functions of the central nervous system, having a direct effect on its various parts of the brain or spinal cord.

According to the morphological structure, the central nervous system can be considered as a collection of many neurons. Communication between neurons is ensured by contact of their processes with the bodies or processes of other neurons. Such interneuron contacts are called synapses.

The transmission of nerve impulses in the synapses of the central nervous system, as well as in the synapses of the peripheral nervous system, is carried out using chemical excitation transmitters - mediators. The role of mediators in the synapses of the central nervous system is played by acetylcholine, norepinephrine, dopamine, serotonin, gamma-aminobutyric acid (GABA), etc.

Drugs that affect the central nervous system change (stimulate or inhibit) the transmission of nerve impulses at synapses. The mechanisms of action of substances on CNS synapses are different. Substances can excite or block receptors on which mediators act, affect the release of mediators or their inactivation.

Medicinal substances acting on the central nervous system are represented by the following groups:

Anesthesia;

Ethyl alcohol;

Sleeping pills;

Antiepileptic drugs;

Antiparkinsonian drugs;

Analgesics;

Psychotropic drugs (neuroleptics, antidepressants, lithium salts, anxiolytics, sedatives, psychostimulants, nootropic drugs);

Analeptics.

Some of these drugs have a depressant effect on the central nervous system (anesthetics, hypnotics and antiepileptic drugs), others have a stimulating effect (analeptics, psychostimulants). Some groups of substances can cause both stimulating and depressant effects (for example, antidepressants).

Drugs that depress the central nervous system

The group of drugs that most strongly depress the central nervous system is general anesthetics (anesthetics). Next come sleeping pills. This group is inferior to general anesthetics in terms of potency. Next, as the strength of action decreases, there are alcohol, anticonvulsants, and antiparkinsonian drugs. There is also a group of drugs that have a depressing effect on the psycho-emotional sphere - these are central psychotropic drugs: the strongest group is antipsychotic neuroleptics, the second group, inferior in strength to neuroleptics, is tranquilizers, and the third group is general sedatives.

There is a type of general anesthesia called neuroleptanalgesia. For this type of analgesia, mixtures of antipsychotics and analgesics are used. This is a state of anesthesia, but with preservation of consciousness.

For general anesthesia, inhalation and non-inhalation methods are used. Inhalation methods include the use of liquids (chloroform, fluorothan) and gases (nitrous oxide, cyclopropane). Inhalation drugs are now usually combined with non-inhalation drugs, which include barbiturates, steroids (preulol, veadrin), eugenal derivatives - sombrevin, derivatives - hydroxybutyric acid, ketamine, ketalar. The advantages of non-inhalation drugs are that to obtain anesthesia you do not need complex equipment, just a syringe. The disadvantage of this anesthesia is that it is uncontrollable. It is used as an independent, introductory, basic anesthesia. All these remedies are short-acting (from several minutes to several hours).

There are 3 groups of non-inhaled drugs:

1. Ultra-short action (sombrevin, 3-5 minutes).

2. Average duration up to half an hour (hexenal, termital).

3. Long-acting - sodium hydroxybutyrate 40 min - 1.5 hours.

Today, neuroleptanalgesics are widely used. This is a mixture that contains antipsychotics and analgesics. Among the neuroleptics, you can use droperidol, and among the analgesics, phentamine (several hundred times stronger than morphine). This mixture is called talomonal. You can use aminazine instead of droperidol, and instead of phentamine - promedol, the effect of which will be potentiated by some tranquilizer (seduxen) or clonidine. Instead of promedol, you can even use analgin.

ANTIDEPRESSANTS

These drugs appeared in the late 50s, when it turned out that isonicotinic acid hydrazide (isoniazid) and its derivatives (ftivazide, soluzide, etc.), used in the treatment of tuberculosis, cause euphoria, increase emotional activity, improve mood (thymoleptic effect) . Their antidepressant effect is based on the blockade of monoamine oxinase (MAO) with the accumulation of monoamines - dopamine, norepinephrine, serotonin in the central nervous system, which leads to the relief of depression. There is another mechanism for enhancing synaptic transmission - blockade of the reuptake of norepinephrine and serotonin by the presynaptic membrane of nerve endings. This mechanism is typical for so-called tricyclic antidepressants

Antidepressants are divided into the following groups:

1. Antidepressants - monoamine oxidase inhibitors (MAO):

a) irreversible - nialamide;

b) reversible - pirlindole (pyrazidol).

2. Antidepressants - neuronal uptake inhibitors (tricyclic and tetracyclic):

a) non-selective inhibitors of neuronal uptake - imipramine (imisin), amitriptyline, pipofezin (azafen);

b) selective inhibitors of neuronal uptake - fluoxetine (Prozac).

The thymoleptic effect (from the Greek thymos - soul, leptos - gentle) is the main one for antidepressants of all groups.

In patients with severe depression, depression, feelings of uselessness, unmotivated deep melancholy, hopelessness, suicidal thoughts, etc. are relieved. The mechanism of thymoleptic action is associated with central serotonergic activity. The effect develops gradually, after 7-10 days.

Antidepressants have a stimulating psychoenergetic effect (activation of noradrenergic transmission) on the central nervous system - initiative increases, thinking and normal daily activities are activated, and physical fatigue disappears. This effect is most pronounced with MAO inhibitors. They do not provide sedation (unlike tricyclic antidepressants - amitriptyline and azaphene), but the reversible MAO inhibitor pyrazidol may have a calming effect in patients with anxiety and depression (the drug has a regulatory sedative-stimulating effect). MAO inhibitors inhibit REM sleep.

By inhibiting the activity of liver MAO and other enzymes, including histaminase, they slow down the biotransformation of xenobiotics and many drugs - non-inhalation anesthetics, narcotic analgesics, alcohol, antipsychotics, barbiturates, ephedrine. MAO inhibitors enhance the effect of narcotic, local anesthetic and analgesic substances. Blockade of hepatic MAO explains the development of a hypertensive crisis (the so-called “cheese syndrome”) when taking MAO inhibitors with foods containing tyramine (cheese, milk, smoked meats, chocolate). Tyramine is destroyed in the liver and in the intestinal wall by monoamine oxidase, but when its inhibitors are used, it accumulates and deposited norepinephrine is released from the nerve endings.

MAO inhibitors are antagonists of reserpine (even pervert its effect). The sympatholytic reserpine reduces the levels of norepinephrine and serotonin, leading to a drop in blood pressure and depression of the central nervous system; MAO inhibitors, on the contrary, increase the content of biogenic amines (serotonin, norepinephrine).

Nialamid - irreversibly blocks MAO. It is used for depression with increased lethargy, lethargy, trigeminal neuralgia and other pain syndromes. Its side effects include: insomnia, headache, disruption of the gastrointestinal tract (diarrhea or constipation). When treating with nialamide, it is also necessary to exclude foods rich in tyramine from the diet (prevention of “cheese syndrome”).

Pirlindol (pyrazidol) - a four-cyclic compound - a reversible MAO inhibitor, also inhibits the reuptake of norepinephrine, a four-cyclic compound, has a thymoleptic effect with a sedative-stimulating component, has nootropic activity (increases cognitive functions). Basically, the destruction (deamination) of serotonin and norepinephrine is blocked, but not tyramine (as a result, “cheese syndrome” develops very rarely). Pyrazidol is well tolerated, does not have an M-anticholinergic effect (unlike tricyclic antidepressants), complications are rare - slight dry mouth, tremor, tachycardia, dizziness. All MAO inhibitors are contraindicated in inflammatory liver diseases.

Another group of antidepressants are neuronal uptake inhibitors. Non-selective inhibitors include tricyclic antidepressants: imipramine (imisin), amitriptyline, azaphen, fluacizin (fluoroacizin), etc. The mechanism of action is associated with inhibition of the neuronal uptake of norepinephrine and serotonin by presynaptic nerve endings, as a result of which their content in the synaptic cleft increases and adrenergic and serotonergic activity increases transfers. The central M-anticholinergic effect plays a certain role in the psychotropic effect of these drugs (except for azafen).

Imipramine (imisin) is one of the first drugs in this group and has a pronounced thymoleptic and psychostimulating effect. Mainly used for depression with general lethargy and lethargy. The drug has a central and peripheral M-anticholinergic and antihistamine effect. The main complications are associated with the M-anticholinergic effect (dry mouth, impaired accommodation, tachycardia, constipation, urinary retention). When taking the drug there may be a headache, allergic reactions; in case of overdose - insomnia, agitation. Imizin is close in chemical structure to aminazine and, like it, can cause jaundice, leukopenia, and agranulocytosis (rarely).

Amitriptyline successfully combines thymoleptic activity with a pronounced sedative effect. The drug has no psychostimulating effect, M-anticholinergic and antihistamine properties are pronounced. Widely used for anxiety-depressive, neurotic conditions, for depression in patients with somatic chronic diseases and pain syndromes (coronary artery disease, hypertension, migraines, oncology). Side effects are mainly associated with the M-anticholinergic effect of the drug: dry mouth, blurred vision, tachycardia, constipation, difficulty urinating, as well as drowsiness, dizziness, allergies.

Fluacizin (fluoroacizin) is similar in action to amitriptyline, but has a more pronounced sedative effect.

Azafen, unlike other tricyclic antidepressants, does not have M-anticholinergic activity; a moderate thymoleptic effect in combination with a mild sedative effect ensures the use of the drug for mild to moderate depression, neurotic conditions and long-term use of antipsychotics. Azafen is well tolerated, does not disturb sleep, does not cause cardiac arrhythmias, and can be used for glaucoma (unlike other tricyclic antidepressants that block M-cholinergic receptors).

Recently, the drugs fluoxetine (Prozac) and trazodone have appeared, which are active selective serotonin reuptake inhibitors (the antidepressant effect is associated with an increase in its level). These drugs have almost no effect on the neuronal uptake of norepinephrine, dopamine, cholinergic and histamine receptors. Well tolerated by patients, rarely cause drowsiness or headache. nausea.

Antidepressants - inhibitors of neuronal uptake have found wider use in psychiatry, however, drugs in this group cannot be prescribed simultaneously with MAO inhibitors, as severe complications (convulsions, coma) can occur. Antidepressants have become widely used in the treatment of neuroses, sleep disorders (for anxiety-depressive conditions), in elderly people with somatic diseases, for prolonged pain to prolong the effect of analgesics, to reduce severe depression associated with pain. Antidepressants also have their own pain-relieving effect.

PSYCHOTROPIC MEDICINES. NEUROLEPTICS

Psychotropic drugs include drugs that affect human mental activity. In a healthy person, the processes of excitation and inhibition are in balance. A huge flow of information, various kinds of overload, negative emotions and other factors affecting a person are the cause of stressful conditions that lead to the emergence of neuroses. These diseases are characterized by partial mental disorders (anxiety, obsession, hysterical manifestations, etc.), a critical attitude towards them, somatic and autonomic disorders, etc. Even with a protracted course of neuroses, they do not lead to gross behavioral disorders. There are 3 types of neuroses: neurasthenia, hysteria and obsessive-compulsive neurosis.

Mental illnesses are characterized by more serious mental disorders with the inclusion of delusions (impaired thinking, causing incorrect judgments, conclusions), hallucinations (imaginary perception of non-existent things), which can be visual, auditory, etc.; memory impairments that occur, for example, when the blood supply to brain cells changes during sclerosis of cerebral vessels, during various infectious processes, injuries, when the activity of enzymes involved in the metabolism of biologically active substances changes, and in other pathological conditions. These deviations in the psyche are the result of metabolic disorders in nerve cells and the ratio of the most important biologically active substances in them: catecholamines, acetylcholine, serotonin, etc. Mental illnesses can occur with a sharp predominance of excitation processes, for example, manic states in which motor excitation is observed and delirium, as well as with excessive suppression of these processes, the appearance of a state of depression - a mental disorder accompanied by a depressed, melancholy mood, impaired thinking, and suicide attempts.

Psychotropic drugs used in medical practice can be divided into the following groups: antipsychotics, tranquilizers, sedatives, antidepressants, psychostimulants, among which a group of nootropic drugs is distinguished.

Drugs from each of these groups are prescribed for corresponding mental illnesses and neuroses.

Neuroleptics. The drugs have an antipsychotic (eliminate delusions, hallucinations) and sedative (reduce feelings of anxiety, restlessness) effect. In addition, antipsychotics reduce motor activity, reduce the tone of skeletal muscles, have a hypothermic and antiemetic effect, and potentiate the effects of drugs that depress the central nervous system (anesthetics, hypnotics, analgesics, etc.).

Neuroleptics act in the area of ​​the reticular formation, reducing its activating effect on the brain and spinal cord. They block adrenergic and dopaminergic receptors of different parts of the central nervous system (limbic system, neostriatum, etc.) and affect the exchange of mediators. The influence on dopaminergic mechanisms can also explain the side effect of neuroleptics - the ability to cause symptoms of parkinsonism.

Based on their chemical structure, antipsychotics are divided into the following main groups:

¦ phenothiazine derivatives;

¦ derivatives of butyrophenone and diphenylbutylpiperidine;

¦ thioxanthene derivatives;

¦ indole derivatives;

¦ neuroleptics of different chemical groups.

Medicines that stimulate the central nervous system

CNS stimulants include drugs that can increase mental and physical performance, endurance, reaction speed, eliminate feelings of fatigue and drowsiness, increase attention span, memory ability and speed of information processing. The most unpleasant characteristics of this group are general fatigue of the body that occurs after the cessation of their influence, a decrease in motivation and performance, as well as a strong psychological dependence that arises relatively quickly.

Among the mobilizing type stimulants, the following groups of drugs can be distinguished:

1. Adrenergic agonists of indirect or mixed action:

phenylalkylamines: amphetamine (phenamine), methamphetamine (pervitin), centedrine and pyriditol;

piperidine derivatives: meridyl;

sydnonimine derivatives: mesocarb (sydnocarb), sydnophen;

purine derivatives: caffeine (caffeine sodium benzoate).

2. Analeptics:

· acting primarily on the respiratory and vasomotor centers: bemegride, camphor, niketamide (cordiamin), etimizol, lobeline;

· acting primarily on the spinal cord: strychnine, securinine, echinopsin.

Phenylalkylamines are the closest synthetic analogues of the world-famous psychostimulant - cocaine, but differ from it in less euphoria and a stronger stimulating effect. They are capable of inducing extraordinary elation, a desire for activity, eliminate the feeling of fatigue, create a feeling of vigor, clarity of mind and ease of movement, quick intelligence, confidence in one’s strengths and abilities. The effect of phenylalkylamines is accompanied by an elevated mood. The use of amphetamine began during World War II as a means to relieve fatigue, combat sleep, and increase alertness; then phenylalkylamines entered psychotherapeutic practice and gained mass popularity.

The mechanism of action of phenylalkylamines is the activation of adrenergic transmission of nerve impulses at all levels of the central nervous system and in the executive organs due to:

· displacement of norepinephrine and dopamine into the synaptic cleft from the easily mobilized pool of presynaptic endings;

· increased release of adrenaline from chromaffin cells of the adrenal medulla into the blood;

· inhibition of the reverse neuronal uptake of catecholamines from the synaptic cleft;

· reversible competitive inhibition of MAO.

Phenylalkylamines easily penetrate the BBB and are not inactivated by COMT and MAO. They implement the sympatho-adrenal mechanism of urgent adaptation of the body to emergency conditions. Under conditions of prolonged tension of the adrenergic system, under severe stress, debilitating loads, and in a state of fatigue, the use of these drugs can lead to depletion of the catecholamine depot and disruption of adaptation.

Phenylalkylamines have psychostimulating, actoprotective, anorexigenic and hypertensive effects. Drugs in this group are characterized by accelerated metabolism, activation of lipolysis, increased body temperature and oxygen consumption, and decreased resistance to hypoxia and hyperthermia. During physical activity, lactate increases excessively, which indicates inadequate expenditure of energy resources. Phenylalkylamines suppress appetite, cause constriction of blood vessels and increase blood pressure. Dry mouth, dilated pupils, and rapid pulse are observed. Breathing deepens and ventilation of the lungs increases. Methamphetamine has a more pronounced effect on peripheral vessels.

Phenylalkylamines are used in very small doses in the United States to treat sexual disorders. Methamphetamine causes a sharp increase in libido and sexual potency, although amphetamine has little activity.

Phenylalkylamines are indicated:

· for a temporary rapid increase in mental performance (operator activity) in emergency conditions;

· for a one-time increase in physical endurance in extreme conditions (rescue operations);

· to weaken the side psychosedative effect of drugs that depress the central nervous system;

· for the treatment of enuresis, adynamia, depression, withdrawal syndrome in chronic alcoholism.

In psychoneurological practice, amphetamine is used to a limited extent in the treatment of narcolepsy, the consequences of encephalitis and other diseases accompanied by drowsiness, lethargy, apathy, and asthenia. For depression, the drug is ineffective and inferior to antidepressants.

The following drug interactions are possible for amphetamine:

·increasing pain relief and reducing the sedative effect of narcotic analgesics;

· weakening of the peripheral sympathomimetic effects of amphetamine under the influence of tricyclic depressants due to the blockade of amphetamine entry into adrenergic axons, as well as an increase in the central stimulating effect of amphetamine due to a decrease in its inactivation in the liver;

· it is possible to potentiate the euphoric effect when used in combination with barbiturates, which increases the likelihood of developing drug dependence;

Lithium preparations can reduce the psychostimulant and anorexigenic effects of amphetamine;

· neuroleptic drugs also reduce the psychostimulant and anorexigenic effect of amphetamine by blocking dopamine receptors and can be used for amphetamine poisoning;

amphetamine reduces the antipsychotic effect of phenothiazine derivatives;

· amphetamine increases the body's endurance to the action of ethyl alcohol (although the inhibition of motor activity remains);

· under the influence of amphetamine, the hypotensive effect of clonidine decreases; Amphetamine enhances the stimulating effect of midantan on the central nervous system.

Side effects include tachycardia, hypertension, arrhythmias, addiction, drug dependence, exacerbation of anxiety, tension, delirium, hallucinations, and sleep disturbances. With repeated use, depletion of the nervous system, disruption of the regulation of cardiovascular functions, and metabolic disorders are possible.

Contraindications to the use of phenylalkylamines are severe cardiovascular diseases, diabetes mellitus, obesity, and productive psychopathological symptoms.

Due to a variety of side effects, the main thing being the possibility of developing drug dependence, phenylalkylamines find limited use in medical practice. At the same time, the number of drug and substance abuse patients using various phenylalkylamine derivatives is constantly growing.

The use of mesocarb (sydnocarb) causes a psychostimulating effect more slowly than that of amphetamine, and it is not accompanied by euphoria, speech and motor disinhibition, and does not cause such a deep depletion of the energy reserve of nerve cells. According to the mechanism of action, mesocarb is also somewhat different from amphetamine, since it stimulates mainly the noradrenergic systems of the brain, causing the release of norepinephrine from stable depots.

Unlike amphetamine, mesocarb has less pronounced stimulation with a single dose, and its gradual increase is observed from dose to dose. Sidnocarb is usually well tolerated, does not cause dependence or addiction, and its use may increase blood pressure, decrease appetite, and also hyperstimulation phenomena.

Mesocarb is used for various types of asthenic conditions, after fatigue, central nervous system injuries, infections and intoxications. It is effective for sluggish schizophrenia with a predominance of asthenic disorders, withdrawal syndrome in chronic alcoholism, developmental delay in children as a result of organic lesions of the central nervous system with adynamia. Mesocarb is an effective remedy that relieves asthenic phenomena associated with the use of antipsychotic drugs and tranquilizers.

Sidnofen is close in structure to mesocarb, but stimulates the central nervous system weaker and has pronounced antidepressant activity (due to a reversible inhibitory effect on MAO activity), therefore it is used for the treatment of asthenodepressive conditions.

Meridil is similar to mesocarb, but is less active. Increases activity, associative abilities, has an analeptic effect.

Caffeine is a mild psychostimulant, the effects of which are realized by inhibiting the activity of phosphodiesterase and, therefore, prolonging the life of secondary intracellular mediators, mostly cAMP and somewhat less cGMP in the central nervous system, heart, smooth muscle organs, adipose tissue, and skeletal muscles.

The effect of caffeine has a number of features: it does not excite adrenergic transmission in all synapses, but enhances and prolongs the work of those neurons that are currently involved in ongoing physiological reactions and in which cyclic nucleotides are synthesized in response to the action of their mediators. There is information about the antagonism of xanthines towards endogenous purines: adenosine, inosine, hypoxanthine, which are ligands of inhibitory benzodiazepine receptors. Coffee contains substances that are antagonists of endorphins and enkephalins.

Caffeine acts only on neurons that can respond to neurotransmitters by producing cyclic nucleotides. These neurons are sensitive to adrenaline, dopamine, acetylcholine, neuropeptides, and only a few neurons are sensitive to serotonin and norepinephrine.

Under the influence of caffeine the following are realized:

· stabilization of dopaminergic transmission - psychostimulating effect;

· stabilization of b-adrenergic transmission in the hypothalamus and medulla oblongata - increased tone of the vasomotor center;

· stabilization of cholinergic synapses of the cortex - activation of cortical functions;

· stabilization of cholinergic synapses of the medulla oblongata - stimulation of the respiratory center;

· stabilization of noradrenergic transmission - increased physical endurance.

Caffeine has complex effects on the cardiovascular system. Due to the activation of the sympathetic influence on the heart, contractility and conduction are increased (in healthy people, when taken in small doses, the frequency of contractions may slow down due to excitation of the vagus nerve nuclei; in large doses, tachycardia may occur due to peripheral influences). Caffeine has a direct antispasmodic effect on the vascular wall in the vessels of the brain, heart, kidneys, skeletal muscles, skin, but not limbs! (stabilization of cAMP, activation of the sodium pump and hyperpolarization of membranes), increases venous tone.

Caffeine increases the secretion of digestive glands, diuresis (reduces tubular reabsorption of metabolites), increases basal metabolism, glycogenolysis, lipolysis. The drug increases the level of circulating fatty acids, which promotes their oxidation and utilization. However, caffeine does not suppress appetite, but, on the contrary, stimulates it. In addition, it increases the secretion of gastric juice so that drinking caffeine without food can lead to gastritis and even peptic ulcers.

Caffeine is indicated:

· to improve mental and physical performance;

· for emergency care for hypotension of various origins (trauma, infection, intoxication, overdose of ganglion blockers, sympatho- and adrenergic agents, deficiency of circulating blood volume);

· with spasms of cerebral vessels;

· in mild forms of bronchial obstruction as a bronchodilator.

The following side effects are characteristic of caffeine: increased excitability, cardiac arrhythmias, chest pain, insomnia, tachycardia, with long-term use - myocarditis, trophic disorders in the limbs, hypertension, caffeineism. Acute caffeine poisoning produces early symptoms of anorexia, tremors and restlessness. Nausea, tachycardia, hypertension and confusion then appear. Severe intoxication can cause delirium, seizures, supraventricular and ventricular tachyarrhythmias, hypokalemia and hyperglycemia. Chronic use of high doses of caffeine can lead to nervousness, irritability, anger, persistent tremors, muscle twitching, insomnia and hyperreflexia.

Contraindications to the use of the drug are states of excitement, insomnia, hypertension, atherosclerosis, glaucoma.

Caffeine also has various types of drug interactions. The drug weakens the effect of central nervous system depressants, so it is possible to combine caffeine with histamine blockers, antiepileptic drugs, and tranquilizers to prevent central nervous system depression. Caffeine reduces the depression of the central nervous system caused by ethyl alcohol, but does not eliminate the impairment of psychomotor reactions (coordination of movements). Caffeine and codeine preparations are used in combination for headaches. Caffeine can enhance the analgesic effect of acetylsalicylic acid and ibuprofen, and enhances the effect of ergotamine in the treatment of migraines. In combination with midantan, it is possible to enhance the stimulating effect on the central nervous system. When taken simultaneously with cimetidine, the side effects of caffeine are likely to increase due to a decrease in its inactivation in the liver. Oral contraceptives also slow down the inactivation of caffeine in the liver, and symptoms of overdose may occur. When taken together with theophylline, the total clearance of theophylline decreases almost 2 times. If it is necessary to use drugs together, the dose of theophylline should be reduced.

Analeptics (from the Greek analeptikos - restorative, strengthening) are a group of medicines that help restore consciousness in a patient who is in a state of fainting or coma.

Among analeptic drugs, there is a group of drugs that primarily stimulate the centers of the medulla oblongata: vasomotor and respiratory. In large doses, they can stimulate the motor areas of the brain and cause seizures. In therapeutic doses they are usually used for weakening of vascular tone, collapse, respiratory depression, circulatory disorders in infectious diseases, in the postoperative period, poisoning with sleeping pills and narcotic drugs. Previously, a special subgroup of respiratory analeptics (lobeline) was identified from this group, which have a reflex stimulating effect on the respiratory center. Currently, these drugs have limited use.

One of the safest analeptics is cordiamine. Its structure is similar to nicotinamide and has a weak antipellagritic effect. Cordiamine stimulates the central nervous system by direct action on the respiratory center and reflexively through the chemoreceptors of the carotid sinus. In small doses, the drug has no effect on the cardiovascular system. Toxic doses can increase blood pressure, cause tachycardia, vomiting, cough, arrhythmias, muscle rigidity, and tonic and clonic seizures.

Etimizole, in addition to stimulating the respiratory center, induces the secretion of corticoliberin in the hypothalamus, which leads to an increase in the level of glucocorticoids in the blood; inhibits phosphodiesterase, which promotes the accumulation of intracellular cAMP, enhances glycogenolysis, activates metabolic processes in the central nervous system and muscle tissue. Inhibits the cerebral cortex, eliminates anxiety. Due to the stimulation of the adrenocorticotropic function of the pituitary gland, etimizol can be used as an anti-inflammatory agent for arthritis.

Analeptics that primarily increase reflex excitability include: strychnine (an alkaloid from the seeds of the African chilibuha vine), securinine (an alkaloid from the herb of the Far Eastern shrub securinega) and echinopsin (obtained from the seeds of the common echinops). According to the mechanism of action, they are direct antagonists of the inhibitory mediator glycine, blocking receptors of brain neurons sensitive to it. Blockade of inhibitory influences leads to an increase in the flow of impulses in the afferent pathways of activation of reflex reactions. The drugs stimulate the sense organs, excite the vasomotor and respiratory centers, tone the skeletal muscles, and are indicated for paresis, paralysis, fatigue, and functional disorders of the visual apparatus.

The main effects of drugs in this group are:

· increased muscle tone, acceleration and strengthening of motor reactions;

· improving the functions of the pelvic organs (for paralysis and paresis, after injuries, strokes, polio);

· increased visual and hearing acuity after intoxication, injury;

· increase in general tone, activation of metabolic processes, functions of the endocrine glands;

· slight increase in blood pressure and heart function.

The main indications for use of this group: paresis, paralysis, fatigue, asthenic conditions, functional disorders of the visual apparatus. Previously, strychnine was used to treat acute barbiturate poisoning; now the main drug used in this case is bemegride.

Securinine is less active than strychnine, but also much less toxic; it is also used for hypo- and asthenic forms of neurasthenia, and for sexual impotence due to functional nervous disorders.

An overdose of drugs causes tension in the masticatory and occipital muscles, difficulty breathing, swallowing, and attacks of clonic-tonic convulsions. They are contraindicated in case of increased convulsive readiness, bronchial asthma, thyrotoxicosis, coronary artery disease, arterial hypertension, atherosclerosis, hepatitis, glomerulonephritis.

Due to their high toxicity, reflex-type analeptics are used extremely rarely and only in hospital settings.

medicinal nervous system antidepressant psychotropic

Literature used

Katzung B.G. “Basic and clinical pharmacology. In 2 volumes" 1998

V.G. Kukes "Clinical Pharmacology" 1999

Belousov Yu.B., Moiseev V.S., Lepakhin V.K. “Clinical pharmacology and pharmacotherapy” 1997

Alyautdin R.N. "Pharmacology. Textbook for universities" 2004

Kharkevich D.A. "Pharmacology" 2006

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This group of drugs includes substances that change the functions of the central nervous system, having a direct effect on its various parts - the brain, medulla oblongata or spinal cord.

According to the morphological structure, the central nervous system can be considered as a collection of many individual neurons *, the number of which in humans reaches 14 billion. Communication between neurons is ensured by contact of their processes with each other or with the bodies of nerve cells. Such interneuron contacts are called synapses (sinapsis - connection, connection).

* (Neuron is a nerve cell with all its processes.)

The transmission of nerve impulses in the synapses of the central nervous system, as well as in the synapses of the peripheral nervous system, is carried out using chemical excitation transmitters - mediators. The role of mediators in the synapses of the central nervous system is played by acetylcholine, norepinephrine, dopamine and other substances.

Drugs that affect the central nervous system change (stimulate or inhibit) the transmission of nerve impulses at synapses. The mechanisms of action of substances on CNS synapses are different. Thus, some substances can excite or block receptors in synapses with which certain mediators interact. For example, narcotic analgesics stimulate the so-called opiate receptors, and antipsychotics block dopamine and adrenergic receptors. There are also substances that change the synaptic transmission of nerve impulses by influencing the release of certain mediators. For example, the antiparkinsonian drug midantan increases the release of the neurotransmitter dopamine. Certain substances alter the synaptic transmission of nerve impulses by influencing the inactivation of certain transmitters. Thus, antidepressants from the group of monoamine oxidase (MAO) enzyme inhibitors prevent the inactivation of norepinephrine under the influence of this enzyme.

By influencing the synaptic transmission of nerve impulses, drugs change the functions of the central nervous system and, as a result, cause various pharmacological effects. Drugs that affect the central nervous system are usually classified according to their main effects. For example, substances that cause anesthesia are grouped into the group of anesthetics, sleep-inducing substances are grouped into the group of sleeping pills, etc.

Below is a general classification of drugs that affect the central nervous system.

Medicines affecting the central nervous system

1. Anesthesia. 2. Ethyl alcohol. 3. Sleeping pills. 4. Antiepileptic drugs. 5. Antiparkinsonian drugs. 6. Analgesics. 7. Analeptics. 8. Psychotropic drugs: a) neuroleptics; b) tranquilizers; c) sedatives; d) lithium salts; e) antidepressants; f) psychostimulants; g) nootropic drugs.

Among the listed substances there are drugs that have a depressing effect on most functions of the central nervous system. Such substances include anesthetics, ethyl alcohol, and sleeping pills. Along with this, many substances (antiepileptic drugs, neuroleptics, tranquilizers, sedatives) have a more selective inhibitory effect on the functions of the central nervous system.

I. CNS DEPRESSANTS (general action):

Anesthesia;

Sleeping pills;

Alcohols.

II. CNS EXCITANTS (CNS stimulants):

Psychostimulants (psychomotor and psychometabolic);

Analeptics;

Spinal cord stimulators;

General tonics (adaptogens).

III. PSYCHOTROPIC DRUGS (selective depressants):

Sedatives;

Tranquilizers;

Neuroleptics;

Antimanic;

Antidepressants;

IV. ANTI-EPILEPTIC DRUGS.

V. ANTIPARKINSONICS DRUGS.

VI. NARCOTIC AND NON-NARCOTIC ANALGESICS.

Let's start our analysis of drugs that affect the central nervous system with a group of drugs that depress the central nervous system completely. Let's start, first of all, with ALCOHOL. For the clinic, aliphatic alcohols, which are hydroxy derivatives of aliphatic hydrocarbons (that is, with an open carbon chain), are important. They may contain one or two hydroxyl groups or more and, depending on their content, they are divided into monohydroxyl (ethyl, methyl, propyl alcohols), dihydroxyl, also called glycols, since they have a sweet taste (ethylene glycol, propylene glycol), trihydroxyl (glycerol or glycerin ) and polyhydroxyl (mannitol, sorbitol).

ETHYL ALCOHOL is a typical agent that has a general depressant effect on the central nervous system. In addition, it has a pronounced antiseptic effect. Ethyl alcohol is the main component of various alcoholic beverages. It is a colorless, volatile liquid, highly flammable.

ABSORPTION, METABOLISM AND EXCRETION (PHARMACOKINETICS OF ETHANOL).

Ethanol is quickly absorbed in the stomach, duodenum and jejunum. 25% of the dose taken is absorbed into the stomach. It very quickly penetrates all cell membranes and is distributed in the body fluids. Almost half of the ethanol taken is absorbed after 15 minutes and the absorption process is completely completed in about 1-2 hours. Absorption slows down in the presence of water in the stomach. Carbohydrates and fats delay absorption. Ethanol is found in all tissues and, as the concentration in the blood decreases, diffuses from them into the blood. From the vessels of the lungs, ethanol passes into the exhaled air (the ratio of alcohol in the blood and air is 2100: 1).

More than 90-98% of ethanol is metabolized in the liver with the participation of non-microsomolic enzymes, the rest (2-4%) is excreted unchanged by the kidneys and lungs, as well as the sweat glands. First, ethanol is oxidized in the liver to acetaldehyde, which is converted to acetyl coenzyme A, and then oxidized to carbon dioxide and water (carbon dioxide and water).

Alcohol is metabolized at a constant rate, independent of its concentration in the blood, but proportional to body weight. This rate is 10 ml/hour, it is constant, and has significance in forensic examination.

PHARMACOLOGICAL EFFECT: ethanol has a depressant effect on the central nervous system, and it depresses the central nervous system in a descending manner, its effect falls into 3 stages (subject to a large dose taken):

The so-called “excitement” stage;

Stage of anesthesia;

Agonal stage.

The “excitement” stage is the result of inhibition of the brain’s inhibitory mechanisms. It is well expressed and long lasting. Euphoria occurs, mood improves, the person becomes overly sociable and talkative. In this case, psychomotor reactions are disturbed, a person’s behavior sharply suffers, self-control decreases, and character traits such as doubt, caution, critical self-esteem and adequate assessment are leveled out. Performance decreases. A state of mood instability arises, and there may be emotional outbursts.

When the concentration of ethyl alcohol in the blood increases, analgesia, drowsiness, and impaired consciousness occur. Spinal reflexes are suppressed. In this way, the stage of anesthesia develops, which very quickly passes into the agonal stage. The small narcotic breadth of action, as well as the pronounced stage of excitation, do not allow the use of ethyl alcohol as an anesthetic. You can quickly reach the stage of paralysis and agony.

As the dose of injected alcohol increases, a person loses the ability to feel, speech becomes difficult, gait instability appears and self-control is completely lost. Next comes pronounced depression of the central nervous system up to loss of consciousness. Breathing slows down, the face becomes pale, cyanosis appears, and blood pressure drops. Death occurs, as a rule, due to depression of the respiratory center.

The primary effect of alcohol is associated with inhibition of the reticular activating system. (In this regard, the stage of excitation is not at all associated with excitation of the central nervous system, but, on the contrary, is due to the removal of the inhibitory effect of the cortex). The cortex is thus freed from the controlling, inhibitory function necessary for conscious human activity.

Therefore, first of all, alcoholics suffer from what is brought into the personality by culture and many years of training. All drinkers exaggerate their capabilities. Shakespeare, in his famous tragedy “Macbeth,” rightly noted that alcohol creates desires, but deprives opportunities.

EFFECT OF ETHYL ALCOHOL ON VARIOUS ORGANS AND FUNCTIONAL SYSTEMS

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 myrogomal enzymes occurs, and its chronic use causes stimulation of 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 feeling 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.

INDICATIONS FOR USE

In medical practice, the resorptive effect of ethyl alcohol is rarely 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.

Naturally, such people represent a huge medical and social problem for the country. Currently, in Russia, more than 4 million people are registered in drug dispensaries. For comparison, in the USA, official statistics report 9 million people. Alcoholism is the cause of various crimes and social ills. In addition to the development of chronic alcoholism, drinking alcohol can lead to acute poisoning, the degree of which depends on the concentration of alcohol in the blood. The lethal dose of ethanol for a single dose ranges from 4 to 12 grams per 1 kg of body weight (an average of 300 ml of 96 percent alcohol in the absence of tolerance).

Treatment of such a patient consists of applying general measures for detoxification (lavage), maintaining the function of vital organs (respiration, heart), reducing cerebral edema with mannitol and intravenous glucose to correct hypoglycemia, alkalization with intravenous sodium bicarbonate solutions.

Chronic alcoholism is of greater importance, since there are still practically no effective drug treatments for this suffering.

Alcoholism is treated in hospitals. The main task is to stop taking ethyl alcohol and develop a negative attitude towards it. Alcohol addiction is often reversible if treatment is started early and if the person understands that drinking has become a problem for him. The only way to overcome such a condition is to convince the patient that he is sick and that further consumption of alcohol will bring him even more harm. Psychotherapy is the basis of treatment, but it must be supported by medications that create an attitudinal reflex that causes a feeling of aversion to alcohol.

Attempts to develop a negative conditioned reflex to alcohol have been carried out for a long time. In this case, the only centrally effective emetic drug in medicine was used - APOMORPHINE. Subcutaneous administration of apomorphine. This method has 2 main disadvantages:

1) the conditioned reflex requires confirmation (a small dose of alcohol is given and the drug is administered);

2) this reflex is nonspecific.

In connection with the above, the researchers’ thoughts were aimed at creating a drug that would distort the exchange of ethanol and its metabolism. One of these drugs, currently widely used to treat patients with alcoholism, is TETURAM or ANTABUS.

Teturamum (tablets of 500 mg of active ingredient).

Teturam is a pale yellow substance, slightly soluble in water. Small doses have no effect. The drug is prescribed daily to patients and is not effective without alcohol intake.

Due to its slow accumulation in the body, teturam is given to patients for several days. Antabuse is usually prescribed in tablets containing 500 mg of the active principle, once a day for a week. Subsequently, maintenance therapy is carried out with a daily dose of 250 mg of the drug. Then, after a few weeks, the patient is given a small dose of alcohol, that is, Teturam is prescribed in combination with taking small amounts of ethyl alcohol.

This is due to the fact that the mechanism of action of teturam is that it delays the oxidation of ethyl alcohol at the level of acetaldehyde. The latter is due to the inhibition of the enzyme alcoholdehydrogenase by teturam.

As a result of drinking alcohol against the background of Teturam, acetaldehyde will immediately accumulate in the tissues, which is a highly toxic substance to tissues. Acetaldehyde is especially toxic to blood vessels, which results in vascular paralysis, manifested by a peculiar clinical picture. After 15-20 minutes, the patient’s face “flashes up”, the skin becomes red, all blood vessels dilate sharply. Blood pressure drops, very sharply, to the point of collapse. Weakness, sweating, dizziness, headache, confusion, tachycardia, pain in the heart, nausea, vomiting develop. Thus, the patient develops a negative conditioned reflex. The patient becomes convinced that after treatment he will not be able to tolerate even small amounts of alcohol. The latter forces you to abstain from drinking alcoholic beverages.

DISADVANTAGES OR ADVERSE REACTIONS FROM TAKING TETURAM

1) Not all patients can be prescribed teturam (heart damage, atherosclerosis, angina pectoris, hypertension, endocrine diseases, in patients with mental disorders). But among alcoholics there are practically no healthy people; often these people already suffer from these diseases.

2) The conditioned reflex fades away and requires reinforcement.

3) The drug causes weakness, nausea, headaches, cramps, fatigue, and a metallic taste in the mouth.

4) During treatment with Teturam, anesthesia and paraldehyde should not be used, as they cause effects similar to those of ethanol. In addition, some drugs from completely different groups can have teturam-like activity, that is, they cause intolerance to alcohol. These are, first of all, chlorpropamide and other antidiabetic sulfonamide drugs, metronidazole (Trichopol), griseofulvin, butadione. When prescribing these drugs, the doctor must warn the patient about their characteristics.

For the constant (or long-term) presence of teturam in the body, there is a long-acting drug called teturam, called ESPERAL (radotel).

Esperal (radotel) - sterile Teturam tablets are implanted into the patient’s subcutaneous tissue (creating a drug depot).

Available drugs can reduce the consumption of ethyl alcohol only in some patients and only for a few months. Unfortunately, there are no sufficiently effective medications to suppress the craving for alcohol.

The main thing is that it is necessary to change the existing personality structure, although this is incredibly difficult.

METHYL ALCOHOL (METHANOL)

Methanol is widely used in technology, and also in the form of 5 percent concentration for the denaturation of ethyl alcohol. For doctors it is interesting from the point of view of toxicology, since poisoning with this alcohol very often occurs.

Methanol absorption and distribution are similar to those of ethanol. But the metabolism of methanol occurs very slowly in the body and has other metabolic products. Methanol slowly oxidizes to formaldehyde and then to formolic acid, making it very toxic. The conversion of formaldehyde to formic acid is carried out by the same enzyme as ethyl alcohol (alcohol dehydrogenase).

PHARMACOLOGICAL EFFECTS OF METHANOL

Initially, the effects resemble those of ethanol exposure and are due to central nervous system depression. Symptoms are associated with inhibition of central nervous system function, the development of acidosis (formolic acid), as well as selective toxicity of metabolites, in particular formaldehyde to retinal cells.

We must remember that:

1) Formaldehyde has a specific, selective effect on the optic nerves. Loss of vision occurs before death. Complete loss of vision can also occur from very small amounts of methanol (taking about 15 ml of methanol leads to blindness in 100 percent of cases).

2) The lethal dose of methanol without treatment is 70-100 ml. Coma quickly develops and death occurs.

MEASURES OF HELP:

1) Combating acidosis as quickly as possible (intravenous administration of sodium bicarbonate solutions).

2) Inhibit, slow down the formation of formic acid by diverting alcohol dehydrogenase to another alcohol - ethanol. Therefore, ethanol is prescribed intravenously, as it slows down the oxidation of methanol, acting in the process of metabolic transformations according to a competitive type.

CNS DEPRESSANTS. HYPOPICS.

Sleep is a vital necessity for humans. Healthy people spend approximately 1/3 of their lives sleeping. At the same time, sufficient sleep time is an extremely important factor in human health. Meanwhile, in our age, many people complain of lack of sleep and insomnia, as a result of which the amount of sleeping pills and sedatives consumed increases. They are often used indiscriminately because their number is large. Often addiction develops to them, and acute poisoning also develops.

Sleeping pills include drugs that promote the development and normalization of sleep (causing the desire to sleep). The number of sleeping pills is currently large. But only a few groups of drugs are of practical importance.

In this lecture we will analyze 2 groups most often used in clinical practice.

Group 1 - barbituric acid derivatives (barbiturates). These include phenobarbital (luminal), barbital, barbital sodium, barbamyl, etaminal sodium. The most widely used of these drugs is phenobarbital.

The 2nd group of sleeping pills are benzodiazepine derivatives. Of these derivatives, we will analyze only one drug - NITRAZEPAM (Nitrazepamum).

PHENOBARBITALUM (powder and tablets of 0.005, 0.05, 0, 1).

There are 3 main pharmacological effects of barbiturates and, in particular, phenobarbital:

1) Hypnotic effect. Typically, this effect appears 30-40-50 minutes after ingestion of a phenobarbital tablet and lasts on average 8-10 hours. This is a long-acting drug.

2) In small doses, 1/3-1/5 or less of the hypnotic dose, phenobarbital has a sedative, calming effect.

3) Anticonvulsant, or rather, antiepileptic effect. It must be said that all barbiturates have an anticonvulsant effect. This drug is specifically active for the prevention of large, generalized convulsive epileptic seizures (Grand mal). Practically inactive in petit mal seizures.

4) In addition, phenobarbital increases the activity of microsomal liver enzymes.

Based on the pharmacological effects, INDICATIONS FOR THE USE of barbiturates (phenobarbital) are formulated.

1) Phenobarbital is used as a sedative. Barbiturates are rarely used for this purpose, since they are now in most cases replaced by benzodiazepines, which have clear advantages. Today, the sedative effect of phenobarbital has faded into the background.

2) Phenobarbital is used as a sleeping pill. It is prescribed as a sleeping pill for all types of insomnia. However, there is one thing that you must always remember. When writing a prescription for phenobarbital as a sleeping pill, the doctor must indicate in the signature that the patient should take the pill 40-50 minutes before bedtime. Moreover, it should be clearly explained to the patient what this means. The fact is that the nature of sleep is very individual and varies from person to person. Some people have deep sleep, others have shallow and sensitive sleep. In the latter case, a person falls asleep with a turd, sleeps less, and wakes up more often. The duration of sleep for such a person decreases, or the sleep is heavy, with dreams and nightmares.

Before prescribing sleeping pills, the doctor must clearly understand the genesis of insomnia. Sometimes it can be a consequence of physical discomfort caused by pain, breathing problems, fever, mental status disorders (agitation, depression, psychosis). Sometimes insomnia can be drug-induced, for example, when using large doses of drugs such as ephedrine, amphetamines, or drinks containing caffeine.

It is important for the doctor to make sure that the cause of insomnia is not some organ pathology that should be eliminated.

Sometimes, with mental disorders, insomnia requires a thorough examination by specialists. In these cases, sleeping pills are ineffective.

With primary insomnia, sometimes simple procedures help the patient: patients should not sleep during the day; a few hours before bedtime, they should be recommended to do some physical activity. Patients should go to bed at a certain time and only in a state when they have a desire to sleep. After all, sleeping pills are drugs that cause a desire to sleep, namely, after 30-60 minutes, under the influence of phenobarbital, the desire to sleep develops; the patient should be advised not to engage in mental work before going to bed, and to drink a glass of milk (d-tryptophan, which shortens the time of falling asleep). Walk in the fresh air before bed.

If insomnia remains after all the general recommendations of the doctor, then he should have no doubt about the need to prescribe sleeping pills.

3) Phenobarbital, stimulating liver function, increases the production of glucuronyl transferase, which ensures the metabolism of bilirubin, therefore it is used to treat certain types of jaundice in newborns.

SIDE EFFECTS OF BARBITURATES (PHENOBARBITAL)

The most significant side effect of all sleeping pills, and barbiturates especially, is the aftereffect. This effect is manifested in the fact that even after a single dose of barbiturates, the next day after waking up, a person feels lethargy, weakness, impaired psychomotor reactions, adynamia, a feeling of dissatisfaction with sleep, drowsiness, irritability, and nausea. This state is the effect of the consequence, the aftereffect. In English this is called the apt term “Hang over” effect, that is literally “hangover”. The consequence is due to 2 reasons.

1) Barbiturates are slowly eliminated from the body, which means they act for a long time. The slower the drug is eliminated (inactivated), the more pronounced the effect. So, for example, a decrease in the content of phenobarbital in the blood plasma by 50 percent (t 1/2 - half-life of elimination) occurs after approximately 3.5 days, and therefore the consequence is almost always observed and is very pronounced.

Various processes take part in stopping the hypnotic effect of barbiturates. One of the ways to eliminate phenobarbital is through enzymatic inactivation by microsomal liver enzymes. Only part of it, constituting 50-80 percent of the administered dose, undergoes biotransformation of phenobarbital in the liver, and 20-30 percent is excreted unchanged in the urine. Urinary excretion depends on urine pH and quantity. Considering the above, it becomes clear that in case of liver pathology, accompanied by a decrease in the activity of enzyme systems, the duration of action of babiturates increases. It should be taken into account that barbiturates, especially phenobarbital, cause the induction of microsomal enzymes, that is, it stimulates its own biotransformation in the liver and many other drugs (ralal anticoagulants, butadione, etc.). Apparently, this is one of the main reasons for the development of addiction to barbiturates.

If renal function is impaired, the effect of barbiturates is also prolonged (20-30 percent is eliminated through the kidneys).

It should also be noted that barbiturates, when used repeatedly, are characterized by material accumulation, which is associated with their slow elimination and binding of barbiturates to plasma proteins.

2) The second reason for the effect, more important than noted above, is that barbiturates significantly disrupt the normal structure of sleep.

In the sleep structure of a healthy person, there are 2 types of sleep. This division was carried out on the basis of EEG, electrooculo- and electromyogram data using electrophysiological studies of human sleep. One type of sleep is characterized by the appearance of “sleep spindles” and slow, fairly high waves on the EEG, immobility of the eyeballs and muscle tension in the submandibular region. This is the so-called “slow” sleep, slow-wave sleep (orthodox, pre-brain, synchronized sleep).

Another type of sleep is characterized by the disappearance of “sleep spindles” on the EEG, the eyeballs are in rapid motion, and the muscles of the submandibular region are relaxed. This type of sleep is referred to as rapid eye movement or paradoxical sleep (post-brain, desynchronized). Fast-wave sleep in English-language literature is also referred to as the REM phase. REM sleep is characterized by increased blood pressure and tachycardia. The paradox of this dream is that despite a person’s deep sleep, the EEG records a picture characteristic of the period of wakefulness; this indicates a high intensity of metabolic processes in neurons and memory consolidation processes at this time.

REM sleep is accompanied by dreams and increased blood flow in the brain. In healthy young people, slow-wave sleep precedes fast sleep, which occurs at intervals of about 90 minutes throughout the night. REM sleep lasts 20-30 minutes several times a night and generally takes up about 20-25 percent of total sleep time. Normal sleep, consisting of two types, can change with various diseases, as well as under the influence of medications.

Inhibition of the functional activity of specific and nonspecific structures of the brain stem and cortical analyzers by phenobarbital leads to the development of the hypnotic effect of the drug. It turned out that most sleeping pills, or rather all drugs, and especially barbiturates, significantly alter the normal structure of sleep. First of all, this concerns “fast wave” sleep, when the latent period for the appearance of the first phase of “rapid” sleep increases and its total duration decreases. The duration, the “specific gravity” of the slow-wave sleep phase, increases accordingly. In other words, barbiturates (phenobarbital) inhibit the REM phase and suppress it. Therefore, the development of the aftereffect is noted.

The second side effect is that the withdrawal of sleeping pills and barbiturates is accompanied by a “recoil” phenomenon, the severity of which depends on the dose of the drugs and the period of their use. At the same time, the duration of REM sleep for a certain time exceeds the usual values, there is an abundance of dreams, nightmares, and frequent awakenings. In this regard, the search for ideal sleeping pills is very important.

3rd effect - with repeated use of barbiturates, tolerance quickly develops, which is associated with the ability of barbiturates to induce the activity of microsomal enzymes in hepatocytes. The latter accelerates the metabolism of oral anticoagulants, glucocorticoids, and butadione.

4) Phenobarbital can interact with and enhance (potentiate) the effects of alcohol, antihistamines (histamine), and tranquilizers.

5) Drug dependence (mental and physical) develops on barbiturates.

In addition, side effects also include agitation, headache, vomiting, muscle pain, allergic reactions, and anemia.

Due to the use of large doses of drugs over a long period of time, barbiturate poisoning is not uncommon. Acute barbiturate poisoning occurs as a result of an accidental or deliberate (for the purpose of a suicide attempt) overdose of drugs. Barbiturate poisoning with suicidal intent is in first place. CNS depression occurs, characterized by the following chain of events: sleep - deep sleep - coma - paralysis of the respiratory center.

TREATMENT OF PATIENTS WITH ACUTE POISONING includes all known measures of assistance. Carry out gastric lavage, give adsorbents and saline laxatives. Forced diuresis is performed (large amounts of liquid plus furosemide). Specific assistance measures include the introduction of alkaline solutions (IV soda), that is, urine is alkalized.

At very high concentrations of barbiturates in the blood, hemosorption is performed and the patient is transferred to artificial respiration. In order to correct the developed collapse (a sharp drop in blood pressure of central origin, the direct effect of barbiturates on the ganglia and the direct myotropic vasodilator effect), EPHEDRINE is administered, which both increases blood pressure and excites the central nervous system.

The next group of sleeping pills is the sleeping pills from the group of tranquilizers. First of all, NITRAZEPAM (Nitrazepamum - tablets of 0.005 and 0.01), which is a benzodiazepine derivative. Many tranquilizers belonging to the benzodiazepine group have pronounced hypnotic activity (nitrazelam, sibazon, or diazepam, phenazepam). But in nitrazepam this property is dominant, which is why the latter is currently widely used as a hypnotic. Despite the fact that this is one of the drugs of modern tranquilizers, according to the main pharmacological effect, nitrazpam is classified as a hypnotic. In our country the drug is produced under the name nitrazepam, in Hungary - eunoctine, in Germany it is produced as radedorm.

Nitrazepam is one of the best sleeping pills. Possesses:

1) sleeping pills,

2) sedative (tranquilizing),

3) anticonvulsant,

4) myorelaxing (muscle-relaxing) activity.

It has a number of advantages as a sleeping pill over barbiturates.

1) It takes effect 20-30 minutes after taking the tablet.

2) The hypnotic effect lasts 6-8 hours.

3) It has a greater breadth of therapeutic action and therefore practically eliminates the possibility of poisoning; nitrazepam is less toxic.

4) The main advantage is that nitroozepam, to a lesser extent than barbiturates, suppresses the REM phase of sleep, that is, it changes the structure of sleep to a lesser extent. Clinically, the sleep induced by nitrozepam is more refreshing, with a less pronounced aftereffect compared to barbiturates (T 1/2 = 18-34 hours).

5) Nitrazepam almost does not induce the activity of the microsomal enzyme system of the liver.

6) Interacts less with other drugs, although, like barbiturates, it can enhance and prolong the effect of anesthesia, ethyl alcohol, and narcotic analgesics.

7) Drug addiction develops less often with nitrazepam.

Due to these advantages, nitrazepam and similar benzodiazepines are currently considered the drugs of choice as hypnotics. Such remedies are especially effective for sleep disorders associated with emotional stress, restlessness, and anxiety.

Continuing the topic “CNS depressants” briefly, touching only on the pharmacological effects, we will examine the next group, namely ANESTHIC DRUGS. Regarding terminology, you cannot say “narcotic”; you need to say either ANESTHETICS, or GENERAL ANESTHETICS.

NARCOSIS is a condition characterized by reversible general depression of the central nervous system, manifested by loss of consciousness, suppression of sensitivity (primarily pain), reflex reactions, muscle tone while maintaining vital functions (breathing, circulation, metabolism).

THE MECHANISMS OF ACTION of anesthesia drugs are associated with the fact that they inhibit the interneuronal (synaptic) transmission of excitation to the central nervous system. There is a disruption in the transmission of afferent impulses, a change in cortical-subcortical relationships. The emerging functional disintegration of the central nervous system, associated with disruption of synaptic transmission, causes the development of anesthesia.

The sequence of action of anesthetic agents on the central nervous system is as follows:

Cerebral cortex (consciousness);

Spinal cord (skeletal muscles);

Medulla oblongata (vital centers - breathing, blood circulation).

Synaptic formations at different levels of the central nervous system and different morphofunctional organizations have unequal sensitivity to anesthesia. For example, the synapses of the activating reticular formation of the brain stem are especially highly sensitive to anesthesia, while the synapses of the centers of the medulla oblongata are most resistant to them. The difference in the sensitivity of synapses at different levels of the central nervous system explains the presence of certain stages in the action of general anesthetics.

THERE ARE CERTAIN STAGES OF NARCOSIS, which are observed when using most anesthetics.

1st stage of analgesia, stunning, rausch anesthesia. Analgesia is loss of pain sensitivity. From Greek "an" - denial, algos - pain. The analgesia stage begins from the moment the drug is inhaled (if this is the route of administration) and continues until the patient loses consciousness. Thus, consciousness is preserved at this stage. Sensitivity is reduced, reflexes and muscle tone are preserved. At this stage, only superficial operations are possible: opening of felon, abscess, tooth extraction, some obstetric operations (interventions).

Stage 2 - stage of excitement (delirium). It begins with loss of consciousness to a state of surgical anesthesia. During this stage, agitation, screaming, increased muscle activity, breath holding, tachypnea, and hyperventilation may be observed. Consciousness is absent, reflexes and tone are all strengthened (removal of the inhibitory function of the cerebral cortex is observed).

Undesirable effects of this stage (motor agitation, increased tone of skeletal muscles, vomiting) can be minimized by proper premedication.

Stage 3 - stage of surgical anesthesia. There are 4 levels of this stage: 1st - superficial; 2nd - light; 3rd - deep; 4th - ultra-deep surgical anesthesia. As the dose of the drug increases, the anesthesia deepens. Anesthesia during major surgical interventions is carried out at the 2nd-3rd levels of the 3rd stage. This stage is characterized by the gradual loss of reflexes, rhythmic breathing and relaxation of skeletal muscles. Reflexes are lost. Almost the loss of the eyelid reflex and the development of rhythmic breathing indicates the onset of surgical anesthesia. Finally, the 4th stage is the paralysis stage or agonal stage. It is characterized by pronounced depression of the centers of the medulla oblongata. Gradually, complete paralysis of the respiratory muscles and diaphragm develops, breathing stops, which is accompanied by vasomotor collapse - the heartbeat stops.